BMD-related genetic risk scores predict site-specific fractures as well as trabecular and cortical bone microstructure

Nethander, Maria; Pettersson-Kymmer, Ulrika; Vandenput, Liesbeth; Lorentzon, Mattias; Karlsson, Magnus; Mellström, Dan; Ohlsson, Claes

Affiliations

¹Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, SE-413 45 Gothenburg, Sweden

²Bioinformatics Core Facility, Sahlgrenska Academy, University of Gothenburg, SE-405 30 Gothenburg, Sweden

³Clinical Pharmacology, Department of Pharmacology and Clinical Neuroscience, Umea University, SE-901 87 Umea, Sweden

⁴Geriatric Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, SE-431 80 Gothenburg, Sweden

⁵Mary MacKillop Institute for Health Research, Australian Catholic University, Melbourne VIC 9000, Australia

⁶Clinical and Molecular Osteoporosis Research Unit, Department of Orthopedics and Clinical Sciences, Lund University, Skåne University Hospital, SE-221 00 Malmö, Sweden

⁷Sahlgrenska University Hospital, Department of Drug Treatment, SE-413 45 Gothenburg, Sweden

Abstract and keywords

Context: It is important to identify patients at highest risk of fractures.

Objective: To compare the separate and combined performances of bone-related genetic risk scores (GRSs) for prediction of forearm, hip and vertebral fractures separately, as well as of trabecular and cortical bone microstructure parameters separately.

Design, Setting, and Participants: Using 1103 single nucleotide polymorphisms (SNPs) independently associated with estimated bone mineral density of the heel (eBMD), we developed a weighted GRS for eBMD and determined its contribution to fracture prediction beyond 2 previously developed GRSs for femur neck BMD (49 SNPs) and lumbar spine BMD (48 SNPs). Associations between these GRSs and forearm (ncases = 1020; ncontrols = 2838), hip (ncases = 1123; ncontrols = 2630) and vertebral (ncases = 288; ncontrols = 1187) fractures were evaluated in 3 Swedish cohorts. Associations between the GRSs and trabecular and cortical bone microstructure parameters (n = 426) were evaluated in the MrOS Sweden cohort.

Results: We found that eBMD_GRS was the only significant independent predictor of forearm and vertebral fractures while both FN-BMDGRS and eBMD_GRS were significant independent predictors of hip fractures. The eBMD_GRS was the major GRS contributing to prediction of trabecular bone microstructure parameters while both FN-BMDGRS and eBMD_GRS contributed information for prediction of cortical bone microstructure parameters.

Conclusions: The eBMD_GRS independently predicts forearm and vertebral fractures while both FN-BMDGRS and eBMD_GRS contribute independent information for prediction of hip fractures. We propose that eBMD_GRS captures unique information about trabecular bone microstructure useful for prediction of forearm and vertebral fractures. These findings may facilitate personalized medicine to predict site-specific fractures as well as cortical and trabecular bone microstructure separately.

Keywords: bone mineral density; genetic risk scores; fractures; bone microstructure; trabecular; cortical

Links

DOI: 10.1210/clinem/dgaa082

PubMed: 32067027

WoS: 000525950100036

History

Received: 2019-11-13

Accepted: 2020-02-14

Online: 2020-02-18

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