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A large international meta-analysis using primary data from 64 cohorts has quantified the increased risk of fracture associated with a previous history of fracture for future use in FRAX., Introduction: The aim of this study was to quantify the fracture risk associated with a prior fracture on an international basis and to explore the relationship of this risk with age, sex, time since baseline and bone mineral density (BMD)., Methods: We studied 665,971 men and 1,438,535 women from 64 cohorts in 32 countries followed for a total of 19.5 million person-years. The effect of a prior history of fracture on the risk of any clinical fracture, any osteoporotic fracture, major osteoporotic fracture, and hip fracture alone was examined using an extended Poisson model in each cohort. Covariates examined were age, sex, BMD, and duration of follow-up. The results of the different studies were merged by using the weighted β-coefficients., Results: A previous fracture history, compared with individuals without a prior fracture, was associated with a significantly increased risk of any clinical fracture (hazard ratio, HR = 1.88; 95% CI = 1.72-2.07). The risk ratio was similar for the outcome of osteoporotic fracture (HR = 1.87; 95% CI = 1.69-2.07), major osteoporotic fracture (HR = 1.83; 95% CI = 1.63-2.06), or for hip fracture (HR = 1.82; 95% CI = 1.62-2.06). There was no significant difference in risk ratio between men and women. Subsequent fracture risk was marginally downward adjusted when account was taken of BMD. Low BMD explained a minority of the risk for any clinical fracture (14%), osteoporotic fracture (17%), and for hip fracture (33%). The risk ratio for all fracture outcomes related to prior fracture decreased significantly with adjustment for age and time since baseline examination., Conclusion: A previous history of fracture confers an increased risk of fracture of substantial importance beyond that explained by BMD. The effect is similar in men and women. Its quantitation on an international basis permits the more accurate use of this risk factor in case finding strategies., (© 2023. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

The current study explored the possible utilization in dual-X-ray-absorptiometry scanning (DXA) of the ultra-distal radius (UDR). This region of interest is currently unused and mostly unstudied in this context. The study findings suggest UDR as potential useful region of interest in DXA scanning and warrant further study of the site., Purpose: Bone mineral density (BMD) measurement of a non-dominant arm is not routinely performed during dual-X-ray-absorptiometry (DXA) test, and the possible utility of ultra-distal (UDR) radius BMD is not well-studied. We evaluated in women, correlations of UDR BMD with fracture prevalence, fracture risk prediction by the fracture risk assessment tool (FRAX), and osteoporosis diagnosed by traditional sites., Methods: Women who underwent a routine DXA (including their non-dominant forearm and including UDR BMD) in a tertiary medical center were included. Risk factors relevant to FRAX calculation were assessed via a self-administered questionnaire. Spearman correlations of UDR BMD to 10-year risks of major osteoporotic and hip fractures (assessed by FRAX) were explored. The possible added value of UDR BMD in explaining prevalent osteoporotic fractures was assessed using a multivariable regression model incorporating age and traditional osteoporosis diagnosis., Results: The study included 1245 women with a median age of 66 years (interquartile range: 59-73), of whom 298 (24%) had UDR T-score ≤  - 2.5 and 154 (12%) reported prior fractures. UDR BMD was significantly negatively correlated with FRAX risk score for hip and major osteoporotic fractures (R =  - 0.5 and R =  - 0.41, respectively; P < 0.001). UDR T-score ≤  - 2.5 was associated with higher fracture prevalence (19% vs 10%; P < 0.001) and remained significant after adjusting for traditional BMD and age (OR 1.49, 1.01-2.19; P = 0.043)., Conclusion: UDR BMD correlates both with prior fractures and with predicted fracture risks and might pose added value over traditional DXA sites., (© 2023. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

We describe the collection of cohorts together with the analysis plan for an update of the fracture risk prediction tool FRAX with respect to current and novel risk factors. The resource comprises 2,138,428 participants with a follow-up of approximately 20 million person-years and 116,117 documented incident major osteoporotic fractures., Introduction: The availability of the fracture risk assessment tool FRAX® has substantially enhanced the targeting of treatment to those at high risk of fracture with FRAX now incorporated into more than 100 clinical osteoporosis guidelines worldwide. The aim of this study is to determine whether the current algorithms can be further optimised with respect to current and novel risk factors., Methods: A computerised literature search was performed in PubMed from inception until May 17, 2019, to identify eligible cohorts for updating the FRAX coefficients. Additionally, we searched the abstracts of conference proceedings of the American Society for Bone and Mineral Research, European Calcified Tissue Society and World Congress of Osteoporosis. Prospective cohort studies with data on baseline clinical risk factors and incident fractures were eligible., Results: Of the 836 records retrieved, 53 were selected for full-text assessment after screening on title and abstract. Twelve cohorts were deemed eligible and of these, 4 novel cohorts were identified. These cohorts, together with 60 previously identified cohorts, will provide the resource for constructing an updated version of FRAX comprising 2,138,428 participants with a follow-up of approximately 20 million person-years and 116,117 documented incident major osteoporotic fractures. For each known and candidate risk factor, multivariate hazard functions for hip fracture, major osteoporotic fracture and death will be tested using extended Poisson regression. Sex- and/or ethnicity-specific differences in the weights of the risk factors will be investigated. After meta-analyses of the cohort-specific beta coefficients for each risk factor, models comprising 10-year probability of hip and major osteoporotic fracture, with or without femoral neck bone mineral density, will be computed., Conclusions: These assembled cohorts and described models will provide the framework for an updated FRAX tool enabling enhanced assessment of fracture risk (PROSPERO (CRD42021227266))., (© 2022. International Osteoporosis Foundation and National Osteoporosis Foundation.)

Objective: To investigate the added value of 1/3 radius (1/3R) for the diagnosis of osteoporosis by spine and hip sites and its correlation with prevalent fractures and predicted fracture risk., Methods: Fracture Risk Assessment Tool (FRAX) scores for hip and major osteoporotic fractures (MOF) with/without trabecular bone score were considered proxy for fracture risk. The contribution of 1/3R to risk prediction was depicted via linear regression models with FRAX score as the dependent variable-first only with central and then with radius T-score as an additional covariate. Significance of change in the explained variance was compared by F-test., Results: The study included 1453 patients, 86% women, aged 66 ± 10 years. A total of 32% (n = 471) were osteoporotic by spine/hip and 8% (n = 115) by radius only, constituting a 24.4% increase in the number of subjects defined as osteoporotic (n = 586, 40%). Prior fracture prevalence was similar among patients with osteoporosis by spine/hip (17.4%) and radius only (19.1%) (P = .77). FRAX prediction by a regression model using spine/hip T-score yielded explained variance of 51.8% and 49.9% for MOF and 39.8% and 36.4% for hip (with/without trabecular bone score adjustment, respectively). The contribution of 1/3R was statistically significant (P < .001) and slightly increased the explained variance to 52.3% and 50.4% for MOF and 40.9% and 37.4% for hip, respectively., Conclusion: Reclassification of BMD results according to radius measurements results in higher diagnostic output. Prior fractures were equally prevalent among patients with radius-only and classic-site osteoporosis. FRAX tool performance slightly improved by incorporating radius BMD. Whether this approach may lead to a better fracture prediction warrants further prospective evaluation., (Copyright © 2020 AACE. Published by Elsevier Inc. All rights reserved.)

Computerized alerts for primary care physicians, provided during visits of patients who met treatment guidelines based on their electronic medical records, are an efficient method to raise awareness to many otherwise missed cases, especially after fracture., Purpose: Measure the efficacy of an automated real-time alert which was developed to assist osteoporosis management in the community., Methods: The study population included treatment naïve patients with T-score ≤ - 2.5 or hip or vertebral fracture in a 2 million member Israeli health fund. On each ambulatory visit to a primary care physician or endocrinologist, a pop-up screen reminded the caregiver to consider treatment initiation. A follow-up "smart-set" screen conveniently gathered links to common actions (namely, (a) issue first line therapy prescription, (b) referral to nutritionist consultation, (c) laboratory tests relevant for osteoporosis, and (d) printing an information page for the patient). Time till treatment initiation was compared between the 3 years prior to and following the intervention., Results: Within 2 years since alert activation, a total of n = 21,070 cases were alerted, 52% of which were long standing cases: untreated for over 6 months since the event. During this period, a total of 30% initiated treatment purchases. As compared with the 3 years prior to the intervention, time till treatment initiation decreased following the intervention with HR = 1.05, 1.94, 1.29 (p values = 0.020, < 0.001, 0.005) for T-score, hip, and vertebral cases respectively. Initiation rates within 6 months increased from 52.0 to 59.8%, from 12.3 to 27.7%, and from 17.4 to 27.1% among T-score, hip, and vertebral cases, respectively (p value < 0.001). Male sex, nursing home residence, having diabetes or a cardiovascular disease and age younger than 60 or older than 80 were associated with lower treatment rates., Conclusions: A computerized decision support system can efficiently raise attention to many otherwise missed high-risk osteoporotic cases, particularly those after fractures.

This study analyzed data on 87,224 osteoporotic patients with up to 18 years of computerized medical history. Patients with osteoporosis and type 2 diabetes had higher bone density yet more fractures than non-diabetic osteoporotic patients. Fracture incidence among the diabetic patients was associated with retinopathy and cardiovascular disease, but not with diabetes duration., Purpose: Little is known about the association between type 2 diabetes mellitus (T2DM) and fragility fractures or the mechanism(s) involved. We examined fracture correlates among T2DM patients with osteoporosis., Methods: We used electronic health records of an osteoporosis (OP) registry cross-linked with a diabetes registry of a large payer provider healthcare organization in Israel. A cross-sectional analysis compared osteoporosis patients with and without T2DM, and a longitudinal Cox proportional hazard regression was used to identify incident fracture correlates., Results: As of December 2015 a total of 87,224 current OP patients were identified, of whom 15,700 (18%) had T2DM. The T2DM OP patients were characterized by older age (mean 74.6 vs. 69.5), more males (20.3 vs. 14.0%), and a higher rate of chronic comorbidities compared to OP without diabetes. All major OP fractures (hip, spine, humerus, and forearm) were significantly more prevalent among T2DM OP patients (44 vs. 32%), with an overall age-standardized ratio of 1.22 (95% CI 1.19 to 1.25) and 1.15 (95% CI 1.10 to 1.21) for females and males respectively. The average T-scores were higher (femur neck - 1.8 vs. - 1.9, total hip - 1.2 vs. - 1.6, and vertebrae - 1.3 vs. - 1.7) for the T2DM OP patients compared to the non-T2DM OP patients. Among women with coexisting T2DM and osteoporosis (n = 10,812), fracture incidence was significantly associated with retinopathy (HR = 1.24, 95% CI 1.05 to 1.47) and cardiovascular disease (HR = 1.22, 95% CI 1.10 to 1.36) after controlling for age, bone mineral density T-score, rheumatoid arthritis, glucocorticoids, alcohol, and smoking)., Conclusion: This large population-based study confirms the higher fracture risk of osteoporotic patients with T2DM, as compared to osteoporotic patients without T2DM, despite higher bone mineral density levels. The presence of micro- and macrovascular disease appears to increase this risk.

Background: Hip fracture is a major complication of osteoporosis. Bisphosphonate medication is the mainstay of treatment for osteoporosis. However, concerns have been raised regarding the effectiveness of bisphosphonates in reducing hip fracture risk after long-term use, particularly among patients with suboptimal adherence., Objective: To examine the association between adherence with bisphosphonate therapy and long-term risk of hip fracture., Methods: Included in the present nested case-control study were osteoporotic women (n = 14 357) who initiated bisphosphonate therapy in 2000-2010 and were retrospectively followed for incident hip fracture through November 2014. Within this cohort, each case of primary hip fractures was individually matched to 3 controls without a primary hip fracture. Proportion of follow-up days covered (PDC) with bisphosphonates was calculated from bisphosphonate purchases. Adherence was categorized into the following groups: purchase of 1 or 2 months' supply (reference group), at least 3 months' supply to PDC ≤20%, PDC >20% to ≤80%, PDC >80% to ≤100%., Results: Included in the analysis were 426 case-control groups with a mean age (SD) of 73.7 years (7.9). Compared with the reference group, PDC of 80% to 100% with bisphosphonates was associated with a significant reduction in hip fracture risk for patients with 8 to 15 years of follow-up (OR = 0.39; 95% CI = 0.18-0.87). Among patients with a follow-up of up to 3 years, OR was 0.58 (95% CI = 0.31-1.06)., Conclusions: Adherence with bisphosphonates among osteoporotic patients is associated with lower risk of hip fracture, with no indication of diminished effectiveness with long-term use.

Background: Osteoporosis is a systemic skeletal disorder characterized by impaired bone quality and microstructural deterioration leading to an increased propensity to fractures. This is a major health problem for older adults, which comprise an increasingly greater proportion of the general population. Due to a large number of patients and the insufficient availability of specialists in Israel and worldwide, osteoporosis is treated in large part by primary care physicians. We assessed the knowledge of primary care physicians on the diagnosis and treatment of osteoporosis., Methods: Physician's knowledge, sources of knowledge acquisition and self-evaluation of knowledge were assessed using a multiple choice questionnaire. Professional and demographic characteristics were assessed as well., Results: Of 490 physicians attending a conference, 363 filled the questionnaires (74% response rate). The physicians demonstrated better expertise in diagnosis than in medications (mechanism of action, side effects or contra-indications) but less than for other treatment related decisions. Overall, 50% demonstrated adequate knowledge of calcium and vitamin D supplementation, 51% were aware of the main therapeutic purpose of osteoporosis pharmacotherapy and 3% were aware that bisphosphonates should be avoided in patients with impaired renal function. Respondents stated frontal lectures at meetings as their main source of information on the subject., Conclusion: The study indicates the need to intensify efforts to improve the knowledge of primary care physicians regarding osteoporosis, in general; and osteoporosis pharmacotherapy, in particular.

Introduction: The benefits of osteoporosis therapy are compromised by low adherence, thus requiring a better understanding of its barriers and unmet needs. The objective of this study was to assess reasons for non-adherence with oral bisphosphonates among osteoporotic women., Methods: A cross-sectional patient survey of women who initiated therapy with risedronate or alendronate between the years 2010 and 2012 were non-adherent [Medication Possession Ratio (MPR) <70%] or switched therapy within the first year. Survey participants were identified using Maccabi Health Services computerized database. Patients who gave informed consent completed a 20-min telephonic survey, assessing reasons for discontinuation or switching, including physician involvement, side effects, administration regimen, perceptions of bone health, and medications' efficacy., Results: The study population included 493 females (mean age = 66 ± 7) of whom 40% discontinued all anti-osteoporotic therapy (mean MPR = 19%), 9% remained on initial therapy (mean MPR = 47%), and 51% switched therapy (mean MPR = 62%). Family history, fracture history, socioeconomic status, and index drug class and frequency were similar in all groups. The most common reasons for switching or discontinuation of the first-line therapy were gastrointestinal side effects, such as heartburn, acid reflux or other (40.0%), and physician recommendation (26.7%). The major reasons for complete discontinuation of therapy were side effects (26.9%) and physician recommendation (20.0%). Perceived low importance was more commonly mentioned than high cost of medication (14% vs. 3%)., Conclusion: Our findings highlight the importance of low tolerability to non-adherence with osteoporosis therapy and underlines poor patients' awareness and sub-optimal physicians' involvement in conveying the importance of this therapy., Funding: Merck & Co Inc.

Osteoporosis-related fractures at the spine and hip have a substantial impact on mortality, morbidity, and quality of life in older adults worldwide. Adherence to bisphosphonates is essential for effective treatment and fracture prevention. Nevertheless, numerous studies from various populations and study designs clearly indicated that adherence and persistence are poor with more than 50% of patients discontinuing therapy within one year. This is primarily explained by mild adverse effects, dosing regimens, and costs. Studies have also shown that good adherence is associated with reduced osteoporosis-related and non-related healthcare costs as soon as 2 years from therapy initiation. Nonetheless, we found only little improvement in adherence rates over the years. In light of the importance of medication adherence and the limited success of previous programs, other than reducing dosing frequency, new directions should be explored to engage patients and care givers in order to improve adherence and prevent fractures.

Background: Adherence to osteoporosis treatment remains poor despite available treatments and physician and patient education. This study aims to determine the effect of low adherence in real-world data., Objective: To examine the association between adherence with oral bisphosphonate therapy and fracture risk as well as health care resource utilization., Methods: Women included in this retrospective analysis were 55 years or older and had started oral bisphosphonate therapy between 2005 and 2011 in a large not-for-profit health care center in Israel. Adherence to therapy was measured by the medication possession ratio (MPR) during the first year from therapy initiation. Patients with MPR lower than 70% were considered nonadherent. Study outcomes were osteoporotic fracture events and health care utilization (including physician visits and hospitalizations) during the second year from therapy initiation., Results: Among the 17 770 women included in the analysis (mean age = 66.5 years; SD = ±8.3 years), 48.9% were nonadherent to therapy during the first year of treatment. Osteoporotic fracture risks during the second year among adherent and nonadherent patients were 2.1% and 2.5%, respectively (P = 0.1). When analysis was limited to patients 75 years or older, nonadherence with bisphosphonates was associated with an adjusted odds ratio of 1.49 (95% CI = 1.08-2.04) for osteoporotic fractures compared with adherent patients. Nonadherent patients had 13.4% higher medical costs than their adherent counterparts among patients 75 years and older (P = 0.002)., Conclusions: In patients 75 years and older, nonadherence with oral bisphosphonates can be associated with significantly greater short-term risk of osteoporotic fractures and higher utilization of health care services., (© The Author(s) 2016.)

Background: The objective was to examine the association of gastrointestinal (GI) events and osteoporosis treatment initiation patterns among postmenopausal women following an osteoporosis diagnosis from an Israeli health plan., Methods: This retrospective analysis of claims records included women aged ≥ 55 years with ≥ 1 osteoporosis diagnosis (date of first diagnosis was index date). Osteoporosis treatment initiation was defined as use of osteoporosis therapy (oral bisphosphonates or other) during 12 months postindex. GI events (diagnosis of GI conditions) were reported for 12 months preindex and postindex (from index to treatment initiation or 1 year postindex, whichever occurred first). The association of postindex GI events (yes/no) with the initiation of osteoporosis treatment (yes/no) and with type of therapy initiated (oral bisphosphonate vs. other) were examined with logistic regression and Cox proportional hazard regression (as sensitivity analysis)., Results: Among 30,788 eligible patients, 17.5% had preindex GI events and 13.0% had postindex GI events. About 70.6% of patients received no osteoporosis therapy within 1 year of diagnosis, 24.9% received oral bisphosphonates and 4.5% received other medications. Postindex GI events were associated with lower odds of osteoporosis medication initiation (85-86% reduced likelihood; p < 0.01). Upon treatment initiation, postindex GI was not significantly associated with the type of osteoporosis therapy initiated, controlling for baseline GI events and patient characteristics., Conclusions: Among newly diagnosed osteoporotic women from a large Israeli health plan, 70.6% did not receive osteoporosis treatment within 1 year of diagnosis. The presence of GI events was associated with reduced likelihood of osteoporosis treatment initiation., (© 2015 The Authors. International Journal of Clinical Practice Published by John Wiley & Sons Ltd.)

Unlabelled: Bisphosphonates are a first-line treatment for osteoporosis but require adequate renal function. We estimated the prevalence of renal impairment among osteoporotic women in Israeli. Approximately 2.3 % of women had renal impairment at a level that makes them inappropriate for bisphosphonate use, demonstrating the need for alternative therapies for osteoporosis treatment., Purpose: The purpose of this study is to estimate the prevalence of renal impairment among postmenopausal osteoporotic women within a large Israeli health plan., Methods: This was a retrospective analysis of Maccabi electronic medical records, including Israeli women aged ≥55 with either an osteoporosis diagnosis or osteoporosis-related fracture between January 1, 2007, and December 31, 2011. The estimated glomerular filtration rate (eGFR), which was calculated from the lowest serum creatinine levels reported during the study period, was used to classify stage 1-5 renal impairment: normal ≥90, mild 60-89, moderate 30-59, severe 15-29, and failure <15 mL/min/1.73 m(2), respectively. Outcomes were distributions of renal impairment across the study population and stratified by age and osteoporosis-defining event., Results: A total of 15,608 patients met all eligibility criteria. Patients with stage 1-5 renal function accounted for 25.2, 54.9, 18.5, 1.2, and 0.3 %, respectively, of all patients. Of osteoporotic patients, 2.3 % had eGFR levels (<35 mL/min/1.73 m(2)) that make them inappropriate for bisphosphonate use. This rate was 1.6 % among patients with an osteoporosis diagnosis and 3.8 % among patients with osteoporosis-related fracture. Within the group of renally impaired patients, older patients were overrepresented. Of the fracture group, patients with hip fractures had a higher prevalence of renal dysfunction (9.3 %) than those having vertebral fractures (3.2 %) or other fractures (2.0 %)., Conclusions: Among postmenopausal women with osteoporosis, 2.3 % had renal impairment which makes them inappropriate for bisphosphonate use in Israel.