Purpose of review: Description of recent progress in genetics and pharmacogenetics of osteoporosis.
Recent findings: Osteoporosis and its consequence of fragility fracture are characterized by highly complex phenotypes, which include bone mineral density, bone strength, bone turnover markers, and nonskeletal traits. Recent developments in the genome-wide studies using high-throughput single-nucleotide polymorphisms have yielded reliable findings. Four genome-wide studies have identified 40 single-nucleotide polymorphisms in various chromosomes that were modestly associated with either bone mineral density or fracture risk. Clinical response, including adverse reactions, to antiosteoporosis therapy (such as bisphosphonates and selective estrogen receptor modulators) is highly variable among treated individuals. Candidate gene studies have found that common polymorphic variations within the collagen I alpha 1 and vitamin D receptor genes were associated with variability in response to antiosteoporosis treatment. Moreover, a recent genome-wide study identified four single-nucleotide polymorphisms that were associated with bisphosphonate-related osteonecrosis of the jaw with relative risk being between 10 and 13.
Summary: The evaluation of osteoporosis and fracture risk is moving from a risk stratification approach to a more individualized approach, in which an individual's absolute risk of fracture is evaluable as a constellation of the individual's environmental exposure and genetic makeup. Therefore, the identification of gene variants that are associated with osteoporosis phenotypes or response to therapy can eventually help individualize the prognosis, treatment and prevention of fracture and its adverse outcomes.