FRAX Probability Research Articles

Clinical and demographic factors determining patient fracture risk decision point (FRDP): The improving risk communication in osteoporosis (RICO) project.

This part of the Improving Risk Communication in Osteoporosis (RICO) study aims to understand patients' willingness to initiate osteoporosis treatment given a hypothetical fracture probability-derived from the FRAX® Risk Assessment Tool-and how age, fracture history, and numeric literacy may influence this. In 2022-2023, 332 postmenopausal women at risk of fracture were interviewed from nine countries to determine participants' Fracture Risk Decision Point (FRDP), the lowest probability of major osteoporotic fracture at which they would accept an osteoporosis medication. Participants' FRDP was evaluated given eight hypothetical 10-year FRAX scores. In countries with FRAX-based treatment thresholds, over half of the participants per country reported an FRDP that was below the threshold. Collectively, 79.2% demonstrated FRDPs at or below their respective threshold. Age and fracture history did not have a strong influence on FRDP; however, those who demonstrated higher levels of numeric literacy reported a significantly higher median FRDP (10%) compared to those who showed lower levels (5%, p < 0.001). Most patients were willing to accept an osteoporosis medication prescription at a hypothetical FRAX probability that was even lower than that of their nationally recommended treatment threshold. Literacy scores had a significant influence on FRDP whereas age and fracture history did not.

Prevalence of HIV-associated osteoporosis and fracture risk in midlife women: a cross-sectional study in Zimbabwe.

Antiretroviral therapy roll-out has dramatically reduced HIV-related mortality; more women are living to reach menopause. Menopausal estrogen loss causes bone loss, as does HIV and some of its treatments. However, data describing HIV's impact on osteoporosis prevalence and fracture risk are scarce in southern Africa. A cross-sectional study of women aged 40-60years (49% women with HIV [WLH]) was conducted in Harare, Zimbabwe. Menopause, fracture, and HIV history were collected, and anthropometry and BMD (by DXA) measured, and FRAX 10-year fracture probabilities quantified. The FRAX probability of a major osteoporotic fracture (MOF) included HIV as a risk factor for secondary osteoporosis. Linear and Poisson regression determined the relationships between clinical risk factors and both femoral neck (FN) BMD and the 10-year FRAX probability of MOF respectively. The 393 participants had a mean (SD) age of 49.6 (5.8) years and mean (SD) BMI of 29.1 (6.0) kg/m2. 95% of WLH were antiretroviral therapy (ART) established (85% tenofovir disoproxil fumarate) and 81% had a viral load <50 copies/mL. A BMD T-score ≤ -2.5 was more common in WLH than those without, at both FN and lumbar spine (LS) (FN, 22 [11.4%] vs 5 [2.5%]; LS, 40 [20.8%] vs 9 [4.5%], respectively). Prior fracture was more prevalent in WLH: any fracture type (27 [14%] vs 14 [7%]); MOF (14 [7.3%] vs 5 [2.5%]). WLH had a higher 10-year MOF probability (median, 1.2%; IQR, 0.9-1.8) compared with those without HIV (1.0%; IQR, 0.9-1.5) (p < .001), although probabilities were low. Older age, low weight, and HIV infection were strongly associated with lower FN BMD. Higher probability of MOF was associated with older age, HIV infection, parental hip fracture and prior fracture, although adjustment attenuated the association with HIV. No woman reported anti-osteoporosis medication use. While osteoporosis and previous fractures were common and untreated in this relatively young population, particularly in WLH, the FRAX-predicted 10-year MOF risk was low. Clinical risk factors considered in fracture risk prediction tools in Zimbabwe may need contextual modification.

Clinical Use of Trabecular Bone Score: The 2023 ISCD Official Positions

Osteoporosis can currently be diagnosed by applying the WHO classification to bone mineral density (BMD) assessed by dual-energy x-ray absorptiometry (DXA). However, skeletal factors other than BMD contribute to bone strength and fracture risk. Lumbar spine TBS, a grey-level texture measure which is derived from DXA images has been extensively studied, enhances fracture prediction independent of BMD and can be used to adjust fracture probability from FRAX® to improve risk stratification. The purpose of this International Society for Clinical Densitometry task force was to review the existing evidence and develop recommendations to assist clinicians regarding when and how to perform, report and utilize TBS. Our review concluded that TBS is most likely to alter clinical management in patients aged ≥ 40 years who are close to the pharmacologic intervention threshold by FRAX. The TBS value from L1-L4 vertebral levels, without vertebral exclusions, should be used to calculate adjusted FRAX probabilities. L1-L4 vertebral levels can be used in the presence of degenerative changes and lumbar compression fractures. It is recommended not to report TBS if extreme structural or pathological artifacts are present. Monitoring and reporting TBS change is unlikely to be helpful with the current version of the TBS algorithm. The next version of TBS software will include an adjustment based upon directly measured tissue thickness. This is expected to improve performance and address some of the technical factors that affect the current algorithm which may require modifications to these Official Positions as experience is acquired with this new algorithm.

Effect of BMI-Discordant Abdominal Tissue Thickness on Fracture Probability: A Registry-Based Study.

FRAX, which is used to assess fracture probability, considers body mass index (BMI), but BMI may not reflect individual variation in body composition and distribution. We examined the effect of BMI-discordant abdominal thickness on FRAX-derived fracture probability for major osteoporotic fracture (MOF) and hip fracture. We studied 73,105 individuals, mean age 64.2 years. During mean 8.7 years, 7048 (9.6%) individuals sustained incident MOF, including 2155 (3.0%) hip fractures. We defined abdominal thickness index (ATI) as the difference between abdominal thickness measured by dual-energy X-ray absorptiometry (DXA) and thickness predicted by BMI using sex-stratified regression. ATI was categorized from lower (<-2 cm, -2 to -1 cm) to higher (1-2 cm, >+2 cm) with referent around zero (-1 to +1 cm). Adjusted for FRAX probability, increasing ATI was associated with incident MOF and hip fracture (p < 0.001). For the highest ATI category, MOF risk was increased (hazard ratio [HR] = 1.23, 95% confidence interval [CI] 1.12-1.35) independent of FRAX probability. Similar findings were noted for hip fracture probability (HR = 1.28, 95% CI 1.09-1.51). There was significant age-interaction with much larger effects before age 65 years (HR = 1.44, 95% CI 1.23-1.69 for MOF; 2.29, 95% CI 1.65-3.18 for hip fracture). In contrast, for the subset of individuals with diabetes, there was also increased risk for those in the lowest ATI category (HR = 1.73, 95% CI 1.12-2.65 for MOF; 2.81, 95% CI 1.59-4.97 for hip fracture). Calibration plots across ATI categories demonstrated deviation from the line of identity in women (calibration slope 2.26 for MOF, 2.83 for hip fracture). An effect of ATI was not found in men, but this was inconclusive as the sex-interaction terms did not show significant effect modification. In conclusion, these data support the need to investigate increased abdominal thickness beyond that predicted by BMI and sex as a FRAX-independent risk factor for fracture. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

The Fracture Risk Assessment Tool Probability and Trabecular Bone Score Mediate the Relationship between Sphingosine 1-phosphate Levels and Fracture Risk

Background: The sphingosine 1-phosphate (S1P) concentration is a potential biomarker of osteoporotic fracture and is associated with both the fracture risk assessment tool (FRAX) probability and trabecular bone score (TBS), which are well-known predictors of fracture. We sought to estimate the effect of the S1P concentration on fracture risk using the FRAX probability and TBS as mediators.Methods: Plasma S1P concentrations, FRAX variables, and TBSs were measured in 66 postmenopausal women with fractures and 273 postmenopausal women without fractures. Associations between S1P concentration, FRAX probability, TBS, and fracture risk were analyzed using correlation, logistic regression, and mediation analyses.Results: Subjects in the highest S1P concentration tertile had a higher fracture risk (odds ratio [OR], 5.09; 95% confidence interval [CI], 2.22–11.67) than those in the lowest S1P concentration tertile before adjustment. Subjects in the highest FRAX probability tertile had a higher fracture risk (OR, 14.59; 95% CI, 5.01–42.53) than those in the lowest FRAX probability tertile before adjustment. Subjects in the lowest TBS tertile had a higher fracture risk (OR, 4.76; 95% CI, 2.28–9.93) than those in the highest TBS tertile before adjustment. After adjustment for FRAX probability and TBS, the highest S1P concentration tertile was still associated with a higher fracture risk (OR, 3.13; 95% CI, 1.28–7.66). The FRAX probability and TBS accounted for 32.6% and 21.7%, respectively, of the relationship between the S1P concentration and fracture risk.Conclusions: The relationship between the circulating S1P concentration and fracture risk was partly mediated by the FRAX probability, bone microarchitecture, and other factors.

FRAX Adjustment by Trabecular Bone Score with or Without Bone Mineral Density: The Manitoba BMD Registry

Trabecular bone score (TBS), a texture measure derived from spine dual-energy x-ray absorptiometry (DXA) images, is a FRAX®-independent risk factor for fracture. The TBS adjustment to FRAX assumes the presence of femoral neck BMD in the calculation. However, there are many individuals in whom hip DXA cannot be acquired. Whether the TBS-adjustment would apply to FRAX probabilities calculated without BMD has not been studied. The current analysis was performed to evaluate major osteoporotic fracture (MOF) and hip fracture risk adjusted for FRAX with and without femoral neck BMD. The study cohort consisted of 71,209 individuals (89.8% female, mean age 64.0 years). During mean follow-up 8.7 years, 6743 (9.5%) individuals sustained one or more incident MOF, of which 2037 (2.9%) sustained a hip fracture. Lower TBS was significantly associated with increased fracture risk when adjusted for FRAX probabilities, with a slightly larger effect when BMD was not included. Inclusion of TBS in the risk calculation gave a small but significant increase in stratification for fracture probabilities estimated with and without BMD. Calibration plots showed very minor deviations from the line of identity, indicating overall good calibration. In conclusion, the existing equations for incorporating TBS in FRAX estimates of fracture probability work similarly when femoral neck BMD is not used in the calculation. This potentially extends the range of situations where TBS can be used clinically to those individuals in whom lumbar spine TBS is available but femoral neck BMD is not available.

Greater pQCT Calf Muscle Density Is Associated with Lower Fracture Risk, Independent of FRAX, Falls and BMD: A Meta-Analysis in the Osteoporotic Fractures in Men (MrOS) Study.

We investigated the predictive performance of peripheral quantitative computed tomography (pQCT) measures of both calf muscle density (an established surrogate for muscle adiposity, with higher values indicating lower muscle adiposity and higher muscle quality) and size (cross-sectional area [CSA]) for incident fracture. pQCT (Stratec XCT2000/3000) measurements at the tibia were undertaken in Osteoporotic Fractures in Men (MrOS) United States (US), Hong Kong (HK), and Swedish (SW) cohorts. Analyses were by cohort and synthesized by meta-analysis. The predictive value for incident fracture outcomes, illustrated here for hip fracture (HF), using an extension of Poisson regression adjusted for age and follow-up time, was expressed as hazard ratio (HR) per standard deviation (SD) increase in exposure (HR/SD). Further analyses adjusted for femoral neck (fn) bone mineral density (BMD) T-score, Fracture Risk Assessment Tool (FRAX) 10-year fracture probability (major osteoporotic fracture) and prior falls. We studied 991 (US), 1662 (HK), and 1521 (SW) men, mean ± SD age 77.0 ± 5.1, 73.9 ± 4.9, 80 ± 3.4 years, followed for a mean ± SD 7.8 ± 2.2, 8.1 ± 2.3, 5.3 ± 2.0 years, with 31, 47, and 78 incident HFs, respectively. Both greater muscle CSA and greater muscle density were associated with a lower risk of incident HF [HR/SD: 0.84; 95% confidence interval [CI], 0.72-1.0 and 0.78; 95% CI, 0.66-0.91, respectively]. The pattern of associations was not materially changed by adjustment for prior falls or FRAX probability. In contrast, after inclusion of fn BMD T-score, the association for muscle CSA was no longer apparent (1.04; 95% CI, 0.88-1.24), whereas that for muscle density was not materially changed (0.69; 95% CI, 0.59-0.82). Findings were similar for osteoporotic fractures. pQCT measures of greater calf muscle density and CSA were both associated with lower incidence of fractures in older men, but only muscle density remained an independent risk factor for fracture after accounting for fn BMD. These findings demonstrate a complex interplay between measures of bone, muscle size, and quality, in determining fracture risk. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Adjusting conventional FRAX estimates of fracture probability according to the number of prior fractures.

Prior fractures increase subsequent fracture risk. The aim of this study was to quantify the effect of the number of prior fractures on the 10-year probability of fracture determined with FRAX®. The study used data from the Reykjavik Study fracture register that documented prospectively all fractures at all skeletal sites in a large sample of the population of Iceland. Ten-year probabilities of hip fracture and major osteoporotic fracture (MOF) were determined according to the number of prior osteoporotic fractures over a 20-year interval from the hazards of death and fracture. Fracture probabilities were also computed for a prior osteoporotic fracture irrespective of the number of previous fractures. The probability ratios provided adjustments to conventional FRAX estimates of fracture probability according to the number of prior fractures. Probability ratios to adjust 10-year FRAX probabilities of a hip fracture and MOF increased with the number of prior fractures but decreased with age in both men and women. Probability ratios were similar in men and women and for hip fracture and MOF. Mean probability ratios according to the number of prior fractures for all scenarios were 0.95, 1.08, 1.21 and 1.35, for 1,2, 3 and 4 or more prior fractures, respectively. Thus, a simple rule of thumb is to downward adjust FRAX-based fracture probabilities by 5% in the presence of a single prior fracture and to uplift probabilities by 10, 20 and 30% with a history of 2, 3 and 4 or more prior fractures, respectively. The probability ratios provide adjustments to conventional FRAX estimates of fracture probability according to the number of prior fractures.

Menopausal hormone therapy reduces the risk of fracture regardless of falls risk or baseline FRAX probability—results from the Women’s Health Initiative hormone therapy trials

SummaryIn a combined analysis of 25,389 postmenopausal women aged 50–79 years, enrolled in the two Women’s Health Initiative hormone therapy trials, menopausal hormone therapy vs. placebo reduced the risk of fracture regardless of baseline FRAX fracture probability and falls history.IntroductionThe aim of this study was to determine if the anti-fracture efficacy of menopausal hormone therapy (MHT) differed by baseline falls history or fracture risk probability as estimated by FRAX, in a combined analysis of the two Women’s Health Initiative (WHI) hormone therapy trials.MethodsA total of 25,389 postmenopausal women aged 50–79 years were randomized to receive MHT (n = 12,739) or matching placebo (n = 12,650). At baseline, questionnaires were used to collect information on falls history, within the last 12 months, and clinical risk factors. FRAX 10-year probability of major osteoporotic fracture (MOF) was calculated without BMD. Incident clinical fractures were verified using medical records. An extension of Poisson regression was used to investigate the relationship between treatment and fractures in (1) the whole cohort; (2) those with prior falls; and (3) those without prior falls. The effect of baseline FRAX probability on efficacy was investigated in the whole cohort.ResultsOver 4.3 ± 2.1 years (mean ± SD), MHT (vs. placebo) significantly reduced the risk of any clinical fracture (hazard ratio [HR] 0.72 [95% CI, 0.65–0.78]), MOF (HR 0.60 [95% CI, 0.53–0.69]), and hip fracture (0.66 [95% CI, 0.45–0.96]). Treatment was effective in reducing the risk of any clinical fracture, MOF, and hip fracture in women regardless of baseline FRAX MOF probability, with no evidence of an interaction between MHT and FRAX (p > 0.30). Similarly, there was no interaction (p > 0.30) between MHT and prior falls.ConclusionIn the combined WHI trials, compared to placebo, MHT reduces fracture risk regardless of FRAX probability and falls history in postmenopausal women.

FREM predicts 10-year incident fracture risk independent of FRAX® probability: a registry-based cohort study.

FREM was developed from Danish public health registers without DXA information to identify high imminent risk of major osteoporotic fracture (MOF) and hip fracture (HF), while FRAX® estimates 10-year fracture probability from clinical risk factors and femoral neck bone mineral density (BMD) from DXA. The FREM algorithm showed significant 1- and 2-year fracture risk stratification when applied to a clinical population from Manitoba, Canada. We examined whether FREM predicts 10-year fracture risk independent of 10-year FRAX probability computed with BMD. Using the Manitoba BMD Program registry, we identified women and men aged ≥ 45years undergoing baseline BMD assessment. We calculated FREM and FRAX scores, and identified incident fractures over 10years. Hazard ratios (HRs) for incident fracture were estimated according to FREM quintile, adjusted for FRAX probability. We compared predicted with observed 10-year cumulative fracture probability estimated with competing mortality. The study population comprised 74,446 women, mean age 65.2years; 7945 men, mean age 67.5years. There were 7957 and 646 incident MOF and 2554 and 294 incident HF in women and men, respectively. Higher FREM scores were associated with increased risk for MOF (highest vs middle quintile HRs 1.49 women, 2.06 men) and HF (highest vs middle quintile HRs 2.15 women, 2.20 men) even when adjusted for FRAX. Greater mortality with higher FREM scores attenuated its effect on 10-year fracture probability. In the highest FREM quintile, observed slightly exceeded predicted 10-year probability for MOF (ratios 1.05 in women, 1.49 in men) and HF (ratios 1.29 in women, 1.34 in men). Higher FREM scores identified women and men at increased fracture risk even when adjusted for FRAX probability that included BMD; hence, FREM provides additional predictive information to FRAX. FRAX slightly underestimated 10-year fracture probability in those falling within the highest FREM quintile.

Validation of the Taiwan FRAX® calculator for the prediction of fracture risk.

FRAX® is an algorithm used to calculate fracture probabilities based on clinical risk factors (CRFs) and bone mineral density (BMD). The country-specific Taiwan FRAX calculator has not been validated since its establishment in 2010. The aim of the present study is to evaluate the predictive performance of the Taiwan FRAX calculator using longitudinal fracture data. A total of 1975 subjects, aged ≧ 40years old, from Yunlin and Tianliao cohorts in Taiwan during the period 2009-2010, were identified and completely connected with the 2008-2016 National Health Insurance Research Database. During the average 6.8 ± 1.1years of follow-up, 160 incident major osteoporotic fractures (MOFs) were identified. The predictive ability assessing based on the observed to expected fractures (O/E) ratio calculated with the FRAX probability adjusted for 6.8years were 1.19 (95%CI 1.02-1.39) for MOF, and 1.07 (95%CI 0.82-1.39) for hip fractures. In the discriminative statistics, the AUC for prediction of major osteoporotic fractures using FRAX was 0.75 without and 0.77 with BMD (AUC for hip fracture was 0.75 without and 0.77 with BMD). The optimal cutoff value was 9.5% of the FRAX score with BMD for all major osteoporotic fractures, with good sensitivity (76.9%) and specificity (65.3%). For hip fractures, the optimal cutoff point for the FRAX probability with BMD was 4.0%, and the sensitivity and specificity were 74.4% and 68.3%, respectively. The Taiwan FRAX® calculator was validated to predict incident fractures preliminarily. Cutoffs are proposed for predicting fracture risk in Taiwanese individuals.

High Alcohol Intake in Older Men and the Probability of Osteoporotic Fracture According to the FRAX Algorithm.

We aimed to determine the contribution of high alcohol intake to fracture probability, calculated using a fracture-risk assessment tool (FRAX). Participants were 262 men (ages 60–90 y) in the Geelong Osteoporosis Study. Alcohol consumption was documented via a food frequency questionnaire; 46 (17.6%) consumed three or more units per day, fulfilling the criterion for high alcohol intake. Bone mineral density (BMD) was measured by dual energy x-ray absorptiometry. We determined FRAX probabilities (%) for major osteoporotic fracture (MOF) and hip fracture (HF), calculated with and without alcohol intake. Thresholds for high FRAX probabilities, calculated with or without BMD, were ≥20% for MOF and ≥3% for HF. Proportions of men with high HF-FRAX probabilities were consistently greater for drinkers compared with non-drinkers. For drinkers, paired differences showed that median MOF-FRAXwithoutBMD probabilities calculated with and without alcohol changed by −2.3, HF-FRAXwithoutBMD by −1.7, MOF-FRAXwithBMD by −1.4, and HF-FRAXwithBMD by −0.9 (all p < 0.001). We estimated that, should drinkers lower their alcohol consumption to <3 units/d, up to 66.7% of those at high risk for MOF and up to 41.0% at high risk for HF would reduce their FRAX probabilities to below the thresholds for high fracture risk. In the context of the Australian environment, these data describe the extent to which older men with high alcohol consumption are at increased risk for fracture.

FRAX-based intervention thresholds for Pakistan.

The fracture risk assessment algorithm FRAX® has been recently calibrated for Pakistan, but guidance is needed on how to apply fracture probabilities to clinical practice. The age-specific 10-year probabilities of a major osteoporotic fracture were calculated in women with average BMI to determine fracture probabilities at two potential intervention thresholds. The first comprised the age-specific fracture probabilities associated with a femoral neck T-score of - 2.5. The second approach determined age-specific fracture probabilities that were equivalent to a woman with a prior fragility fracture, without bone mineral density (BMD). The parsimonious use of BMD was additionally explored by the computation of upper and lower assessment thresholds for BMD testing. When a BMD T-score ≤ - 2.5 was used as an intervention threshold, FRAX probabilities in women aged 50years were approximately two-fold higher than in women of the same age but with no risk factors and average BMD. The relative increase in risk associated with the BMD threshold decreased progressively with age such that, at the age of 80years or more, a T-score of - 2.5 was actually protective. The 10-year probability of a major osteoporotic fracture by age, equivalent to women with a previous fracture, rose with age from 2.1% at the age of 40years to 17%, at the age of 90years, and identified women at increased risk at all ages. Intervention thresholds based on BMD alone do not effectively target women at high fracture risk, particularly in the elderly. In contrast, intervention thresholds based on fracture probabilities equivalent to a 'fracture threshold' target women at high fracture risk.

The effects of falls on the prediction of osteoporotic fractures: epidemiological cohort study.

The Fracture Risk Assessment Tool (FRAX) calculates 10-year fracture risk using 11 clinical risk factors and bone mineral density (BMD); however, it does not include fall history in its risk assessment. Here, we investigated whether fall history is an independent risk factor on fracture prediction after adjustment of FRAX scores in two age subgroups (40-75 and ≥ 75years). Beginning in 2009 to 2010, 1975 people (914 men) from Taiwan were followed for 6.8 ± 1.1years by matching them with their records in the 2008-2016 National Health Insurance databank. We validated FRAX predictive accuracy with or without fall history by Cox proportional hazards regression. After adjusting for FRAX risk, a history of falling was still a significant predictor of major osteoporotic fractures (MOFs) (using BMD, hazard ratio [HR], 1.47; p = 0.03; without using BMD, HR, 1.54; p = 0.01). A history of recurrent falls was also a significant predictor of both incident MOFs and hip fractures. However, when the subjects were stratified based on age group, a history of falling and recurrent falls were strong predictors of MOFs and hip fractures in the younger but not the older subgroup. A fall history can predict incident fracture independently of FRAX probability, particularly in subjects younger than 75years old.

Impact of population-based or targeted BMD interventions on fracture incidence.

To investigate the impact of population level or targeted alterations to BMD on the incidence of fractures. We used a simulated cohort of 49,242 women with age and body mass index distribution from the UK, and prevalence of other clinical risk factors based on European FRAX® cohorts. Using FRAX probabilities of major osteoporotic fracture (MOF: hip, clinical vertebral, distal forearm, proximal humerus) and hip fracture, calculated with femoral neck BMD, we determined the expected number of fractures over 10 years, stratified by 10-year age band from 50 years. We then investigated the effect of (i) uplifting all individuals with T-score below -2.5 to be exactly -2.5 (high-risk strategy) and (ii) shifting the entire BMD distribution upwards (population strategy). Overall, the high-risk strategy prevented 573 MOF including 465 hip fractures. Moving the BMD T-score distribution upward by 0.27SD gave an equivalent reduction in numbers of MOF; for hip fractures prevented, this was 0.35SD. A global upward 0.25SD BMD shift prevented 524 MOF including 354 hip fractures, with corresponding figures for an increase of 0.5SD being 973 MOF prevented and 640 hip fractures prevented. The ratio of hip fracture to MOF prevented differed by the two approaches, such that for the high-risk strategy, the ratio was 0.81, and for the population strategy was 0.68 (0.25SD BMD uplift) and 0.66 (0.5SD BMD uplift). The numbers of fractures prevented by the high-risk strategy increased with age. In contrast, the age-related increase in numbers of fractures prevented with the population strategy rose with age, but peaked in the 70-79-year age band and declined thereafter. Both strategies reduced the numbers of expected incident fractures, with contrasting relative impacts by age and fracture site. Whilst the current analysis used UK/European anthropometric/risk factor distributions, further analyses calibrated to the distributions in other settings globally may be readily undertaken. Overall, these findings support the investigation of both population level interventions and those targeted at high fracture risk groups.

FRAX-based fracture probabilities in South Africa

SummaryThe hip fracture rates in South Africa were used to create ethnic-specific FRAX® models to facilitate fracture risk assessment.IntroductionThe aim of this study was to develop FRAX models to compute the 10-year probability of hip fracture and major osteoporotic fracture and assess their potential clinical application.MethodsAge- and sex-specific incidence of hip fracture and national mortality rates were incorporated into a FRAX model for the White, Black African, Coloured and Indian population of South Africa. Age-specific 10-year probabilities of a major osteoporotic fracture were calculated in women to determine fracture probabilities at a femoral neck T score of -2.5 SD, or those equivalent to a woman with a prior fragility fracture. Fracture probabilities were compared with those from selected countries.ResultsProbabilities were consistently higher in Indian than in Coloured men and women, in turn, higher than in Black South Africans. For White South Africans, probabilities were lower than in Indians at young ages up to the age of about 80 years. When a BMD T score of −2.5 SD was used as an intervention threshold, FRAX probabilities in women age 50 years were approximately 2-fold higher than in women of the same age but with an average BMD and no risk factors. The increment in risk associated with the BMD threshold decreased progressively with age such that, at the age of 80 years or more, a T score of −2.5 SD was no longer a risk factor. Probabilities equivalent to women with a previous fracture rose with age and identified women at increased risk at all ages.ConclusionsThese FRAX models should enhance accuracy of determining fracture probability amongst the South African population and help guide decisions about treatment.

A Statistical Approach Regarding the Diagnosis of Osteoporosis and Osteopenia From DXA: Are We Underdiagnosing Osteoporosis?

ABSTRACTOsteoporosis and osteopenia are diagnosed most commonly by evaluating the lowest T‐score of BMD measurements, typically taken at three sites: the L1‐L4 lumbar spine, femoral neck, and total hip. This study aimed to evaluate the effect of using all three BMD measurements and multivariate statistical theory to evaluate how the diagnoses of osteoporosis and osteopenia change in simulation studies and in real data. First, it was found that the T‐scores from these three BMD measurements rarely give concordant diagnoses using the same World Health Organization (WHO) and International Society for Clinical Densitometry (ISCD) guidelines, so that the diagnosis strongly depends on the BMD sites measured. Next, strong correlations were found between the BMD measurements at different sites within the same person, which resulted in increased congruence/concordance between the diagnoses obtained from the BMD T‐scores. Multivariate statistical theory was used to show that the joint distribution of the BMD T‐scores at different sites follows a multivariate t distribution and found that the marginal distribution of any BMD T‐score follows a univariate t distribution. Confidence ellipsoids were derived that are equivalent to the univariate WHO/ISCD thresholds for osteoporosis (T‐score ≤−2.5) and osteopenia (−2.5 < T‐score <−1). The study found that more patients are diagnosed with osteoporosis using the multivariate version of the WHO/ISCD guidelines rather than the current WHO/ISCD guidelines in both real data and simulation studies. Diagnoses of osteoporosis using the statistics derived method were also associated with higher FRAX (fracture risk assessment tool) probabilities of major osteoporotic (p = 0.001) and hip fractures (p = 2.2 × 10−6). In conclusion, this study shows that considering all three BMD T‐scores is potentially more informative than using the single lowest BMD T‐score. © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.

Predictive Value of DXA Appendicular Lean Mass for Incident Fractures, Falls, and Mortality, Independent of Prior Falls, FRAX, and BMD: Findings from the Women's Health Initiative (WHI).

ABSTRACTIn the Women's Health Initiative (WHI), we investigated associations between baseline dual‐energy X‐ray absorptiometry (DXA) appendicular lean mass (ALM) and risk of incident fractures, falls, and mortality (separately for each outcome) among older postmenopausal women, accounting for bone mineral density (BMD), prior falls, and Fracture Risk Assessment Tool (FRAX®) probability. The WHI is a prospective study of postmenopausal women undertaken at 40 US sites. We used an extension of Poisson regression to investigate the relationship between baseline ALM (corrected for height2) and incident fracture outcomes, presented here for major osteoporotic fracture (MOF: hip, clinical vertebral, forearm, or proximal humerus), falls, and death. Associations were adjusted for age, time since baseline and randomization group, or additionally for femoral neck (FN) BMD, prior falls, or FRAX probability (MOF without BMD) and are reported as gradient of risk (GR: hazard ratio for first incident fracture per SD increment) in ALM/height2 (GR). Data were available for 11,187 women (mean [SD] age 63.3 [7.4] years). In the base models (adjusted for age, follow‐up time, and randomization group), greater ALM/height2 was associated with lower risk of incident MOF (GR = 0.88; 95% confidence interval [CI] 0.83–0.94). The association was independent of prior falls but was attenuated by FRAX probability. Adjustment for FN BMD T‐score led to attenuation and inversion of the risk relationship (GR = 1.06; 95% CI 0.98–1.14). There were no associations between ALM/height2 and incident falls. However, there was a 7% to 15% increase in risk of death during follow‐up for each SD greater ALM/height2, depending on specific adjustment. In WHI, and consistent with our findings in older men (Osteoporotic Fractures in Men [MrOS] study cohorts), the predictive value of DXA‐ALM for future clinical fracture is attenuated (and potentially inverted) after adjustment for femoral neck BMD T‐score. However, intriguing positive, but modest, associations between ALM/height2 and mortality remain robust. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Association Between Muscle Mass Determined by D3 -Creatine Dilution and Incident Fractures in a Prospective Cohort Study of Older Men.

The relation between a novel measure of total skeletal muscle mass (assessed by D3 -creatine dilution [D3 Cr]) and incident fracture is unknown. In 1363 men (mean age 84.2 years), we determined D3 Cr muscle mass; Fracture Risk Assessment Tool (FRAX) 10-year probability of hip and major osteoporotic (hip, humerus, vertebral, forearm) fracture; and femoral neck bone mineral density (BMD) (by dual-energy X-ray absorptiometry [DXA]). Incident fractures were centrally adjudicated by review of radiology reports over 4.6 years. Correlations adjusted for weight and height were calculated between femoral neck BMD and D3 Cr muscle mass. Across quartiles of D3 Cr muscle mass/weight, proportional hazards models calculated hazard ratios (HRs) for any (n=180); nonspine (n=153); major osteoporotic fracture (n=85); and hip fracture (n=40) after adjustment for age, femoral neck BMD, recurrent fall history, and FRAX probability. Models were then adjusted to evaluate the mediating influence of physical performance (walking speed, chair stands, and grip strength). D3 Cr muscle mass was weakly correlated with femoral BMD (r=0.10, p < 0.001). Compared to men in the highest quartile, those in the lowest quartile of D3 Cr muscle mass/weight had an increased risk of any clinical fracture (HR 1.8; 95% confidence interval [CI], 1.1-2.8); nonspine fracture (HR 1.8; 95% CI, 1.1-3.0), major osteoporotic fracture (HR 2.3; 95% CI, 1.2-4.6), and hip fracture (HR 5.9; 95% CI, 1.6-21.1). Results were attenuated after adjustment for physical performance, but associations remained borderline significant for hip and major osteoporotic fractures (p ≥ 0.05 to 0.10). Low D3 Cr muscle mass/weight is associated with a markedly high risk of hip and potentially other fractures in older men; this association is partially mediated by physical performance. © 2022 American Society for Bone and Mineral Research (ASBMR).

Sarcopenia Definitions as Predictors of Fracture Risk Independent of FRAX® , Falls, and BMD in the Osteoporotic Fractures in Men (MrOS) Study: A Meta-Analysis.

Dual-energy X-ray absorptiometry (DXA)-derived appendicular lean mass/height2 (ALM/ht2 ) is the most commonly used estimate of muscle mass in the assessment of sarcopenia, but its predictive value for fracture is substantially attenuated by femoral neck (fn) bone mineral density (BMD). We investigated predictive value of 11 sarcopenia definitions for incident fracture, independent of fnBMD, fracture risk assessment tool (FRAX® ) probability, and prior falls, using an extension of Poisson regression in US, Sweden, and Hong Kong Osteoporois Fractures in Men Study (MrOS) cohorts. Definitions tested were those of Baumgartner and Delmonico (ALM/ht2 only), Morley, the International Working Group on Sarcopenia, European Working Group on Sarcopenia in Older People (EWGSOP1 and 2), Asian Working Group on Sarcopenia, Foundation for the National Institutes of Health (FNIH) 1 and 2 (using ALM/body mass index [BMI], incorporating muscle strength and/or physical performance measures plus ALM/ht2 ), and Sarcopenia Definitions and Outcomes Consortium (gait speed and grip strength). Associations were adjusted for age and time since baseline and reported as hazard ratio (HR) for first incident fracture, here major osteoporotic fracture (MOF; clinical vertebral, hip, distal forearm, proximal humerus). Further analyses adjusted additionally for FRAX-MOF probability (n=7531; calculated ± fnBMD), prior falls (y/n), or fnBMD T-score. Results were synthesized by meta-analysis. In 5660 men in USA, 2764 Sweden and 1987 Hong Kong (mean ages 73.5, 75.4, and 72.4 years, respectively), sarcopenia prevalence ranged from 0.5% to 35%. Sarcopenia status, by all definitions except those of FNIH, was associated with incident MOF (HR=1.39 to 2.07). Associations were robust to adjustment for prior falls or FRAX probability (without fnBMD); adjustment for fnBMD T-score attenuated associations. EWGSOP2 severe sarcopenia (incorporating chair stand time, gait speed, and grip strength plus ALM) was most predictive, albeit at low prevalence, and appeared only modestly influenced by inclusion of fnBMD. In conclusion, the predictive value for fracture of sarcopenia definitions based on ALM is reduced by adjustment for fnBMD but strengthened by additional inclusion of physical performance measures. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).