Deficient acquisition of bone during maturation underlies idiopathic osteoporosis in men: evidence from a three-generation family study.

To address the issue whether deficient acquisition of bone during maturation or adult-onset bone loss is primarily to blame for idiopathic osteoporosis in men, we assessed indices of bone mineral density and size, as well as biochemical markers of bone turnover in 61 probands (ages 20-65 years) with idiopathic osteoporosis (z-score < or = -2.0 at the spine or hip), their first-degree relatives (n = 130), and age-matched controls. There was no indication of accelerated bone loss. Indeed, in probands, the observed bone deficit versus controls was unrelated to the age of probands, and indices of bone turnover were not significantly different from controls. On the other hand, a specific deficit in bone acquisition was suggested by findings of lower bone mineral density values in three generations of male and female relatives of the probands, including their offspring; bone turnover in relatives was not different from controls. The bone mineral density deficit was more pronounced in male compared with female relatives; approximately 60% of the sons had a spinal bone mineral density z-score of less than -2.0. There also was a skeletal site-specificity in probands and their male relatives with a larger areal bone mineral density deficit at the spine compared with the hip and the forearm. The deficit at the spine corresponded to a reduction of both volumetric bone mineral density and bone size; a similar less pronounced deficit in volumetric bone mineral density, but not in bone size, was observed at the femoral neck. These findings in probands and their first-degree relatives point toward a major contributory role of a genetically determined maturational defect in bone acquisition in the pathogenesis of idiopathic osteoporosis in men.