Chapter 12 - The Genetics of Peak Bone Mass

Abstract

Genetic factors play a key role in the pathogenesis of skeletal fragility and osteoporosis in both genders. Several studies using twin pairs or parent–offspring models have shown high levels of heritability of bone mineral density (BMD), the most commonly used skeletal trait to evaluate the genetic basis of bone strength and, ultimately, osteoporotic fractures. Theoretically, inheritance could affect bone strength and fracture risk in at least two ways. Genetic factors could influence skeletal growth and the amount of bone mass attained in early adulthood (peak bone mass) and subjects with genetically determined low bone mass might be more susceptible to develop osteoporosis with subsequent aging. Alternatively, or in conjunction with the above, genetic factors could influence the rate of age-related bone loss. To date, twin and family studies have shown a predominant genetic effect on peak bone mineral mass acquisition rather than on age-related bone loss. In fact, both male and female offspring of subjects with osteoporosis have reduced bone mass well before age-related or postmenopausal bone loss, suggesting the expression of inherited determinants of osteoporotic risk from an early age.