Genetic influence on bone phenotypes and body composition: a Swedish twin study
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ORIGINAL ARTICLE
Genetic influence on bone phenotypes and body composition: a Swedish twin study Helene Wagner • Ha˚kan Melhus • Nancy L. Pedersen Karl Michae¨lsson
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Received: 5 December 2012 / Accepted: 13 March 2013 Ó The Japanese Society for Bone and Mineral Research and Springer Japan 2013
Abstract Bone mineral density (BMD), bone size and bone turnover are independent determinants of fractures in elderly. Earlier twin studies of these phenotypes have revealed high heritability for BMD and bone area, and more moderate heritability for bone turnover markers. No previous Scandinavian study has evaluated the genetic and environmental contribution to the variance of these phenotypes, despite the fact that Scandinavian countries have the highest incidence of osteoporotic fractures worldwide. Participants were selected from the Swedish Twin Registry. All intact like-sexed twin pairs born in 1965 or earlier and living in the county of Uppsala were invited to participate. A total of 102 twin pairs (45 monozygotic and 57 dizygotic) accepted the invitation to participate. All twins underwent measurement of BMD and bone area using dual-energy X-ray absorptiometry. Hip geometry was also calculated. Markers for bone formation (osteocalcin) and bone resorption (CrossLaps) were measured in serum. We observed a substantial heritability for BMD at the lumbar spine (0.85; 95 % CI 0.54–0.90), the femoral neck (0.75; 95 % CI 0.62–0.83), and the proximal femur (0.84; 95 % CI 0.74–0.90). The values for bone area were approximately similar to those for BMD. Bone turnover markers had a slightly lower genetic influence
H. Wagner (&) K. Michae¨lsson Section of Orthopedics, Department of Surgical Sciences, Uppsala University, S75185 Uppsala, Sweden e-mail: [email protected] H. Melhus Section of Clinical Pharmacology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden N. L. Pedersen Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
with a value of 0.69 (0.53–0.80) for osteocalcin and 0.58 (95 % CI 0.33–0.75) for CrossLaps. As a comparison, the heritabilities of body height and weight were 0.95 and 0.82, respectively. The high heritability on bone phenotypes among Swedish middle-aged and older men and women should encourage further work on the identification of specific genetic pathways. Continuing research in this area could reveal the mechanisms behind the strong genetic susceptibility of bone-related phenotypes. Keywords Bone mineral density Bone area Bone markers Heritability Osteoporosis
Introduction Osteoporosis, defined by a low bone mineral density (BMD), is a common multi-factorial disorder of reduced bone strength that causes fragility fractures. The principal components of such fractures are, however, not only a low BMD [1–3] but also normally a fall [4]. In addition, bone size, femoral neck geometry and bone turnover are all BMD independent bonerelated predictors of fracture risk [1, 5–9]. While lifestyle factors have been reported to affe
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