In this meta-analysis of international cohorts, current smoking is confirmed as a significant BMD-independent predictor of future fracture with a stronger relationship in men than in women. A causative and reversible effect of smoking on fracture risk is suggested by past smoking having a significantly lower risk than current smoking. In this meta-analysis of international cohorts, the aim was to examine the relationship of current and past smoking with fracture risk to provide an update for future iterations of the FRAX tool. The risk of fracture associated with current and past smoking was estimated using an extended Poisson model applied separately to each of 58 prospective international cohort studies. Covariates included current time since start of follow up, current age, and in an additional model, BMD at the femoral neck. The results of the different studies were merged by using inverse-variance weighted β-coefficients. This analysis included a total of 1,691,024 participants (61.2

In the largest meta-analysis of international cohorts to date, a family history of fracture is confirmed as a significant BMD-independent predictor of future fracture risk. Parental and sibling histories of fracture carry the same significance for future fracture, including the impact of family hip fracture on future hip fracture risk. PURPOSE:We have undertaken a meta-analysis of international prospective cohorts to quantify the relationship between a family history of fracture and future fracture incidence. METHODS:The analysis dataset comprised 350,542 men and women from 42 cohorts in 29 countries followed for 2.8 million person-years. We investigated the relationship between family history of hip fracture or any fracture and the risk of any clinical fracture, any osteoporotic fracture, major osteoporotic fracture (MOF), and hip fracture alone using an extended Poisson model in each cohort. Models were adjusted for current age, sex, BMD, and follow-up time. RESULTS:As no difference in influence of family history of fracture was seen between genders, results are presented for men and women combined. A parental history of hip fracture was associated with a higher risk of incident fracture across all fracture outcome categories, with a stronger relationship with future hip fracture (hazard ratios (HR, 95% CI) for hip and MOF 1.37, 1.23-1.52 and 1.19, 1.12-1.27, respectively). Associations were slightly reduced but remained significant when additionally adjusted for BMD and did not vary by baseline offspring age, follow-up time, or parent affected. In a more limited analysis, parental history of any fracture or a sibling history of hip or any fracture showed similar associations to those observed with parental history of hip fracture. CONCLUSIONS:A family history of fracture is confirmed as a significant BMD-independent predictor of future fracture risk. While parental hip fracture appears the strongest factor for future hip fracture, a family history of other fractures might be appropriate for inclusion in future iterations of the FRAX tool.

FRAXplus® facilitates adjustment of FRAX® fracture probabilities for additional clinical risk factors. This study examined how FRAXplus adjustments affect the proportion of older Swedish women eligible for treatment at a major osteoporotic fracture (MOF) probability intervention threshold (IT) ≥ 26

This study examines associations between muscle mass, strength, and bone microarchitecture in 160 postmenopausal women from the OsteoPreP Study. Findings reveal that greater appendicular lean mass index (ALMI) and hand grip strength correlate with increased cortical area and trabecular vBMD, although ALMI was associated with lower cortical bone density, explained by physical activity. To investigate associations between muscle mass, strength, and bone microarchitecture in postmenopausal women. Postmenopausal women (n = 160) (mean ± standard deviation: 55.9 ± 2.6 years) were included as part of the baseline examination from the OsteoPreP Study. Appendicular lean mass (ALM) was calculated as the sum of lean mass in the upper and lower limbs obtained using dual-energy X-ray absorptiometry. Participants completed hand grip strength testing using a dynamometer. Bone microarchitecture parameters including cortical and trabecular volumetric bone mineral density (vBMD), trabecular thickness, cortical area, and porosity were analyzed by using high-resolution peripheral quantitative computed tomography (HR-pQCT) at the distal tibia and radius. Metabolic equivalents (METs) were objectively determined by accelerometer. Linear regression (unstandardised β-coefficients; p-values) analyses were performed with adjustments for confounders. Higher appendicular lean mass index (ALMI; ALM/height2 in kg/m2) was significantly associated with greater cortical area (2.55 mm2 per 1 kg/m2 increase in ALMI, p < 0.001) and greater trabecular vBMD (9.44 mg/cm3 per 1 kg/m2, p = 0.013), but with lower cortical vBMD (− 11.37 mg/cm3 per 1 kg/m2, p = 0.039) at the radius, after adjustment. Higher hand grip strength (kg) was also significantly associated with greater cortical area at the radius (0.67 mm2 per 1 kg, p = 0.001), with similar associations at the tibia. Additionally, physical activity levels (MET-hours/week) partially mediated the association between ALMI and cortical vBMD (− 2.01 mg/cm3, 95

Using data from a meta-analysis including 606,715 women, we found that the predictive value of a fall the past year for future hip fractures in women significantly decreases with age, resulting in a diminishing population attributable risk with increasing age.PurposeIn a recent meta-analysis of 40 cohorts, we demonstrated that a fall history in the past year was associated with an increased risk of hip fracture. An interaction between fall history and age was observed in women, with lower hazard ratios (HR) for older women. This study aimed to determine the population-attributable risk (PAR) for hip fracture due to increased fall risk in women of different ages.MethodsFall history associated attributable risk (AR, %) for hip fracture was calculated [100(1-1/relative risk (HR))] for women per age stratum, using previously calculated HRs. PAR (%) of hip fractures in the female population (>= 50 years) that could be prevented if the fall history-mediated risk increase could be eliminated was calculated as 100Pexp(HR-1)/[1 + Pexp(HR-1)] where Pexp was the exposed proportion of the population (i.e. the proportion with past falls).ResultsA total of 606,715 women included from 40 cohorts, with fall risk documented in the past year (fall history yes/no or 2 or more falls) and prospective information about hip fracture and death, were analysed. The proportion of fallers increased progressively with age from 24.6% at age 50-54 years to 45.5% at age 90-94 years. In contrast, the AR due to falls decreased, from 54.8% at age 50-54 years to 8.3% at age 90-94 years, and the PAR diminished with age, from 23.9% in women 50-54 years old to 3.9% in women 90-94 years old.ConclusionsAs falls become more common with age, their predictive value for future hip fractures in women significantly decreases. This suggests that the effectiveness of fall prevention strategies in reducing hip fractures is lower in older women, who are at higher risk for serious falls and hip fractures.

The relationship between rheumatoid arthritis (RA) and fracture risk was estimated in an international meta-analysis of individual-level data from 29 prospective cohorts. RA was associated with an increased fracture risk in men and women, and these data will be used to update FRAX®. RA is a well-documented risk factor for subsequent fracture that is incorporated into the FRAX algorithm. The aim of this study was to evaluate, in an international meta-analysis, the association between rheumatoid arthritis and subsequent fracture risk and its relation to sex, age, duration of follow-up, and bone mineral density (BMD) with a view to updating FRAX. The resource comprised 1,909,896 men and women, aged 20–116 years, from 29 prospective cohorts in which the prevalence of RA was 3

The aim of this international meta-analysis was to quantify the predictive value of BMI for incident fracture and relationship of this risk with age, sex, follow-up time, and BMD. A total of 1 667 922 men and women from 32 countries (63 cohorts), followed for a total of 16.0 million person-years were studied. 293 325 had FN BMD measured (2.2 million person-years follow-up). An extended Poisson model in each cohort was used to investigate relationships between WHO-defined BMI categories (Underweight: <18.5 kg/m2; Normal: 18.5-24.9 kg/m2; Overweight: 25.0-29.9 kg/m2; Obese I: 30.0-34.9 kg/m2; Obese II: ≥35.0 kg/m2) and risk of incident osteoporotic, major osteoporotic and hip fracture (HF). Inverse-variance weighted β-coefficients were used to merge the cohort-specific results. For the subset with BMD available, in models adjusted for age and follow-up time, the hazard ratio (95% CI) for HF comparing underweight with normal weight was 2.35 (2.10-2.60) in women and for men was 2.45 (1.90-3.17). Hip fracture risk was lower in overweight and obese categories compared to normal weight [obese II vs normal: women 0.66 (0.55-0.80); men 0.91 (0.66-1.26)]. Further adjustment for FN BMD T-score attenuated the increased risk associated with underweight [underweight vs normal: women 1.69 (1.47-1.96); men 1.46 (1.00-2.13)]. In these models, the protective effects of overweight and obesity were attenuated, and in both sexes, the direction of association reversed to higher fracture risk in Obese II category [Obese II vs Normal: women 1.24 (0.97-1.58); men 1.70 (1.06-2.75)]. Results were similar for other fracture outcomes. Underweight is a risk factor for fracture in both men and women regardless of adjustment for BMD. However, while overweight/obesity appeared protective in base models, they became risk factors after additional adjustment for FN BMD, particularly in the Obese II category. This effect in the highest BMI categories was of greater magnitude in men than women. These results will inform the second iteration of FRAX®.

The purpose of this study was to investigate the prevalence of three sarcopenia definitions and their associations with fracture risk in older Swedish women when adjusted for fracture risk assessment (FRAX)-based risk factors; 2,883 women with a mean age of 77.8 years were included. Sarcopenia was defined based on the Sarcopenia Definitions and Outcomes Consortium (SDOC; low handgrip strength [kg] and gait speed (m/s)), revised European Working Group on Sarcopenia in Older People (EWGSOP2; low appendicular lean mass index, appendicular lean mass [ALM]/height; kg/m2], and hand grip strength [kg]), and Asian Working Group for Sarcopenia (AWGS; low ALM (kg), and hand grip strength [kg]) definitions. Femoral neck T-score was obtained from dual-energy X-ray absorptiometry. All fractures, confirmed by X-ray or medical record review, were subsequently categorized as major osteoporotic fractures (MOFs) and hip fractures. Deaths were verified through regional registers. The total follow-up time was 6.4 ± 1.3 (mean ± SD) yr. Cox regression (hazard ratios [HR] and 95% CIs) analyses were performed with adjustment for age, FRAX variables, and femoral neck T-score. Sarcopenia prevalence was 4.5% (n = 129) according to SDOC, 12.5% (n = 360) for EWGSOP2, and 10.3% (n = 296) defined by AWGS. Individuals with sarcopenia defined by SDOC had a higher mortality risk than individuals without sarcopenia (HR: 3.41; 95% CI: 2.51, 4.62) after adjusting for age and FRAX variables. Sarcopenia according to EWGSOP2 and AWGS was not associated with an increased fracture risk after adjusting for age and FRAX variables. Individuals with sarcopenia defined by SDOC had a higher risk for any fractures (HR: 1.48; 95% CI: 1.10, 1.99) and MOF (HR: 1.42; 95% CI: 1.03, 1.98) compared with individuals without sarcopenia after adjusting for clinical risk factors used in FRAX. In conclusion, sarcopenia defined by SDOC, incorporating muscle function/strength, was the only sarcopenia definition associated with fracture risk in older women.

The 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. Previous 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). The resource comprised 906,359 women and men (66.9

Associations between different sarcopenia definitions and the risk of injurious falls were investigated in 75–80-year-old women in the Swedish SUPERB cohort. Only sarcopenia according to the Sarcopenia Definitions and Outcomes Consortium (SDOC) definition was associated with incident injurious falls with and without fractures in older women. To investigate the association between three commonly used sarcopenia definitions and the risk of injurious falls in a population of older Swedish women. A total of 2,883 75–80-year-old women with complete data on relevant sarcopenia definitions from the Swedish SUPERB cohort were studied. Sarcopenia was defined based on the Sarcopenia Definitions and Outcomes Consortium (SDOC: low handgrip strength and gait speed), revised European Working Group on Sarcopenia in Older People (EWGSOP2: low appendicular lean mass index (ALMI, dual-energy X-ray absorptiometry (DXA)-derived), appendicular lean mass (kg)/height (m2), hand grip strength (kg), or low chair stand time (s)), and Asian Working Group for Sarcopenia (AWGS: low ALMI and hand grip strength (kg) or low gait speed (m/s)). Questionnaires captured the occurrence of falls in the past 12 months. Incident injurious falls were identified using national registers. Cox regression (hazard ratios (HR) and 95

Background/Objectives: Correction of decreased diversity of the gut microbiome, which is characteristic of menopause, by supplementation with a synbiotic may attenuate or prevent dysbiosis processes and preserve bone mass. We describe the rationale and design of the OsteoPreP trial aimed at evaluating the effects of 12 months of supplementation with a synbiotic on bone and metabolic health in postmenopausal Caucasian women. Methods: This is a randomized, double-blinded, placebo-controlled trial among 160 Caucasian, postmenopausal women with no current diagnosis of osteoporosis or supplementation with pro- or prebiotics, and no medical treatment affecting bone turnover. Dual-energy X-ray absorptiometry scans will be conducted at screening to confirm absence of osteoporosis. The primary outcome is the relative change (%) in total bone mineral density of the distal tibia at 12 months post-treatment between the active and placebo groups, as determined via high-resolution peripheral quantitative computed tomography. Secondary outcomes are the effects on immune system modulation and cognition, gut microbiota composition, and musculoskeletal and metabolic functions, with particular emphasis on blood glucose regulation. Conclusions: The trial will inform on the efficacy and safety of a synbiotic containing both aerobic and anerobic bacterial strains and a prebiotic fiber on reduction in bone loss and on indices of blood glucose regulation. This trial may pave the way for an exciting field of translational research and be the underpinnings of the prevention strategy of osteoporosis and the management of metabolic dysfunction in postmenopausal women. The trial is registered with clinicaltrials.gov (NCT05348694).

Task Force on ‘Clinical Algorithms for Fracture Risk’ commissioned by the American Society for Bone and Mineral Research (ASBMR) Professional Practice Committee has recommended that FRAX® models in the US do not include adjustment for race and ethnicity. This position paper finds that an agnostic model would unfairly discriminate against the Black, Asian and Hispanic communities and recommends the retention of ethnic and race-specific FRAX models for the US, preferably with updated data on fracture and death hazards. In contrast, the use of intervention thresholds based on a fixed bone mineral density unfairly discriminates against the Black, Asian and Hispanic communities in the US. This position of the Working Group on Epidemiology and Quality of Life of the International Osteoporosis Foundation (IOF) is endorsed both by the IOF and the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO).