Postmenopausal and senile osteoporosis: current concepts of etiology and treatment

Abstract

Postmenopausal osteoporosis and senile osteoporosis are heterogeneous disorders that appear to be caused by several nonhormonal and hormonal factors. Of nonhormonal factors, age-related bone loss, the degree of bone density achieved in young adult life, and dietary intake and absorption of calcium appear to be important. Hormones that may be important in pathogenesis are parathyroid hormone (PTH), estrogen, 1, 25(OH)2D, and possibly calcitonin. Postmenopausal estrogen deficiency accelerates bone loss by increasing responsiveness of bone to endogenous PTH. The resultant increase in release of calcium from bone is associated with normal or low values for serum immunoreactive PTH (iPTH) (except for a subset of 15% of the total which have high values and appear to represent a separate population). Some evidence suggests that subnormal calcium absorption, which is a common finding in postmenopausal osteoporosis and which may contribute to negative calcium balance, is caused by decreased conversion of 25-OH-D to 1,25(OH)2D. Treatment of osteoporosis with either sex steroids (by antagonizing the effect of PTH on bone resorption) or orally administered calcium with or without vitamin D (by decreasing PTH secretion) decreases bone resorption. Long-term therapy with these agents, however, decreases bone formation; thus, bone loss is only arrested or slowed. Although combined therapy with fluoride and calcium stimulates bone formation and appears to be capable of increasing bone mass, its long-term safety and efficacy in decreasing the the occurrence of fractures remain to be demonstrated.