Sarcopenia definitions as predictors of fracture risk independent of FRAX, falls, and BMD in the osteoporotic fractures in men (MrOS) study: a meta-analysis

Authors: HARVEY, NICHOLAS - University Of Southampton; ORWOLL, ERIC - Oregon Health & Science University; KWOK, TIMOTHY - The Chinese University Of Hong Kong (CUHK); KARLSSON, MAGNUS - Skane University Hospital; ROSENGREN, BJORN - Skane University Hospital; RIBOM, EVA - Uppsala University; CAULEY, JANE - University Of Pittsburgh; CAWTHON, PEGGY - University Of California; ENSRUD, KRISTINE - University Of Minnesota; LIU, ENWU - Australian Catholic University; CRUZ-JENTOFT, ALFONSO - Hospital Ramon Y Cajal; FIELDING, ROGER - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; COOPER, CYRUS - University Of Southampton; KANIS, JOHN - University Of Sheffield; LORENTZON, MATTIAS - Sahlgrenska University Hospital; OHLSSON, CLAES - Sahlgrenska University Hospital; MELLSTROM, DAN - University Of Gothenburg; JOHANSSON, HELENA - Australian Catholic University; MCCLOSKEY, EUGENE - University Of Sheffield

Submitted to: Journal of Bone and Mineral Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/16/2021
Publication Date: 4/8/2021
Citation: Harvey, N.C., Orwoll, E., Kwok, T., Karlsson, M.K., Rosengren, B.E., Ribom, E., Cauley, J.A., Cawthon, P.M., Ensrud, K., Liu, E., Cruz-Jentoft, A.J., Fielding, R.A., Cooper, C., Kanis, J.A., Lorentzon, M., Ohlsson, C., Mellstrom, D., Johansson, H., Mccloskey, E. 2021. Sarcopenia definitions as predictors of fracture risk independent of FRAX, falls, and BMD in the osteoporotic fractures in men (MrOS) study: a meta-analysis. Journal of Bone and Mineral Research. 36(7):1235-1244. https://doi.org/10.1002/JBMR.4293.
DOI: https://doi.org/10.1002/JBMR.4293

Interpretive Summary: There are now multiple definitions of sarcopenia, the age-associated decrease in muscle mass and function. Dual-energy X-ray absorptiometry (DXA) is a technique that is most commonly used to measure muscle mass in the assessment of sarcopenia. The value of using muscle mass as a predictor of bone fracture risk is reduced by knowing the actual bone mineral density (BMD). We examined the ability of 11 sarcopenia definitions to predict bone fracture (while accounting for BMD), fracture risk, and prior falls. 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% depending on the definition that was applied. Sarcopenia status, by most definitions was associated with bone fracture. In addition associations of sarcopenia with prior falls and risk of fracture were also found. When BMD was accounted for in the analysis these relationships became less strong. In conclusion, bone fracture can be predicted using sarcopenia definitions but the strength of this prediction is reduced when BMD is taken into account.

Technical Abstract: Dual-energy X-ray absorptiometry (DXA)-derived appendicular lean mass/height^2 (ALM/ht^2) 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/ht^2 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/ht^2), 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.