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Genetic Determinants and Pharmacogenetics of Osteoporosis and Osteoporotic Fracture

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Osteoporosis

Part of the book series: Contemporary Endocrinology ((COE))

Abstract

In contrast to Mendelian diseases that are usually caused by a mutation in a single gene, common diseases and disease-associated quantitative traits such as osteoporotic fractures and BMD do not segregate in a Mendelian manner within families and are influenced by multiple genetic and environmental factors. Estimated from twins and siblings, the narrow-sense genetic heritability h2 of BMD is >0.50, suggesting a strong genetic contribution to the risk of osteoporosis. BMD is considered as one of the highly heritable disease-associated quantitative traits. The feasibility of carrying out genome-wide association studies (GWAS) on common variants has led to rapid progress in the field of complex-disease genetics, and provided valuable information about the contribution of genetic variants to phenotypes. In the past 10 years, GWAS have identified ~604 GWAS loci that are associated with bone-health-related phenotypes; including DXA-derived area BMD; qCT-derived volumetric BMD; estimated BMD (eBMD) and heel bone properties from heel quantitative ultrasound; bone geometry, shape, and microstructure; osteoporotic fractures and nonunion; pediatric bone density; serum vitamin D and other serum bone biomarkers. The discovery of underlying genetic determinants may create opportunities for novel diagnostics and drug targets to support a personalized approach to treating osteoporosis and prevent osteoporotic fracture. Although several osteoporotic medications have shown to be effective in reducing the risk of fracture in postmenopausal women and are recommended as the first-line therapies for patients with osteoporosis, the response to these anti-osteoporotic therapies is highly variable among individuals and such variability may also be partly determined by genetic factors. Pharmacogenetics is the study of the genetic variation between individuals that affects their response to drugs as well as treatment-related adverse effects, such as osteonecrosis of the jaw (ONJ) and atypical femoral fractures (AFF). In this chapter, we review and discuss findings from GWAS along with pharmacogenetics studies of osteoporotic treatments.

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Authors and Affiliations

  1. Department of Medicine, Hebrew SeniorLife Marcus Institute for Aging Research and Harvard Medical School, Boston, MA, USA

    Yi-Hsiang Hsu, Xue Xu & Sohyun Jeong

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  1. Yi-Hsiang Hsu
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  2. Xue Xu
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Correspondence to Yi-Hsiang Hsu .

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  1. Massachusetts General Hospital, Boston, MA, USA

    Benjamin Z. Leder

  2. Massachusetts General Hospital, Boston, MA, USA

    Marc N. Wein

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Hsu, YH., Xu, X., Jeong, S. (2020). Genetic Determinants and Pharmacogenetics of Osteoporosis and Osteoporotic Fracture. In: Leder, B., Wein, M. (eds) Osteoporosis. Contemporary Endocrinology. Humana, Cham. https://doi.org/10.1007/978-3-319-69287-6_25

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