The pathogenesis of osteoporosis.

Consensus and WHO definitions of osteoporosis are provided. The pathogenesis of the disorder has genetic, hormonal and environmental influences which affect peak bone mass, perimenopausal bone loss and age-dependent bone loss. Peak bone mass is mainly genetically determined, though dietary factors and physical activity can have positive effects. Peak bone mass is attained at the point when skeletal growth ceases, after which time bone loss starts. Loss of oestrogen with the menopause results in accelerated bone loss. Bone remodelling balance tips in favour of osteoclastic bone resorption, with osteoblastic bone formation not able to match the level of resorption. Hormone replacement therapy can reverse this trend. Proposed mechanisms and the parts played by the different cell populations and factors are discussed. Osteoblasts are particularly sensitive to ageing phenomena--more sensitive than are osteoclasts, so the negative bone balance increases with increasing age. Age-dependent bone loss is aggravated by reduced calcium absorption, a mutation in the collagen gene and polymorphism in TGF-beta and oestrogen receptor proteins.