Sarcopenia definitions as predictors of fracture risk independent of FRAX®, falls, and BMD in the Osteoporotic Fractures in Men (MrOS) Study:​ a meta-analysis

Harvey, Nicholas C.<sup>1,2</sup>; Orwoll, Eric<sup>3</sup>; Kwok, Timothy<sup>4</sup>; Karlsson, Magnus K.<sup>5</sup>; Rosengren, Björn E.<sup>5</sup>; Ribom, Eva<sup>6</sup>; Cauley, Jane A.<sup>7</sup>; Cawthon, Peggy M.<sup>8,9</sup>; Ensrud, Kristine<sup>10</sup>; Liu, Enwu<sup>11</sup>; Cruz-Jentoft, Alfonso J.<sup>12</sup>; Fielding, Roger A.<sup>13</sup>; Cooper, Cyrus<sup>1,2,14</sup>; Kanis, John A.<sup>11,15</sup>; Lorentzon, Mattias<sup>11,16</sup>; Ohlsson, Claes<sup>17,18</sup>; Mellström, Dan<sup>17</sup>; Johansson, Helena<sup>11,15</sup>; McCloskey, Eugene<sup>15,19</sup>

Affiliations

¹MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK

²NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK

³Oregon Health & Science University, Portland, OR, USA

⁴Department of Medicine and Therapeutics and School of Public Health, The Chinese University of Hong Kong, Shatin, Hong Kong

⁵Clinical and Molecular Osteoporosis Research Unit, Department of Clinical Sciences Malmo, Lund University and Department of Orthopedics, Skane University Hospital, Malmo, Sweden

⁶Department of Surgical Sciences, University of Uppsala, Uppsala, Sweden

⁷Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA

⁸Research Institute, California Pacific Medical Center, San Francisco, CA, USA

⁹Department of Epidemiology and Biostatistics, University of California, San Francisco, CA, USA

¹⁰Medicine and Epidemiology & Community Health, University of Minnesota, Minneapolis, MN, USA

¹¹Mary MacKillop Institute for Health Research, Australian Catholic University, Melbourne, Australia

¹²Servicio de Geriatría, Hospital Universitario Ramón y Cajal (IRYCIS), Madrid, Spain

¹³Nutrition, Exercise Physiology, and Sarcopenia Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA

¹⁴NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UK

¹⁵Centre for Metabolic Bone Diseases, University of Sheffield, Sheffield, UK

¹⁶Geriatric Medicine, Institute of Medicine, Sahlgrenska Academy, Sahlgrenska University Hospital, Mölndal, Sweden

¹⁷Department of Internal Medicine and Clinical Nutrition, Center for Bone and Arthritis Research, Institute of Medicine, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden

¹⁸Region Västra Götaland, Sahlgrenska University Hospital, Department of Drug Treatment, Gothenburg, Sweden

¹⁹Centre for Integrated research in Musculoskeletal Ageing (CIMA), Mellanby Centre for Bone Research, University of Sheffield, Sheffield, UK

Abstract and keywords

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

Keywords: EPIDEMIOLOGY; FALLS; FRACTURE; FRAX; INTERACTION; OSTEOPOROSIS; SARCOPENIA

Links

DOI: 10.1002/jbmr.4293

PubMed: 33831257

WoS: 000637899400001

History

Received: 2020-11-27

Revised: 2021-03-01

Accepted: 2021-03-16

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Cited By (5)

Year	Entry
2023	Alajlouni DA, Bliuc D, Tran TS, Blank RD, Center JR. Muscle strength and physical performance contribute to and improve fracture risk prediction in older people: a narrative review. Bone. July 2023;172:116755.
2022	Kirk B, Duque G. Muscle and bone: an indissoluble union. J Bone Miner Res. July 2022;37(7):1211-1212.
2023	Hong N, Burm SW, Kim HC, Kim CO, Rhee Y. Jump power predicts fracture risk in older adults independent of sarcopenia and FRAX. J Bone Miner Res. July 2023;38(7):958-967.
2023	Kirk B, Harrison SL, Zanker J, Burghardt AJ, Orwoll E, Duque G, Cawthon PM. 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. J Bone Miner Res. September 2023;38(9):1245-1257.
2022	Laskou F. Understanding the Relationship Between Muscle and Bone in Older Adults: An Investigation of Two Cohorts [MD thesis]. University of Southampton; November 28, 2022.