Repurposing a fracture risk calculator (FRAX) as a screening tool for women at risk for sarcopenia.

Osteoporosis and sarcopenia share risk profiles, so we tested a fracture risk assessment tool (FRAX) as a screening tool for sarcopenia. FRAX probabilities without bone mineral density predicted sarcopenia with high sensitivity and reasonable specificity. There is potential to use this FRAX as a screening tool for sarcopenia. PURPOSE: There is a need for simple screening tools for sarcopenia. As osteoporosis and sarcopenia share risk profiles, we tested the performance of a fracture risk assessment tool for discriminating individuals at risk for sarcopenia. METHODS: In this longitudinal study, FRAX (Australia) probabilities were calculated for 354 women (ages 40-90 years) in the Geelong Osteoporosis Study. Sarcopenia was assessed a decade later using DXA-derived low appendicular lean mass (Lunar; ALM/height2 < 5.5 kg/m2) and low handgrip strength (Jamar; HGS < 16 kg), according to EWGSOP2. We determined FRAX probabilities (%) for hip fracture (HF-FRAX) and major osteoporotic fracture (MOF-FRAX), with and without BMD. Area under the receiver operator characteristic (AUROC) curves quantified the performance of FRAX for predicting sarcopenia. RESULTS: Baseline median (IQR) values for HF-FRAX without BMD were 0.4 (0.1-1.3) and for MOF-FRAX without BMD, 2.4 (1.2-5.2); comparable figures for HF-FRAX with BMD were 0.2 (0.0-0.7) and for MOF-FRAX with BMD, 2.1 (1.1-4.4). At follow-up, sarcopenia was identified for 11 (3.1%) women. When FRAX was calculated without BMD, the AUROC was 0.90 for HF-FRAX and 0.88 for MOF-FRAX. Optimal thresholds were 0.9 for HF-FRAX (sensitivity 90.9%, specificity 62.4%) and 5.3 for MOF-FRAX (sensitivity 81.8%, specificity 71.7%). Calculating FRAX with BMD did not improve the predictive performance of FRAX for sarcopenia. CONCLUSION: Here we provide preliminary evidence to suggest that FRAX probabilities without BMD might predict sarcopenia with high sensitivity and reasonable specificity. Given that FRAX clinical risk factors are identified without equipment, there is potential to use this or a modified version of the FRAX tool to screen for individuals at risk of sarcopenia.

How well do the FRAX (Australia) and Garvan calculators predict incident fractures? Data from the Geelong Osteoporosis Study.

This study reports that both FRAX and Garvan calculators underestimated fractures in Australian men and women, particularly in those with osteopenia or osteoporosis. Major osteoporotic fractures were poorly predicted, while both calculators performed acceptably well for hip fractures. INTRODUCTION: This study assessed the ability of the FRAX (Australia) and Garvan calculators to predict fractures in Australian women and men. METHODS: Women (n = 809) and men (n = 821) aged 50-90 years, enrolled in the Geelong Osteoporosis Study, were included. Fracture risk was estimated using FRAX and Garvan calculators with and without femoral neck bone mineral density (BMD) (FRAXBMD, FRAXnoBMD, GarvanBMD, GarvannoBMD). Incident major osteoporotic (MOF), fragility, and hip fractures over the following 10 years were verified radiologically. Differences between observed and predicted numbers of fractures were assessed using a chi-squared test. Diagnostics indexes were calculated. RESULTS: In women, 115 MOF, 184 fragility, and 42 hip fractures occurred. For men, there were 73, 109, and 17 fractures, respectively. FRAX underestimated MOFs, regardless of sex or inclusion of BMD. FRAX accurately predicted hip fractures, except in women with BMD (20 predicted, p = 0.004). Garvan underestimated fragility fractures except in men using BMD (88 predicted, p = 0.109). Garvan accurately predicted hip fractures except for women without BMD (12 predicted, p < 0.001). Fractures were underestimated primarily in the osteopenia and osteoporosis groups; MOFs in the normal BMD group were only underestimated by FRAXBMD and fragility fractures by GarvannoBMD, both in men. AUROCs were not different between scores with and without BMD, except for fragility fractures predicted by Garvan in women (0.696, 95% CI 0.652-0.739 and 0.668, 0.623-0.712, respectively, p = 0.008) and men, which almost reached significance (0.683, 0.631-0.734, and 0.667, 0.615-0.719, respectively, p = 0.051). Analyses of sensitivity and specificity showed overall that MOFs and fragility fractures were poorly predicted by both FRAX and Garvan, while hip fractures were acceptably predicted. CONCLUSIONS: Overall, the FRAX and Garvan calculators underestimated MOF and fragility fractures, particularly in individuals with osteopenia or osteoporosis. Hip fractures were predicted better by both calculators. AUROC analyses suggest that GarvanBMD performed better than GarvannoBMD for prediction of fragility fractures.

Vitamin D during pregnancy and offspring body composition: a prospective cohort study.

BACKGROUND: Evidence regarding the association between gestational vitamin D status and offspring body composition during childhood is inconsistent. Therefore, we aimed to determine the association between maternal vitamin D and offspring lean and fat mass in the Vitamin D in Pregnancy birth cohort. METHODS: Subjects were mother-child pairs recruited from the Australian-based Vitamin D in Pregnancy cohort study. Mothers were recruited before 16 weeks' gestation and provided a blood sample at both recruitment and at 28-32 weeks' gestation. Serum vitamin D [25(OH)D] was measured by radioimmunoassay (Tyne and Wear, UK). Offspring lean and fat mass were quantified by using dual-energy X-ray absorptiometry (GE Lunar Prodigy, Madison, WI, USA) at 11 years of age. RESULTS: Median maternal 25(OH)D levels were 55.9 (42.2-73.3) and 56.1 (43.6-73.9) at recruitment and 28-32 weeks' gestation, respectively. Maternal smoking was identified as an effect modifier in the association between maternal vitamin D status at recruitment and offspring body composition. In smokers, but not non-smokers, serum 25(OH)D status at recruitment was negatively associated with offspring fat mass percentage and positively associated with lean mass (both p < 0.05). There was no association with 25(OH)D status at 28-32 weeks' gestation. CONCLUSIONS: Maternal vitamin D status in early pregnancy, in smokers, is associated with offspring body composition. These important findings warrant confirmation in larger studies and trials.

Prediction of major osteoporotic and hip fractures in Australian men using FRAX scores adjusted with trabecular bone score.

There 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. INTRODUCTION: FRAX 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. METHODS: This 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. RESULTS: Sensitivity 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. CONCLUSIONS: Prediction 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.

Maternal vitamin D and offspring trabecular bone score.

No studies have explored the relationship with maternal vitamin D (25(OH)D) in pregnancy and offspring trabecular bone score (TBS). Our data suggest that maternal 25(OH)D in early pregnancy, but not late, may be associated with offspring TBS in boys. These data act as hypothesis-generating findings for confirmation in larger, longer-term studies. INTRODUCTION: Trabecular bone score (TBS), a novel tool derived from dual-energy X-ray absorptiometry (DXA), reflects the microarchitecture of the vertebrae. It has been shown to predict fracture independent of standard DXA parameters in adult populations. Previously, we demonstrated that maternal serum 25-hydroxyvitamin D (25(OH)D) during pregnancy is associated with offspring bone mineral content at age 11 years. However, associations with TBS have not been explored, thus we aimed to determine associations between maternal 25(OH)D and offspring TBS. METHODS: Data were collected from the Vitamin D in Pregnancy (VIP) study. Venous blood samples were taken at recruitment and at 28-32 weeks' gestation. Maternal 25(OH)D was measured by radioimmunoassay. Offspring (n = 195, n = 181 with complete measures) underwent spine DXA (GE Lunar), at age 11 years (median = 10.9 (IQR 10.9-11.4)). TBS was calculated using TBS iNsight software. RESULTS: Offspring of mothers with sufficient 25(OH)D levels (≥50 nmol/L) at recruitment had a higher TBS (1.363 vs. 1.340, p = 0.04). In multivariable linear regression models, after adjustment for child relative lean mass, sex and pubertal stage, a 10 nmol/L increase in maternal 25(OH)D was associated with a 0.005 (95% CI 0.000, 0.010, p = 0.04) increase in TBS. However when stratified by sex (p for interaction = 0.16), the association was significant in boys, but not girls. There were no associations with TBS and maternal 25(OH)D at 28-32 weeks. CONCLUSIONS: We speculate that maternal 25(OH)D in early pregnancy may be associated with TBS in offspring at age 11 in boys. These hypothesis-generating findings warrant confirmation with larger interventional and long-term follow-up studies.