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Genetics of Osteoporosis

Department of Medicine (M.P., M.J.E.), Department of Orthopaedic Surgery (C.H.T.), and Department of Medical and Molecular Genetics (M.J.E., T.F.), Indiana University School of Medicine, Indianapolis, Indiana 46202; and Department of Biomedical Engineering (C.H.T.), Indiana University Purdue University, Indianapolis, Indiana 46202

Correspondence: Address all correspondence and requests for reprints to: Munro Peacock, M.D., General Clinical Research Center, University Hospital and Outpatient Center, Room 5595, 550 North University Boulevard, Indianapolis, Indiana 46202. E-mail: mpeacock{at}iupui.edu

Osteoporosis is a common multifactorial disorder of reduced bone mass. The disorder in its most common form is generalized, affecting the elderly, both sexes, and all racial groups. Multiple environmental factors are involved in the pathogenesis. Genes also play a major role as reflected by heritability of many components of bone strength. Quantitative phenotypes in bone strength in the normal population do not conform to a monogenetic mode of inheritance. The common form of osteoporosis is generally considered to be a polygenic disorder arising from the interaction of common polymorphic alleles at quantitative trait loci, with multiple environmental factors. Finding the susceptibility genes underlying osteoporosis requires identifying specific alleles that coinherit with key heritable phenotypes in bone strength. Because of the close correspondence among mammalian genomes, identification of the genes underlying bone strength in mammals such as the mouse is likely to be of major assistance in human studies. Identification of susceptibility genes for osteoporosis is one of several important approaches toward the long-term goal of understanding the molecular biology of the normal variation in bone strength and how it may be modified to prevent osteoporosis. As with all genetic studies in humans, these scientific advances will need to be made in an environment of legal and ethical safeguards that are acceptable to the general public.

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