Comparison of Bone Mineral Density And Treatment Initation Among Treatment-Naive Post-Menopausal Women with Distal Radius Fracture and Without: A Case-Control Study from Southern Europe

Comparison of Bone Mineral Density And Treatment Initation Among Treatment-Naive Post-Menopausal Women with Distal Radius Fracture and Without: A Case-Control Study from Southern Europe | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Comparison of Bone Mineral Density And Treatment Initation Among Treatment-Naive Post-Menopausal Women with Distal Radius Fracture and Without: A Case-Control Study from Southern Europe Vasileios Giannatos, Irini Tatani, Konstantinos Stathopoulos, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5919538/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Objectives To compare bone mineral density (BMD), FRAX scores, comorbidities, risk factors and biochemical blood markers among postmenopausal women with distal radius fractures and those without such fractures. Materials and Methods 63 postmenopausal women with distal radius fractures were compared to 64 postmenopausal women with no history of fractures. Primary objectives included comparing BMD at the femoral neck and lumbar spine, as well as FRAX scores between the two groups. Secondary goals involved assessing comorbidities, risk factors, and biochemical blood markers (Ca + 2, albumin, PTH, VItD) between the two groups. Results BMD and T-scores for the hip and lumbar spine were compared between groups, revealing no statistically significant differences. However, FRAX scores (Major & Hip) differed significantly in the fracture group (p = 0.005), aligning with expectations that a previous fracture elevates the FRAX risk for future fractures. Biochemical markers were similar between the two groups, except for Vitamin D. Among risk factors and comorbidities, only multi-drug regimens and epileptic seizures were significantly higher in the fracture group. Conclusion Our study found similar BMD between the two groups. Nonetheless, a lower FRAX in the fracture group necessitates increased consideration for osteoporosis treatment. Multiple-drug regimens and lower vitamin D levels were also linked to the fracture group. osteoporosis post-menopausal distal radius osteopenia vitamin d Figures Figure 1 Figure 2 Introduction Osteoporosis is a systemic skeletal disorder characterized by low bone mineral density (BMD), micro-architectural deterioration of bone tissue, and consequent increase in fracture risk [1–3]. Osteoporosis is classified in two types: Postmenopausal osteoporosis (type 1) occurs in women within 15–20 years after menopause, is related to or exacerbated by estrogen deficiency and presented usually with fractures in the distal radius and spine. Age-related osteoporosis (type 2) occurs in men and women over 75 years of age and may be more directly related to reduced osteoblastic activity, Vitamin D deficiency and Calcium malabsorption; most common fractures occur in the hip, proximal humerus, pelvis, tibia and ribs [4]. The morbidity and mortality of osteoporotic fractures in the elderly is a major healthcare concern, especially regarding hip fractures, as it has been estimated that they present up to 30% mortality within the first year in male patients [5–7]. Mortality rates up to 20% have also been observed in osteoporotic vertebral fractures mainly due to weight loss, frailty and pulmonary dysfunction [8–11]. For this reason, numerous studies have been dedicated to the treatment and prevention of these fractures. Distal radius fractures show a bimodal age distribution occuring more commonly in the pediatric population, during sporting activities, around the time of puberty when bone mineralization is low, and in the elderly population, mainly women, after a fall from a standing height [12–13]. In the elderly population distal radius fractures are the second most common fracture after hip fractures, affecting their overall performance and daily living activities [12–13]. Over the age of 50, in both genders, distal radius fractures have been associated with higher rates of osteoporosis as measured by Dual-energy X-ray absorptiometry (DEXA) and low vitamin D levels and are thus considered as a predisposing factor for early diagnosis of osteoporosis and prevention of future hip or spinal fractures [14–21]. The Americam Academy of Orthopaedic Surgeons (AAOS) has proposed in 2009 the indications for surgical management of distal radius fractures consisting of post-reduction radial shortening > 3 mm, dorsal tilt > 10° and intra-articular displacement or step-off > 2 mm [22]. However, in patients older than 65 years-old or in patients with limited functional demands, conservative treatment in a cast is the gold standard, due to postoperative complication rates reaching 33% (vs 14% for conservative treatment) and no obvious clinical superiority in this particular population, according even to the latest AAOS guidelines of 2020 [23–26]. While not much can be offered in regards of fracture treatment in this population, with conservative and surgical options both presenting with their downsides, prevention of future fractures can have a large impact being life saving for these patients. Post-fracture investigation of osteoporosis and the prevention of secondary fractures has been a hot topic of discussion during the last years, with fracture liaison services intervening in the most developed countries [27–31]. In the literature, only few case-control studies exist directly comparing the BMD among post-menopausal women with distal radius fractures and not [15]. In the present study, we conducted a retrospective clinical trial comparing the prevelance of osteoporosis among women > 50 years old with a distal radius fracture, with those without a fracture from our center. Materials and Methods Our study is a retrospective case-control study conducted in our Metabolic Bone Diseases Outpatient Clinic from January 2018 to June 2021. Women above 50 years-old who presented to our Emergency Department with distal radius fractures were referred to our osteoporosis outpatient clinic for a secondary evaluation. The control group was women over 50 years-old with no fracture history who had a scheduled appointment in our osteoporosis clinic. All patiens were informed about the study protocol and provided written informed consent to publication. Before the initiation of the study, the protocol was approved by the Universital Hospital of Patras’ ethics committee and institutional board approval was obtained (University Hospital of Patras, approval number 684/12.10.18- 56/21.11.2018). Inclusion criteria were: 1) female gender, 2) age > 50 years old, 3) distal radius fracture (for the fracture group). Exclusion criteria were 1) secondary osteoporosis and 2) high energy fracture (motorvehicle accident, fall from height > 2 meters). The primary goal was to compare osteoporosis status according to BMD values at the lumbar spine and femoral neck, as well as the Fracture Risk Assessment Tool (FRAX). Secondary goals were to compare other clinical risk factors and comorbidities between the two groups, namely, thyroid disease, dyslipedemia, hypertension, gastrointestinal disorders, arrhythmia, emotional disorders and epileptic seizures, antidepressants, thyroxine, smoking, osteoporosis family history, cortisone intake, diabetes, chemotherapy, early menopause, history of fracture, family history of fracture, chronic obstructive pulmonary disorder (COPD), multiple drug regimen, rheumatoid arthritis, protein pump inhibitors (PPIs), > 3 falls/year, furosemide. Multiple drug regimen was defined as systematic consumption of 5 or more different medication. Biochemical blood tests were also analyzed including serum calcium, albumin (corrected Calcium to albumin), 25-OH-Vitamin D and parathormone (PTH) levels. Patients were assigned into two groups. Group 1 was the fracture group included women older than 50 years old with a recent history of distal radius fracture (within the last 3 years). Group 2 included women older than 50 years old with no recent fracture history who had been appointed in the outpatient osteoporosis clinic. The total BMD values were recorded for both the lumbar spine (L1-L4) and femoral neck using the same DEXA machine operated by the same technician (P.G). The FRAX score was calculated also. At the same time blood samples were collected and analyzed for calcium, albumin, PTH and Vitamin D. A thorough medical history was collected by a consultant orthopaedic surgeon (I.T.) including age, weight, height, comorbidities, medications, height loss and other risk factors as described above. Treatment of osteoporosis when detected, was offered according to the international guidelines. Statistical Analysis Data were expressed as mean ± standard deviation (S.D.) or median, IQR ( in case of violation of normality ) for continuous variables and as frequencies, percentages for categorical variables. The Kolmogorov—Smirnov test was utilized for normality analysis of the parameters. The comparisons of the continuous variables between groups were analyzed using the independent samples t-test or Mann-Whitney U test in case of violation of normality. The comparisons of the categorical variables between groups were analyzed using the X 2 test of Fisher’s exact test. All tests were two-sided, statistical significance was set at p < 0,05 .All analyses were carried out using the statistical package SPSS vr 21.00 (IBM Corporation, Somers, NY, USA). Results The total number of patients initially considered were 388. After applying the inclusion and exclusion criteria, 127 patients were enrolled in the study, assigned into two groups. Group A included 63 patients with distal radius fracture and Group B 64 patients without any fracture history. Table 1 shows the baseline demographic characteristics of the two groups. The only statistical significant demographic parameter was age (p = 0.008), with a mean age in group A of 64.3 years-old vs 60 years-old in the non-fracture group.The BMD and T-scores for both hip and lumbar spine were compared between groups but no statistical significant difference was found (Table 1 ). In the fracture group 16 patients were diagnosed with osteoporosis and 39 with osteopenia. In the no-fracture group, 10 patients were found to have osteoporosis and 54 patients were diagnosed with osteopenia as depicted in Fig. 1 . The metabolic and biochemical values (PTH, albumin and corrected calcium) were found similar between the two groups but Vitamin D showed a significant difference (p = 0.044) with mean values of 25.82 and 20.82 on the non-fracture and fracture groups respectively (Table 2 ). The FRAX scores (Major & Hip) were significantly different in the fracture group (p = 0.005) as was expected, because a previous fracture increases the FRAX risk for another fracture in the future (Table 2 ). Comorbidities were also analyzed but no differences were found between the two groups for thyroid disease, dyslipidemia, hypertensions, emotional disorders, gastrointestinal disorders, arrhythmia and epileptic seizures (Table 3 ). It is of interest, however, that epileptic seizures showed a prevalence of 0% and 6.3% on the non-fracture and fracture group respectively (p = 0.058). Other proven risk factors were compared also and only multi-drug regimens were found to be significantly higher on the fracture group (p = 0.001, 0% and 14.3% respectively). Antidepressants, thyroxine, smoking, family history of osteoporosis, diabetes, chemotherapy, cortisone, early menopause, history of fracture, history of fracture of mother, COPD, rheumatoid arthritis, >3falls/year, furosemide and PPIs showed similar prevalence between the two groups. Finally, the presence of ≥ 1- and ≥ 2- risk factors showed high p-values between the two groups. 100% of the fracture-group patients recorded at least one risk factor and 54% at least two. On the contrary, 65.6% and 26.6% of the non-fracture group showed at least one or two risk factors respectively. The loss of height showed also significance (p = 0.033) with 40.6% and 60.3% between the non-fracture and fracture patients. The need for antiosteoporotic treatment according to the latest guidelines was 25% and 50.8% for the control and fracture groups respectively (p = 0.003). (Fig. 2 ) Table 1 Comparison of parametrical variables Non-fracture Distal radius fracture p-value Mean SD Mean SD Age 60.06 7.29 64.33 10.22 0.008 Weight 68.79 11.08 70.38 15.87 0.516 Height 1.58 .06 1.57 .08 0.807 ΒΜΙ 27.81 4.81 28.41 5.81 0.525 T-score lumbar spine -1.69 .83 -1.60 1.08 0.603 BMD lumbar spine .87 .09 .88 .14 0.466 T-score femoral neck -1.31 .67 -1.41 .95 0.502 BMD femoral neck .71 .07 .70 .12 0.481 Table 2 Comparison of non-parametrical variables. Non-fracture Distal radius fracture p-value Median IQR Median IQR 25OH VITD 22.94 16.42 19.04 12.00 0.044 PTH 48.95 20.08 49.20 19.40 0.687 ALB 4.00 .30 4.20 .40 0.180 Corrected serum Ca 9.34 .46 9.20 .42 0.102 FRAX Major 5.40 4.72 9.40 7.80 < 0.005 FRAX Hip 1.05 1.53 1.80 3.70 < 0.005 Table 3 Comparison of Comorbidities Non-fracture Distal radius fracture p-value Ν(%) Ν(%) Thyroid disease 23,4% 23,8% 1.000 Dyslipidemia 39,1% 27,0% 0.187 Hypertension 32,8% 34,9% 0.853 Emotional disorders 14,1% 14,3% 1.000 Gastrointestinal disorders 4,7% 7,9% 0.492 Arrhythmia 6.3% 6.3% 1.000 Epileptic Seizures 0% 6.3% 0.058 Antidepressants 9.4% 17.5% 0.203 Thyroxine 18.8% 12.7% 0.466 Smoking 43.8% 34.9% 0.365 Osteoporosis Mother 23.4% 17.5% 0.510 Diabetes 4.7% 11.1% 0.206 Cortisone 4.7% 3.2% 1.000 Chemotherapy 3.1% 0% 0.496 Early Menopause 23.4% 17.5% 0.510 History of fracture 12.5% 7.9% 0.560 Mother history of fracture 9.4% 7.8% 1.000 COPD 1.6% 3.2% 0.619 Multi-drug regimen 0% 14.3% 0.001 > 3 Falls/year 0% 3.2% 0.244 Rheumatoid Arthritis 0% 3.2% 0.244 PPIs 3.1% 6.3% 0.440 Furosemide 1.6% 3.2% 0.619 Risk factors ≥ 1 65.6% 100% < 0.0005 Risk factors ≥ 2 26.6% 54% 50 years-old, have been a topic of interest during the last decade, as they constitute the second commonest fracture managed in the clinical setting [28–31]. Treatment plan is not the only parameter raising interest, as osteoporosis prevalence and morbidity rises, and a distal radius fracture in a middle-aged woman might be the first sign of the disease requiring immediate treatment on that direction [31–32]. Other studies indicate that distal radius fractures might be the first signs of sarcopenia and frailty syndrome [33]. Even with normal BMD values, these patients remain at high risk for falls and subsequent fractures and the interventions should follow a multidisciplinary approach for prevention incuding vision problems, exercise and environmental modifications [34]. Most similar studies concluded that distal radius fractures in women > 50 years old are characterized by lower ultra-distal radius BMD [35–37], however less and conflicting evidence exists regarding BMD at the hip and lumbar spine and general osteoporotic status [37–41]. After thorough literature review, we concluded that the majority of studies originate from northern Europe and find distal radius fracture in post-menopausal women to be correlated with higher osteoporosis prevalence [38–41]. Our study showed that women older than 50 years-old with a distal radius fracture do not have lower BMD or T-scores than the non-fracture group of similar age, a difference that could be explained by the location of our study. Most studies showing a BMD difference among the groups were perfomed in Northern Europe countries, were it is known that osteoporosis presents a higher prevalence [43]. Our study as well as the study from Barcelona are the only studies from the Mediterennean region and showed no difference in hip and lumbar spine BMD values among the two groups [37]. Nevertheless, there is a consensus that the risk for a subsequent hip fracture increases after a distal radius fracture in postmenopausal women [44], and this was confirmed by our study, as 50% of the fracture group presented with a need for anti-osteoporitc treatment after FRAX-score. Among the different comorbidities and risk factors studied, only the multi-drug regimens showed a significant difference. It is not clear ,however ,whether this occurred due to the drugs’ side effects or due to the high comorbidities associated with multi-drug regimens. Loss of height was another statistically significant risk factor among fracture patients and this indicates its potential prognostic value in this patient group, but extensive further clinical studies should be conducted in order to be incorporated in the treatment algorithm. Loss of height has been attributed to vertebral osteoporosis and fractures, along with kyphosis and it is of interest wether it is correlated with such in this, younger than the usual vertebral osteoporotic, group [45]. Nevertheless, it remains a standalone risk factor for another fracture, and high suspicion must be maintained when combined with distal radius fracture in post-menopausal women [46]. Epileptic seizures showed also a higher prevalence among the fracture group, although not statistically significant. Epileptic activity and osteoporosis share a complex and unclear relationship through various studies. Some studies suggest that the hypocalcemic effect of classic antiosteoporotic drugs might be severe enough to create seizures, however our population was treatment-naïve [47]. Other studies stress that antiepileptic agents can lower BMD, especially hepatic enzyme inducers like carbamazepine, phenobarbital and phenytoin, while the frequency of seizures can increase during perimenopause, possibly increasing the fracture risk as well due to injury during epileptic episodes [48–50]. The reason that distal radius fractures in the elderly are so extensively studied in the literature, is mainly due to the healthcare burden and morbidity of the accompanied osteoporotic hip and vertebral fracture. A Colle’s fracture after minor trauma is estimated to result in a subsequent hip fracture during the following years in 50% of the patients [26]. NICE guidelines have been suggested on secondary prevention of osteoporotic fractures, but most centers do not seem to widely implement these, as referral for further investigation should be initiated as early as in the emergency department [51–53]. Nevertheless, elderly patients with a low energy distal radius fracture should be referred for a BMD measurement with DEXA, as there is a high prevelance of osteoporosis according to many studies, but not as high as to guarantee universal anti-osteoclastic treatment as in hip fractures [20, 22]. Vitamin D and perhaps a secondary osteoporosis laboratory tests should also be ordered, as Oyen et al in 2011 showed high prevelance of Vitamin D inadequacy among these patients, although Rozental did not confirm this finding, possibly due to regional differences [54–55]. Our study showed no differences in calcium levels between the two groups, and even calcium supplementation by Lamke et al showed no difference [56]. Patient education and consultation by the treating surgeon are also proven methods of increased osteoporosis screening and should be implemented as much as possible [54]. There are a number of limitations regarding our study. First of all, patients in the fracture group were found to be statistically significant older than the non-fracture group, although the difference was minor considering absolute numbers. Moreover, our group sizes were relatively small. However, this is one of the few studies in Greece, from a special osteoporosis clinic with the collection of data beign performed by one researcher (I.T.), one technician and one DEXA machine. Conclusion Although distal radius fractures in middle-aged women have been associated with low BMD and have been identified as an osteoporosis precurssor, our study did not verify this hypothesis. Regional differences seem to exist, showing that the distal radius fracture and its connection to osteoporosis is not fully understood. Nevertheless, this group of patients continues to present higher FRAX scores and therefore higher risk for future fractures, leading to higher treatment rates, but not high enough for universal treatment. Lower Vitamin-D among these patients should be considered as both a prevention target as well as a therapeutic target. Loss of height and multi-drug regimens are also met at a higher prevalence among the fracture group and could be utilized as part of prevention and early diagnosis strategies, as well as epileptic seizures. Abbreviations Dual-Energy X-ray Absorptiometry (DEXA) American Academy of Ortopaedic Surgeons (AAOS) Bone Mineral Density (BMD) Fracture Risk Assessment Tool (FRAX) Chronic Obstructive Pulmonary Disorder (COPD) Protein Pump Inhibitors (PPIs) Parathormone (PTH) Standard Deviation (S.D.) Open Reduction and Internal Fixation (ORIF) Declarations Ethics approval: The protocol was approved by the hospital’s ethics committee and institutional board approval was obtained (approval number 684/12.10.18- 56/21.11.2018) Consent for publication: Informed written consent for participation in the study was obtained from each individual Availability of data and materials: The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. Conflicts of interest: All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest or non-financial interest in the subject matter or materials discussed in this manuscript. Funding: The authors did not receive support from any organization for the submitted work. Acknowledgements : Not applicable References Consensus development conference: diagnosis, prophylaxis, and treatment of osteoporosis. 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Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA, 21(7), 1161–1169. https://doi.org/10.1007/s00198-009-1047-2 Wigderowitz, C. A., Cunningham, T., Rowley, D. I., Mole, P. A., & Paterson, C. R. (2003). Peripheral bone mineral density in patients with distal radial fractures. The Journal of bone and joint surgery. British volume, 85(3), 423–425. https://doi.org/10.1302/0301-620x.85b3.13336 Kanterewicz E, Yañez A, Pérez-Pons A, Codony I, Del Rio L, Díez-Pérez A. Association between Colles' fracture and low bone mass: age-based differences in postmenopausal women. Osteoporos Int. 2002 Oct;13(10):824-828. doi: 10.1007/s001980200114. PMID: 12378365. Hung, L. K., Wu, H. T., Leung, P. C., & Qin, L. (2005). Low BMD is a risk factor for low-energy Colles' fractures in women before and after menopause. Clinical orthopaedics and related research, (435), 219–225. https://doi.org/10.1097/01.blo.0000155345.04782.14 Øyen J, Gjesdal CG, Brudvik C, et al. Low-energy distal radius fractures in middle-aged and elderly men and women--the burden of osteoporosis and fracture risk : A study of 1794 consecutive patients. Osteoporos Int . 2010;21(7):1257-1267. doi:10.1007/s00198-009-1068-x Bahari S, Morris S, Lenehan B, McElwain JP. "Osteoporosis and orthopods" incidences of osteoporosis in distal radius fracture from low energy trauma. Injury . 2007;38(7):759-762. doi:10.1016/j.injury.2006.11.007 Oyen J, Brudvik C, Gjesdal CG, Tell GS, Lie SA, Hove LM. Osteoporosis as a risk factor for distal radial fractures: a case-control study. J Bone Joint Surg Am . 2011;93(4):348-356. doi:10.2106/JBJS.J.00303 Jutberger H, Sinclair H, Malmqvist B, Obrant K. Utredning av postmenopausal osteoporos. Kvinnor med distal radiusfraktur bör bentäthetsmätas [Screening for postmenopausal osteoporosis. Women with distal radius fractures should be evaluated for bone density]. Lakartidningen . 2003;100(1-2):31-34. Fogarty P, O'Beirne B, Casey C. Epidemiology of the most frequent diseases in the European a-symptomatic post-menopausal women. Is there any difference between Ireland and the rest of Europe?. Maturitas . 2005;52 Suppl 1:S3-S6. doi:10.1016/j.maturitas.2005.06.018 Johnson NA, Stirling ER, Divall P, Thompson JR, Ullah AS, Dias JJ. Risk of hip fracture following a wrist fracture-A meta-analysis. Injury . 2017;48(2):399-405. doi:10.1016/j.injury.2016.11.002 Xu W, Perera S, Medich D, et al. Height loss, vertebral fractures, and the misclassification of osteoporosis. Bone . 2011;48(2):307-311. doi:10.1016/j.bone.2010.09.027 Pluskiewicz W, Adamczyk P, Drozdzowska B. The significance of height loss in postmenopausal women. The results from GO Study. Int J Clin Pract . 2021;75(5):e14009. doi:10.1111/ijcp.14009 Sturgill K, Reinert JP. Seizures Associated With Bone Density Conservation Agents. J Pharm Technol . 2022;38(2):119-126. doi:10.1177/87551225211070978 Miziak B, Błaszczyk B, Chrościńska-Krawczyk M, Danilkiewicz G, Jagiełło-Wójtowicz E, Czuczwar SJ. The problem of osteoporosis in epileptic patients taking antiepileptic drugs. Expert Opin Drug Saf . 2014;13(7):935-946. doi:10.1517/14740338.2014.919255 Erel T, Guralp O. Epilepsy and menopause. Arch Gynecol Obstet . 2011;284(3):749-755. doi:10.1007/s00404-011-1936-4 Kanner AM, Bicchi MM. Antiseizure Medications for Adults With Epilepsy: A Review. JAMA . 2022;327(13):1269-1281. doi:10.1001/jama.2022.3880 NICE. The clinical effectiveness and cost effectiveness of technologies for the secondary prevention of osteoporotic fractures in postmenopausal women. TA087. http://www.nice.org.uk/TA087guidance; January 2005. Chami G, Jeys L, Freudmann M, Connor L, Siddiqi M. Are osteoporotic fractures being adequately investigated? A questionnaire of GP & orthopaedic surgeons. BMC Fam Pract. 2006 Apr 5;7:7. doi: 10.1186/1471-2296-7-7. PMID: 16597322; PMCID: PMC1471788. Jantzen C, Cieslak LK, Barzanji AF, Johansen PB, Rasmussen SW, Schmidt TA. Colles' fractures and osteoporosis--A new role for the Emergency Department. Injury. 2016 Apr;47(4):930-933. doi: 10.1016/j.injury.2015.11.029. PMID: 26685638 Rozental, T. D., Herder, L. M., Walley, K. C., Zurakowski, D., Coyle, K., Bouxsein, M. L., & Wolf, J. M. (2015). 25-Hydroxyvitamin-D and Bone Turnover Marker Levels in Patients with Distal Radial Fracture. The Journal of bone and joint surgery. American volume, 97(20), 1685–1693. https://doi.org/10.2106/JBJS.O.00313 Oyen J, Apalset EM, Gjesdal CG, Brudvik C, Lie SA, Hove LM. Vitamin D inadequacy is associated with low-energy distal radius fractures: a case-control study. Bone. 2011 May;48(5):1140-1145. doi: 10.1016/j.bone.2011.01.021. PMID: 21288799. Lamke B, Sjöberg HE, Sylvén M. Bone mineral content in women with Colles' fracture: effect of calcium supplementation. Acta Orthop Scand. 1978 Apr;49(2):143-146. doi: 10.3109/17453677809005740. PMID: 659500. Sarfani S, Scrabeck T, Kearns AE, Berger RA, Kakar S. Clinical efficacy of a fragility care program in distal radius fracture patients. J Hand Surg Am. 2014 Apr;39(4):664-669. doi: 10.1016/j.jhsa.2014.01.009. PMID: 24581683. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted 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. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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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-5919538","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":411894052,"identity":"3dee5b7b-c9d4-4591-bf92-0738f43a868a","order_by":0,"name":"Vasileios 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Athens","correspondingAuthor":false,"prefix":"","firstName":"Antonios","middleName":"","lastName":"Galanos","suffix":""},{"id":411894063,"identity":"4a4ce91d-4aa5-44c8-a896-3b7a239356cc","order_by":5,"name":"Andreas Panagopoulos","email":"","orcid":"","institution":"General University Hospital of Patras","correspondingAuthor":false,"prefix":"","firstName":"Andreas","middleName":"","lastName":"Panagopoulos","suffix":""}],"badges":[],"createdAt":"2025-01-28 15:38:19","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5919538/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5919538/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":75709148,"identity":"7eff5c0d-2c0f-4e14-9c36-fe318efeba94","added_by":"auto","created_at":"2025-02-07 10:48:28","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":27762,"visible":true,"origin":"","legend":"\u003cp\u003eResults of osteoporotic status.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-5919538/v1/0d838068d3554de682a4ab3b.png"},{"id":75708638,"identity":"efee1ffb-f035-4c6b-bd70-24088e57d076","added_by":"auto","created_at":"2025-02-07 10:40:28","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":44510,"visible":true,"origin":"","legend":"\u003cp\u003eResults after statistical analysis\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-5919538/v1/dd51092f91bc805ce3e6415f.png"},{"id":79876416,"identity":"1e1eae3f-7b6b-41a7-ad36-74d20ab6f9cc","added_by":"auto","created_at":"2025-04-04 02:16:29","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":731208,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5919538/v1/11eaeb72-8765-4a6c-a07c-76f20b8d201e.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eComparison of Bone Mineral Density And Treatment Initation Among Treatment-Naive Post-Menopausal Women with Distal Radius Fracture and Without: A Case-Control Study from Southern Europe\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eOsteoporosis is a systemic skeletal disorder characterized by low bone mineral density (BMD), micro-architectural deterioration of bone tissue, and consequent increase in fracture risk [1\u0026ndash;3]. Osteoporosis is classified in two types: Postmenopausal osteoporosis (type 1) occurs in women within 15\u0026ndash;20 years after menopause, is related to or exacerbated by estrogen deficiency and presented usually with fractures in the distal radius and spine. Age-related osteoporosis (type 2) occurs in men and women over 75 years of age and may be more directly related to reduced osteoblastic activity, Vitamin D deficiency and Calcium malabsorption; most common fractures occur in the hip, proximal humerus, pelvis, tibia and ribs [4]. The morbidity and mortality of osteoporotic fractures in the elderly is a major healthcare concern, especially regarding hip fractures, as it has been estimated that they present up to 30% mortality within the first year in male patients [5\u0026ndash;7]. Mortality rates up to 20% have also been observed in osteoporotic vertebral fractures mainly due to weight loss, frailty and pulmonary dysfunction [8\u0026ndash;11]. For this reason, numerous studies have been dedicated to the treatment and prevention of these fractures.\u003c/p\u003e \u003cp\u003eDistal radius fractures show a bimodal age distribution occuring more commonly in the pediatric population, during sporting activities, around the time of puberty when bone mineralization is low, and in the elderly population, mainly women, after a fall from a standing height [12\u0026ndash;13]. In the elderly population distal radius fractures are the second most common fracture after hip fractures, affecting their overall performance and daily living activities [12\u0026ndash;13]. Over the age of 50, in both genders, distal radius fractures have been associated with higher rates of osteoporosis as measured by Dual-energy X-ray absorptiometry (DEXA) and low vitamin D levels and are thus considered as a predisposing factor for early diagnosis of osteoporosis and prevention of future hip or spinal fractures [14\u0026ndash;21]. The Americam Academy of Orthopaedic Surgeons (AAOS) has proposed in 2009 the indications for surgical management of distal radius fractures consisting of post-reduction radial shortening\u0026thinsp;\u0026gt;\u0026thinsp;3 mm, dorsal tilt\u0026thinsp;\u0026gt;\u0026thinsp;10\u0026deg; and intra-articular displacement or step-off \u0026gt;\u0026thinsp;2 mm [22]. However, in patients older than 65 years-old or in patients with limited functional demands, conservative treatment in a cast is the gold standard, due to postoperative complication rates reaching 33% (vs 14% for conservative treatment) and no obvious clinical superiority in this particular population, according even to the latest AAOS guidelines of 2020 [23\u0026ndash;26]. While not much can be offered in regards of fracture treatment in this population, with conservative and surgical options both presenting with their downsides, prevention of future fractures can have a large impact being life saving for these patients. Post-fracture investigation of osteoporosis and the prevention of secondary fractures has been a hot topic of discussion during the last years, with fracture liaison services intervening in the most developed countries [27\u0026ndash;31].\u003c/p\u003e \u003cp\u003eIn the literature, only few case-control studies exist directly comparing the BMD among post-menopausal women with distal radius fractures and not [15]. In the present study, we conducted a retrospective clinical trial comparing the prevelance of osteoporosis among women\u0026thinsp;\u0026gt;\u0026thinsp;50 years old with a distal radius fracture, with those without a fracture from our center.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cp\u003eOur study is a retrospective case-control study conducted in our Metabolic Bone Diseases Outpatient Clinic from January 2018 to June 2021. Women above 50 years-old who presented to our Emergency Department with distal radius fractures were referred to our osteoporosis outpatient clinic for a secondary evaluation. The control group was women over 50 years-old with no fracture history who had a scheduled appointment in our osteoporosis clinic. All patiens were informed about the study protocol and provided written informed consent to publication. Before the initiation of the study, the protocol was approved by the Universital Hospital of Patras\u0026rsquo; ethics committee and institutional board approval was obtained (University Hospital of Patras, approval number 684/12.10.18- 56/21.11.2018). Inclusion criteria were: 1) female gender, 2) age\u0026thinsp;\u0026gt;\u0026thinsp;50 years old, 3) distal radius fracture (for the fracture group). Exclusion criteria were 1) secondary osteoporosis and 2) high energy fracture (motorvehicle accident, fall from height\u0026thinsp;\u0026gt;\u0026thinsp;2 meters).\u003c/p\u003e \u003cp\u003eThe primary goal was to compare osteoporosis status according to BMD values at the lumbar spine and femoral neck, as well as the Fracture Risk Assessment Tool (FRAX).\u003c/p\u003e \u003cp\u003eSecondary goals were to compare other clinical risk factors and comorbidities between the two groups, namely, thyroid disease, dyslipedemia, hypertension, gastrointestinal disorders, arrhythmia, emotional disorders and epileptic seizures, antidepressants, thyroxine, smoking, osteoporosis family history, cortisone intake, diabetes, chemotherapy, early menopause, history of fracture, family history of fracture, chronic obstructive pulmonary disorder (COPD), multiple drug regimen, rheumatoid arthritis, protein pump inhibitors (PPIs), \u0026gt;\u0026thinsp;3 falls/year, furosemide. Multiple drug regimen was defined as systematic consumption of 5 or more different medication. Biochemical blood tests were also analyzed including serum calcium, albumin (corrected Calcium to albumin), 25-OH-Vitamin D and parathormone (PTH) levels.\u003c/p\u003e \u003cp\u003ePatients were assigned into two groups. Group 1 was the fracture group included women older than 50 years old with a recent history of distal radius fracture (within the last 3 years). Group 2 included women older than 50 years old with no recent fracture history who had been appointed in the outpatient osteoporosis clinic. The total BMD values were recorded for both the lumbar spine (L1-L4) and femoral neck using the same DEXA machine operated by the same technician (P.G). The FRAX score was calculated also.\u003c/p\u003e \u003cp\u003eAt the same time blood samples were collected and analyzed for calcium, albumin, PTH and Vitamin D. A thorough medical history was collected by a consultant orthopaedic surgeon (I.T.) including age, weight, height, comorbidities, medications, height loss and other risk factors as described above. Treatment of osteoporosis when detected, was offered according to the international guidelines.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eData were expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (S.D.) or median, IQR ( in case of violation of normality ) for continuous variables and as frequencies, percentages for categorical variables. The Kolmogorov\u0026mdash;Smirnov test was utilized for normality analysis of the parameters.\u003c/p\u003e \u003cp\u003eThe comparisons of the continuous variables between groups were analyzed using the independent samples t-test or Mann-Whitney U test in case of violation of normality.\u003c/p\u003e \u003cp\u003eThe comparisons of the categorical variables between groups were analyzed using the X\u003csup\u003e2\u003c/sup\u003e test of Fisher\u0026rsquo;s exact test.\u003c/p\u003e \u003cp\u003eAll tests were two-sided, statistical significance was set at p\u0026thinsp;\u0026lt;\u0026thinsp;0,05 .All analyses were carried out using the statistical package SPSS vr 21.00 (IBM Corporation, Somers, NY, USA).\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eThe total number of patients initially considered were 388. After applying the inclusion and exclusion criteria, 127 patients were enrolled in the study, assigned into two groups. Group A included 63 patients with distal radius fracture and Group B 64 patients without any fracture history. Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e shows the baseline demographic characteristics of the two groups. The only statistical significant demographic parameter was age (p\u0026thinsp;=\u0026thinsp;0.008), with a mean age in group A of 64.3 years-old vs 60 years-old in the non-fracture group.The BMD and T-scores for both hip and lumbar spine were compared between groups but no statistical significant difference was found (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn the fracture group 16 patients were diagnosed with osteoporosis and 39 with osteopenia. In the no-fracture group, 10 patients were found to have osteoporosis and 54 patients were diagnosed with osteopenia as depicted in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe metabolic and biochemical values (PTH, albumin and corrected calcium) were found similar between the two groups but Vitamin D showed a significant difference (p\u0026thinsp;=\u0026thinsp;0.044) with mean values of 25.82 and 20.82 on the non-fracture and fracture groups respectively (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe FRAX scores (Major \u0026amp; Hip) were significantly different in the fracture group (p\u0026thinsp;=\u0026thinsp;0.005) as was expected, because a previous fracture increases the FRAX risk for another fracture in the future (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eComorbidities were also analyzed but no differences were found between the two groups for thyroid disease, dyslipidemia, hypertensions, emotional disorders, gastrointestinal disorders, arrhythmia and epileptic seizures (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). It is of interest, however, that epileptic seizures showed a prevalence of 0% and 6.3% on the non-fracture and fracture group respectively (p\u0026thinsp;=\u0026thinsp;0.058). Other proven risk factors were compared also and only multi-drug regimens were found to be significantly higher on the fracture group (p\u0026thinsp;=\u0026thinsp;0.001, 0% and 14.3% respectively). Antidepressants, thyroxine, smoking, family history of osteoporosis, diabetes, chemotherapy, cortisone, early menopause, history of fracture, history of fracture of mother, COPD, rheumatoid arthritis, \u0026gt;3falls/year, furosemide and PPIs showed similar prevalence between the two groups.\u003c/p\u003e \u003cp\u003eFinally, the presence of \u0026ge;\u0026thinsp;1- and \u0026ge;\u0026thinsp;2- risk factors showed high p-values between the two groups. 100% of the fracture-group patients recorded at least one risk factor and 54% at least two. On the contrary, 65.6% and 26.6% of the non-fracture group showed at least one or two risk factors respectively. The loss of height showed also significance (p\u0026thinsp;=\u0026thinsp;0.033) with 40.6% and 60.3% between the non-fracture and fracture patients. The need for antiosteoporotic treatment according to the latest guidelines was 25% and 50.8% for the control and fracture groups respectively (p\u0026thinsp;=\u0026thinsp;0.003). (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e)\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\u003eComparison of parametrical variables\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eNon-fracture\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eDistal radius fracture\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMean\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSD\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMean\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSD\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e60.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e7.29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e64.33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e10.22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e0.008\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWeight\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e68.79\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e11.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e70.38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e15.87\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.516\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHeight\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.57\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.807\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eΒΜΙ\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e27.81\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4.81\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e28.41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e5.81\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.525\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eT-score lumbar spine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e-1.69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e.83\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e-1.60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.603\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMD lumbar spine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e.87\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e.09\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e.88\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e.14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.466\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eT-score femoral neck\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e-1.31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e.67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e-1.41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e.95\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.502\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMD femoral neck\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e.71\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e.70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e.12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.481\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\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\u003eComparison of non-parametrical variables.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eNon-fracture\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eDistal radius fracture\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMedian\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eIQR\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMedian\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eIQR\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e25OH VITD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e22.94\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e16.42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e19.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e12.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e0.044\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePTH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e48.95\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e20.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e49.20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e19.40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.687\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eALB\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e.30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e4.20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e.40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.180\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCorrected serum Ca\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9.34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e.46\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e9.20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e.42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.102\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFRAX Major\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5.40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4.72\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e9.40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e7.80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.005\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFRAX Hip\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.53\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e3.70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.005\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \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\u003eComparison of Comorbidities\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\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNon-fracture\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eDistal radius fracture\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eΝ(%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eΝ(%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eThyroid disease\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23,4%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23,8%\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\u003eDyslipidemia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e39,1%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e27,0%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.187\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypertension\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e32,8%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e34,9%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.853\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEmotional disorders\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14,1%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14,3%\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\u003eGastrointestinal disorders\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4,7%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7,9%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.492\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eArrhythmia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.3%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.3%\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\u003eEpileptic Seizures\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\u003e6.3%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.058\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAntidepressants\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9.4%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17.5%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.203\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eThyroxine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18.8%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12.7%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.466\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSmoking\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e43.8%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e34.9%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.365\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOsteoporosis Mother\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23.4%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17.5%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.510\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiabetes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.7%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11.1%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.206\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCortisone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.7%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.2%\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\u003eChemotherapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.1%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.496\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEarly Menopause\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23.4%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17.5%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.510\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHistory of fracture\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12.5%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.9%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.560\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMother history of fracture\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9.4%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.8%\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\u003eCOPD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.6%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.2%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.619\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMulti-drug regimen\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\u003e14.3%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;3 Falls/year\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\u003e3.2%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.244\u003c/p\u003e \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\u003e0%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.2%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.244\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePPIs\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.1%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.3%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.440\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFurosemide\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.6%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.2%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.619\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRisk factors\u0026thinsp;\u0026ge;\u0026thinsp;1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e65.6%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e100%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.0005\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRisk factors\u0026thinsp;\u0026ge;\u0026thinsp;2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26.6%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e54%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.002\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHeight loss\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e40.6^\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e60.3%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.033\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeed for treatment\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e50.8%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.003\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDEXA osteoporosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15.6%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25.4%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.193\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eOsteoporotic distal radius fractures, particularly among women\u0026thinsp;\u0026gt;\u0026thinsp;50 years-old, have been a topic of interest during the last decade, as they constitute the second commonest fracture managed in the clinical setting [28\u0026ndash;31]. Treatment plan is not the only parameter raising interest, as osteoporosis prevalence and morbidity rises, and a distal radius fracture in a middle-aged woman might be the first sign of the disease requiring immediate treatment on that direction [31\u0026ndash;32]. Other studies indicate that distal radius fractures might be the first signs of sarcopenia and frailty syndrome [33]. Even with normal BMD values, these patients remain at high risk for falls and subsequent fractures and the interventions should follow a multidisciplinary approach for prevention incuding vision problems, exercise and environmental modifications [34].\u003c/p\u003e \u003cp\u003eMost similar studies concluded that distal radius fractures in women\u0026thinsp;\u0026gt;\u0026thinsp;50 years old are characterized by lower ultra-distal radius BMD [35\u0026ndash;37], however less and conflicting evidence exists regarding BMD at the hip and lumbar spine and general osteoporotic status [37\u0026ndash;41]. After thorough literature review, we concluded that the majority of studies originate from northern Europe and find distal radius fracture in post-menopausal women to be correlated with higher osteoporosis prevalence [38\u0026ndash;41]. Our study showed that women older than 50 years-old with a distal radius fracture do not have lower BMD or T-scores than the non-fracture group of similar age, a difference that could be explained by the location of our study. Most studies showing a BMD difference among the groups were perfomed in Northern Europe countries, were it is known that osteoporosis presents a higher prevalence [43]. Our study as well as the study from Barcelona are the only studies from the Mediterennean region and showed no difference in hip and lumbar spine BMD values among the two groups [37]. Nevertheless, there is a consensus that the risk for a subsequent hip fracture increases after a distal radius fracture in postmenopausal women [44], and this was confirmed by our study, as 50% of the fracture group presented with a need for anti-osteoporitc treatment after FRAX-score.\u003c/p\u003e \u003cp\u003eAmong the different comorbidities and risk factors studied, only the multi-drug regimens showed a significant difference. It is not clear ,however ,whether this occurred due to the drugs\u0026rsquo; side effects or due to the high comorbidities associated with multi-drug regimens. Loss of height was another statistically significant risk factor among fracture patients and this indicates its potential prognostic value in this patient group, but extensive further clinical studies should be conducted in order to be incorporated in the treatment algorithm. Loss of height has been attributed to vertebral osteoporosis and fractures, along with kyphosis and it is of interest wether it is correlated with such in this, younger than the usual vertebral osteoporotic, group [45]. Nevertheless, it remains a standalone risk factor for another fracture, and high suspicion must be maintained when combined with distal radius fracture in post-menopausal women [46]. Epileptic seizures showed also a higher prevalence among the fracture group, although not statistically significant. Epileptic activity and osteoporosis share a complex and unclear relationship through various studies. Some studies suggest that the hypocalcemic effect of classic antiosteoporotic drugs might be severe enough to create seizures, however our population was treatment-na\u0026iuml;ve [47]. Other studies stress that antiepileptic agents can lower BMD, especially hepatic enzyme inducers like carbamazepine, phenobarbital and phenytoin, while the frequency of seizures can increase during perimenopause, possibly increasing the fracture risk as well due to injury during epileptic episodes [48\u0026ndash;50].\u003c/p\u003e \u003cp\u003eThe reason that distal radius fractures in the elderly are so extensively studied in the literature, is mainly due to the healthcare burden and morbidity of the accompanied osteoporotic hip and vertebral fracture. A Colle\u0026rsquo;s fracture after minor trauma is estimated to result in a subsequent hip fracture during the following years in 50% of the patients [26]. NICE guidelines have been suggested on secondary prevention of osteoporotic fractures, but most centers do not seem to widely implement these, as referral for further investigation should be initiated as early as in the emergency department [51\u0026ndash;53]. Nevertheless, elderly patients with a low energy distal radius fracture should be referred for a BMD measurement with DEXA, as there is a high prevelance of osteoporosis according to many studies, but not as high as to guarantee universal anti-osteoclastic treatment as in hip fractures [20, 22]. Vitamin D and perhaps a secondary osteoporosis laboratory tests should also be ordered, as Oyen et al in 2011 showed high prevelance of Vitamin D inadequacy among these patients, although Rozental did not confirm this finding, possibly due to regional differences [54\u0026ndash;55]. Our study showed no differences in calcium levels between the two groups, and even calcium supplementation by Lamke et al showed no difference [56]. Patient education and consultation by the treating surgeon are also proven methods of increased osteoporosis screening and should be implemented as much as possible [54].\u003c/p\u003e \u003cp\u003eThere are a number of limitations regarding our study. First of all, patients in the fracture group were found to be statistically significant older than the non-fracture group, although the difference was minor considering absolute numbers. Moreover, our group sizes were relatively small. However, this is one of the few studies in Greece, from a special osteoporosis clinic with the collection of data beign performed by one researcher (I.T.), one technician and one DEXA machine.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eAlthough distal radius fractures in middle-aged women have been associated with low BMD and have been identified as an osteoporosis precurssor, our study did not verify this hypothesis. Regional differences seem to exist, showing that the distal radius fracture and its connection to osteoporosis is not fully understood. Nevertheless, this group of patients continues to present higher FRAX scores and therefore higher risk for future fractures, leading to higher treatment rates, but not high enough for universal treatment. Lower Vitamin-D among these patients should be considered as both a prevention target as well as a therapeutic target. Loss of height and multi-drug regimens are also met at a higher prevalence among the fracture group and could be utilized as part of prevention and early diagnosis strategies, as well as epileptic seizures.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eDual-Energy X-ray Absorptiometry (DEXA)\u003c/p\u003e\n\u003cp\u003eAmerican Academy of Ortopaedic Surgeons (AAOS)\u003c/p\u003e\n\u003cp\u003eBone Mineral Density (BMD)\u003c/p\u003e\n\u003cp\u003eFracture Risk Assessment Tool (FRAX)\u003c/p\u003e\n\u003cp\u003eChronic Obstructive Pulmonary Disorder (COPD)\u003c/p\u003e\n\u003cp\u003eProtein Pump Inhibitors (PPIs)\u003c/p\u003e\n\u003cp\u003eParathormone (PTH)\u003c/p\u003e\n\u003cp\u003eStandard Deviation (S.D.)\u003c/p\u003e\n\u003cp\u003eOpen Reduction and Internal Fixation (ORIF)\u003c/p\u003e\n"},{"header":"Declarations","content":"\u003cp\u003e\u003cem\u003eEthics approval:\u003c/em\u003e The protocol was approved by the hospital\u0026rsquo;s ethics committee and institutional board approval was obtained (approval number 684/12.10.18- 56/21.11.2018)\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eConsent for publication:\u003c/em\u003e Informed written consent for participation in the study was obtained from each individual\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAvailability of data and materials:\u003c/em\u003e The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eConflicts of interest:\u0026nbsp;\u003c/em\u003eAll authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest or non-financial interest in the subject matter or materials discussed in this manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eFunding:\u0026nbsp;\u003c/em\u003eThe authors did not receive support from any organization for the submitted work.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAcknowledgements\u003c/em\u003e: Not applicable\u003c/p\u003e\n"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eConsensus development conference: diagnosis, prophylaxis, and treatment of osteoporosis. 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Acta Orthop Scand. 1978 Apr;49(2):143-146. doi: 10.3109/17453677809005740. PMID: 659500.\u003c/li\u003e\n\u003cli\u003eSarfani S, Scrabeck T, Kearns AE, Berger RA, Kakar S. Clinical efficacy of a fragility care program in distal radius fracture patients. J Hand Surg Am. 2014 Apr;39(4):664-669. doi: 10.1016/j.jhsa.2014.01.009. PMID: 24581683.\u003c/li\u003e\n\u003c/ol\u003e "}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"osteoporosis, post-menopausal, distal radius, osteopenia, vitamin d","lastPublishedDoi":"10.21203/rs.3.rs-5919538/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5919538/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eObjectives\u003c/h2\u003e \u003cp\u003eTo compare bone mineral density (BMD), FRAX scores, comorbidities, risk factors and biochemical blood markers among postmenopausal women with distal radius fractures and those without such fractures.\u003c/p\u003e\u003ch2\u003eMaterials and Methods\u003c/h2\u003e \u003cp\u003e63 postmenopausal women with distal radius fractures were compared to 64 postmenopausal women with no history of fractures. Primary objectives included comparing BMD at the femoral neck and lumbar spine, as well as FRAX scores between the two groups. Secondary goals involved assessing comorbidities, risk factors, and biochemical blood markers (Ca\u0026thinsp;+\u0026thinsp;2, albumin, PTH, VItD) between the two groups.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eBMD and T-scores for the hip and lumbar spine were compared between groups, revealing no statistically significant differences. However, FRAX scores (Major \u0026amp; Hip) differed significantly in the fracture group (p\u0026thinsp;=\u0026thinsp;0.005), aligning with expectations that a previous fracture elevates the FRAX risk for future fractures. Biochemical markers were similar between the two groups, except for Vitamin D. Among risk factors and comorbidities, only multi-drug regimens and epileptic seizures were significantly higher in the fracture group.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eOur study found similar BMD between the two groups. Nonetheless, a lower FRAX in the fracture group necessitates increased consideration for osteoporosis treatment. Multiple-drug regimens and lower vitamin D levels were also linked to the fracture group.\u003c/p\u003e","manuscriptTitle":"Comparison of Bone Mineral Density And Treatment Initation Among Treatment-Naive Post-Menopausal Women with Distal Radius Fracture and Without: A Case-Control Study from Southern Europe","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-02-07 10:40:24","doi":"10.21203/rs.3.rs-5919538/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"addb98d5-85de-45eb-a4f7-3d74ae31a453","owner":[],"postedDate":"February 7th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-04-04T02:08:23+00:00","versionOfRecord":[],"versionCreatedAt":"2025-02-07 10:40:24","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5919538","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5919538","identity":"rs-5919538","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}