Comparison of Denosumab with Romosozumab in the Treatment of Male Osteoporosis: A Retrospective Cohort Study

Comparison of Denosumab with Romosozumab in the Treatment of Male Osteoporosis: A Retrospective Cohort Study | 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 Article Comparison of Denosumab with Romosozumab in the Treatment of Male Osteoporosis: A Retrospective Cohort Study Tomonori Kobayakawa, Yasuhide Kanayama, Yuji Hirano, Yukio Nakamura This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4421829/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 01 Oct, 2024 Read the published version in Scientific Reports → Version 1 posted 11 You are reading this latest preprint version Abstract We aimed to investigate the efficacy of romosozumab treatment compared with that of denosumab in especially male osteoporosis patients. This retrospective cohort study included 174 Japanese male patients receiving either denosumab or romosozumab for 12 months. Propensity score matching extracted 50 patients per treatment group for standardization of group characteristics. The endpoints include the rate of change in the bone mineral density (BMD) of the lumbar spine, total hip, and femoral neck after 12 months of treatment as well as the changes in serum bone metabolism markers. The mean 12-month percentage increase in the lumbar spine BMD from baseline was significantly greater with romosozumab (13.0%±1.7%) than with denosumab (4.5%±0.6%) (P < 0.01). The total hip and femoral neck BMD exhibited a similar trend at 12 months; however, no significant between-group differences were observed. With denosumab, bone formation, and resorption marker levels significantly decreased at 6 and 12 months. Conversely, with romosozumab, the levels of bone formation markers increased transiently at 6 months before returning to baseline, whereas bone resorption markers significantly decreased at both time points. Romosozumab demonstrated significantly superior effects over denosumab in improving BMD, especially of the lumbar spine, suggesting that romosozumab can be used for treating male osteoporosis. Male Osteoporosis Romosozumab Denosumab Dual-energy X-ray Absorptiometry Bone turnover Bone mineral density Figures Figure 1 Figure 2 Figure 3 INTRODUCTION As society ages, the annual increase in the number of male osteoporosis cases is notable despite the condition being primarily associated with women 1 . Furthermore, men encounter more significant challenges in activities of daily living and mortality than women 2 , 3 . Men with osteoporosis typically exhibit a higher prevalence of secondary osteoporosis than primary osteoporosis, lower bone turnover, and differences in bone structure compared with women 4 – 6 . However, similar to women, the occurrence of bone fractures owing to bone vulnerability can lead to consequences such as restrictions in daily activities and recurrent fractures, which may ultimately lead to being bedridden. Therefore, enhancing bone mineral density (BMD) and employing appropriate treatment strategies are imperative for managing osteoporosis effectively. The present study focused on comparisons of BMD improvement as an index of therapeutic efficacy since a greater increase in BMD would presumably lead to augmented prevention of fragility fractures 7 . In actual clinical practice, the therapeutic effects of medications need to be confirmed by evaluating changes in BMD, and it is recommended to target a t-score of 2.0 or higher for effective treatment 8 . Treatment with romosozumab promotes bone formation and suppresses bone resorption by inhibiting sclerostin 9 , 10 . Although growing real-world evidence on the efficacy of romosozumab in postmenopausal patients with osteoporosis exists 11 – 13 , studies demonstrating its efficacy in men with osteoporosis are insufficient. Moreover, clinical data regarding denosumab in male osteoporosis are still limited, and there are few real-world data available for the Japanese male population 14 – 16 . Furthermore, there are no reports directly comparing romosozumab and denosumab in male osteoporosis. Therefore, this study aimed to directly compare the clinical efficacy of romosozumab and denosumab for the treatment of male osteoporosis, which is globally underrepresented in terms of firm clinical data. METHODS Study population and ethical approval This retrospective cohort study was conducted in our clinic and six collaborating institutions. Male Japanese patients with osteoporosis who were administered either denosumab or romosozumab for 12 months were included. The diagnosis and treatment of osteoporosis were conducted according to the Japanese Osteoporosis Guidelines 17 , 18 . Especially romosozumab has also been used to treat patients diagnosed with severe osteoporosis who are at a high risk of fractures, regardless of previous osteoporosis treatment. The World Health Organization defines severe osteoporosis as a BMD of 2.5 standard deviations (SDs) or more below the average value for young healthy women (i.e., a T-score <-2.5 SD) in the presence of one or more fragility fractures, a lumbar spine BMD of <-3.3 SD, or the presence of two or more existing vertebral fractures or semi-quantitative evaluation of existing grade-3 vertebral fractures 19 – 22 . Notably, patients with allergies to both medications and those with hypocalcemia were excluded. Additionally, patients who had experienced a cardiovascular event within the past year were excluded from receiving romosozumab treatment. Since the treatment criteria differed between denosumab and romosozumab, patient backgrounds were adjusted using propensity score matching. The patients were divided into patients who received denosumab (Deno group) or romosozumab (Romo group). The key variables considered for propensity score matching were age, body mass index, lumbar spine BMD at baseline, history of prevalent vertebral fractures after 45 years of age, and type of osteoporosis (primary or secondary). Patients with lower 25-hydroxy vitamin D levels were offered an active vitamin-D3 analog. Alternatively, if they declined, they were advised to take commercially available vitamin D3 and calcium supplements. Patients who experienced allergic reactions to these drugs, hypocalcemia, or cardiovascular events within a year before drug administration were excluded. Denosumab (60 mg, administered subcutaneously [s.c.] once every 6 months) or romosozumab (210 mg, administered s.c. once every month) was used for osteoporosis treatment. This study was approved by the ethics committee of Chutoen General Medical Center (Approval No. 3002230822) and conducted in accordance with the tenets of the Declaration of Helsinki. Due to the retrospective nature of the study, the need to obtain informed consent was waived. Primary and secondary outcomes The primary outcome of the study was the change in lumbar spine BMD during the 12 months of denosumab and romosozumab administration. Lumbar spine BMD was evaluated using dual-energy X-ray absorptiometry (DXA) with a Prodigy Fuga device (GE Healthcare, Madison, WI, USA) at all participating institutions. DXA was performed at baseline and 6 and 12 months after treatment. As secondary outcomes, the BMD of the total hip and femoral neck were evaluated using DXA under the same conditions as described above. Moreover, the serum levels of bone turnover markers, procollagen type-1 N-terminal propeptide 1 (P1NP), and tartrate-resistant acid phosphatase isoform 5b (TRACP-5b) were determined at baseline before treatment initiation and at 6- and 12- months during treatment to monitor changes throughout the study period. A previous report demonstrated that TRACP-5b levels were useful bone resorption markers that demonstrated higher clinical sensitivity and signal-to-noise ratio as compared with serum C-telopeptide cross-linked type I collagen levels 23 . Enzyme immunoassays and chemiluminescent enzyme immunoassays were used to quantify these markers for each participant at baseline and after 6 and 12 months. Additionally, we recorded adverse events during the treatment to assess drug safety. Statistical analyses Patient background parameters are presented as the mean ± SD, whereas P1NP and TRACP-5b levels are presented as the median (interquartile range). Percentage changes from baseline to the 6- and 12-month time points for BMD, P1NP levels, and TRACP-5b levels were assessed using Wilcoxon’s signed-rank test. Wilcoxon’s rank-sum test was employed to evaluate between-group differences in percentage change from baseline. Fisher’s exact test was used to determine differences between the characteristics of the study groups. All statistical tests were conducted using EZR (version 1.52; Saitama Medical Center, Jichi Medical University, Saitama, Japan), a graphical user interface for R (The R Foundation for Statistical Computing, Vienna, Austria). More precisely, it is a modified version of the R commander designed to include statistical functions that are frequently used in biostatistics. Statistical significance was set at P values < 0.05. RESULTS Figure 1 shows the flow diagram of the selection process of participants included in this study. Between April 2015 and December 2022, 247 male patients with osteoporosis received denosumab or romosozumab for osteoporosis treatment. Among 103 patients who received denosumab for 12 months and 71 who received romosozumab for 12 months, 50 individuals were extracted from each treatment group using propensity score matching to ensure balanced baseline characteristics between the two groups being compared. Table 1 shows the baseline characteristics of each group before propensity score matching. The standardized characteristics of the patients after propensity score matching are presented in Table 2 , revealing no remarkable differences between the groups and thus requiring no further investigation. Similarly, Supplementary Tables S1 and S2 illustrate the details of diseases related to secondary osteoporosis before (Supplementary Table S1 ) and after (Supplementary Table S2) propensity score matching. The mean ± SD age of patients was 76.6 ± 10.5 years in the Deno group and 75.5 ± 15.4 years in the Romo group. The mean T-scores for the Deno and Romo groups were − 2.13 ± 1.41 and − 2.00 ± 1.42, respectively, for the lumbar spine; -2.44 ± 0.71 and − 2.69 ± 0.94, respectively, for the total hip; and − 2.79 ± 0.74 and − 3.01 ± 1.04, respectively, for the femoral neck. Sixteen (32.0%) and 19 (38%) patients in the Deno and Romo groups, respectively, had secondary osteoporosis. Twenty-nine (58.0%) and 28 (56.0%) patients in the Deno and Romo groups, respectively, had a history of vertebral fractures. The number of treatment-naïve participants was 29 (58.0%) in the Deno group and 31 (62.0%) in the Romo group. Table 1 Baseline patient characteristics before propensity score matching Denosumab Romosozumab P-value N 103 71 Age (years) 70.1 ± 20.4 73.0 ± 17.2 0.328 BMI (kg/m 2 ) 20.6 ± 3.5 20.4 ± 3.2 0.682 Bone mineral density T-score Lumbar spine -1.82 ± 1.52 -2.01 ± 1.23 0.402 Total hip -2.50 ± 0.73 -2.69 ± 0.97 0.170 Femoral neck -2.74 ± 0.86 -3.02 ± 1.08 0.066 Type of osteoporosis, n (%) Primary 59 (57.3) 35 (49.3) 0.354 Secondary 44 (42.7) 36 (50.7) Prior vertebral fracture, n (%) 40 (38.8) 47 (66.2) 0.001 Prior non-vertebral fracture, n (%) 11 (10.7) 12 (16.9) 0.260 History of prior treatment, n (%) Naïve 66 (64.1) 41 (57.7) 0.431 Switch 37 (35.9) 30 (42.3) Bisphosphonates 21 (20.4) 16 (21.1) Denosumab - 7 (9.9) Teriparatide 7 (6.8) 7 (9.9) Romosozumab 9 (8.7) - SERM - 1 (1.4) Combined use of active vitamin D, n (%) 64 (62.1) 41 (57.7) 0.637 P1NP (µg/L, median [IQR]) 54.6 [30.7, 78.0] 65.3 [37.7, 91.9] 0.175 TRACP-5b (mU/dL, median [IQR]) 495.5 [323.5, 648.5] 481.0 [375.0, 705.0] 0.530 Serum albumin (g/dL) 4.0 ± 0.5 4.0 ± 0.4 0.643 Serum-corrected calcium (mg/dL) 9.2 ± 0.5 9.2 ± 0.5 0.675 eGFR (mL/min/1.73 m 2 ) 64.4 ± 26.9 72.5 ± 38.7 0.128 25OHD (ng/mL) 19.8 ± 6.4 19.0 ± 9.0 0.578 Data are presented as mean ± standard deviation or number (%) of all patients who completed the 12-month treatment with either denosumab or romosozumab. P1NP and TRACP-5b levels are presented as median [IQR]. Between-group differences were analyzed using Student’s t-tests, Wilcoxon’s rank-sum test, or Fisher’s exact test. SERM, selective estrogen receptor modulator; 25OHD, 25-hydroxyvitamin D; BMI, body mass index; eGFR, estimated glomerular filtration rate; IQR, interquartile range; P1NP, procollagen type-1 N-terminal propeptide; TRACP-5b, tartrate-resistant acid phosphatase isoform 5b Table 2 Baseline patient characteristics after propensity score matching Denosumab Romosozumab P-value N 50 50 Age (years) 76.6 ± 10.5 75.5 ± 15.4 0.678 BMI (kg/m 2 ) 20.5 ± 2.7 20.8 ± 3.1 0.653 Bone mineral density T-score Lumbar spine -2.13 ± 1.41 -2.00 ± 1.42 0.355 Total hip -2.44 ± 0.71 -2.69 ± 0.94 0.151 Femoral neck -2.79 ± 0.74 -3.01 ± 1.04 0.238 Type of osteoporosis, n (%) Primary 34 (68.0) 31 (62.0) 0.675 Secondary 16 (32.0) 19 (38.0) Prior vertebral fracture, n (%) 29 (58.0) 28 (56.0) Prior non-vertebral fracture, n (%) 7 (14.0) 8 (16.0) 1.000 History of prior treatment, n (%) Naïve 29 (58.0) 31 (62.0) 0.838 Switch 21 (42.0) 19 (38.0) Bisphosphonates 11 (22.0) 10 (20.0) Denosumab - 5 (10.0) Teriparatide 4 (8.0) 3 (6.0) Romosozumab 6 (12.0) - Combined use of active vitamin D, n (%) 33 (66.0) 26 (52.0) 0.222 P1NP (µg/L, median [IQR]) 56.6 [41.4, 74.4] 65.1 [39.2, 100.4] 0.331 TRACP-5b (mU/dL, median [IQR]) 498.0 [358.0, 635.0] 499.5 [381.0, 715.0] 0.320 Serum albumin (g/dL) 4.0 ± 0.4 4.0 ± 0.5 0.966 Serum-corrected calcium (mg/dL) 9.2 ± 0.5 9.2 ± 0.5 0.341 eGFR (mL/min/1.73 m 2 ) 65.2 ± 23.5 72.6 ± 36.4 0.259 25OHD (ng/mL) 19.7 ± 6.2 19.8 ± 8.0 0.954 Data are presented as mean ± standard deviation or number (%) of all patients who completed the 12-month treatment with either denosumab or romosozumab. P1NP and TRACP-5b levels are presented as median [IQR]. Between-group differences were analyzed using Student’s t-tests, Wilcoxon’s rank-sum test, or Fisher’s exact test. 25OHD, 25-hydroxyvitamin D; BMI, body mass index; eGFR, estimated glomerular filtration rate; IQR, interquartile range; P1NP, procollagen type-1 N-terminal propeptide; TRACP-5b, tartrate-resistant acid phosphatase isoform 5b Primary outcome The primary outcome analysis included 50 patients each in the Deno and Romo groups. The percentage (mean ± standard error) changes in lumbar spine areal BMD, assessed using DXA, from baseline to 6 and 12 months were 1.9%±0.8 (P < 0.01 vs. baseline) and 4.5%±0.6 (P < 0.001 vs. baseline), respectively, in the Deno group and 9.1%±1.7 (P < 0.001 vs. baseline) and 13.0%±1.7 (P < 0.001 vs. baseline), respectively, in the Romo group (Fig. 2 a). The percentage change in the lumbar spine BMD was significantly higher than that in the Deno group at 6 (P < 0.01) and 12 months (P < 0.001). Secondary outcomes The percentage changes in total hip BMD from baseline to 6 and 12 months were 2.2%±0.6 and 3.2%±0.7 (both P < 0.001), respectively, in the Deno group and 0.4%±0.6 (P = 0.385) and 2.1%±0.8 (P < 0.05), respectively, in the Romo group (Fig. 2 b). Similarly, the changes in femoral neck BMD at 6 and 12 months were 1.8%±1.0 and 1.7%±1.0 (both P < 0.05), respectively, in the Deno group and 1.6%±1.1 (P < 0.05) and 3.3%±1.0 (P < 0.01), respectively, in the Romo group (Fig. 2 c). Significant increases in BMD at 12 months were observed compared with baseline values for both treatment groups. No significant differences were found in the percentage increases in BMD of the total hip and femoral neck between the Deno and Romo groups throughout the study (total hip, P = 0.110; femoral neck, P = 0.711). Bone turnover markers The serum P1NP level significantly decreased at 6 (-60.5%; P < 0.001) and 12 (-61.9%; P < 0.001) months compared with that at baseline in the Deno group. In contrast, in the Romo group, the P1NP level did not significantly change at 6 months (+ 11.5%; P = 0.138); however, the level decreased at 12 months relative to baseline (-8.0%; P = 0.088) (Fig. 3 a). Significant differences in the P1NP level were observed between the two groups at 6 and 12 months (both P < 0.001). In the Deno group, serum TRACP-5b levels significantly decreased at 6 (-46.5%; P < 0.001) and 12 (-47.2%; P < 0.001) months compared with the baseline levels (Fig. 3 b). The Romo group exhibited a similar trend at 6 (-32.2%; P < 0.001) and 12 (-44.2%; P < 0.001) months. Although a significant difference between the groups was found at 6 months (P < 0.05), no significant difference was observed at 12 months (P = 0.311). Adverse events and new fractures Several adverse events were recorded during the 12 months of treatment (Table 3 ). Nine (5.8%) patients in the Deno group and five (5.5%) in the Romo group dropped out of the study; however, no significant difference was observed between the groups (P = 1.000). Although injection site reactions occurred more frequently in the Romo group than in the Deno group, they did not result in drug discontinuation. Injection site reactions often occurred during the initial administration. Other remarkable events were recorded in both groups, yet their incidence did not differ significantly (3.8% in the Deno group and 5.5% in the Romo group; P = 0.540). Table 3 Adverse events and new fractures documented during the 12-month treatment period Denosumab (N = 156) Romosozumab (N = 91) P-value All adverse events 16 (10.3) 21 (23.0) < 0.01 Adverse events leading to study discontinuation 9 (5.8) 5 (5.5) 1.000 Dementia 1 (0.6) 0 Malignant lymphoma 1 (0.6) 0 Hyperkalemia 1 (0.6) 0 Poor condition 2 (1.2) 1 (1.1) Pulmonary infarction 0 1 (1.1) Cerebral infarction 0 1 (1.1) Cerebral hemorrhage 0 1 (1.1) Hospitalization (reason unknown) 1 (0.6) 0 Death Pneumonia 2 (1.2) 1 (1.1) Reason unknown 1 (0.6) 0 Serious adverse events 1 (0.6) 1 (1.1) 1.000 Cerebral infarction 1 (0.6) 0 Lower leg necrosis 0 1 (1.1) Injection site reaction a 0 10 (10.1) < 0.001 Pain 0 8 (8.8) Swelling 0 2 (2.2) Other events of interest 6 (3.8) 5 (5.5) 0.540 Development of kidney stone 1 (0.6) 0 Renal function decline 2 (1.2) 0 Thrombocytopenia 1 (0.6) 0 Rheumatoid arthritis 1 (0.6) 0 Iliopsoas tumor 1 (0.6) 0 Cellulitis 0 1 (1.1) Fatigue 0 2 Hypocalcemia 0 1 (1.1) Hypozincemia 0 1 (1.1) New fractures during the therapy 6 (3.8) 3 (3.3) 1.000 Lumbar vertebra 1 (0.6) 1 (1.1) Thoracic vertebra 1 (0.6) 0 Distal phalanx of great toe 1 (0.6) 0 Rib 2 (1.2) 0 Supracondylar humerus 0 1 (1.1) Distal radius 1 (0.6) 1 (1.1) Data are presented as the number (%) of patients. Between-group differences were analyzed using Fisher’s exact test. a Injection-site reactions included adverse events on the skin at the injection site lasting for 2 days or more. Regarding the occurrence of new bone fractures during treatment, six (3.8%) patients in the Deno group and three (3.3%) in the Romo group experienced new fractures, including vertebral body fractures. There were no significant differences in the occurrence of new fractures between the groups (P = 1.000). DISCUSSION In men with osteoporosis, the loss of cancellous (trabecular) bone is mainly caused by decreased bone formation, which progresses with age 24 , 25 . When trabecular bone thinning occurs, the number and connectivity of trabecular bones remain relatively maintained. In contrast, trabecular bone loss in postmenopausal women is primarily caused by increased bone resorption. This results in several detrimental changes to the trabecular bone microarchitecture, including a decrease in the number of trabecular bone elements, disrupted connectivity between the remaining trabeculae (female type), and in severe cases, complete perforations or loss of trabecular structures 26 . A decrease in the number of trabeculae impairs bone strength more than trabecular thinning (male type) 5 , 26 , 27 . In the assessment of osteoporosis treatments, the use of bisphosphonate agents and denosumab, which are both popular bone resorption suppressors, is considered to be less effective in men compared with that in women because of the different mechanisms of action between sexes, as men typically have lower bone turnover rates. Postmenopausal osteoporosis in women is primarily attributed to enhanced bone resorption, whereas aging-related male osteoporosis is largely associated with decreased bone formation. Therefore, the administration of a bone-formation-promoting agent is considered a rational treatment for male osteoporosis to activate and balance rates of bone turnover. However, treatment with teriparatide, a bone-formation-promoting drug widely used in clinical practice, is also known to stimulate bone resorption, leading to cortical bone porosity. Consequently, its efficacy in femoral bone is considered limited 28 . In contrast, romosozumab therapy exerts a dual effect by accelerating bone formation and suppressing bone resorption; therefore, it is anticipated to be an effective treatment option for men from the perspective of bone metabolism. Furthermore, clinical trials 29 , 30 and real-world data 11 – 13 have demonstrated a significant increase in femoral BMD in postmenopausal women with osteoporosis. Although romosozumab therapy exhibits a “mild” bone resorption inhibitory effect compared with that of denosumab therapy 31 , it may potentially lead to a reduced drug effect in male patients with osteoporosis compared with that in postmenopausal female patients with osteoporosis. Nonetheless, romosozumab is still considered to be effective for treating osteoporosis in men to a reasonable extent. In the current study, the Romo group exhibited a significantly superior effect than the Deno group in increasing lumbar spine BMD. Although our data showed that the Deno group demonstrated a higher increase in total hip and femoral neck BMD compared with the Romo group, there was no significant difference in the BMD changes at 12 months. The only previous study that investigated the therapeutic effects of romosozumab therapy for male osteoporosis was the BRIDGE trial 32 . The results of the present study, which demonstrated changes in lumbar spine, total hip, and femoral neck BMD, were consistent with those of the BRIDGE trial. This study had some limitations. First, the small sample size of patients included in this study may limit the generalizability of our findings. Second, patients with both primary and secondary osteoporosis were included in the study population. Finally, the study did not consider differences based on the administration of active vitamin D preparations. These points for improvement should be considered in further studies to substantiate the empirical evidence in clinical practice. CONCLUSIONS Considering the inherently limited number of male patients with osteoporosis compared to that of female patients with postmenopausal osteoporosis, this study holds value in suggesting an approach for treating male osteoporosis. Particularly, among male patients with osteoporosis, the Romo group showed a significantly increased lumbar spine BMD compared to the Deno group, demonstrating the superior pharmacodynamics of romosozumab for modern osteoporosis treatment over denosumab in increasing BMD. This implies that romosozumab, rather than denosumab, should be prioritized when selecting and designing a treatment strategy for male osteoporosis. Declarations Acknowledgments The authors are grateful to Thiago França, PhD. for careful English proofreading and valuable discussions. Author contribution statement TK was engaged in the direction of this study, statistical analysis, and drafting and editing of this manuscript. AM, YK, YH, and YN were involved in the data acquisition. TK and all other authors participated in the data interpretation and critical revision of the manuscript. All authors have approved the final manuscript for publication. Data availability statement The datasets analyzed in this study and presented in this material are available from the corresponding author upon reasonable request. Conflict of interest statement All authors declare no competing interests. Funding This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Ethical approval All procedures performed in studies involving human participants were following the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. References Gullberg, B., Johnell, O. & Kanis, J. A. World-wide projections for hip fracture. Osteoporos Int 7 , 407-413, doi:10.1007/pl00004148 (1997). Center, J. R., Nguyen, T. V., Schneider, D., Sambrook, P. N. & Eisman, J. A. Mortality after all major types of osteoporotic fracture in men and women: an observational study. 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J Bone Miner Res 30 , 39-45, doi:10.1002/jbmr.2315 (2015). Cosman, F. et al. Romosozumab Treatment in Postmenopausal Women with Osteoporosis. The New England journal of medicine 375 , 1532-1543, doi:10.1056/NEJMoa1607948 (2016). Saag, K. G. et al. Romosozumab or Alendronate for Fracture Prevention in Women with Osteoporosis. The New England journal of medicine 377 , 1417-1427, doi:10.1056/NEJMoa1708322 (2017). Lambertini, M. et al. Cancer and fertility preservation: international recommendations from an expert meeting. BMC medicine 14 , 1, doi:10.1186/s12916-015-0545-7 (2016). Lewiecki, E. M. et al. A Phase III Randomized Placebo-Controlled Trial to Evaluate Efficacy and Safety of Romosozumab in Men With Osteoporosis. The Journal of clinical endocrinology and metabolism 103 , 3183-3193, doi:10.1210/jc.2017-02163 (2018). Additional Declarations No competing interests reported. Supplementary Files SupplementalInformation.pdf Cite Share Download PDF Status: Published Journal Publication published 01 Oct, 2024 Read the published version in Scientific Reports → Version 1 posted Editorial decision: Revision requested 05 Aug, 2024 Reviews received at journal 03 Aug, 2024 Reviewers agreed at journal 23 Jul, 2024 Reviews received at journal 07 Jul, 2024 Reviewers agreed at journal 25 Jun, 2024 Reviewers agreed at journal 18 Jun, 2024 Reviewers invited by journal 18 Jun, 2024 Editor assigned by journal 18 Jun, 2024 Editor invited by journal 05 Jun, 2024 Submission checks completed at journal 05 Jun, 2024 First submitted to journal 14 May, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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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-4421829","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":315518037,"identity":"105dea05-db70-4653-9611-44752afbeae5","order_by":0,"name":"Tomonori Kobayakawa","email":"","orcid":"","institution":"Kobayakawa Orthopedic and Rheumatologic Clinic","correspondingAuthor":false,"prefix":"","firstName":"Tomonori","middleName":"","lastName":"Kobayakawa","suffix":""},{"id":315518038,"identity":"e6828774-2566-4ad5-a662-3c05c93e7e3b","order_by":1,"name":"Yasuhide Kanayama","email":"","orcid":"","institution":"Toyota Kosei Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yasuhide","middleName":"","lastName":"Kanayama","suffix":""},{"id":315518040,"identity":"6152b309-f74b-491d-8064-89b9e9b97b9b","order_by":2,"name":"Yuji Hirano","email":"","orcid":"","institution":"Toyohashi Municipal Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yuji","middleName":"","lastName":"Hirano","suffix":""},{"id":315518042,"identity":"d284976e-ee86-47fa-b27e-06d04715fc4f","order_by":3,"name":"Yukio Nakamura","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAp0lEQVRIiWNgGAWjYJCCAxIVDAx8DAwJROtgPGBxhoGBjRQtzAcq28BaiAQGN3IPHLg5z04OqOXZA+K0nDmXcHDmtmRjoJZ0A+K0HO8xOCy5jTkR6LY0CeK0HOYxOPx3Tj0pWoC2HJBsOEyCFskzZwwOSBw7bszGTKxf+G7kGH+QqKmW42fvSXtAlBaFAzAWM08aUToY5BvgTPZjxGkZBaNgFIyCEQcAGosuZ1s65vwAAAAASUVORK5CYII=","orcid":"","institution":"Iida hospital","correspondingAuthor":true,"prefix":"","firstName":"Yukio","middleName":"","lastName":"Nakamura","suffix":""}],"badges":[],"createdAt":"2024-05-15 01:23:19","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4421829/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4421829/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s41598-024-73398-5","type":"published","date":"2024-10-01T15:58:03+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":58757021,"identity":"27a454c3-b96a-43da-ac4c-2a113b3aeac1","added_by":"auto","created_at":"2024-06-20 17:23:40","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":45979,"visible":true,"origin":"","legend":"\u003cp\u003eFlow diagram illustrating the distribution of participants throughout the study period\u003c/p\u003e","description":"","filename":"Fig1.png","url":"https://assets-eu.researchsquare.com/files/rs-4421829/v1/a705ee3d7f1e14e7a77b0089.png"},{"id":58757017,"identity":"e9415f05-7116-420d-a91c-6a9d9f518292","added_by":"auto","created_at":"2024-06-20 17:23:35","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":53870,"visible":true,"origin":"","legend":"\u003cp\u003eMean percentage change in BMD of the \u003cstrong\u003ea.\u003c/strong\u003e lumbar spine, \u003cstrong\u003eb\u003c/strong\u003e. total hip, and \u003cstrong\u003ec.\u003c/strong\u003e femoral neck from baseline to 6 and 12 months after treatment\u003c/p\u003e\n\u003cp\u003eBars indicate the mean±standard errors. *P\u0026lt;0.05, **P\u0026lt;0.01, and ***P\u0026lt;0.001 versus baseline (Wilcoxon's signed-rank test).†P\u0026lt;0.05, ††P\u0026lt;0.01, and †††P\u0026lt;0.001 versus the Romo group (Wilcoxon's rank-sum test). BMD, bone mineral density\u003c/p\u003e","description":"","filename":"Fig2.png","url":"https://assets-eu.researchsquare.com/files/rs-4421829/v1/6f542bee527612cbfd44e695.png"},{"id":58757069,"identity":"40a8afe3-5f44-4f3b-be15-af9a641d0e10","added_by":"auto","created_at":"2024-06-20 17:23:44","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":42873,"visible":true,"origin":"","legend":"\u003cp\u003eMedian percentage change in serum levels of bone turnover markers\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ea.\u003c/strong\u003eP1NP and \u003cstrong\u003eb.\u003c/strong\u003e TRACP-5b. ***P\u0026lt;0.001 versus baseline (Wilcoxon's signed-rank test). †P\u0026lt;0.05, and †††P\u0026lt;0.001 versus the Romo group (Wilcoxon's rank-sum test). P1NP, procollagen type-1 N-terminal propeptide; TRACP-5b, tartrate-resistant acid phosphatase isoform 5b\u003c/p\u003e","description":"","filename":"Fig3.png","url":"https://assets-eu.researchsquare.com/files/rs-4421829/v1/68ae9dc53dac4358bc6feb50.png"},{"id":66097404,"identity":"e8f76448-c54c-4a64-a1b1-02dbc96ea94f","added_by":"auto","created_at":"2024-10-07 16:14:03","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":806983,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4421829/v1/3fe31474-ffd5-42aa-a16f-315d93aecfaa.pdf"},{"id":58756996,"identity":"7685db88-c130-4f1b-8a15-ff89d988d6be","added_by":"auto","created_at":"2024-06-20 17:23:32","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":359865,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementalInformation.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4421829/v1/b69c865595fe0598e291f41a.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Comparison of Denosumab with Romosozumab in the Treatment of Male Osteoporosis: A Retrospective Cohort Study","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eAs society ages, the annual increase in the number of male osteoporosis cases is notable despite the condition being primarily associated with women \u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e. Furthermore, men encounter more significant challenges in activities of daily living and mortality than women \u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e,\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e. Men with osteoporosis typically exhibit a higher prevalence of secondary osteoporosis than primary osteoporosis, lower bone turnover, and differences in bone structure compared with women \u003csup\u003e\u003cspan additionalcitationids=\"CR5\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e. However, similar to women, the occurrence of bone fractures owing to bone vulnerability can lead to consequences such as restrictions in daily activities and recurrent fractures, which may ultimately lead to being bedridden. Therefore, enhancing bone mineral density (BMD) and employing appropriate treatment strategies are imperative for managing osteoporosis effectively. The present study focused on comparisons of BMD improvement as an index of therapeutic efficacy since a greater increase in BMD would presumably lead to augmented prevention of fragility fractures \u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e. In actual clinical practice, the therapeutic effects of medications need to be confirmed by evaluating changes in BMD, and it is recommended to target a t-score of 2.0 or higher for effective treatment \u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eTreatment with romosozumab promotes bone formation and suppresses bone resorption by inhibiting sclerostin \u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e,\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e. Although growing real-world evidence on the efficacy of romosozumab in postmenopausal patients with osteoporosis exists \u003csup\u003e\u003cspan additionalcitationids=\"CR12\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e, studies demonstrating its efficacy in men with osteoporosis are insufficient. Moreover, clinical data regarding denosumab in male osteoporosis are still limited, and there are few real-world data available for the Japanese male population \u003csup\u003e\u003cspan additionalcitationids=\"CR15\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e. Furthermore, there are no reports directly comparing romosozumab and denosumab in male osteoporosis. Therefore, this study aimed to directly compare the clinical efficacy of romosozumab and denosumab for the treatment of male osteoporosis, which is globally underrepresented in terms of firm clinical data.\u003c/p\u003e"},{"header":"METHODS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy population and ethical approval\u003c/h2\u003e \u003cp\u003eThis retrospective cohort study was conducted in our clinic and six collaborating institutions. Male Japanese patients with osteoporosis who were administered either denosumab or romosozumab for 12 months were included. The diagnosis and treatment of osteoporosis were conducted according to the Japanese Osteoporosis Guidelines \u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e,\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e. Especially romosozumab has also been used to treat patients diagnosed with severe osteoporosis who are at a high risk of fractures, regardless of previous osteoporosis treatment. The World Health Organization defines severe osteoporosis as a BMD of 2.5 standard deviations (SDs) or more below the average value for young healthy women (i.e., a T-score \u0026lt;-2.5 SD) in the presence of one or more fragility fractures, a lumbar spine BMD of \u0026lt;-3.3 SD, or the presence of two or more existing vertebral fractures or semi-quantitative evaluation of existing grade-3 vertebral fractures \u003csup\u003e\u003cspan additionalcitationids=\"CR20 CR21\" citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e. Notably, patients with allergies to both medications and those with hypocalcemia were excluded. Additionally, patients who had experienced a cardiovascular event within the past year were excluded from receiving romosozumab treatment. Since the treatment criteria differed between denosumab and romosozumab, patient backgrounds were adjusted using propensity score matching. The patients were divided into patients who received denosumab (Deno group) or romosozumab (Romo group). The key variables considered for propensity score matching were age, body mass index, lumbar spine BMD at baseline, history of prevalent vertebral fractures after 45 years of age, and type of osteoporosis (primary or secondary).\u003c/p\u003e \u003cp\u003ePatients with lower 25-hydroxy vitamin D levels were offered an active vitamin-D3 analog. Alternatively, if they declined, they were advised to take commercially available vitamin D3 and calcium supplements. Patients who experienced allergic reactions to these drugs, hypocalcemia, or cardiovascular events within a year before drug administration were excluded. Denosumab (60 mg, administered subcutaneously [s.c.] once every 6 months) or romosozumab (210 mg, administered s.c. once every month) was used for osteoporosis treatment.\u003c/p\u003e \u003cp\u003eThis study was approved by the ethics committee of Chutoen General Medical Center (Approval No. 3002230822) and conducted in accordance with the tenets of the Declaration of Helsinki. Due to the retrospective nature of the study, the need to obtain informed consent was waived.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003ePrimary and secondary outcomes\u003c/h2\u003e \u003cp\u003eThe primary outcome of the study was the change in lumbar spine BMD during the 12 months of denosumab and romosozumab administration. Lumbar spine BMD was evaluated using dual-energy X-ray absorptiometry (DXA) with a Prodigy Fuga device (GE Healthcare, Madison, WI, USA) at all participating institutions. DXA was performed at baseline and 6 and 12 months after treatment.\u003c/p\u003e \u003cp\u003eAs secondary outcomes, the BMD of the total hip and femoral neck were evaluated using DXA under the same conditions as described above. Moreover, the serum levels of bone turnover markers, procollagen type-1 N-terminal propeptide 1 (P1NP), and tartrate-resistant acid phosphatase isoform 5b (TRACP-5b) were determined at baseline before treatment initiation and at 6- and 12- months during treatment to monitor changes throughout the study period. A previous report demonstrated that TRACP-5b levels were useful bone resorption markers that demonstrated higher clinical sensitivity and signal-to-noise ratio as compared with serum C-telopeptide cross-linked type I collagen levels \u003csup\u003e\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e. Enzyme immunoassays and chemiluminescent enzyme immunoassays were used to quantify these markers for each participant at baseline and after 6 and 12 months. Additionally, we recorded adverse events during the treatment to assess drug safety.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analyses\u003c/h2\u003e \u003cp\u003ePatient background parameters are presented as the mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD, whereas P1NP and TRACP-5b levels are presented as the median (interquartile range). Percentage changes from baseline to the 6- and 12-month time points for BMD, P1NP levels, and TRACP-5b levels were assessed using Wilcoxon\u0026rsquo;s signed-rank test. Wilcoxon\u0026rsquo;s rank-sum test was employed to evaluate between-group differences in percentage change from baseline. Fisher\u0026rsquo;s exact test was used to determine differences between the characteristics of the study groups. All statistical tests were conducted using EZR (version 1.52; Saitama Medical Center, Jichi Medical University, Saitama, Japan), a graphical user interface for R (The R Foundation for Statistical Computing, Vienna, Austria). More precisely, it is a modified version of the R commander designed to include statistical functions that are frequently used in biostatistics. Statistical significance was set at P values\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e \u003c/div\u003e"},{"header":"RESULTS","content":"\u003cp\u003eFigure \u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e shows the flow diagram of the selection process of participants included in this study. Between April 2015 and December 2022, 247 male patients with osteoporosis received denosumab or romosozumab for osteoporosis treatment. Among 103 patients who received denosumab for 12 months and 71 who received romosozumab for 12 months, 50 individuals were extracted from each treatment group using propensity score matching to ensure balanced baseline characteristics between the two groups being compared. Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e shows the baseline characteristics of each group before propensity score matching. The standardized characteristics of the patients after propensity score matching are presented in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, revealing no remarkable differences between the groups and thus requiring no further investigation. Similarly, Supplementary Tables S1 and S2 illustrate the details of diseases related to secondary osteoporosis before (Supplementary Table \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e) and after (Supplementary Table S2) propensity score matching. The mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD age of patients was 76.6\u0026thinsp;\u0026plusmn;\u0026thinsp;10.5 years in the Deno group and 75.5\u0026thinsp;\u0026plusmn;\u0026thinsp;15.4 years in the Romo group. The mean T-scores for the Deno and Romo groups were \u0026minus;\u0026thinsp;2.13\u0026thinsp;\u0026plusmn;\u0026thinsp;1.41 and \u0026minus;\u0026thinsp;2.00\u0026thinsp;\u0026plusmn;\u0026thinsp;1.42, respectively, for the lumbar spine; -2.44\u0026thinsp;\u0026plusmn;\u0026thinsp;0.71 and \u0026minus;\u0026thinsp;2.69\u0026thinsp;\u0026plusmn;\u0026thinsp;0.94, respectively, for the total hip; and \u0026minus;\u0026thinsp;2.79\u0026thinsp;\u0026plusmn;\u0026thinsp;0.74 and \u0026minus;\u0026thinsp;3.01\u0026thinsp;\u0026plusmn;\u0026thinsp;1.04, respectively, for the femoral neck. Sixteen (32.0%) and 19 (38%) patients in the Deno and Romo groups, respectively, had secondary osteoporosis. Twenty-nine (58.0%) and 28 (56.0%) patients in the Deno and Romo groups, respectively, had a history of vertebral fractures. The number of treatment-na\u0026iuml;ve participants was 29 (58.0%) in the Deno group and 31 (62.0%) in the Romo group.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \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 \u003cp\u003eBaseline patient characteristics before propensity score matching\u003c/p\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\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eDenosumab\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRomosozumab\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eP-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eN\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e103\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e71\u003c/p\u003e \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 \u003cp\u003eAge (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e70.1\u0026thinsp;\u0026plusmn;\u0026thinsp;20.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e73.0\u0026thinsp;\u0026plusmn;\u0026thinsp;17.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.328\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI (kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20.6\u0026thinsp;\u0026plusmn;\u0026thinsp;3.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e20.4\u0026thinsp;\u0026plusmn;\u0026thinsp;3.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.682\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBone mineral density T-score\u003c/p\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 \u003cp\u003eLumbar spine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-1.82\u0026thinsp;\u0026plusmn;\u0026thinsp;1.52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-2.01\u0026thinsp;\u0026plusmn;\u0026thinsp;1.23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.402\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal hip\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-2.50\u0026thinsp;\u0026plusmn;\u0026thinsp;0.73\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-2.69\u0026thinsp;\u0026plusmn;\u0026thinsp;0.97\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.170\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemoral neck\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-2.74\u0026thinsp;\u0026plusmn;\u0026thinsp;0.86\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-3.02\u0026thinsp;\u0026plusmn;\u0026thinsp;1.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.066\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eType of osteoporosis, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePrimary\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e59 (57.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e35 (49.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.354\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSecondary\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e44 (42.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e36 (50.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrior vertebral fracture, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e40 (38.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e47 (66.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrior non-vertebral fracture, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11 (10.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12 (16.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.260\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHistory of prior treatment, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNa\u0026iuml;ve\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e66 (64.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e41 (57.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.431\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSwitch\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e37 (35.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e30 (42.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eBisphosphonates\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21 (20.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e16 (21.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eDenosumab\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7 (9.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eTeriparatide\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (6.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7 (9.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eRomosozumab\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9 (8.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eSERM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (1.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCombined use of active vitamin D, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e64 (62.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e41 (57.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.637\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eP1NP (\u0026micro;g/L, median [IQR])\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e54.6 [30.7, 78.0]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e65.3 [37.7, 91.9]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.175\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTRACP-5b (mU/dL, median [IQR])\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e495.5 [323.5, 648.5]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e481.0 [375.0, 705.0]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.530\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSerum albumin (g/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.643\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSerum-corrected calcium (mg/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9.2\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9.2\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.675\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eeGFR (mL/min/1.73 m\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e64.4\u0026thinsp;\u0026plusmn;\u0026thinsp;26.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e72.5\u0026thinsp;\u0026plusmn;\u0026thinsp;38.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.128\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e25OHD (ng/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19.8\u0026thinsp;\u0026plusmn;\u0026thinsp;6.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e19.0\u0026thinsp;\u0026plusmn;\u0026thinsp;9.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.578\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eData are presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation or number (%) of all patients who completed the 12-month treatment with either denosumab or romosozumab. P1NP and TRACP-5b levels are presented as median [IQR]. Between-group differences were analyzed using Student\u0026rsquo;s t-tests, Wilcoxon\u0026rsquo;s rank-sum test, or Fisher\u0026rsquo;s exact test.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eSERM, selective estrogen receptor modulator; 25OHD, 25-hydroxyvitamin D; BMI, body mass index; eGFR, estimated glomerular filtration rate; IQR, interquartile range; P1NP, procollagen type-1 N-terminal propeptide; TRACP-5b, tartrate-resistant acid phosphatase isoform 5b\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\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 \u003cp\u003eBaseline patient characteristics after propensity score matching\u003c/p\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\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eDenosumab\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRomosozumab\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eP-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eN\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e50\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e50\u003c/p\u003e \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 \u003cp\u003eAge (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e76.6\u0026thinsp;\u0026plusmn;\u0026thinsp;10.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e75.5\u0026thinsp;\u0026plusmn;\u0026thinsp;15.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.678\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI (kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20.5\u0026thinsp;\u0026plusmn;\u0026thinsp;2.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e20.8\u0026thinsp;\u0026plusmn;\u0026thinsp;3.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.653\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBone mineral density T-score\u003c/p\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 \u003cp\u003eLumbar spine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-2.13\u0026thinsp;\u0026plusmn;\u0026thinsp;1.41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-2.00\u0026thinsp;\u0026plusmn;\u0026thinsp;1.42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.355\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal hip\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-2.44\u0026thinsp;\u0026plusmn;\u0026thinsp;0.71\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-2.69\u0026thinsp;\u0026plusmn;\u0026thinsp;0.94\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.151\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemoral neck\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-2.79\u0026thinsp;\u0026plusmn;\u0026thinsp;0.74\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-3.01\u0026thinsp;\u0026plusmn;\u0026thinsp;1.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.238\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eType of osteoporosis, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePrimary\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e34 (68.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e31 (62.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.675\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSecondary\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16 (32.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e19 (38.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrior vertebral fracture, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e29 (58.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e28 (56.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrior non-vertebral fracture, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (14.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8 (16.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHistory of prior treatment, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNa\u0026iuml;ve\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e29 (58.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e31 (62.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.838\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSwitch\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21 (42.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e19 (38.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eBisphosphonates\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11 (22.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10 (20.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eDenosumab\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5 (10.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eTeriparatide\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (8.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3 (6.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eRomosozumab\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (12.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCombined use of active vitamin D, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e33 (66.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e26 (52.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.222\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eP1NP (\u0026micro;g/L, median [IQR])\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e56.6 [41.4, 74.4]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e65.1 [39.2, 100.4]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.331\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTRACP-5b (mU/dL, median [IQR])\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e498.0 [358.0, 635.0]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e499.5 [381.0, 715.0]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.320\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSerum albumin (g/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.966\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSerum-corrected calcium (mg/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9.2\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9.2\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.341\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eeGFR (mL/min/1.73 m\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e65.2\u0026thinsp;\u0026plusmn;\u0026thinsp;23.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e72.6\u0026thinsp;\u0026plusmn;\u0026thinsp;36.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.259\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e25OHD (ng/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19.7\u0026thinsp;\u0026plusmn;\u0026thinsp;6.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e19.8\u0026thinsp;\u0026plusmn;\u0026thinsp;8.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.954\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eData are presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation or number (%) of all patients who completed the 12-month treatment with either denosumab or romosozumab. P1NP and TRACP-5b levels are presented as median [IQR]. Between-group differences were analyzed using Student\u0026rsquo;s t-tests, Wilcoxon\u0026rsquo;s rank-sum test, or Fisher\u0026rsquo;s exact test.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e25OHD, 25-hydroxyvitamin D; BMI, body mass index; eGFR, estimated glomerular filtration rate; IQR, interquartile range; P1NP, procollagen type-1 N-terminal propeptide; TRACP-5b, tartrate-resistant acid phosphatase isoform 5b\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003ePrimary outcome\u003c/h2\u003e \u003cp\u003eThe primary outcome analysis included 50 patients each in the Deno and Romo groups. The percentage (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard error) changes in lumbar spine areal BMD, assessed using DXA, from baseline to 6 and 12 months were 1.9%\u0026plusmn;0.8 (P\u0026thinsp;\u0026lt;\u0026thinsp;0.01 vs. baseline) and 4.5%\u0026plusmn;0.6 (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001 vs. baseline), respectively, in the Deno group and 9.1%\u0026plusmn;1.7 (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001 vs. baseline) and 13.0%\u0026plusmn;1.7 (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001 vs. baseline), respectively, in the Romo group (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ea). The percentage change in the lumbar spine BMD was significantly higher than that in the Deno group at 6 (P\u0026thinsp;\u0026lt;\u0026thinsp;0.01) and 12 months (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eSecondary outcomes\u003c/h2\u003e \u003cp\u003eThe percentage changes in total hip BMD from baseline to 6 and 12 months were 2.2%\u0026plusmn;0.6 and 3.2%\u0026plusmn;0.7 (both P\u0026thinsp;\u0026lt;\u0026thinsp;0.001), respectively, in the Deno group and 0.4%\u0026plusmn;0.6 (P\u0026thinsp;=\u0026thinsp;0.385) and 2.1%\u0026plusmn;0.8 (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05), respectively, in the Romo group (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eb). Similarly, the changes in femoral neck BMD at 6 and 12 months were 1.8%\u0026plusmn;1.0 and 1.7%\u0026plusmn;1.0 (both P\u0026thinsp;\u0026lt;\u0026thinsp;0.05), respectively, in the Deno group and 1.6%\u0026plusmn;1.1 (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05) and 3.3%\u0026plusmn;1.0 (P\u0026thinsp;\u0026lt;\u0026thinsp;0.01), respectively, in the Romo group (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ec). Significant increases in BMD at 12 months were observed compared with baseline values for both treatment groups. No significant differences were found in the percentage increases in BMD of the total hip and femoral neck between the Deno and Romo groups throughout the study (total hip, P\u0026thinsp;=\u0026thinsp;0.110; femoral neck, P\u0026thinsp;=\u0026thinsp;0.711).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eBone turnover markers\u003c/h2\u003e \u003cp\u003eThe serum P1NP level significantly decreased at 6 (-60.5%; P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and 12 (-61.9%; P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) months compared with that at baseline in the Deno group. In contrast, in the Romo group, the P1NP level did not significantly change at 6 months (+\u0026thinsp;11.5%; P\u0026thinsp;=\u0026thinsp;0.138); however, the level decreased at 12 months relative to baseline (-8.0%; P\u0026thinsp;=\u0026thinsp;0.088) (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ea). Significant differences in the P1NP level were observed between the two groups at 6 and 12 months (both P\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eIn the Deno group, serum TRACP-5b levels significantly decreased at 6 (-46.5%; P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and 12 (-47.2%; P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) months compared with the baseline levels (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eb). The Romo group exhibited a similar trend at 6 (-32.2%; P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and 12 (-44.2%; P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) months. Although a significant difference between the groups was found at 6 months (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05), no significant difference was observed at 12 months (P\u0026thinsp;=\u0026thinsp;0.311).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003eAdverse events and new fractures\u003c/h2\u003e \u003cp\u003eSeveral adverse events were recorded during the 12 months of treatment (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Nine (5.8%) patients in the Deno group and five (5.5%) in the Romo group dropped out of the study; however, no significant difference was observed between the groups (P\u0026thinsp;=\u0026thinsp;1.000). Although injection site reactions occurred more frequently in the Romo group than in the Deno group, they did not result in drug discontinuation. Injection site reactions often occurred during the initial administration. Other remarkable events were recorded in both groups, yet their incidence did not differ significantly (3.8% in the Deno group and 5.5% in the Romo group; P\u0026thinsp;=\u0026thinsp;0.540).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eAdverse events and new fractures documented during the 12-month treatment period\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\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=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDenosumab\u003c/p\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;156)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eRomosozumab\u003c/p\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;91)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAll adverse events\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16 (10.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21 (23.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAdverse events leading to study discontinuation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (5.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (5.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDementia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (0.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMalignant lymphoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (0.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHyperkalemia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (0.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePoor condition\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (1.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (1.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePulmonary infarction\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (1.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCerebral infarction\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (1.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCerebral hemorrhage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (1.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHospitalization (reason unknown)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (0.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDeath\u003c/p\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 \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePneumonia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (1.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (1.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eReason unknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (0.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSerious adverse events\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (0.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (1.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCerebral infarction\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (0.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLower leg necrosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (1.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInjection site reaction\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10 (10.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePain\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 (8.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSwelling\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (2.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther events of interest\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (3.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (5.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.540\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDevelopment of kidney stone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (0.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRenal function decline\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (1.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eThrombocytopenia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (0.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRheumatoid arthritis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (0.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIliopsoas tumor\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (0.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCellulitis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (1.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFatigue\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypocalcemia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (1.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypozincemia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (1.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNew fractures during the therapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (3.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (3.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLumbar vertebra\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (0.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (1.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eThoracic vertebra\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (0.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDistal phalanx of great toe\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (0.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRib\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (1.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSupracondylar humerus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (1.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDistal radius\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (0.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (1.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eData are presented as the number (%) of patients. Between-group differences were analyzed using Fisher\u0026rsquo;s exact test.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003e\u003csup\u003ea\u003c/sup\u003eInjection-site reactions included adverse events on the skin at the injection site lasting for 2 days or more.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eRegarding the occurrence of new bone fractures during treatment, six (3.8%) patients in the Deno group and three (3.3%) in the Romo group experienced new fractures, including vertebral body fractures. There were no significant differences in the occurrence of new fractures between the groups (P\u0026thinsp;=\u0026thinsp;1.000).\u003c/p\u003e \u003c/div\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eIn men with osteoporosis, the loss of cancellous (trabecular) bone is mainly caused by decreased bone formation, which progresses with age \u003csup\u003e\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e,\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e. When trabecular bone thinning occurs, the number and connectivity of trabecular bones remain relatively maintained. In contrast, trabecular bone loss in postmenopausal women is primarily caused by increased bone resorption. This results in several detrimental changes to the trabecular bone microarchitecture, including a decrease in the number of trabecular bone elements, disrupted connectivity between the remaining trabeculae (female type), and in severe cases, complete perforations or loss of trabecular structures \u003csup\u003e\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e. A decrease in the number of trabeculae impairs bone strength more than trabecular thinning (male type) \u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e,\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e,\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eIn the assessment of osteoporosis treatments, the use of bisphosphonate agents and denosumab, which are both popular bone resorption suppressors, is considered to be less effective in men compared with that in women because of the different mechanisms of action between sexes, as men typically have lower bone turnover rates. Postmenopausal osteoporosis in women is primarily attributed to enhanced bone resorption, whereas aging-related male osteoporosis is largely associated with decreased bone formation. Therefore, the administration of a bone-formation-promoting agent is considered a rational treatment for male osteoporosis to activate and balance rates of bone turnover.\u003c/p\u003e \u003cp\u003eHowever, treatment with teriparatide, a bone-formation-promoting drug widely used in clinical practice, is also known to stimulate bone resorption, leading to cortical bone porosity. Consequently, its efficacy in femoral bone is considered limited \u003csup\u003e\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eIn contrast, romosozumab therapy exerts a dual effect by accelerating bone formation and suppressing bone resorption; therefore, it is anticipated to be an effective treatment option for men from the perspective of bone metabolism. Furthermore, clinical trials \u003csup\u003e\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e,\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u003c/sup\u003e and real-world data \u003csup\u003e\u003cspan additionalcitationids=\"CR12\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e have demonstrated a significant increase in femoral BMD in postmenopausal women with osteoporosis.\u003c/p\u003e \u003cp\u003eAlthough romosozumab therapy exhibits a \u0026ldquo;mild\u0026rdquo; bone resorption inhibitory effect compared with that of denosumab therapy \u003csup\u003e\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u003c/sup\u003e, it may potentially lead to a reduced drug effect in male patients with osteoporosis compared with that in postmenopausal female patients with osteoporosis. Nonetheless, romosozumab is still considered to be effective for treating osteoporosis in men to a reasonable extent.\u003c/p\u003e \u003cp\u003eIn the current study, the Romo group exhibited a significantly superior effect than the Deno group in increasing lumbar spine BMD. Although our data showed that the Deno group demonstrated a higher increase in total hip and femoral neck BMD compared with the Romo group, there was no significant difference in the BMD changes at 12 months. The only previous study that investigated the therapeutic effects of romosozumab therapy for male osteoporosis was the BRIDGE trial \u003csup\u003e\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e\u003c/sup\u003e. The results of the present study, which demonstrated changes in lumbar spine, total hip, and femoral neck BMD, were consistent with those of the BRIDGE trial.\u003c/p\u003e \u003cp\u003eThis study had some limitations. First, the small sample size of patients included in this study may limit the generalizability of our findings. Second, patients with both primary and secondary osteoporosis were included in the study population. Finally, the study did not consider differences based on the administration of active vitamin D preparations. These points for improvement should be considered in further studies to substantiate the empirical evidence in clinical practice.\u003c/p\u003e"},{"header":"CONCLUSIONS","content":"\u003cp\u003eConsidering the inherently limited number of male patients with osteoporosis compared to that of female patients with postmenopausal osteoporosis, this study holds value in suggesting an approach for treating male osteoporosis. Particularly, among male patients with osteoporosis, the Romo group showed a significantly increased lumbar spine BMD compared to the Deno group, demonstrating the superior pharmacodynamics of romosozumab for modern osteoporosis treatment over denosumab in increasing BMD. This implies that romosozumab, rather than denosumab, should be prioritized when selecting and designing a treatment strategy for male osteoporosis.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors are grateful to Thiago Fran\u0026ccedil;a, PhD. for careful English proofreading and valuable discussions.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contribution\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTK was engaged in the direction of this study, statistical analysis, and drafting and editing of this manuscript. AM, YK, YH, and YN were involved in the data acquisition. TK and all other authors participated in the data interpretation and critical revision of the manuscript. All authors have approved the final manuscript for publication.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets analyzed in this study and presented in this material are available from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interest statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical approval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll procedures performed in studies involving human participants were following the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eGullberg, B., Johnell, O. \u0026amp; Kanis, J. 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L.\u003cem\u003e et al.\u003c/em\u003e A 24-month study evaluating the efficacy and safety of denosumab for the treatment of men with low bone mineral density: results from the ADAMO trial. \u003cem\u003eThe Journal of clinical endocrinology and metabolism\u003c/em\u003e \u003cstrong\u003e100\u003c/strong\u003e, 1335-1342, doi:10.1210/jc.2014-4079 (2015).\u003c/li\u003e\n\u003cli\u003eJeong, C.\u003cem\u003e et al.\u003c/em\u003e The efficacy of denosumab in Korean male patients with osteoporosis. \u003cem\u003eThe Korean journal of internal medicine\u003c/em\u003e \u003cstrong\u003e37\u003c/strong\u003e, 1011-1020, doi:10.3904/kjim.2022.064 (2022).\u003c/li\u003e\n\u003cli\u003eSoen, S.\u003cem\u003e et al.\u003c/em\u003e Diagnostic criteria for primary osteoporosis: year 2012 revision. \u003cem\u003eJournal of bone and mineral metabolism\u003c/em\u003e \u003cstrong\u003e31\u003c/strong\u003e, 247-257, doi:10.1007/s00774-013-0447-8 (2013).\u003c/li\u003e\n\u003cli\u003eOrimo, H.\u003cem\u003e et al.\u003c/em\u003e Japanese 2011 guidelines for prevention and treatment of osteoporosis--executive summary. \u003cem\u003eArchives of osteoporosis\u003c/em\u003e \u003cstrong\u003e7\u003c/strong\u003e, 3-20, doi:10.1007/s11657-012-0109-9 (2012).\u003c/li\u003e\n\u003cli\u003eKanis, J. 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Teriparatide reduces the fracture risk associated with increasing number and severity of osteoporotic fractures. \u003cem\u003eThe Journal of clinical endocrinology and metabolism\u003c/em\u003e \u003cstrong\u003e90\u003c/strong\u003e, 1583-1587, doi:10.1210/jc.2004-0826 (2005).\u003c/li\u003e\n\u003cli\u003eNenonen, A.\u003cem\u003e et al.\u003c/em\u003e Serum TRACP 5b is a useful marker for monitoring alendronate treatment: comparison with other markers of bone turnover. \u003cem\u003eJ Bone Miner Res\u003c/em\u003e \u003cstrong\u003e20\u003c/strong\u003e, 1804-1812, doi:10.1359/JBMR.050403 (2005).\u003c/li\u003e\n\u003cli\u003eKurland, E. S.\u003cem\u003e et al.\u003c/em\u003e Insulin-like growth factor-I in men with idiopathic osteoporosis. \u003cem\u003eThe Journal of clinical endocrinology and metabolism\u003c/em\u003e \u003cstrong\u003e82\u003c/strong\u003e, 2799-2805, doi:10.1210/jcem.82.9.4253 (1997).\u003c/li\u003e\n\u003cli\u003eKurland, E. 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N.\u003cem\u003e et al.\u003c/em\u003e Comparative effects of teriparatide, denosumab, and combination therapy on peripheral compartmental bone density, microarchitecture, and estimated strength: the DATA-HRpQCT Study. \u003cem\u003eJ Bone Miner Res\u003c/em\u003e \u003cstrong\u003e30\u003c/strong\u003e, 39-45, doi:10.1002/jbmr.2315 (2015).\u003c/li\u003e\n\u003cli\u003eCosman, F.\u003cem\u003e et al.\u003c/em\u003e Romosozumab Treatment in Postmenopausal Women with Osteoporosis. \u003cem\u003eThe New England journal of medicine\u003c/em\u003e \u003cstrong\u003e375\u003c/strong\u003e, 1532-1543, doi:10.1056/NEJMoa1607948 (2016).\u003c/li\u003e\n\u003cli\u003eSaag, K. G.\u003cem\u003e et al.\u003c/em\u003e Romosozumab or Alendronate for Fracture Prevention in Women with Osteoporosis. \u003cem\u003eThe New England journal of medicine\u003c/em\u003e \u003cstrong\u003e377\u003c/strong\u003e, 1417-1427, doi:10.1056/NEJMoa1708322 (2017).\u003c/li\u003e\n\u003cli\u003eLambertini, M.\u003cem\u003e et al.\u003c/em\u003e Cancer and fertility preservation: international recommendations from an expert meeting. \u003cem\u003eBMC medicine\u003c/em\u003e \u003cstrong\u003e14\u003c/strong\u003e, 1, doi:10.1186/s12916-015-0545-7 (2016).\u003c/li\u003e\n\u003cli\u003eLewiecki, E. M.\u003cem\u003e et al.\u003c/em\u003e A Phase III Randomized Placebo-Controlled Trial to Evaluate Efficacy and Safety of Romosozumab in Men With Osteoporosis. \u003cem\u003eThe Journal of clinical endocrinology and metabolism\u003c/em\u003e \u003cstrong\u003e103\u003c/strong\u003e, 3183-3193, doi:10.1210/jc.2017-02163 (2018).\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Male Osteoporosis, Romosozumab, Denosumab, Dual-energy X-ray Absorptiometry, Bone turnover, Bone mineral density","lastPublishedDoi":"10.21203/rs.3.rs-4421829/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4421829/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eWe aimed to investigate the efficacy of romosozumab treatment compared with that of denosumab in especially male osteoporosis patients. This retrospective cohort study included 174 Japanese male patients receiving either denosumab or romosozumab for 12 months. Propensity score matching extracted 50 patients per treatment group for standardization of group characteristics. The endpoints include the rate of change in the bone mineral density (BMD) of the lumbar spine, total hip, and femoral neck after 12 months of treatment as well as the changes in serum bone metabolism markers. The mean 12-month percentage increase in the lumbar spine BMD from baseline was significantly greater with romosozumab (13.0%\u0026plusmn;1.7%) than with denosumab (4.5%\u0026plusmn;0.6%) (P\u0026thinsp;\u0026lt;\u0026thinsp;0.01). The total hip and femoral neck BMD exhibited a similar trend at 12 months; however, no significant between-group differences were observed. With denosumab, bone formation, and resorption marker levels significantly decreased at 6 and 12 months. Conversely, with romosozumab, the levels of bone formation markers increased transiently at 6 months before returning to baseline, whereas bone resorption markers significantly decreased at both time points. Romosozumab demonstrated significantly superior effects over denosumab in improving BMD, especially of the lumbar spine, suggesting that romosozumab can be used for treating male osteoporosis.\u003c/p\u003e","manuscriptTitle":"Comparison of Denosumab with Romosozumab in the Treatment of Male Osteoporosis: A Retrospective Cohort Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-06-20 17:23:12","doi":"10.21203/rs.3.rs-4421829/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-08-05T04:47:03+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-08-03T20:45:30+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"218855929382067048518933924201008890024","date":"2024-07-23T21:49:35+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-07-07T16:04:19+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"31953536333021346986955961745950295089","date":"2024-06-25T09:03:04+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"264416201092864019548690674099345490538","date":"2024-06-18T16:35:30+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-06-18T06:57:33+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-06-18T06:46:23+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2024-06-05T06:54:59+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-06-05T06:53:31+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2024-05-15T01:10:38+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"3cb47ba3-d399-40ad-bc57-70e9950a3790","owner":[],"postedDate":"June 20th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-10-07T16:08:43+00:00","versionOfRecord":{"articleIdentity":"rs-4421829","link":"https://doi.org/10.1038/s41598-024-73398-5","journal":{"identity":"scientific-reports","isVorOnly":false,"title":"Scientific Reports"},"publishedOn":"2024-10-01 15:58:03","publishedOnDateReadable":"October 1st, 2024"},"versionCreatedAt":"2024-06-20 17:23:12","video":"","vorDoi":"10.1038/s41598-024-73398-5","vorDoiUrl":"https://doi.org/10.1038/s41598-024-73398-5","workflowStages":[]},"version":"v1","identity":"rs-4421829","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4421829","identity":"rs-4421829","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}