Explore the vast range of titles available.

Summary 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.

SummaryThe relationship between self-reported falls and fracture risk was estimated in an international meta-analysis of individual-level data from 46 prospective cohorts. Previous falls were associated with an increased fracture risk in women and men and should be considered as an additional risk factor in the FRAX® algorithm.IntroductionPrevious falls are a well-documented risk factor for subsequent fracture but have not yet been incorporated into the FRAX algorithm. The aim of this study was to evaluate, in an international meta-analysis, the association between previous falls and subsequent fracture risk and its relation to sex, age, duration of follow-up, and bone mineral density (BMD).MethodsThe resource comprised 906,359 women and men (66.9% female) from 46 prospective cohorts. Previous falls were uniformly defined as any fall occurring during the previous year in 43 cohorts; the remaining three cohorts had a different question construct. The association between previous falls and fracture risk (any clinical fracture, osteoporotic fracture, major osteoporotic fracture, and hip fracture) was examined using an extension of the Poisson regression model in each cohort and each sex, followed by random-effects meta-analyses of the weighted beta coefficients.ResultsFalls in the past year were reported in 21.4% of individuals. During a follow-up of 9,102,207 person-years, 87,352 fractures occurred of which 19,509 were hip fractures. A previous fall was associated with a significantly increased risk of any clinical fracture both in women (hazard ratio (HR) 1.42, 95% confidence interval (CI) 1.33–1.51) and men (HR 1.53, 95% CI 1.41–1.67). The HRs were of similar magnitude for osteoporotic, major osteoporotic fracture, and hip fracture. Sex significantly modified the association between previous fall and fracture risk, with predictive values being higher in men than in women (e.g., for major osteoporotic fracture, HR 1.53 (95% CI 1.27–1.84) in men vs. HR 1.32 (95% CI 1.20–1.45) in women, P for interaction = 0.013). The HRs associated with previous falls decreased with age in women and with duration of follow-up in men and women for most fracture outcomes. There was no evidence of an interaction between falls and BMD for fracture risk. Subsequent risk for a major osteoporotic fracture increased with each additional previous fall in women and men.ConclusionsA previous self-reported fall confers an increased risk of fracture that is largely independent of BMD. Previous falls should be considered as an additional risk factor in future iterations of FRAX to improve fracture risk prediction.

SummaryAmong 377,561 female Medicare beneficiaries who sustained a fracture, 10% had another fracture within 1 year, 18% within 2 years, and 31% within 5 years. Timely management to reduce risk of subsequent fracture is warranted following all nontraumatic fractures, including nonhip nonvertebral fractures, in older women.IntroductionPrior fracture is a strong predictor of subsequent fracture; however, postfracture treatment rates are low. Quantifying imminent (12–24 month) risk of subsequent fracture in older women may clarify the need for early postfracture management.MethodsThis retrospective cohort study used Medicare administrative claims data. Women ≥ 65 years who sustained a clinical fracture (clinical vertebral and nonvertebral fracture; index date) and were continuously enrolled for 1-year pre-index and ≥ 1-year (≥  2 or ≥ 5 years for outcomes at those time points) post-index were included. Cumulative incidence of subsequent fracture was calculated from 30 days post-index to 1, 2, and 5 years post-index. For appendicular fractures, only those requiring hospitalization or surgical repair were counted. Death was considered a competing risk.ResultsAmong 377,561 women (210,621 and 10,969 for 2- and 5-year outcomes), cumulative risk of subsequent fracture was 10%, 18%, and 31% at 1, 2, and 5 years post-index, respectively. Among women age 65–74 years with initial clinical vertebral, hip, pelvis, femur, or clavicle fractures and all women ≥ 75 years regardless of initial fracture site (except ankle and tibia/fibula), 7–14% fractured again within 1 year depending on initial fracture site; risk rose to 15–26% within 2 years and 28–42% within 5 years. Risk of subsequent hip fracture exceeded 3% within 5 years in all women studied, except those < 75 years with an initial tibia/fibula or ankle fracture.ConclusionsWe observed a high and early risk of subsequent fracture following a broad array of initial fractures. Timely management with consideration of pharmacotherapy is warranted in older women following all fracture types evaluated.

Summary 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. IntroductionThe 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.MethodsA 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.ResultsOf 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.ConclusionsThese assembled cohorts and described models will provide the framework for an updated FRAX tool enabling enhanced assessment of fracture risk (PROSPERO (CRD42021227266)).

SummaryWe analyzed patterns in recurrent major osteoporotic fracture (MOF) following a first major osteoporotic fracture in a large population-based cohort. Re-fracture risk remained elevated over 10 years, with only modest and inconsistent attenuation in risk over time.IntroductionRecurrent fracture risk remains elevated for up to 25 years, and is reportedly highest in the initial 2 years (imminent risk). Our aim was to characterize early time dependency in re-fracture rates up to 10 years after a first fracture in a population-based cohort.MethodsUsing Province of Manitoba (Canada) healthcare databases, we performed a matched cohort study in 22,105 women (mean age 74.1 ± 10.6 years) and 7589 men (mean age 71.8 ± 11.2 years) after a first MOF (age ≥ 50 years) during 1989–2006 and matched fracture-free controls (3 for each case). Incident fractures were ascertained over the next 10 years. Fracture rate ratios (RRs, cases versus controls) stratified by sex and age were computed, and tested for linear trend using linear regression. Joinpoint regression was performed to determine non-linear change in fracture rates over time, with particular attention to the first 2-year post-fracture.ResultsRRs for incident MOF and hip fracture exceeded unity for the primary analyses in all subgroups and follow-up intervals. There was a tendency of RRs to decline over time, but this was inconsistent. Absolute rates per 100,000 person-years for fracture cases were consistently greater than for controls in all subgroups and observation times. Among fracture cases, there was a tendency for rates to decline gradually in all subgroups except younger women, but these temporal trends appeared monotonic without an inflection at 2 years. Joinpoint regression analyses did not detect an inflection in risk between the first 2 years and subsequent years. No significant time dependency was seen for incident hip fracture.ConclusionsMOF and hip re-fracture risk was elevated in all age and sex subgroups over 10 years. There was inconsistent and only modest time dependency in early MOF risk, most evident in women after age 65 years. No strong transition in risk was seen between the first 2-year post-fracture and subsequent years.

Purpose To identify risk factors, including FRAX (a tool for assessing osteoporosis) scores, for development of proximal junctional kyphosis (PJK), defined as Type 2 in the Yagi–Boachie classification (bone failure), with vertebral fracture (VF) after surgery for symptomatic adult spinal deformity. Methods This was a retrospective, single institution study of 127 adults who had undergone corrective long spinal fusion of six or more spinal segments for spinal deformity and been followed up for at least 2 years. The main outcome was postoperative development of PJK with VF. Possible predictors of this outcome studied included age at surgery, BMI, selected radiographic measurements, bone mineral density, and 10-year probability of major osteoporotic fracture (MOF) as determined by FRAX. We also analyzed use of medications for osteoporosis. Associations between the selected variables and PJK with VF were assessed by the Mann–Whitney, Fishers exact, and Wilcoxon signed-rank tests, and Kaplan–Meier analysis, as indicated. Results Forty patients (31.5%) developed PJK with VF postoperatively,73% of them within 6 months of surgery. Statistical analysis of the selected variables found that only a preoperative estimate by FRAX of a > 15% risk of MOF within 10 years, pelvic tilt > 30° at first standing postoperatively and lower instrumented level (fusion terminating at the pelvis) were significantly associated with development of PJK with VF. Conclusion Preoperative assessment of severity of osteoporosis using FRAX provides an accurate estimate of risk of postoperative PJK with VF after surgery for adult spinal deformity.

SummaryCeliac disease is associated with an increased fracture risk but is not a direct input to the FRAX® calculation. When celiac disease is considered as a secondary osteoporosis risk factor or BMD is included in the FRAX assessment, FRAX accurately predicts fracture risk.IntroductionThe fracture risk assessment tool (FRAX®) uses clinical factors and bone mineral density (BMD) measurement to predict 10-year major osteoporotic (MOF) fracture probability. The study aim was to determine whether celiac disease affects MOF risk independent of FRAX score.MethodsThe Manitoba BMD Registry includes clinical data, BMD measurements, 10-year probability of MOF calculated for each individual using the Canadian FRAX tool and diagnosed celiac disease. Using linkage to population-based healthcare databases, we identified incident MOF diagnoses over the next 10 years for celiac disease and general population cohorts.ResultsCeliac disease (N = 693) was associated with increased fracture risk adjusted for FRAX score computed without secondary osteoporosis or BMD (adjusted hazard ratio [HR] 1.43, 95% confidence interval [CI] 1.11–1.86). Celiac disease was no longer a significant risk factor for fracture when secondary osteoporosis or BMD were included in the FRAX calculation (p > 0.1). In subjects with celiac disease, each SD increase in FRAX score (calculated with and without secondary osteoporosis or BMD) was associated with higher risk of incident MOF (adjusted HR 1.66 to 1.80), similar to the general population (p-interaction > 0.2). Including celiac disease as secondary osteoporosis or including BMD in FRAX 10-year MOF probability calculations (10.1% and 8.6% respectively) approximated the observed cumulative 10-year MOF probability (10.8%, 95% CI 7.8–13.9%).ConclusionsCeliac disease is associated with an increased risk of major osteoporotic fractures. When celiac disease is considered as a secondary osteoporosis risk factor or BMD is included in FRAX assessment, FRAX accurately predicts fracture risk.

Summary The role of exercise in preventing osteoporotic fractures is vague, and further recommendations for optimized exercise protocols are very rare. In the present work, we provided positive evidence for exercise effects on the number of osteoporotic fractures in adults, albeit without observing any significant relevance of intensity progression or study duration. Introduction Osteoporotic fractures are a major challenge confronting our aging society. Exercise might be an efficient agent for reducing osteoporotic fractures in older adults, but the most promising exercise protocol for that purpose has yet to be identified. The present meta-analysis thus aimed to identify important predictors of the exercise effect on osteoporotic fractures in adults. Methods We conducted a systematic search of six literature databases according to the PRISMA guideline that included controlled exercise studies and reported the number of low-trauma major osteoporotic fractures separately for exercise (EG) and control (CG) groups. Primary study outcome was incidence ratio (IR) for major osteoporotic fractures. Sub-analyses were conducted for progression of intensity (yes vs. no) during the trial and the study duration (≤ 12 months vs. > 12 months). Results In summary, 11 studies with a pooled number of 9715 participant-years in the EG and 9592 in the CG were included. The mixed-effects conditional Poisson regression revealed positive exercise effects on major osteoporotic fractures (RR: 0.75, 95% CI: 0.54–0.94, p  = .006). Although studies with intensity progression were more favorable, our subgroup analysis did not determine significant differences for diverging intensity progression ( p  = .133) or study duration ( p  = .883). Heterogeneity among the trials of the subgroups (I 2  ≤ 0–7.1%) was negligible. Conclusion The present systematic review and meta-analysis provided significant evidence for the favorable effect of exercise on major osteoporotic fractures. However, diverging study and exercise characteristics along with the close interaction of exercise parameters prevented the derivation of reliable recommendations for exercise protocols for fracture reductions. PROSPERO ID: CRD42021250467.

SummaryThere was no significant difference between the areas under receiver operating characteristics (AUROCs) and diagnostic indexes (sensitivity, specificity, positive predictive value, negative predictive value) for either major osteoporotic or hip fracture FRAX scores when comparing the unadjusted and trabecular bone score (TBS)-adjusted scores.IntroductionFRAX 10-year probability of fracture can be calculated with adjustment for the TBS. Studies have shown that TBS can improve FRAX assessments in some populations. This study aimed to determine if TBS-adjusted FRAX score is better than the unadjusted score for predicting major osteoporotic fracture (MOF) and hip fracture in Australian men.MethodsThis study involved 591 men aged 40–90 years, enrolled in the Geelong Osteoporosis Study. Incident MOF (n = 50) and hip fractures (n = 14) were ascertained using radiological reports. Median follow-up time was 9.5 years (IQR7.5–11.4). Diagnostic indexes were calculated using cut points of ≥20% for MOF and ≥3% for the hip. AUROC curves were also determined for adjusted and unadjusted scores as continuous variables.ResultsSensitivity was higher in the TBS-adjusted scores (MOF 4%, hip 78.6%) than the unadjusted scores (MOF 2%, hip 57.1%), with a decrease in specificity (MOF 98.9 vs 99.3%; hip 79.9 vs 83.9%). When considering TBS-adjusted and unadjusted FRAX as continuous scores, AUROCs were 0.738 and 0.740, respectively, for MOF and 0.849 and 0.848 for the hip.ConclusionsPrediction of fractures by MOF or hip FRAX was not substantially improved by TBS adjustment. There was no difference in AUROCs or diagnostic indexes for cut-off points of ≥20 for MOF and ≥3% for hip FRAX.

SummaryIn elderly men included in MrOS-Sweden, subclinical hyperthyroidism (SHyper) was markedly associated with increased risk of vertebral fractures.IntroductionOvert hyperthyroidism is associated with increased risk of fractures. However, only a few studies have investigated whether SHyper is associated with fracture risk in elderly men. We therefore investigated if SHyper was a risk factor for fractures in Swedish men.MethodsWe followed (median 9.8 years) elderly men (n = 1856; mean age 75, range 69–81 years) participating in the Gothenburg and Malmö subcohorts of the prospective, population-based MrOS-Sweden study. The statistical analyses included Cox proportional hazards regression. SHyper was defined as serum thyroid-stimulating hormone (TSH) < 0.45 mIU/L (n = 38).ResultsSHyper was associated with increased risk of all fractures [n = 456; hazard ratio (HR) adjusted for age, study center, and levothyroxine treatment = 1.99, 95% confidence interval (CI): 1.20–3.32], major osteoporotic fractures (MOF, n = 338; HR 2.44, 95% CI: 1.42–4.21), and vertebral fractures (n = 176; HR 3.79, 95% CI: 2.02–7.11). These associations remained after full adjustment for covariates including total hip bone mineral density and in subanalyses including only men with serum free thyroxine ≤ the upper normal limit. However, after exclusion of men receiving levothyroxine treatment, the associations with all fractures and MOF lost significance.ConclusionsIn elderly Swedish men, there was a strong association between SHyper and increased risk of vertebral fractures, whereas the associations with all incident fractures and MOF need to be confirmed in further studies.