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

Abstract

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 AE SD age 77.0 AE 5.1, 73.9 AE 4.9, 80 AE 3.4 years, followed for a mean AE SD 7.8 AE 2.2, 8.1 AE 2.3, 5.3 AE 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 BMDThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Interactions Between HR‐pQCT Bone Density and D3Cr Muscle Mass (or HR‐pQCT Bone Structure and HR‐pQCT Muscle Density) in Predicting Fractures: The Osteoporotic Fractures in Men Study

“…Aside from the comprehensive inclusion of demographic, lifestyle, and clinical covariates, the main strength of our study is the use of accurate imaging techniques to quantify volumetric BMD and bone structure (HR‐pQCT), muscle mass (D 3 Cr), and muscle density (HR‐pQCT), all of which independently predict fractures. ( 1,2,17 ) This is in contrast to previous studies ( 10,11,14,29‐31 ) that used inferior imaging techniques such as DXA lean mass (a surrogate measure of muscle mass) that show inconsistent associations with fractures. ( 12,13 ) A recent study ( 7 ) also showed that older women with osteosarcopenia (defined as osteoporosis plus low grip strength and/or chair rise time by EWGSOP2) had significantly lower HR‐pQCT cortical bone parameters but similar DXA values when compared with osteoporosis alone.…”

“…Findings revealed no consistent interactions between these measures of musculoskeletal health in predicting these adverse outcomes. The basis of this analysis was that (i) both low BMD and low muscle mass or muscle density independently increase the risk of fractures in previous MrOs studies (1,2,17) and thus there may be an synergistic effect on fracture risk and (ii) both tissues can impact one another through biomechanical and biochemical mechanisms (6) and thus there may be an interactive effect on fracture risk (eg, in men with very low BMD the impact of muscle on the risk of fracture may be stronger than in those with higher BMD and vice versa). Indeed, evidence (largely from animal work) shows that bone and muscle are influenced by the same factors (such as physical activity, nutrition, and disease states) and affected by local cross-talk between bone, muscle, and fat cells.…”

“…( 13 ) Other studies support these findings. ( 14,15 ) A possible explanation for the discrepancy in these findings relates to the poor prognostic value of DXA lean mass for fractures ( 13 ) (commonly used as a surrogate for muscle mass in sarcopenia definitions ( 3,16 ) ) due to the influence of non‐muscle tissues when compared with other muscle measures such as D 3 Cr muscle mass ( 2 ) or muscle density, ( 17 ) which predict fractures.…”

“…(2) Muscle density (of the calf or gluteal region) has also emerged as a consistent predictor of incident fractures after adjustment for BMD in separate studies using pQCT or HR-pQCT. (17,18) Other MrOS studies using HR-pQCT have demonstrated that volumetric BMD or bone structure (expressed as cortical area) are among the strongest predictors of incident fractures. (1) Yet the interactions between these bone and muscle variables (ie, volumetric BMD and D 3 -creatine dilution (D 3 Cr) muscle mass or cortical bone area and muscle density) in estimating the risk of fractures is currently unknown, as recently highlighted in an editorial.…”