Impact of MRONJ-Associated Medications on Mandibular Cortical Index: A Cross-Sectional Analysis

Impact of MRONJ-Associated Medications on Mandibular Cortical Index: A Cross-Sectional Analysis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Impact of MRONJ-Associated Medications on Mandibular Cortical Index: A Cross-Sectional Analysis Halil İbrahim Durmus, Mehmet Emrah Polat, Şeğmus Özdemir This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7098395/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Objectives: Medication-related osteonecrosis of the jaw (MRONJ) is a serious complication associated with antiresorptive and antiangiogenic medications, such as bisphosphonates and denosumab, frequently prescribed for osteoporosis and oncologic bone conditions. This study aimed to evaluate the effects of MRONJ-associated medications on mandibular cortical bone morphology using the Mandibular Cortical Index (MCI) on panoramic radiographs, and to compare these findings with those from a healthy control population undergoing routine dental evaluation. Materials and Methods: This cross-sectional study included 62 participants, divided equally into two groups: 31 patients currently receiving medications known to be associated with MRONJ risk, and 31 healthy individuals without a history of such medication use. Panoramic radiographs were obtained for all participants, and the mandibular cortex was evaluated using the MCI classification. Additionally, demographic data, systemic disease presence, and duration of medication use were recorded and analyzed to identify any correlations with cortical bone changes. Results: The comparison of MCI scores between the study and control groups revealed a statistically significant difference (p = 0.003), with the C1 category—representing normal cortical morphology—being more prevalent in the control group. Although no significant differences were identified among the various medication subgroups (e.g., bisphosphonates vs. denosumab), the study group had a significantly higher prevalence of systemic diseases and longer durations of medication use. These findings suggest a possible link between prolonged exposure to MRONJ-associated drugs and early radiographic signs of mandibular bone alteration. Conclusion: Although no specific medication group showed distinct radiographic signs of MRONJ, overall MCI differences between medication users and controls may assist in early diagnosis and clinical decision-making in MRONJ management. Medication-related osteonecrosis of the jaw (MRONJ) Osteoporosis Radiographic assessment Bifosfonat Mandibuler kortikal index (MCI) Figures Figure 1 Figure 2 1. Introduction Bisphosphonates have demonstrated significant efficacy in reducing osteoclast-mediated bone resorption by inhibiting osteoclast activity. These pharmacological agents are employed in the management of various conditions where bone resorption must be mitigated or controlled. While oral bisphosphonates (BPs) are frequently advised for the treatment of osteopenia and osteoporosis, intravenous formulations are utilized to prevent skeletal-related events in patients with malignancies such as multiple myeloma and cancers that metastasize to bone, including prostate, breast, lung, and renal cancers [1]. One of the major iatrogenic complications associated with long-term bisphosphonate administration is the occurrence of bisphosphonate-related osteonecrosis of the jaw (BRONJ), characterized by necrotic bone exposure and impaired healing of the maxillofacial region. The estimated incidence of BRONJ is approximately 2–3% for intravenous BP use and 0.02–0.4% for oral administration [2]. The jaw bones are among the most vulnerable areas of the body with respect to both healing and bacterial exposure, factors that may significantly play a role in shaping the appearance of BRONJ. Tooth extraction is recognized as one of the main risk factors for the onset of BRONJ in patients undergoing BP therapy. Research suggests that the risk of BRONJ occurring after tooth extraction is approximately 122.6 times higher in patients treated with BP than in those not on such therapy [3]. Extensive research has been conducted to develop drugs that provide the therapeutic benefits of bisphosphonates while minimizing side effects, especially the occurrence of BRONJ. As a result of these efforts, the human monoclonal antibody denosumab was developed, which effectively inhibits osteoclast activity [4]. Research indicates that DMB may match or surpass bisphosphonates in its capacity to inhibit bone resorption [5].) In contrast to BP, DMB is specifically designed to block a protein involved in the key signaling pathways of bone resorption, referred to as the nuclear factor [6].However, findings indicate that denosumab-related osteonecrosis of the jaw (DRONJ) exhibits clinical features similar to BRONJ [7]. Anti-resorptive agents are considered significant risk factors for the progression of MRONJ, particularly in cancer patients. The American Association of Oral and Maxillofacial Surgeons (AAOMS) defines MRONJ as a severe complication which may present in patients with a background of using antiresorptive or antiangiogenic agents. This condition is defined by exposed bone or a chronic fistula persisting for over eight weeks, without any prior history of radiotherapy In 2014, due to the rising incidence of osteonecrosis linked to treatments other than bisphosphonates, the AAOMS formally revised the terminology from BRONJ to MRONJ [8]. Early radiographic identification of bisphosphonate-related bone changes may serve as an indicator for the potential development of BRONJ. Consequently, in patients receiving bisphosphonate therapy who Indicate the need for tooth treatment extraction or other aggressive dental procedures, the detection of bone alterations on radiographs can inform dental treatment planning [3]. Panoramic radiography is a frequently utilized imaging technique in dentistry. Therefore, it may be regarded as an important diagnostic tool for dental professionals [9].However, it is crucial to ensure diagnostic accuracy by avoiding projection errors due to head positioning [10].Panoramic radiographs are also used to detect changes in the mandibular cortex. The interaction between mandibular bone mass and skeletal integrity regions suggests that panoramic radiographs can be useful in evaluating osteoporosis [11]. MCI is a simple, descriptive tool used for classifying the radiographic images of the mandible[10,12]. Some studies suggest that panoramic radiographs may be helpful in identifying individuals with diminished bone mineral density or osteoporosis [13], while others argue that panoramic radiographs cannot definitively diagnose osteoporosis and recommend bone densitometry, especially for postmenopausal women with cortical erosion [10,14]. Our research intends to examine the mandibular bone structure through the MCI in patients using medications associated with the potential for MRONJ, in comparison with a healthy population undergoing regular dental check-ups. 2. Materials and Methods This study, based on retrospective data, was performed in line with the regulations of the Declaration of Helsinki and was approved by the Ethics Committee for Clinical Research at Harran University (approval date and number: 13.01.2025; HRÜ / 25.01.15). In our study, panoramic radiographs of 31 patients using medication with potential to cause MRONJ and 31 individuals in the control group, Patients who sought care at the Department of Oral and Maxillofacial Surgery at Harran University Faculty of Dentistry between June 2023 and October 2024 for dental treatment, were analyzed. MCI analysis was used on these radiographs to evaluate the quantity of cortical bone and changes in mandibular bone density. Each patient was asked to submit a health-related form. Medical records were obtained, including whether patients had systemic diseases, and if so, the type, dosage, and duration of medication used. Panoramic radiographs were obtained using standard methodology at the Harran University Faculty of Dentistry. Radiographic images were acquired using a PaX-I (Vatech, South Korea) device (mA=8, kVp=60, time=10s) and evaluated using EasyDent software (Ver. 4.1.5.9). The structure of the mandibular inferior cortical bone was evaluated based on the analysis of both the right and left regions of the mandible distal to the mental foramen, using Klemetti’s classification. (10) (Figures 1 and 2): C1: The cortical endosteal border appears smooth and well-defined bilaterally. C2: The inner cortical boundary presents with semilunar resorption defects, alongside residual cortical structures measuring one to three lamellar layers. C3: The cortical layer shows significant endosteal remnants and exhibits marked porosity Statistical Analysis Data normality was assessed was first tested using the Shapiro-Wilk test. For age comparisons between groups with normally distributed data, independent sample t-tests and one-way ANOVA were used. For categorical data, if expected cell frequencies were all greater than 5, Pearson’s Chi-square test was used; otherwise, Fisher’s exact test was applied. Multiple comparisons were analyzed using the Bonferroni-adjusted Z test. Quantitative data are presented as mean ± standard deviation (Mean ± SD), while categorical data are expressed as frequency (n) and percentage. The threshold for statistical significance was established at p<0.05. Data evaluation was performed using IBM SPSS software, version 27 (IBM Corp. 2020). 3. Results The population showed no racial or ethnic heterogeneity; all participants were from the Southeastern Anatolia Region of Turkey. The study population was composed of 25 women (mean age: 62) and 6 men (mean age: 57.5), and were classified according to the Klemetti MCI classification as follows: 2 patients as C3, 16 patients as C2, and 13 patients as C1. In contrast, the control group, consisting of 25 women (mean age: 61.8) and 6 men (mean age: 57.5), included 4 patients classified as C3, 17 as C2, and 10 as C1 (Table 1). Table 1 presents Characteristics related to demographics and clinical status of patients in the case and control groups. There were no substantial statistical differences in the age and gender distributions between the groups (p>0.05). Nevertheless, a notable statistical discrepancy was identified between the groups concerning the presence of systemic disorders (p<0.001). All patients in the study group (100%) had systemic diseases, whereas only 32.3% of the control group did. Additionally, a significant statistical variation a significant difference was identified among the groups in terms of the categories of systemic conditions (p<0.001). A remarkable distinction was found between the groups in terms of the occurrence of MCI levels (p=0.003), particularly regarding the proportion of patients with MCI level C1. Significant differences were observed between groups in the use of denosumab and zoledronic acid (p=0.001 and p0.05). A significant variation was observed between the groups regarding the length of medication use (p<0.001). Table 2 presents findings related to the relationship between MCI levels and demographic and clinical characteristics. No statistically substantial correlation was identified between MCIlevels and gender, age, or systemic disease status (p>0.05). No significant relationship was observed between MCI levels and medication use (p>0.05), nor was there a significant relationship between MCI levels and duration of medication use (p=0.051). 4. Discussion MRONJ is an uncommon yet severe and multifactorial pathology generally associated with antiresorptive and antiangiogenic agents used to treat osteoporosis, Paget's, hypercalcemia, and metabolic bone disorders due to malignancies. As outlined by the American Association of Oral and Maxillofacial Surgeons (AAOMS), the diagnosis of MRONJ necessitates the presence of all three of the following conditions: prior or current use of drugs with antiresorptive or antiangiogenic properties, bone that is visible or can be accessed via an intraoral or extraoral tract in the maxillofacial region area persisting for over eight weeks. and no prior exposure to radiotherapy or evidence of metastatic involvement in the jaw bones AAOMS identifies three main drug classes associated with MRONJ: BP, RANKL inhibitors, and antiangiogenic agents [15]. BP, which are analogs of inorganic pyrophosphate, suppress bone resorption and mineralization by promoting osteoclast apoptosis [16]. DMB is a monoclonal antibody targeting RANKL, which suppresses osteoclast development and activity [17]. Despite differing mechanisms, both drugs lead to slowed bone turnover and accumulation of unresorbed, hypermineralized bone [18]. Antiangiogenic agents inhibit neovascularization, leading to circulatory issues such as ischemia and hypoperfusion [17]. This cross-sectional study aimed to investigate bone density and MRONJ risk in patients with histories of using different drugs potentially causing MRONJ, using MCI analysis on panoramic radiographs. BMD Is a critical marker of bone health and can be evaluated through various methods, such as quantitative computer tomography (QCT), single or dual-energy X-ray absorptiometry (SXA or DEXA), and quantitative ultrasound (QUS) [13,19]. Nonetheless, these methods are costly [19,20]. Therefore, developing more economical yet reliable alternatives can be beneficial. Various mandibular radiomorphometric indices are employed in panoramic radiographic imaging to identify conditions affecting bone health, such as low BMD in postmenopausal women. These indices can be evaluated either quantitatively (e.g., cortical thickness) or qualitatively (e.g., mandibular cortical morphology). Although quantitative indices have proven effective, qualitative indices are often preferred in clinical settings due to their simplicity and practicality. The visual assessment of endosteal cortical width (ECW) and MCI are examples of reliable qualitative indices used to detect low BMD [21]. The visibility of the ortical bone of the mandible's inferior portion on dental panoramic radiographs has been widely investigated as a radiological marker of skeletal BMD [22,23]. The MCI, developed by Klemetti et al. [24], classifies the mandibular cortex into three types based on subjective evaluation of porosity, with "C3" representing a cortex with heavy endosteal residues and clear porosity. The prevalence of porosity increases with age [25], and MCI is significantly associated with mandibular BMD [26]. Thus, in our study, we chose to evaluate BMD in patients using BP and DMB through MCI analysis on panoramic radiographs. Rocha et al. suggested that early detection of bone changes through panoramic radiographs facilitates MRONJ diagnosis [27]. Various imaging techniques, such as panoramic radiography, periapical radiography, CT, and MRI, have shown findings like osteolytic lesions, bone proliferation, lamina dura thickening, and increased cortical definition during bisphosphonate treatment [28]. Additionally, cortical bone erosion, sequestrum formation, and pathological mandibular fractures have been reported in panoramic radiographs of bisphosphonate users [29]. In our study, sequestrum formation and post-treatment sequelae were observed in six patients. Torres et al. [30] examined the thickness, cross-sectional dimensions, and volume of the mandibular cortex in patients with MRONJ and control group participants without BP use. MRONJ patients showed significantly higher values. Panoramic radiographs showed that cortical bone thickness in MRONJ patients (6.81 ± 1.35 mm) was significantly higher than in non-MRONJ patients (5.44 ± 1.09 mm) and normal controls (4.79 ± 0.85 mm) As stated by Hamada et al. [22], Patients with MRONJ exhibited augmented cortical bone structure and enhanced trabecular bone radiodensity on computed tomography (CT) compared to healthy controls. Iwata et al. also measured vestibul and lingual cortical bone thickness in three groups: MRONJ patients, patients treated for osteoporosis without signs of MRONJ, and non-osteoporotic individuals. They found significantly thicker cortical bone in MRONJ patients but no significant difference between medicated and healthy non-MRONJ groups [23]. Consistent with this, our study showed that the group using MRONJ-associated drugs had greater mandibular cortical bone thickness than the control group, based on the Klemetti MCI classification. Our study has several constraints. First, it was retrospective, and the oral health status of patients before medication use was unknown. Additionally, the relatively small sample size may influence the statistical strength. Third, radiographic evaluations were based on panoramic radiographs, which are two-dimensional and highly influenced by head and neck positioning. However, due to their lower radiation dose compared to CT and medical imaging, routine availability, ease of access, and suitability for follow-up, panoramic radiographs were preferred. 5. Conclusion Although no prominent differences were found among medicated subgroups in terms of the radiographic characteristics of MRONJ, there was a significant difference between the medicated and control groups in terms of MCI scores. The results obtained may contribute to the accurate diagnosis, effective treatment planning, and prognostic evaluation of MRONJ. Abbreviations MRONJ Medication related osteonecrosis of the jaw BRONJ Bifosfonat related osteonecrosis of the jaw DRONJ Denosumab related osteonecrosis of the jaw BP Bisphosphonates CBCT Cone-beam computer tomography MCI Mandibular cortical index Declarations Authors’ contributions Conceptualization: H.I.D. and S.O.; methodology: H.I.D.; software: H.I.D. and M.E.P; validation: M.E.P, H.I.D. and S.O.; formal analysis: M.E.P and S.O.; investigation: M.E.P.; resources: S.O; da-ta curation: H.I.D.; writing—original draft preparation: H.I.D. and S.O.; writing—review and ed-iting: H.I.D. and S.O.; visualization: M.E.P..; supervision: H.I.D.; project administration: H.I.D. and S.O.; funding acquisition: M.E.P. All authors have read and agreed to the published version of the manuscript. Funding The authors declare that no funding was received for this study. Data Availability The data that support the findings of this study are available from the corresponding author upon request. Declarations Competing interests The authors declare that they have no competing interests. Ethics approval and consent to participate This study was performed in line with the regulations of the Declaration of Helsinki and was approved by the Ethics Committee for Clinical Research at Harran University (approval date and number: 13.01.2025; HRÜ / 25.01.15). Informed consent was obtained from all patients for being included in the study. Consent for publication Not applicable. Halil İbrahim Durmus: 0000-0003-4762-4788 / [email protected] Mehmet Emrah Polat: 0000-0002-0749-0407 / [email protected] Şeğmus Özdemir3: 0000-0002-1279-0893 / [email protected] References Gutta R, Louis PJ. Bisphosphonates and osteonecrosis of the jaws: science and rationale. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2007;104(2):186 – 93. 10.1016/j.tripleo.2006.12.004 . Epub 2007 Apr 20. PMID: 17448709. 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Tables Table 1 Analysis of demographic and clinical characteristics according to groups Control (n = 31) Study (n = 31) Test Stat. p Gender Female 25 (80.6) 26 (83.9) - 1.000 x Male 6 (19.4) 5 (16.1) Age 62.71 ± 9.83 62.55 ± 9.83 0.065 0.949 t Systemic Diseases None 21 (67.7) 0 (0) - < 0.001 x Yes 10 (32.3) 31 (100) Systemic Diseases* None 21 (55.3) a 1 (1.8) b 78.809 < 0.001 k Heart 5 (13.2) a 10 (17.9) a Blood Pressure 3 (7.9) a 8 (14.3) a Asthma 2 (5.3) a 1 (1.8) a Diabetes 7 (18.4) a 5 (8.9) a CML 0 (0) 1 (1.8) Rheumatoid Arthritis 0 (0) 3 (5.4) Breast Cancer 0 (0) 3 (5.4) Multiple Myeloma 0 (0) 1 (1.8) Osteoporosis 0 (0) 23 (41.1) MCİ C1 8 (25.8) a 16 (51.6) b 11.193 0.003 x C2 15 (48.4) a 15 (48.4) a C3 8 (25.8) 0 (0) Denosumab No. 31 (100) 21 (67.7) - 0.001 x Yes 0 (0) 10 (32.3) Zoledronic Acid No. 31 (100) 20 (64.5) - < 0.001 x Yes 0 (0) 11 (35.5) Methotrexate No. 31 (100) 29 (93.5) - 0.492 x Yes 0 (0) 2 (6.5) Aledronate No. 31 (100) 29 (93.5) - 0.492 x Yes 0 (0) 2 (6.5) Imatinip No. 31 (100) 30 (96.8) - 1.000 x Yes 0 (0) 1 (3.2) Ibandronic Acid No. 31 (100) 30 (96.8) - 1.000 x Yes 0 (0) 1 (3.2) Ocralicizumab 1 No. 31 (100) 30 (96.8) - 1.000 x Yes 0 (0) 1 (3.2) Ocralicizumab 2 No. 31 (100) 30 (96.8) - 1.000 x Yes 0 (0) 1 (3.2) Alectinib No. 31 (100) 30 (96.8) - 1.000 x Yes 0 (0) 1 (3.2) Pamidronate No. 31 (100) 30 (96.8) - 1.000 x Yes 0 (0) 1 (3.2) Nibulumab No. 31 (100) 30 (96.8) - 1.000 x Yes 0 (0) 1 (3.2) Rituximab No. 31 (100) 30 (96.8) - 1.000 x Yes 0 (0) 1 (3.2) Duration of Use Not Used 31 (100) 0 (0) 70.868 < 0.001 x 0–6 Months 0 (0) 4 (12.9) 6–12 Months 0 (0) 6 (19.4) 12–18 Months 0 (0) 9 (29) 18–24 Months 0 (0) 7 (22.6) 24 Months and more 0 (0) 5 (16.1) t: Independent two sample t test, k: Pearson chi-square test, x: Fisher test, a-b: No difference between groups with the same letter (Z test with Bonferroni correction), mean ± sd, sd: Standard deviation, n (%) Table 2 Analysis of demographic and clinical characteristics according to MCI levels C1 (n = 24) C2 (n = 30) C3 (n = 8) Test Stat. p Gender Female 18 (75) 26 (86.7) 7 (87.5) 1.334 0.526 x Male 6 (25) 4 (13.3) 1 (12.5) Yaş 61.5 ± 11.88 62.2 ± 7.16 67.63 ± 10.88 1.250 0.294 f Systemic Diseases None 8 (33.3) 11 (36.7) 2 (25) 0.376 0.933 x Yes 16 (66.7) 19 (63.3) 6 (75) Denosumab No. 19 (79.2) 25 (83.3) 8 (100) 1.546 0.505 x Yes 5 (20.8) 5 (16.7) 0 (0) Zoledronic Acid No. 17 (70.8) 26 (86.7) 8 (100) 3.604 0.120 x Yes 7 (29.2) 4 (13.3) 0 (0) Methotrexate No. 23 (95.8) 29 (96.7) 8 (100) 0.667 1.000 x Yes 1 (4.2) 1 (3.3) 0 (0) Aledronate No. 24 (100) 28 (93.3) 8 (100) 1.665 0.622 x Yes 0 (0) 2 (6.7) 0 (0) Imatinip No. 24 (100) 29 (96.7) 8 (100) 1.531 1.000 x Yes 0 (0) 1 (3.3) 0 (0) Ibandronic Acid No. 24 (100) 29 (96.7) 8 (100) 1.531 1.000 x Yes 0 (0) 1 (3.3) 0 (0) Ocralicizumab 1 No. 24 (100) 29 (96.7) 8 (100) 1.531 1.000 x Yes 0 (0) 1 (3.3) 0 (0) Ocralicizumab 2 No. 23 (95.8) 30 (100) 8 (100) 1.978 0.517 x Yes 1 (4.2) 0 (0) 0 (0) Alectinib No. 24 (100) 29 (96.7) 8 (100) 1.531 1.000 x Yes 0 (0) 1 (3.3) 0 (0) Pamidronate No. 23 (95.8) 30 (100) 8 (100) 1.978 0.517 x Yes 1 (4.2) 0 (0) 0 (0) Nibulumab No. 24 (100) 29 (96.7) 8 (100) 1.531 1.000 x Yes 0 (0) 1 (3.3) 0 (0) Rituximab No. 23 (95.8) 30 (100) 8 (100) 1.978 0.517 x Yes 1 (4.2) 0 (0) 0 (0) Duration of Use Not Used 8 (33.3) 15 (50) 8 (100) 15.479 0.051 x 0–6 Months 2 (8.3) 2 (6.7) 0 (0) 6–12 Months 1 (4.2) 5 (16.7) 0 (0) 12–18 Months 4 (16.7) 5 (16.7) 0 (0) 18–24 Months 4 (16.7) 3 (10) 0 (0) 24 Months and more 5 (20.8) 0 (0) 0 (0) f: One-way variance test, x: Fisher test, mean ± ss, ss: Standard deviation, n (%) Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7098395","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":512515180,"identity":"203a6c53-66e3-411c-8037-96931acbc12a","order_by":0,"name":"Halil İbrahim Durmus","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA8klEQVRIiWNgGAWjYDCCAxCSx4CBgY0hgcEGyGFsPECKljSQlgaitDCAtTAwHEYSxAH4buQ+3czz546MufThZw8e5py3W9t+GGhLjU00Li2SN9LNbvO2PeOx7EszN0jcdjt525lEoJZjabkNOLQY3Ehju83bcJjH4AyDmQRIi9kBoBbGhsP4tfD8AWlh/wbUci7Z7PxDYrSwgbTwgGw5YGd2g4Atkmeesd2c23aYx7KHpwyoJTnB7AbQlgQ8fuE7nsZ2482fw/bmPOzbJH9us7M3O5/+8MGHGhucWjBAIlhlArHKQcCeFMWjYBSMglEwMgAA8GtoimWyWp4AAAAASUVORK5CYII=","orcid":"","institution":"Adiyaman University","correspondingAuthor":true,"prefix":"","firstName":"Halil","middleName":"İbrahim","lastName":"Durmus","suffix":""},{"id":512515181,"identity":"af6ea79d-99db-4ef4-b051-bc93d349a65b","order_by":1,"name":"Mehmet Emrah Polat","email":"","orcid":"","institution":"Harran University","correspondingAuthor":false,"prefix":"","firstName":"Mehmet","middleName":"Emrah","lastName":"Polat","suffix":""},{"id":512515182,"identity":"6ceeb79d-4e0a-417a-bbe3-2101522e4fc9","order_by":2,"name":"Şeğmus Özdemir","email":"","orcid":"","institution":"Harran University","correspondingAuthor":false,"prefix":"","firstName":"Şeğmus","middleName":"","lastName":"Özdemir","suffix":""}],"badges":[],"createdAt":"2025-07-11 06:38:16","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7098395/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7098395/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":91076600,"identity":"e6e05057-e51e-4663-90c1-478dc8b3a2d5","added_by":"auto","created_at":"2025-09-11 11:11:23","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":78462,"visible":true,"origin":"","legend":"\u003cp\u003ePanoramic graph of a patient with class 1 MCI classification\u003c/p\u003e","description":"","filename":"figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7098395/v1/c8a4187c73471db6adbf40ce.jpg"},{"id":91072690,"identity":"3500874f-c708-4b2f-827f-fa8d1b29a1df","added_by":"auto","created_at":"2025-09-11 10:55:23","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":92384,"visible":true,"origin":"","legend":"\u003cp\u003ePanoramic graph of a patient with class 3 MCI classification\u003c/p\u003e","description":"","filename":"figure2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7098395/v1/f9fdc7cbe3e2753fb5289779.jpg"},{"id":100029206,"identity":"13eb73a9-ad49-42f6-bb5c-376b9168178a","added_by":"auto","created_at":"2026-01-12 09:09:40","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1072735,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7098395/v1/619c7321-65d4-4432-8722-64ae421ec96d.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eImpact of MRONJ-Associated Medications on Mandibular Cortical Index: A Cross-Sectional Analysis\u003c/p\u003e","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eBisphosphonates have demonstrated significant efficacy in reducing osteoclast-mediated bone resorption by inhibiting osteoclast activity. These pharmacological agents are employed in the management of various conditions where bone resorption must be mitigated or controlled. While oral bisphosphonates (BPs) are frequently\u0026nbsp;\u003cstrong\u003eadvised\u0026nbsp;\u003c/strong\u003efor the treatment of osteopenia and osteoporosis, intravenous formulations are utilized to prevent skeletal-related events in patients with malignancies such as multiple myeloma and cancers that metastasize to bone, including prostate, breast, lung, and renal cancers [1].\u003c/p\u003e\n\u003cp\u003eOne of the major iatrogenic complications associated with long-term bisphosphonate administration is the occurrence of bisphosphonate-related osteonecrosis of the jaw (BRONJ), characterized by necrotic bone exposure and impaired healing of the maxillofacial region. The estimated incidence of BRONJ is approximately 2–3% for intravenous BP use and 0.02–0.4% for oral administration [2].\u003c/p\u003e\n\u003cp\u003eThe jaw bones are among the most vulnerable areas of the body with respect to both healing and bacterial exposure, factors that may significantly play a role in shaping the appearance of BRONJ. Tooth extraction is recognized as one of the main risk factors for the onset of BRONJ in patients undergoing BP therapy. Research suggests that the risk of BRONJ occurring after tooth extraction is approximately 122.6 times higher in patients treated with BP than in those not on such therapy [3].\u003c/p\u003e\n\u003cp\u003eExtensive research has been conducted to develop drugs that provide the therapeutic benefits of bisphosphonates while minimizing side effects, especially the occurrence of BRONJ. As a result of these efforts, the human monoclonal antibody denosumab was developed, which effectively inhibits osteoclast activity [4]. Research indicates that DMB may match or surpass bisphosphonates in its capacity to inhibit bone resorption [5].) In contrast to BP, DMB is specifically designed to block a protein involved in the key signaling pathways of bone resorption, referred to as the nuclear factor [6].However, findings indicate that denosumab-related osteonecrosis of the jaw (DRONJ) exhibits clinical features similar to BRONJ [7].\u003c/p\u003e\n\u003cp\u003eAnti-resorptive agents are considered significant risk factors for the progression of MRONJ, particularly in cancer patients. The American Association of Oral and Maxillofacial Surgeons (AAOMS) defines MRONJ as a severe complication which may present in patients with a background of using antiresorptive or antiangiogenic agents. This condition is defined by exposed bone or a chronic fistula persisting for over eight weeks, without any prior history of radiotherapy In 2014, due to the rising incidence of osteonecrosis linked to treatments other than bisphosphonates, the AAOMS formally revised the terminology from BRONJ to MRONJ [8].\u003c/p\u003e\n\u003cp\u003eEarly radiographic identification of bisphosphonate-related bone changes may serve as an indicator for the potential development of BRONJ. Consequently, in patients receiving bisphosphonate therapy who Indicate the need for tooth treatment extraction or other aggressive dental procedures, the detection of bone alterations on radiographs can inform dental treatment planning [3].\u003c/p\u003e\n\u003cp\u003ePanoramic radiography is a frequently utilized imaging technique in dentistry. Therefore, it may be regarded as an important diagnostic tool for dental professionals [9].However, it is crucial to ensure diagnostic accuracy by avoiding projection errors due to head positioning [10].Panoramic radiographs are also used to detect changes in the mandibular cortex. The interaction between mandibular bone mass and skeletal integrity regions suggests that panoramic radiographs can be useful in evaluating osteoporosis [11]. MCI is a simple, descriptive tool used for classifying the radiographic images of the mandible[10,12]. Some studies suggest that panoramic radiographs may be helpful in identifying individuals\u0026nbsp;\u003cstrong\u003ewith diminished bone\u003c/strong\u003emineral density or osteoporosis [13], while others argue that panoramic radiographs cannot definitively diagnose osteoporosis and recommend bone densitometry, especially for postmenopausal women with cortical erosion [10,14].\u003c/p\u003e\n\u003cp\u003eOur research intends to examine the mandibular bone structure through the MCI in patients using medications associated with the potential for MRONJ, in comparison with a healthy population undergoing regular dental check-ups.\u003c/p\u003e"},{"header":"2. Materials and Methods","content":"\u003cp\u003eThis study, based on retrospective data, was performed in line with the regulations of the Declaration of Helsinki and was approved by the Ethics Committee for Clinical Research at Harran University (approval date and number: 13.01.2025; HRÜ / 25.01.15).\u003c/p\u003e\n\u003cp\u003eIn our study, panoramic radiographs of 31 patients using medication with potential to cause MRONJ and 31 individuals in the control group, Patients who sought care at the Department of Oral and Maxillofacial Surgery at Harran University Faculty of Dentistry between June 2023 and October 2024 for dental treatment, were analyzed. MCI analysis was used on these radiographs to evaluate the quantity of cortical bone and changes in mandibular bone density.\u003c/p\u003e\n\u003cp\u003eEach patient was asked to submit a health-related form. Medical records were obtained, including whether patients had systemic diseases, and if so, the type, dosage, and duration of medication used. Panoramic radiographs were obtained using standard methodology at the Harran University Faculty of Dentistry. Radiographic images were acquired using a PaX-I (Vatech, South Korea) device (mA=8, kVp=60, time=10s) and evaluated using EasyDent software (Ver. 4.1.5.9).\u003c/p\u003e\n\u003cp\u003eThe structure of the mandibular inferior cortical bone was evaluated based on the analysis of both the right and left regions of the mandible distal to the mental foramen, using Klemetti’s classification. (10) (Figures 1 and 2):\u003c/p\u003e\n\u003cp\u003eC1: The cortical endosteal border appears smooth and well-defined bilaterally.\u003c/p\u003e\n\u003cp\u003eC2: The inner cortical boundary presents with semilunar resorption defects, alongside residual cortical structures measuring one to three lamellar layers.\u003c/p\u003e\n\u003cp\u003eC3: The cortical layer shows significant endosteal remnants and exhibits marked porosity\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical Analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData normality was assessed was first tested using the Shapiro-Wilk test. For age comparisons between groups with normally distributed data, independent sample t-tests and one-way ANOVA were used. For categorical data, if expected cell frequencies were all greater than 5, Pearson’s Chi-square test was used; otherwise, Fisher’s exact test was applied. Multiple comparisons were analyzed using the Bonferroni-adjusted Z test. Quantitative data are presented as mean ± standard deviation (Mean ± SD), while categorical data are expressed as frequency (n) and percentage. The threshold for statistical significance was established at p\u0026lt;0.05. Data evaluation was performed using IBM SPSS software, version 27 (IBM Corp. 2020).\u003c/p\u003e"},{"header":"3. Results","content":"\u003cp\u003eThe population showed no racial or ethnic heterogeneity; all participants were from the Southeastern Anatolia Region of Turkey. The study population was composed of 25 women (mean age: 62) and 6 men (mean age: 57.5), and were classified according to the Klemetti MCI classification as follows: 2 patients as C3, 16 patients as C2, and 13 patients as C1. In contrast, the control group, consisting of 25 women (mean age: 61.8) and 6 men (mean age: 57.5), included 4 patients classified as C3, 17 as C2, and 10 as C1 (Table 1).\u003c/p\u003e\n\u003cp\u003eTable 1 presents Characteristics related to demographics and clinical status of patients in the case and control groups. There were no substantial statistical differences in the age and gender distributions between the groups (p\u0026gt;0.05). Nevertheless, a notable statistical discrepancy was identified between the groups concerning the presence of systemic disorders (p\u0026lt;0.001). All patients in the study group (100%) had systemic diseases, whereas only 32.3% of the control group did. Additionally, a significant statistical variation a significant difference was identified among the groups in terms of the categories of systemic conditions (p\u0026lt;0.001). A remarkable distinction was found between the groups in terms of the occurrence of MCI levels (p=0.003), particularly regarding the proportion of patients with MCI level C1. Significant differences were observed between groups in the use of denosumab and zoledronic acid (p=0.001 and p\u0026lt;0.001, respectively), but not in the use of other medications (p\u0026gt;0.05). A significant variation was observed between the groups regarding the length of medication use (p\u0026lt;0.001).\u003c/p\u003e\n\u003cp\u003eTable 2 presents findings related to the relationship between MCI levels and demographic and clinical characteristics. No statistically substantial correlation was identified between MCIlevels and gender, age, or systemic disease status (p\u0026gt;0.05). No significant relationship was observed between MCI levels and medication use (p\u0026gt;0.05), nor was there a significant relationship between MCI levels and duration of medication use (p=0.051).\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eMRONJ is an uncommon yet severe and multifactorial pathology generally associated with antiresorptive and antiangiogenic agents used to treat osteoporosis, Paget's, hypercalcemia, and metabolic bone disorders due to malignancies. As outlined by the American Association of Oral and Maxillofacial Surgeons (AAOMS), the diagnosis of MRONJ necessitates the presence of all three of the following conditions: prior or current use of drugs with antiresorptive or antiangiogenic properties, bone that is visible or can be accessed via an intraoral or extraoral tract in the maxillofacial region area persisting for over eight weeks. and no prior exposure to radiotherapy or evidence of metastatic involvement in the jaw bones\u003cbr\u003e\u0026nbsp;AAOMS identifies three main drug classes associated with MRONJ: BP, RANKL inhibitors, and antiangiogenic agents [15]. BP, which are analogs of inorganic pyrophosphate, suppress bone resorption and mineralization by promoting osteoclast apoptosis [16]. DMB is a monoclonal antibody targeting RANKL, which suppresses osteoclast development and activity [17]. Despite differing mechanisms, both drugs lead to slowed bone turnover and accumulation of unresorbed, hypermineralized bone [18]. Antiangiogenic agents inhibit neovascularization, leading to circulatory issues such as ischemia and hypoperfusion [17].\u003c/p\u003e\n\u003cp\u003eThis cross-sectional study aimed to investigate bone density and MRONJ risk in patients with histories of using different drugs potentially causing MRONJ, using MCI analysis on panoramic radiographs.\u003cbr\u003e\u0026nbsp; BMD Is a critical marker of \u0026nbsp;bone health and can be evaluated through various methods, such as quantitative computer tomography (QCT), single or dual-energy X-ray absorptiometry (SXA or DEXA), and quantitative ultrasound (QUS) [13,19]. Nonetheless, these methods are costly [19,20]. Therefore, developing more economical yet reliable alternatives can be beneficial.\u003cbr\u003e\u0026nbsp; Various mandibular radiomorphometric indices are employed in panoramic radiographic imaging to identify conditions affecting bone health, such as low BMD in postmenopausal women. These indices can be evaluated either quantitatively (e.g., cortical thickness) or qualitatively (e.g., mandibular cortical morphology). Although quantitative indices have proven effective, qualitative indices are often preferred in clinical settings due to their simplicity and practicality. The visual assessment of endosteal cortical width (ECW) and MCI are examples of reliable qualitative indices used to detect low BMD [21].\u003c/p\u003e\n\u003cp\u003eThe visibility of the ortical bone of the mandible's inferior portion on dental panoramic radiographs has been widely investigated as a radiological marker of skeletal BMD [22,23]. The MCI, developed by Klemetti et al. [24], classifies the mandibular cortex into three types based on subjective evaluation of porosity, with \"C3\" representing a cortex with heavy endosteal residues and clear porosity. The prevalence of porosity increases with age [25], and MCI is significantly associated with mandibular BMD [26].\u003cbr\u003e\u0026nbsp; Thus, in our study, we chose to evaluate BMD in patients using BP and DMB through MCI analysis on panoramic radiographs.\u003cbr\u003e\u0026nbsp; Rocha et al. suggested that early detection of bone changes through panoramic radiographs facilitates MRONJ diagnosis [27]. Various imaging techniques, such as panoramic radiography, periapical radiography, CT, and MRI, have shown findings like osteolytic lesions, bone proliferation, lamina dura thickening, and increased cortical definition during bisphosphonate treatment [28]. Additionally, cortical bone erosion, sequestrum formation, and pathological mandibular fractures have been reported in panoramic radiographs of bisphosphonate users [29]. In our study, sequestrum formation and post-treatment sequelae were observed in six patients.\u003cbr\u003e\u0026nbsp; Torres et al. [30] examined the thickness, cross-sectional dimensions, and volume of the mandibular cortex in patients with MRONJ and control group participants without BP use. MRONJ patients showed significantly higher values. Panoramic radiographs showed that cortical bone thickness in MRONJ patients (6.81 ± 1.35 mm) was significantly higher than in non-MRONJ patients (5.44 ± 1.09 mm) and normal controls (4.79 ± 0.85 mm) As stated by Hamada et al. [22], Patients with MRONJ exhibited augmented cortical bone structure and enhanced trabecular bone radiodensity on computed tomography (CT) compared to healthy controls. Iwata et al. also measured vestibul and lingual cortical bone thickness in three groups: MRONJ patients, patients treated for osteoporosis without signs of MRONJ, and non-osteoporotic individuals. They found significantly thicker cortical bone in MRONJ patients but no significant difference between medicated and healthy non-MRONJ groups [23]. Consistent with this, our study showed that the group using MRONJ-associated drugs had greater mandibular cortical bone thickness than the control group, based on the Klemetti MCI classification.\u003c/p\u003e\n\u003cp\u003eOur study has several constraints. First, it was retrospective, and the oral health status of patients before medication use was unknown. Additionally, the relatively small sample size may influence the statistical strength. Third, radiographic evaluations were based on panoramic radiographs, which are two-dimensional and highly influenced by head and neck positioning. However, due to their lower radiation dose compared to CT and medical imaging, routine availability, ease of access, and suitability for follow-up, panoramic radiographs were preferred.\u003c/p\u003e"},{"header":"5. Conclusion","content":"\u003cp\u003eAlthough no prominent differences were found among medicated subgroups in terms of the radiographic characteristics of MRONJ, there was a significant difference between the medicated and control groups in terms of MCI scores. The results obtained may contribute to the accurate diagnosis, effective treatment planning, and prognostic evaluation of MRONJ.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003e\u003cstrong\u003eMRONJ\u003c/strong\u003e\u0026nbsp; Medication related osteonecrosis of the jaw\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eBRONJ\u0026nbsp;\u003c/strong\u003eBifosfonat related osteonecrosis of the jaw\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDRONJ\u0026nbsp;\u003c/strong\u003eDenosumab related osteonecrosis of the jaw\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eBP\u003c/strong\u003e Bisphosphonates\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCBCT\u003c/strong\u003e\u0026nbsp; Cone-beam computer tomography\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMCI\u0026nbsp;\u003c/strong\u003e Mandibular cortical index\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAuthors’ contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eConceptualization: H.I.D. and S.O.; methodology: H.I.D.; software: H.I.D. and M.E.P; validation: M.E.P, H.I.D. and S.O.; formal analysis: M.E.P and S.O.; investigation: M.E.P.; resources: S.O; da-ta curation: H.I.D.; writing—original draft preparation: H.I.D. and S.O.; writing—review and ed-iting: H.I.D. and S.O.; visualization: M.E.P..; supervision: H.I.D.; project administration: H.I.D. and S.O.; funding acquisition: M.E.P. All authors have read and agreed to the published version of the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that no funding was received for this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data that support the findings of this study are available from the\u003c/p\u003e\n\u003cp\u003ecorresponding author upon request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDeclarations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was performed in line with the regulations of the Declaration of Helsinki and was approved by the Ethics Committee for Clinical Research at Harran University (approval date and number: 13.01.2025; HRÜ / 25.01.15). Informed consent was obtained from all patients for being included in the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eHalil İbrahim Durmus: \u0026nbsp;\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/em\u003e\u003c/strong\u003e0000-0003-4762-4788 /\u0026nbsp;\u003cem\u003e\u003cu\[email protected]\u003c/u\u003e\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eMehmet Emrah Polat:\u003c/em\u003e\u003c/strong\u003e\u0026nbsp; \u0026nbsp; 0000-0002-0749-0407 / \u0026nbsp;\u003cem\[email protected]\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eŞeğmus Özdemir3: \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e0000-0002-1279-0893 / \u003cem\u003e\u003cu\[email protected]\u003c/u\u003e\u003c/em\u003e\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eGutta R, Louis PJ. 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Int J Dent. 2017;2017:3190301. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1155/2017/3190301\u003c/span\u003e\u003cspan address=\"10.1155/2017/3190301\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. Epub 2017 Mar 2. PMID: 28352284; PMCID: PMC5352898.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eTorres SR, Chen CS, Leroux BG, Lee PP, Hollender LG, Santos EC, Drew SP, Hung KC, Schubert MM. Mandibular cortical bone evaluation on cone beam computed tomography images of patients with bisphosphonate-related osteonecrosis of the jaw. Oral Surg Oral Med Oral Pathol Oral Radiol. 2012;113(5):695\u0026ndash;703. doi: 10.1016/j.oooo.2011.11.011. Epub 2012 Apr 12. PMID: 22668629.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cdiv class=\"SimplePara\"\u003eAnalysis of demographic and clinical characteristics according to groups\u003c/div\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cdiv class=\"SimplePara\"\u003eControl (n\u0026thinsp;=\u0026thinsp;31)\u003c/div\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cdiv class=\"SimplePara\"\u003eStudy (n\u0026thinsp;=\u0026thinsp;31)\u003c/div\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cdiv class=\"SimplePara\"\u003eTest Stat.\u003c/div\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cdiv class=\"SimplePara\"\u003ep\u003c/div\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003eGender\u003c/div\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003eFemale\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cdiv class=\"SimplePara\"\u003e25 (80.6)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cdiv class=\"SimplePara\"\u003e26 (83.9)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e\u003cdiv class=\"SimplePara\"\u003e-\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u003cdiv class=\"SimplePara\"\u003e1.000\u003csup\u003ex\u003c/sup\u003e\u003c/div\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003eMale\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cdiv class=\"SimplePara\"\u003e6 (19.4)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cdiv class=\"SimplePara\"\u003e5 (16.1)\u003c/div\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eAge\u003c/span\u003e\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cdiv class=\"SimplePara\"\u003e62.71\u0026thinsp;\u0026plusmn;\u0026thinsp;9.83\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cdiv class=\"SimplePara\"\u003e62.55\u0026thinsp;\u0026plusmn;\u0026thinsp;9.83\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cdiv class=\"SimplePara\"\u003e0.065\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cdiv class=\"SimplePara\"\u003e0.949\u003csup\u003et\u003c/sup\u003e\u003c/div\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eSystemic Diseases\u003c/span\u003e\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003eNone\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cdiv class=\"SimplePara\"\u003e21 (67.7)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cdiv class=\"SimplePara\"\u003e0 (0)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e\u003cdiv class=\"SimplePara\"\u003e-\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e\u0026lt;\u0026thinsp;0.001\u003c/span\u003e\u003csup\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003ex\u003c/span\u003e\u003c/sup\u003e\u003c/div\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003eYes\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cdiv class=\"SimplePara\"\u003e10 (32.3)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cdiv class=\"SimplePara\"\u003e31 (100)\u003c/div\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eSystemic Diseases*\u003c/span\u003e\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003eNone\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cdiv class=\"SimplePara\"\u003e21 (55.3)\u003csup\u003ea\u003c/sup\u003e\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cdiv class=\"SimplePara\"\u003e1 (1.8)\u003csup\u003eb\u003c/sup\u003e\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\" morerows=\"9\" rowspan=\"10\"\u003e\u003cdiv class=\"SimplePara\"\u003e78.809\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\" morerows=\"9\" rowspan=\"10\"\u003e\u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e\u0026lt;\u0026thinsp;0.001\u003c/span\u003e\u003csup\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003ek\u003c/span\u003e\u003c/sup\u003e\u003c/div\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003eHeart\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cdiv class=\"SimplePara\"\u003e5 (13.2)\u003csup\u003ea\u003c/sup\u003e\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cdiv class=\"SimplePara\"\u003e10 (17.9)\u003csup\u003ea\u003c/sup\u003e\u003c/div\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003eBlood Pressure\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cdiv class=\"SimplePara\"\u003e3 (7.9)\u003csup\u003ea\u003c/sup\u003e\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cdiv class=\"SimplePara\"\u003e8 (14.3)\u003csup\u003ea\u003c/sup\u003e\u003c/div\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003eAsthma\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cdiv class=\"SimplePara\"\u003e2 (5.3)\u003csup\u003ea\u003c/sup\u003e\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cdiv class=\"SimplePara\"\u003e1 (1.8)\u003csup\u003ea\u003c/sup\u003e\u003c/div\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003eDiabetes\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cdiv class=\"SimplePara\"\u003e7 (18.4)\u003csup\u003ea\u003c/sup\u003e\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cdiv class=\"SimplePara\"\u003e5 (8.9)\u003csup\u003ea\u003c/sup\u003e\u003c/div\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003eCML\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cdiv class=\"SimplePara\"\u003e0 (0)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cdiv class=\"SimplePara\"\u003e1 (1.8)\u003c/div\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003eRheumatoid Arthritis\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cdiv class=\"SimplePara\"\u003e0 (0)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cdiv class=\"SimplePara\"\u003e3 (5.4)\u003c/div\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003eBreast Cancer\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cdiv class=\"SimplePara\"\u003e0 (0)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cdiv class=\"SimplePara\"\u003e3 (5.4)\u003c/div\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003eMultiple Myeloma\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cdiv class=\"SimplePara\"\u003e0 (0)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cdiv class=\"SimplePara\"\u003e1 (1.8)\u003c/div\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003eOsteoporosis\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cdiv class=\"SimplePara\"\u003e0 (0)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cdiv class=\"SimplePara\"\u003e23 (41.1)\u003c/div\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eMCİ\u003c/span\u003e\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003eC1\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cdiv class=\"SimplePara\"\u003e8 (25.8)\u003csup\u003ea\u003c/sup\u003e\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cdiv class=\"SimplePara\"\u003e16 (51.6)\u003csup\u003eb\u003c/sup\u003e\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\" morerows=\"2\" rowspan=\"3\"\u003e\u003cdiv class=\"SimplePara\"\u003e11.193\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\" morerows=\"2\" rowspan=\"3\"\u003e\u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e0.003\u003c/span\u003e\u003csup\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003ex\u003c/span\u003e\u003c/sup\u003e\u003c/div\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003eC2\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cdiv class=\"SimplePara\"\u003e15 (48.4)\u003csup\u003ea\u003c/sup\u003e\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cdiv class=\"SimplePara\"\u003e15 (48.4)\u003csup\u003ea\u003c/sup\u003e\u003c/div\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003eC3\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cdiv class=\"SimplePara\"\u003e8 (25.8)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cdiv class=\"SimplePara\"\u003e0 (0)\u003c/div\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eDenosumab\u003c/span\u003e\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003eNo.\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cdiv class=\"SimplePara\"\u003e31 (100)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cdiv class=\"SimplePara\"\u003e21 (67.7)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e\u003cdiv class=\"SimplePara\"\u003e-\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e0.001\u003c/span\u003e\u003csup\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003ex\u003c/span\u003e\u003c/sup\u003e\u003c/div\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003eYes\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cdiv class=\"SimplePara\"\u003e0 (0)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cdiv class=\"SimplePara\"\u003e10 (32.3)\u003c/div\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eZoledronic Acid\u003c/span\u003e\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003eNo.\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cdiv class=\"SimplePara\"\u003e31 (100)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cdiv class=\"SimplePara\"\u003e20 (64.5)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e\u003cdiv class=\"SimplePara\"\u003e-\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e\u0026lt;\u0026thinsp;0.001\u003c/span\u003e\u003csup\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003ex\u003c/span\u003e\u003c/sup\u003e\u003c/div\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003eYes\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cdiv class=\"SimplePara\"\u003e0 (0)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cdiv class=\"SimplePara\"\u003e11 (35.5)\u003c/div\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eMethotrexate\u003c/span\u003e\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003eNo.\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cdiv class=\"SimplePara\"\u003e31 (100)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cdiv class=\"SimplePara\"\u003e29 (93.5)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e\u003cdiv class=\"SimplePara\"\u003e-\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u003cdiv class=\"SimplePara\"\u003e0.492\u003csup\u003ex\u003c/sup\u003e\u003c/div\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003eYes\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cdiv class=\"SimplePara\"\u003e0 (0)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cdiv class=\"SimplePara\"\u003e2 (6.5)\u003c/div\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eAledronate\u003c/span\u003e\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003eNo.\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cdiv class=\"SimplePara\"\u003e31 (100)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cdiv class=\"SimplePara\"\u003e29 (93.5)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e\u003cdiv class=\"SimplePara\"\u003e-\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u003cdiv class=\"SimplePara\"\u003e0.492\u003csup\u003ex\u003c/sup\u003e\u003c/div\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003eYes\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cdiv class=\"SimplePara\"\u003e0 (0)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cdiv class=\"SimplePara\"\u003e2 (6.5)\u003c/div\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eImatinip\u003c/span\u003e\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003eNo.\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cdiv class=\"SimplePara\"\u003e31 (100)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cdiv class=\"SimplePara\"\u003e30 (96.8)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e\u003cdiv class=\"SimplePara\"\u003e-\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u003cdiv class=\"SimplePara\"\u003e1.000\u003csup\u003ex\u003c/sup\u003e\u003c/div\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003eYes\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cdiv class=\"SimplePara\"\u003e0 (0)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cdiv class=\"SimplePara\"\u003e1 (3.2)\u003c/div\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eIbandronic Acid\u003c/span\u003e\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003eNo.\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cdiv class=\"SimplePara\"\u003e31 (100)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cdiv class=\"SimplePara\"\u003e30 (96.8)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e\u003cdiv class=\"SimplePara\"\u003e-\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u003cdiv class=\"SimplePara\"\u003e1.000\u003csup\u003ex\u003c/sup\u003e\u003c/div\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003eYes\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cdiv class=\"SimplePara\"\u003e0 (0)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cdiv class=\"SimplePara\"\u003e1 (3.2)\u003c/div\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eOcralicizumab 1\u003c/span\u003e\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003eNo.\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cdiv class=\"SimplePara\"\u003e31 (100)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cdiv class=\"SimplePara\"\u003e30 (96.8)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e\u003cdiv class=\"SimplePara\"\u003e-\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u003cdiv class=\"SimplePara\"\u003e1.000\u003csup\u003ex\u003c/sup\u003e\u003c/div\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003eYes\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cdiv class=\"SimplePara\"\u003e0 (0)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cdiv class=\"SimplePara\"\u003e1 (3.2)\u003c/div\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eOcralicizumab 2\u003c/span\u003e\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003eNo.\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cdiv class=\"SimplePara\"\u003e31 (100)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cdiv class=\"SimplePara\"\u003e30 (96.8)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e\u003cdiv class=\"SimplePara\"\u003e-\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u003cdiv class=\"SimplePara\"\u003e1.000\u003csup\u003ex\u003c/sup\u003e\u003c/div\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003eYes\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cdiv class=\"SimplePara\"\u003e0 (0)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cdiv class=\"SimplePara\"\u003e1 (3.2)\u003c/div\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eAlectinib\u003c/span\u003e\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003eNo.\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cdiv class=\"SimplePara\"\u003e31 (100)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cdiv class=\"SimplePara\"\u003e30 (96.8)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e\u003cdiv class=\"SimplePara\"\u003e-\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u003cdiv class=\"SimplePara\"\u003e1.000\u003csup\u003ex\u003c/sup\u003e\u003c/div\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003eYes\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cdiv class=\"SimplePara\"\u003e0 (0)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cdiv class=\"SimplePara\"\u003e1 (3.2)\u003c/div\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003ePamidronate\u003c/span\u003e\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003eNo.\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cdiv class=\"SimplePara\"\u003e31 (100)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cdiv class=\"SimplePara\"\u003e30 (96.8)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e\u003cdiv class=\"SimplePara\"\u003e-\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u003cdiv class=\"SimplePara\"\u003e1.000\u003csup\u003ex\u003c/sup\u003e\u003c/div\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003eYes\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cdiv class=\"SimplePara\"\u003e0 (0)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cdiv class=\"SimplePara\"\u003e1 (3.2)\u003c/div\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eNibulumab\u003c/span\u003e\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003eNo.\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cdiv class=\"SimplePara\"\u003e31 (100)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cdiv class=\"SimplePara\"\u003e30 (96.8)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e\u003cdiv class=\"SimplePara\"\u003e-\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u003cdiv class=\"SimplePara\"\u003e1.000\u003csup\u003ex\u003c/sup\u003e\u003c/div\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003eYes\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cdiv class=\"SimplePara\"\u003e0 (0)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cdiv class=\"SimplePara\"\u003e1 (3.2)\u003c/div\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eRituximab\u003c/span\u003e\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003eNo.\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cdiv class=\"SimplePara\"\u003e31 (100)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cdiv class=\"SimplePara\"\u003e30 (96.8)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e\u003cdiv class=\"SimplePara\"\u003e-\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u003cdiv class=\"SimplePara\"\u003e1.000\u003csup\u003ex\u003c/sup\u003e\u003c/div\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003eYes\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cdiv class=\"SimplePara\"\u003e0 (0)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cdiv class=\"SimplePara\"\u003e1 (3.2)\u003c/div\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eDuration of Use\u003c/span\u003e\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003eNot Used\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cdiv class=\"SimplePara\"\u003e31 (100)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cdiv class=\"SimplePara\"\u003e0 (0)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\" morerows=\"5\" rowspan=\"6\"\u003e\u003cdiv class=\"SimplePara\"\u003e70.868\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\" morerows=\"5\" rowspan=\"6\"\u003e\u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e\u0026lt;\u0026thinsp;0.001\u003c/span\u003e\u003csup\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003ex\u003c/span\u003e\u003c/sup\u003e\u003c/div\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003e0\u0026ndash;6 Months\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cdiv class=\"SimplePara\"\u003e0 (0)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cdiv class=\"SimplePara\"\u003e4 (12.9)\u003c/div\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003e6\u0026ndash;12 Months\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cdiv class=\"SimplePara\"\u003e0 (0)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cdiv class=\"SimplePara\"\u003e6 (19.4)\u003c/div\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003e12\u0026ndash;18 Months\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cdiv class=\"SimplePara\"\u003e0 (0)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cdiv class=\"SimplePara\"\u003e9 (29)\u003c/div\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003e18\u0026ndash;24 Months\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cdiv class=\"SimplePara\"\u003e0 (0)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cdiv class=\"SimplePara\"\u003e7 (22.6)\u003c/div\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003e24 Months and more\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cdiv class=\"SimplePara\"\u003e0 (0)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cdiv class=\"SimplePara\"\u003e5 (16.1)\u003c/div\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"5\"\u003et: Independent two sample t test, k: Pearson chi-square test, x: Fisher test, a-b: No difference between groups with the same letter (Z test with Bonferroni correction), mean\u0026thinsp;\u0026plusmn;\u0026thinsp;sd, sd: Standard deviation, n (%)\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003cbr/\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cdiv class=\"SimplePara\"\u003eAnalysis of demographic and clinical characteristics according to MCI levels\u003c/div\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"6\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cdiv class=\"SimplePara\"\u003eC1 (n\u0026thinsp;=\u0026thinsp;24)\u003c/div\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cdiv class=\"SimplePara\"\u003eC2 (n\u0026thinsp;=\u0026thinsp;30)\u003c/div\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cdiv class=\"SimplePara\"\u003eC3 (n\u0026thinsp;=\u0026thinsp;8)\u003c/div\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cdiv class=\"SimplePara\"\u003eTest Stat.\u003c/div\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cdiv class=\"SimplePara\"\u003ep\u003c/div\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003eGender\u003c/div\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003eFemale\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cdiv class=\"SimplePara\"\u003e18 (75)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cdiv class=\"SimplePara\"\u003e26 (86.7)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cdiv class=\"SimplePara\"\u003e7 (87.5)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u003cdiv class=\"SimplePara\"\u003e1.334\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e\u003cdiv class=\"SimplePara\"\u003e0.526\u003csup\u003ex\u003c/sup\u003e\u003c/div\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003eMale\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cdiv class=\"SimplePara\"\u003e6 (25)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cdiv class=\"SimplePara\"\u003e4 (13.3)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cdiv class=\"SimplePara\"\u003e1 (12.5)\u003c/div\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eYaş\u003c/span\u003e\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cdiv class=\"SimplePara\"\u003e61.5\u0026thinsp;\u0026plusmn;\u0026thinsp;11.88\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cdiv class=\"SimplePara\"\u003e62.2\u0026thinsp;\u0026plusmn;\u0026thinsp;7.16\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cdiv class=\"SimplePara\"\u003e67.63\u0026thinsp;\u0026plusmn;\u0026thinsp;10.88\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cdiv class=\"SimplePara\"\u003e1.250\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cdiv class=\"SimplePara\"\u003e0.294\u003csup\u003ef\u003c/sup\u003e\u003c/div\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eSystemic Diseases\u003c/span\u003e\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003eNone\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cdiv class=\"SimplePara\"\u003e8 (33.3)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cdiv class=\"SimplePara\"\u003e11 (36.7)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cdiv class=\"SimplePara\"\u003e2 (25)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u003cdiv class=\"SimplePara\"\u003e0.376\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e\u003cdiv class=\"SimplePara\"\u003e0.933\u003csup\u003ex\u003c/sup\u003e\u003c/div\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003eYes\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cdiv class=\"SimplePara\"\u003e16 (66.7)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cdiv class=\"SimplePara\"\u003e19 (63.3)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cdiv class=\"SimplePara\"\u003e6 (75)\u003c/div\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eDenosumab\u003c/span\u003e\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003eNo.\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cdiv class=\"SimplePara\"\u003e19 (79.2)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cdiv class=\"SimplePara\"\u003e25 (83.3)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cdiv class=\"SimplePara\"\u003e8 (100)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u003cdiv class=\"SimplePara\"\u003e1.546\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e\u003cdiv class=\"SimplePara\"\u003e0.505\u003csup\u003ex\u003c/sup\u003e\u003c/div\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003eYes\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cdiv class=\"SimplePara\"\u003e5 (20.8)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cdiv class=\"SimplePara\"\u003e5 (16.7)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cdiv class=\"SimplePara\"\u003e0 (0)\u003c/div\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eZoledronic Acid\u003c/span\u003e\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003eNo.\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cdiv class=\"SimplePara\"\u003e17 (70.8)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cdiv class=\"SimplePara\"\u003e26 (86.7)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cdiv class=\"SimplePara\"\u003e8 (100)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u003cdiv class=\"SimplePara\"\u003e3.604\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e\u003cdiv class=\"SimplePara\"\u003e0.120\u003csup\u003ex\u003c/sup\u003e\u003c/div\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003eYes\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cdiv class=\"SimplePara\"\u003e7 (29.2)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cdiv class=\"SimplePara\"\u003e4 (13.3)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cdiv class=\"SimplePara\"\u003e0 (0)\u003c/div\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eMethotrexate\u003c/span\u003e\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003eNo.\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cdiv class=\"SimplePara\"\u003e23 (95.8)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cdiv class=\"SimplePara\"\u003e29 (96.7)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cdiv class=\"SimplePara\"\u003e8 (100)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u003cdiv class=\"SimplePara\"\u003e0.667\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e\u003cdiv class=\"SimplePara\"\u003e1.000\u003csup\u003ex\u003c/sup\u003e\u003c/div\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003eYes\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cdiv class=\"SimplePara\"\u003e1 (4.2)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cdiv class=\"SimplePara\"\u003e1 (3.3)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cdiv class=\"SimplePara\"\u003e0 (0)\u003c/div\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eAledronate\u003c/span\u003e\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003eNo.\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cdiv class=\"SimplePara\"\u003e24 (100)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cdiv class=\"SimplePara\"\u003e28 (93.3)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cdiv class=\"SimplePara\"\u003e8 (100)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u003cdiv class=\"SimplePara\"\u003e1.665\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e\u003cdiv class=\"SimplePara\"\u003e0.622\u003csup\u003ex\u003c/sup\u003e\u003c/div\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003eYes\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cdiv class=\"SimplePara\"\u003e0 (0)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cdiv class=\"SimplePara\"\u003e2 (6.7)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cdiv class=\"SimplePara\"\u003e0 (0)\u003c/div\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eImatinip\u003c/span\u003e\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003eNo.\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cdiv class=\"SimplePara\"\u003e24 (100)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cdiv class=\"SimplePara\"\u003e29 (96.7)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cdiv class=\"SimplePara\"\u003e8 (100)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u003cdiv class=\"SimplePara\"\u003e1.531\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e\u003cdiv class=\"SimplePara\"\u003e1.000\u003csup\u003ex\u003c/sup\u003e\u003c/div\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003eYes\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cdiv class=\"SimplePara\"\u003e0 (0)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cdiv class=\"SimplePara\"\u003e1 (3.3)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cdiv class=\"SimplePara\"\u003e0 (0)\u003c/div\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eIbandronic Acid\u003c/span\u003e\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003eNo.\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cdiv class=\"SimplePara\"\u003e24 (100)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cdiv class=\"SimplePara\"\u003e29 (96.7)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cdiv class=\"SimplePara\"\u003e8 (100)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u003cdiv class=\"SimplePara\"\u003e1.531\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e\u003cdiv class=\"SimplePara\"\u003e1.000\u003csup\u003ex\u003c/sup\u003e\u003c/div\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003eYes\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cdiv class=\"SimplePara\"\u003e0 (0)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cdiv class=\"SimplePara\"\u003e1 (3.3)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cdiv class=\"SimplePara\"\u003e0 (0)\u003c/div\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eOcralicizumab 1\u003c/span\u003e\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003eNo.\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cdiv class=\"SimplePara\"\u003e24 (100)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cdiv class=\"SimplePara\"\u003e29 (96.7)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cdiv class=\"SimplePara\"\u003e8 (100)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u003cdiv class=\"SimplePara\"\u003e1.531\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e\u003cdiv class=\"SimplePara\"\u003e1.000\u003csup\u003ex\u003c/sup\u003e\u003c/div\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003eYes\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cdiv class=\"SimplePara\"\u003e0 (0)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cdiv class=\"SimplePara\"\u003e1 (3.3)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cdiv class=\"SimplePara\"\u003e0 (0)\u003c/div\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eOcralicizumab 2\u003c/span\u003e\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003eNo.\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cdiv class=\"SimplePara\"\u003e23 (95.8)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cdiv class=\"SimplePara\"\u003e30 (100)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cdiv class=\"SimplePara\"\u003e8 (100)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u003cdiv class=\"SimplePara\"\u003e1.978\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e\u003cdiv class=\"SimplePara\"\u003e0.517\u003csup\u003ex\u003c/sup\u003e\u003c/div\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003eYes\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cdiv class=\"SimplePara\"\u003e1 (4.2)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cdiv class=\"SimplePara\"\u003e0 (0)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cdiv class=\"SimplePara\"\u003e0 (0)\u003c/div\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eAlectinib\u003c/span\u003e\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003eNo.\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cdiv class=\"SimplePara\"\u003e24 (100)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cdiv class=\"SimplePara\"\u003e29 (96.7)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cdiv class=\"SimplePara\"\u003e8 (100)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u003cdiv class=\"SimplePara\"\u003e1.531\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e\u003cdiv class=\"SimplePara\"\u003e1.000\u003csup\u003ex\u003c/sup\u003e\u003c/div\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003eYes\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cdiv class=\"SimplePara\"\u003e0 (0)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cdiv class=\"SimplePara\"\u003e1 (3.3)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cdiv class=\"SimplePara\"\u003e0 (0)\u003c/div\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003ePamidronate\u003c/span\u003e\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003eNo.\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cdiv class=\"SimplePara\"\u003e23 (95.8)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cdiv class=\"SimplePara\"\u003e30 (100)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cdiv class=\"SimplePara\"\u003e8 (100)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u003cdiv class=\"SimplePara\"\u003e1.978\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e\u003cdiv class=\"SimplePara\"\u003e0.517\u003csup\u003ex\u003c/sup\u003e\u003c/div\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003eYes\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cdiv class=\"SimplePara\"\u003e1 (4.2)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cdiv class=\"SimplePara\"\u003e0 (0)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cdiv class=\"SimplePara\"\u003e0 (0)\u003c/div\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eNibulumab\u003c/span\u003e\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003eNo.\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cdiv class=\"SimplePara\"\u003e24 (100)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cdiv class=\"SimplePara\"\u003e29 (96.7)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cdiv class=\"SimplePara\"\u003e8 (100)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u003cdiv class=\"SimplePara\"\u003e1.531\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e\u003cdiv class=\"SimplePara\"\u003e1.000\u003csup\u003ex\u003c/sup\u003e\u003c/div\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003eYes\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cdiv class=\"SimplePara\"\u003e0 (0)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cdiv class=\"SimplePara\"\u003e1 (3.3)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cdiv class=\"SimplePara\"\u003e0 (0)\u003c/div\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eRituximab\u003c/span\u003e\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003eNo.\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cdiv class=\"SimplePara\"\u003e23 (95.8)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cdiv class=\"SimplePara\"\u003e30 (100)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cdiv class=\"SimplePara\"\u003e8 (100)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u003cdiv class=\"SimplePara\"\u003e1.978\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e\u003cdiv class=\"SimplePara\"\u003e0.517\u003csup\u003ex\u003c/sup\u003e\u003c/div\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003eYes\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cdiv class=\"SimplePara\"\u003e1 (4.2)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cdiv class=\"SimplePara\"\u003e0 (0)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cdiv class=\"SimplePara\"\u003e0 (0)\u003c/div\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eDuration of Use\u003c/span\u003e\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003eNot Used\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cdiv class=\"SimplePara\"\u003e8 (33.3)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cdiv class=\"SimplePara\"\u003e15 (50)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cdiv class=\"SimplePara\"\u003e8 (100)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\" morerows=\"5\" rowspan=\"6\"\u003e\u003cdiv class=\"SimplePara\"\u003e15.479\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\" morerows=\"5\" rowspan=\"6\"\u003e\u003cdiv class=\"SimplePara\"\u003e0.051\u003csup\u003ex\u003c/sup\u003e\u003c/div\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003e0\u0026ndash;6 Months\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cdiv class=\"SimplePara\"\u003e2 (8.3)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cdiv class=\"SimplePara\"\u003e2 (6.7)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cdiv class=\"SimplePara\"\u003e0 (0)\u003c/div\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003e6\u0026ndash;12 Months\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cdiv class=\"SimplePara\"\u003e1 (4.2)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cdiv class=\"SimplePara\"\u003e5 (16.7)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cdiv class=\"SimplePara\"\u003e0 (0)\u003c/div\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003e12\u0026ndash;18 Months\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cdiv class=\"SimplePara\"\u003e4 (16.7)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cdiv class=\"SimplePara\"\u003e5 (16.7)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cdiv class=\"SimplePara\"\u003e0 (0)\u003c/div\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003e18\u0026ndash;24 Months\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cdiv class=\"SimplePara\"\u003e4 (16.7)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cdiv class=\"SimplePara\"\u003e3 (10)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cdiv class=\"SimplePara\"\u003e0 (0)\u003c/div\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003e24 Months and more\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cdiv class=\"SimplePara\"\u003e5 (20.8)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cdiv class=\"SimplePara\"\u003e0 (0)\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cdiv class=\"SimplePara\"\u003e0 (0)\u003c/div\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"6\"\u003ef: One-way variance test, x: Fisher test, mean\u0026thinsp;\u0026plusmn;\u0026thinsp;ss, ss: Standard deviation, n (%)\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003cbr/\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Medication-related osteonecrosis of the jaw (MRONJ), Osteoporosis, Radiographic assessment, Bifosfonat, Mandibuler kortikal index (MCI)","lastPublishedDoi":"10.21203/rs.3.rs-7098395/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7098395/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eObjectives: \u003c/strong\u003eMedication-related osteonecrosis of the jaw (MRONJ) is a serious complication associated with antiresorptive and antiangiogenic medications, such as bisphosphonates and denosumab, frequently prescribed for osteoporosis and oncologic bone conditions. This study aimed to evaluate the effects of MRONJ-associated medications on mandibular cortical bone morphology using the Mandibular Cortical Index (MCI) on panoramic radiographs, and to compare these findings with those from a healthy control population undergoing routine dental evaluation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMaterials and Methods: \u003c/strong\u003eThis cross-sectional study included 62 participants, divided equally into two groups: 31 patients currently receiving medications known to be associated with MRONJ risk, and 31 healthy individuals without a history of such medication use. Panoramic radiographs were obtained for all participants, and the mandibular cortex was evaluated using the MCI classification. Additionally, demographic data, systemic disease presence, and duration of medication use were recorded and analyzed to identify any correlations with cortical bone changes.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eThe comparison of MCI scores between the study and control groups revealed a statistically significant difference (p = 0.003), with the C1 category—representing normal cortical morphology—being more prevalent in the control group. Although no significant differences were identified among the various medication subgroups (e.g., bisphosphonates vs. denosumab), the study group had a significantly higher prevalence of systemic diseases and longer durations of medication use. These findings suggest a possible link between prolonged exposure to MRONJ-associated drugs and early radiographic signs of mandibular bone alteration.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion: \u003c/strong\u003eAlthough no specific medication group showed distinct radiographic signs of MRONJ, overall MCI differences between medication users and controls may assist in early diagnosis and clinical decision-making in MRONJ management.\u003c/p\u003e","manuscriptTitle":"Impact of MRONJ-Associated Medications on Mandibular Cortical Index: A Cross-Sectional Analysis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-09-11 10:55:19","doi":"10.21203/rs.3.rs-7098395/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"4115d609-f51e-4c43-99c8-cc055cb445ea","owner":[],"postedDate":"September 11th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-01-12T09:08:27+00:00","versionOfRecord":[],"versionCreatedAt":"2025-09-11 10:55:19","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7098395","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7098395","identity":"rs-7098395","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}