Prediction of changes in bone mineral density in the elderly: contribution of “osteogenomic profile”
The contribution of genetic variants to longitudinal bone loss has not been well documented. We constructed an “osteogenomic profile” based on 62 BMD-associated genetic variants and showed that the profile was significantly associated with bone loss, independently from baseline BMD and age. The osteogenomic profile can help predict bone loss in an individual.
The rate of longitudinal bone loss (ΔBMD) is a risk factor for fracture. The variation in ΔBMD is partly determined by genetic factors. This study sought to define the association between an osteogenomic profile and ΔBMD.
The osteogenomic profile was created from 62 BMD-associated SNPs from genome-wide association studies (GWAS) that were genotyped in 1384 elderly men and women aged 60+ years. Weighted genetic risk scores (GRS) were constructed for each individual by summing the products of the number of risk alleles and the sex-specific regression coefficients [associated with BMD from GWAS]. ΔBMD, expressed as annual percent change-in-BMD, was determined by linear regression analysis for each individual who had had at least two femoral neck BMD measurements.
The mean ΔBMD was − 0.65% (SD 1.64%) for women and − 0.57% (SD 1.40%) for men, and this difference was not statistically significant (P = 0.32). In women, each unit increase in GRS was associated with 0.21% (SE 0.10) higher ΔBMD at the femoral neck (P = 0.036), and this association was independent of baseline BMD and age. In logistic regression analysis, each unit increase of GRS was associated with 41% odds (95%CI: 1.07–1.87) of rapid bone loss (ΔBMD ≤ − 1.2%/year; mean of rapid loss group = − 2.2%/year). There was no statistically significant association between ΔBMD and GRS in men.
We conclude that the osteogenomic profile constructed from BMD-associated genetic variants is modestly associated with long-term changes in femoral neck BMD in women, but not in men.
KeywordsOsteoporosis Bone mineral density Genetic variant Genetic profiling Bone loss
Bone mineral density
Rate of longitudinal bone loss
Genome-wide association study
Genetic risk score
Dubbo Osteoporosis Epidemiology Study
Osteoporotic Fractures in Men Study
Study of Osteoporotic Fractures
We gratefully acknowledge the assistance of Sr Janet Watters, Donna Reeves, Shaye Field, and Jodie Martin for the interview, data collection, and measurement bone mineral density. We also appreciate the invaluable help of the staff of Dubbo Base Hospital. We thank the IT group of the Garvan Institute of Medical Research for the management of the database. The Dubbo Osteoporosis Epidemiology Study was supported by the Australian National Health and Medical Research Council, Grant Number APP1031494 (CIA T. Nguyen).
Authors’ roles: TVN has full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study conception: TVN, JAE, and THL. Study design and data collection: TVN, JAE, and JRC. Data analysis: THL, HMP, HTN, and TVN. Interpretation of results: TVN, JAE, JRC, and THL. Drafting manuscript: THL and TVN. Critical reviews and final approval of manuscript content: THL, HMP, JAE, JRC, HTN, and TVN.
Compliance with ethical standards
The study was approved by the St Vincent’s Campus Research Ethics Committee and written informed consent was obtained from all participants.
Conflicts of interest
Professor John A. Eisman has served as consultant on the Scientific Advisory Board for Amgen, Eli Lilly, Merck Sharp & Dohme, Novartis, Sanofi-Aventis, Servier and deCode. Professor J.R. Center has given educational talks for and received travel expenses from Amgen, Merck Sharp & Dohme, Novartis, Sanofi-Aventis. She has received travel expenses from Merck Sharp & Dohme, Amgen and Aspen. Professor Tuan V. Nguyen has received honoraria for consulting and speaking in symposia sponsored by Merck Sharp & Dohme, Roche, Sanofi-Aventis, Novartis, and Bridge Healthcare Pty Ltd. (Vietnam). Professor J. A. Eisman, Professor T. V. Nguyen and Dr. J. R. Center have received grants from Sanofi, BUPA. Professor T. V. Nguyen has received NHMRC project grant. Other authors have no conflicts of interest.
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