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

Kirk, Ben<sup>1,2</sup>; Harrison, Stephanie L.<sup>3</sup>; Zanker, Jesse<sup>1,2</sup>; Burghardt, Andrew J.<sup>4</sup>; Orwoll, Eric<sup>5</sup>; Duque, Gustavo<sup>1,2,6,7</sup>; Cawthon, Peggy M.<sup>3,8</sup>

Affiliations

¹Department of Medicine, Western Health, Melbourne Medical School, The University of Melbourne, Melbourne, Australia

²Australian Institute for Musculoskeletal Science (AIMSS), The University of Melbourne and Western Health, Melbourne, Australia

³Research Institute, California Pacific Medical Center, San Francisco, CA, USA

⁴Department of Radiology & Biomedical Imaging, University of California, San Francisco, CA, USA

⁵Division of Endocrinology, Diabetes and Clinical Nutrition, School of Medicine, Oregon Health & Science University, Portland, OR, USA

⁶Research Institute of the McGill University Health Centre, Faculty of Medicine, Montreal, Canada

⁷Dr. Joseph Kaufmann Chair in Geriatric Medicine, McGill University, Montreal, Canada

⁸Department of Epidemiology and Biostatistics, University of California, San Francisco, CA, USA

Abstract and keywords

We examined if an interaction exists between bone and muscle in predicting fractures in older men. Prospective data from the Osteoporotic Fractures in Men study was used to build Cox proportional hazards models. Predictors included HR-pQCT total volumetric BMD (Tt.BMD), trabecular BMD (Tb.BMD), cortical BMD (Ct.BMD) and cortical area (Ct.Ar) at distal radius/tibia, HR-pQCT muscle volume and density (diaphyseal tibia), D3-creatine dilution (D3Cr) muscle mass, and grip strength and leg force, analyzed as continuous variables and as quartiles. Incident fractures were self-reported every 4 months via questionnaires and centrally adjudicated by physician review of radiology reports. Potential confounders (demographics, comorbidities, lifestyle factors, etc.) were considered. A total of 1353 men (mean age 84.2 ± 4.0 years, 92.7% white) were followed for 6.03 ± 2.11 years. In the unadjusted (continuous) model, there were no interactions (p > 0.05) between any muscle variable (D3Cr muscle mass, muscle volume, muscle density, grip strength or leg force) and Tt.BMD at distal radius/tibia for fractures (all: n = 182–302; nonvertebral: n = 149–254; vertebral: n = 27–45). No consistent interactions were observed when interchanging Tt.BMD for Tb.BMD/Ct.BMD or for Ct.Ar (bone structure) at the distal radius/tibia in the unadjusted (continuous) models. Compared with men in quartiles (Q) 2–4 of D3Cr muscle mass and Q2–4 of distal tibia Tt.BMD, men in Q1 of both had increased risk for all fractures (hazard ratio (HR) = 2.00; 95% confidence interval [CI] 1.24–3.23, p = 0.005) and nonvertebral fractures (HR = 2.10; 95% CI 1.25–3.52, p < 0.001) in the multivariable-adjusted model. Confidence intervals overlapped (p > 0.05) when visually inspecting other quartile groups in the multivariable-adjusted model. In this prospective cohort study of older men, there was no consistent interactions between bone and muscle variables on fracture risk. Larger sample sizes and longer follow-up may be needed to clarify if there is an interaction between bone and muscle on fracture risk in men.

Keywords: BONE-MUSCLE INTERACTIONS; SARCOPENIA; OSTEOPOROSIS; FRACTURE RISK ASSESSMENT

Links

DOI: 10.1002/jbmr.4874

PubMed: 37351915

WoS: 001029402900001

History

Received: 2023-02-21

Revised: 2023-06-16

Accepted: 2023-06-22

Cited Works (9)

Year	Entry
2021	Harvey NC, Orwoll E, Kwok T, Karlsson MK, Rosengren BE, Ribom E, Cauley JA, Cawthon PM, Ensrud K, Liu E, Cruz-Jentoft AJ, Fielding RA, Cooper C, Kanis JA, Lorentzon M, Ohlsson C, Mellström D, Johansson H, McCloskey E. Sarcopenia definitions as predictors of fracture risk independent of FRAX®, falls, and BMD in the Osteoporotic Fractures in Men (MrOS) Study: a meta-analysis. J Bone Miner Res. July 2021;36(7):1235-1244.
2018	Harvey NC, Odén A, Orwoll E, Lapidus J, Kwok T, Karlsson MK, Rosengren BE, Ribom E, Cooper C, Cawthon PM, Kanis JA, Ohlsson C, Mellström D, Johansson H, McCloskey E. Measures of physical performance and muscle strength as predictors of fracture risk independent of FRAX, falls, and aBMD: a meta-analysis of the osteoporotic fractures in men (MrOS) study. J Bone Miner Res. December 2018;33(12):2150-2157.
2022	Kirk B, Duque G. Muscle and bone: an indissoluble union. J Bone Miner Res. July 2022;37(7):1211-1212.
2008	Kanis JA, McCloskey EV, Johansson H, Oden A, Melton LJ III, Khaltaev N. A reference standard for the description of osteoporosis. Bone. March 2008;42(3):467-475.
2018	Langsetmo L, Peters KW, Burghardt AJ, Ensrud KE, Fink HA, Cawthon PM, Cauley JA, Schousboe JT, Barrett-Connor E, Orwoll ES; Osteoporotic Fractures in Men (MrOS) Study Research Group. Volumetric bone mineral density and failure load of distal limbs predict incident clinical fracture independent of FRAX and clinical risk factors among older men. J Bone Miner Res. July 2018;33(7):1302-1311.
2021	Harvey NC, Kanis JA, Liu E, Cooper C, Lorentzon M, Bea JW, Carbone L, Cespedes Feliciano EM, Laddu DR, Schnatz PF, Shadyab AH, Stefanick ML, Wactawski‐Wende J, Crandall CJ, Johansson H, McCloskey E. 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). J Bone Miner Res. April 2021;36(4):654-661.
2005	Orwoll E, Blank JB, Barrett-Connor E, Cauley J, Cummings S, Ensrud K, Lewis C, Cawthon PM, Marcus R, Marshall LM, McGowan J, Phipps K, Sherman S, Stefanick ML, Stone K. Design and baseline characteristics of the osteoporotic fractures in men (MrOS) study: a large observational study of the determinants of fracture in older men. Contemp Clin Trials. October 2005;26(5):569-585.
2014	Cosman F, de Beur SJ, LeBoff MS, Lewiecki EM, Tanner B, Randall S, Lindsay R. Clinician’s guide to prevention and treatment of osteoporosis. Osteoporos Int. October 2014;25(10):2359-2381.
2022	Cawthon PM, Peters KE, Cummings SR, Orwoll ES, Hoffman AR, Ensrud KE, Cauley JA, Evans WJ; Osteoporotic Fractures in Men (MrOS) Study Research Group. Association between muscle mass determined by D₃-creatine dilution and incident fractures in a prospective cohort study of older men. J Bone Miner Res. July 2022;37(7):1213-1220.