Abstract
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).
Highlights
Sarcopenia,(1) while having an associated International Classification of Diseases (ICD) code, presents a diagnostic challenge, given the current wide range of approaches to its operational characterization
The most recent European Working Group algorithm moves the focus from appendicular lean mass (ALM) to that of performance/function and strength as the important attributes.[9]. Given the centrality of dual-energy X-ray absorptiometry (DXA) ALM to current sarcopenia definitions and the apparent weakness of ALM as a predictor of incident fracture after adjustment for BMD, an important unanswered question is whether the predictive capacity for fracture of these sarcopenia definitions remains when bone mineral density is taken into account
Results for EWGSOP2 confirmed together with other representative definitions are presented in Supplemental Table S3. In this large population of older men, uniformly assessed across three international cohorts, we observed that sarcopenia definitions other than those based on ALM divided by body mass index (BMI) were modestly predictive of incident fractures but that this association was attenuated when femoral neck BMD T-score was incorporated in the regression models
Summary
Sarcopenia (accelerated loss of muscle strength, function, and mass),(1) while having an associated International Classification of Diseases (ICD) code, presents a diagnostic challenge, given the current wide range of approaches to its operational characterization. There would seem little point in undertaking the assessments required for sarcopenia definition (including whole-body DXA, gait speed, and grip strength, for example) if the risk information conveyed by the assessment tells us nothing beyond that associated with femoral neck BMD (a very quick measure to obtain). This consideration applies to independence from fracture risk assessment tool (FRAX®) probability and prior history of falls. We undertook a meta-analysis of the three MrOS cohorts (US, Sweden, Hong Kong) to investigate whether the predictive value of sarcopenia definitions for incident fracture was independent of n 2 HARVEY ET AL
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