Forearm BMD predicts fracture independently of FRAX

John A Kanis; Helena Johansson; Nicholas C Harvey; Mattias Lorentzon; Jane A Cauley; Carolyn J Crandall; Martijn Huisman; Sundeep Khosla; Timothy Kwok; Dan Mellström; Eric S Orwoll; Natasja M van Schoor; Pawel Szulc; Eugene V McCloskey; William D Leslie; The Frax Meta-Analysis Cohort Group

doi:10.1007/s00198-026-08048-9

Forearm BMD predicts fracture independently of FRAX

Osteoporos Int. 2026 Apr 23. doi: 10.1007/s00198-026-08048-9. Online ahead of print.

Authors

John A Kanis^{1

2}, Helena Johansson^{3

4}, Nicholas C Harvey^{5

6}, Mattias Lorentzon^{4

7}, Jane A Cauley⁸, Carolyn J Crandall⁹, Martijn Huisman^{10

11}, Sundeep Khosla¹², Timothy Kwok^{13

14}, Dan Mellström^{15

16}, Eric S Orwoll¹⁷, Natasja M van Schoor¹⁰, Pawel Szulc¹⁸, Eugene V McCloskey^{3

19}, William D Leslie²⁰, The Frax Meta-Analysis Cohort Group

Affiliations

¹ Centre for Metabolic Bone Diseases, University of Sheffield, Beech Hill Road, Sheffield, S10 2RX, UK. w.j.pontefract@sheffield.ac.uk.
² Department of Medicine, School of Clinical Sciences, Monash University, Clayton, Australia. w.j.pontefract@sheffield.ac.uk.
³ Centre for Metabolic Bone Diseases, University of Sheffield, Beech Hill Road, Sheffield, S10 2RX, UK.
⁴ Sahlgrenska Osteoporosis Centre, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
⁵ MRC Lifecourse Epidemiology Centre, University of Southampton, Southampton, UK.
⁶ IHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK.
⁷ Geriatric Medicine, Region Västra Götaland, Sahlgrenska University Hospital, Mölndal, Sweden.
⁸ Department of Epidemiology, School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.
⁹ Division of General Internal Medicine and Health Services Research, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
¹⁰ Department of Epidemiology and Data Science, Amsterdam UMC Location, Amsterdam Public Health Research Institute, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
¹¹ Department of Sociology, VU University, Amsterdam, The Netherlands.
¹² Robert and Arlene Kogod Center On Aging and Division of Endocrinology, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, MN, USA.
¹³ Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR.
¹⁴ Jockey Club Centre for Osteoporosis Care and Control, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR.
¹⁵ Geriatric Medicine, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
¹⁶ Geriatric Medicine, Sahlgrenska University Hospital Mölndal, Mölndal, Sweden.
¹⁷ Department of Medicine, Oregon Health and Science University, Portland, OR, USA.
¹⁸ UMR 1033, INSERM, University of Lyon, Hôpital Edouard Herriot, Lyon, France.
¹⁹ MRC Versus Arthritis Centre for Integrated Research in Musculoskeletal Ageing, Mellanby Centre for Musculoskeletal Research, University of Sheffield, Sheffield, UK.
²⁰ Department of Medicine, University of Manitoba, Winnipeg, MB, Canada.

PMID: 42024269
DOI: 10.1007/s00198-026-08048-9

Abstract

The relationship between bone mineral density (BMD) at the forearm and fracture risk was determined in a meta-analysis of primary data from 11 cohort studies of 35,121 men and women. Low forearm BMD was a significant predictor of fracture risk, independently of FRAX®.

Introduction: The aim of this study was to quantify the relationship between forearm BMD, FRAX and fracture risk and examine the effect of age, sex, time since measurement, and initial BMD value on fracture risk.

Methods: We studied 35,121 men and women from 11 predominantly population-based cohorts followed for an average of 11.1 years and a total of 388,654 person-years. The association between forearm BMD, FRAX probabilities (calculated without femoral neck BMD), and the risk of fracture was examined using an extension of the Poisson regression model in each cohort by sex and expressed as the gradient of risk (GR; hazard ratio per 1 SD difference in BMD). The different studies were merged using weighted coefficients.

Results: The GR of forearm BMD for major osteoporotic fracture was 1.41 (95% confidence interval [CI] 1.31-1.51) when adjusted for age and time since baseline and was similar in men and women (p > 0.20). GRs decreased significantly with age. When additionally adjusted for FRAX 10-year probability of major osteoporotic fracture, forearm BMD remained a significant, independent predictor for fracture (GR = 1.34, 95% CI 1.26-1.44). A similar GR was noted for hip fracture (GR = 1.48; 95% CI 1.35-1.62) that persisted after adjustment for FRAX (GR = 1.39; 95% CI 1.27-1.52). Adjustments to FRAX probabilities based on forearm BMD varied by age and Z-score.

Conclusions: Forearm BMD is a risk factor for MOF and hip fracture risk beyond the risk attributable to FRAX. Its validation on an international basis permits its use in case finding with FRAX.

Keywords: FRAX; FRAXplus; Forearm bone density; Fracture probability; Meta-analysis.