Pathophysiology of Human Osteoporosis

A primary determinant of fracture risk resulting from either postmenopausal or senile osteoporosis is the mass of bone accumulated during growth and early adulthood. Cortical bone continues to accumulate after closure of the epiphyses until about the middle of the fourth decade, i.e., for about half of the life span. Skeletal homeostasis is maintained for only about one decade thereafter before aging bone loss ensues. Differences in susceptibility to osteoporotic bone fractures clearly are related to genetic differences in maximal adult bone mass, as manifested in the greater susceptibility of whites compared to blacks and of families with small bones. 

In addition to differences in rates of bone loss in the postmenopausal period, there are differences in the sites of loss and the type of bone affected. There is generally a rapid loss of trabecular bone, particularly during the first 5 yr, which predisposes to compression of the vertebrae, the commonest site of osteoporotic fracture. There is also a progressive, but slower, loss of cortical bone arising from resorption at the endosteal surface and resulting in thinning of the cortex. This is the cause of frequent fractures of the neck of the femur. Loss of one type of bone may ensue relatively independently of loss of the other. 

The average overall rate of bone turnover (remodelling) in man has been estimated at 4% per annum, the rate for compact bone at 2.5%, and that for trabecular bone at 10% (Marshall et aL, 1973). Other estimates place the remodelling rate in the adult at 5-11% (Heaney, 1981). However, localized turnover rates as high as 30% have been reported for vertebral trabecular bone and 60% for iliac trabecular bone. 

Postmenopausal bone loss is effectively inhibited by prophylactic administration of estrogen (Recker et al, 1977), but estrogen administration to osteoporotic patients (the conventional treatment) fails to restore lost bone. Estrogen appears to act primarily by putting a brake on bone resorption, i.e., it inhibits the action of parathyroid hormone, the primary stimulus to osteoclastic bone resorption. The mechanism of this inhibition is unknown receptors for estrogen have not been found in bone. A high intake of calcium during the postmenopausal period (up to 1500 mg/d) also is inhibitory (Heaney, 1981), presumably because it raises the level of ionized calcium in the serum sufficiently to suppress parathormone synthesis. 

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