Elizabeth J Samelson1, Kerry E Broe2, Hanfei Xu3, Laiji Yang2, Steven Boyd4, Emmanuel Biver5, Pawel Szulc6, Jonathan Adachi7, Shreyasee Amin8, Elizabeth Atkinson8, Claudie Berger9, Lauren Burt4, Roland Chapurlat6, Thierry Chevalley5, Serge Ferrari5, David Goltzman10, David A Hanley4, Marian T Hannan11, Sundeep Khosla8, Ching-Ti Liu3, Mattias Lorentzon12, Dan Mellstrom12, Blandine Merle6, Maria Nethander13, René Rizzoli5, Elisabeth Sornay-Rendu6, Bert Van Rietbergen14, Daniel Sundh12, Andy Kin On Wong15, Claes Ohlsson12, Serkalem Demissie3, Douglas P Kiel11, Mary L Bouxsein16. 1. Hinda and Arthur Marcus Institute for Aging Research, Hebrew SeniorLife, Boston, MA, USA; Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. Electronic address: samelson@hsl.harvard.edu. 2. Hinda and Arthur Marcus Institute for Aging Research, Hebrew SeniorLife, Boston, MA, USA. 3. Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA. 4. McCaig Institute for Bone and Joint Health, University of Calgary, Calgary, AB, Canada. 5. Division of Bone Diseases, Geneva University Hospitals and Faculty of Medicine, University of Geneva, Geneva, Switzerland. 6. INSERM UMR1033, Université de Lyon, Hôpital Edouard Herriot, Lyon, France. 7. Department of Medicine, Michael G DeGroote School of Medicine, St Joseph's Healthcare-McMaster University, Hamilton, ON, Canada. 8. Mayo Clinic College of Medicine and Science, Rochester, MN, USA. 9. Research Institute of the McGill University Health Centre, Montreal, QC, Canada. 10. Departments of Medicine, McGill University and McGill University Health Centre, Montreal, QC, Canada. 11. Hinda and Arthur Marcus Institute for Aging Research, Hebrew SeniorLife, Boston, MA, USA; Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. 12. Geriatric Medicine and Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. 13. Geriatric Medicine and Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Bioinformatics Core Facility, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. 14. Department of Biomedical Engineering, Eindhoven University of Technology; Eindhoven, Netherlands. 15. Joint Department of Medical Imaging, University Health Network, Toronto, ON, Canada. 16. Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; Department of Orthopedic Surgery, Harvard Medical School, Center for Advanced Orthopedic Studies, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Abstract
BACKGROUND: Although areal bone mineral density (aBMD) assessed by dual-energy x-ray absorptiometry (DXA) is the clinical standard for determining fracture risk, most older adults who sustain a fracture have T scores greater than -2·5 and thus do not meet the clinical criteria for osteoporosis. Importantly, bone fragility is due to low BMD and deterioration in bone structure. We assessed whether indices of high-resolution peripheral quantitative CT (HR-pQCT) were associated with fracture risk independently of femoral neck aBMD and the Fracture Risk Assessment Tool (FRAX) score. METHODS: We assessed participants in eight cohorts from the USA (Framingham, Mayo Clinic), France (QUALYOR, STRAMBO, OFELY), Switzerland (GERICO), Canada (CaMos), and Sweden (MrOS). We used Cox proportional hazard ratios (HRs) to estimate the association between HR-pQCT bone indices (per 1 SD of deficit) and incident fracture, adjusting for age, sex, height, weight, and cohort, and then additionally for femoral neck DXA aBMD or FRAX. FINDINGS: 7254 individuals (66% women and 34% men) were assessed. Mean baseline age was 69 years (SD 9, range 40-96). Over a mean follow-up of 4·63 years (SD 2·41) years, 765 (11%) participants had incident fractures, of whom 633 (86%) had femoral neck T scores greater than -2·5. After adjustment for age, sex, cohort, height, and weight, peripheral skeleton failure load had the greatest association with risk of fracture: tibia HR 2·40 (95% CI 1·98-2·91) and radius 2·13 (1·77-2·56) per 1 SD decrease. HRs for other bone indices ranged from 1·12 (95% CI 1·03-1·23) per 1 SD increase in tibia cortical porosity to 1·58 (1·45-1·72) per 1 SD decrease in radius trabecular volumetric bone density. After further adjustment for femoral neck aBMD or FRAX score, the associations were reduced but remained significant for most bone parameters. A model including cortical volumetric bone density, trabecular number, and trabecular thickness at the distal radius and a model including these indices plus cortical area at the tibia were the best predictors of fracture. INTERPRETATION: HR-pQCT indices and failure load improved prediction of fracture beyond femoral neck aBMD or FRAX scores alone. Our findings from a large international cohort of men and women support previous reports that deficits in trabecular and cortical bone density and structure independently contribute to fracture risk. These measurements and morphological assessment of the peripheral skeleton might improve identification of people at the highest risk of fracture. FUNDING: National Institutes of Health National Institute of Arthritis Musculoskeletal and Skin Diseases.
BACKGROUND: Although areal bone mineral density (aBMD) assessed by dual-energy x-ray absorptiometry (DXA) is the clinical standard for determining fracture risk, most older adults who sustain a fracture have T scores greater than -2·5 and thus do not meet the clinical criteria for osteoporosis. Importantly, bone fragility is due to low BMD and deterioration in bone structure. We assessed whether indices of high-resolution peripheral quantitative CT (HR-pQCT) were associated with fracture risk independently of femoral neck aBMD and the Fracture Risk Assessment Tool (FRAX) score. METHODS: We assessed participants in eight cohorts from the USA (Framingham, Mayo Clinic), France (QUALYOR, STRAMBO, OFELY), Switzerland (GERICO), Canada (CaMos), and Sweden (MrOS). We used Cox proportional hazard ratios (HRs) to estimate the association between HR-pQCT bone indices (per 1 SD of deficit) and incident fracture, adjusting for age, sex, height, weight, and cohort, and then additionally for femoral neck DXA aBMD or FRAX. FINDINGS: 7254 individuals (66% women and 34% men) were assessed. Mean baseline age was 69 years (SD 9, range 40-96). Over a mean follow-up of 4·63 years (SD 2·41) years, 765 (11%) participants had incident fractures, of whom 633 (86%) had femoral neck T scores greater than -2·5. After adjustment for age, sex, cohort, height, and weight, peripheral skeleton failure load had the greatest association with risk of fracture: tibia HR 2·40 (95% CI 1·98-2·91) and radius 2·13 (1·77-2·56) per 1 SD decrease. HRs for other bone indices ranged from 1·12 (95% CI 1·03-1·23) per 1 SD increase in tibia cortical porosity to 1·58 (1·45-1·72) per 1 SD decrease in radius trabecular volumetric bone density. After further adjustment for femoral neck aBMD or FRAX score, the associations were reduced but remained significant for most bone parameters. A model including cortical volumetric bone density, trabecular number, and trabecular thickness at the distal radius and a model including these indices plus cortical area at the tibia were the best predictors of fracture. INTERPRETATION: HR-pQCT indices and failure load improved prediction of fracture beyond femoral neck aBMD or FRAX scores alone. Our findings from a large international cohort of men and women support previous reports that deficits in trabecular and cortical bone density and structure independently contribute to fracture risk. These measurements and morphological assessment of the peripheral skeleton might improve identification of people at the highest risk of fracture. FUNDING: National Institutes of Health National Institute of Arthritis Musculoskeletal and Skin Diseases.
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