Alterations in calcium, vitamin d, and parathyroid hormone physiology in normal men with aging: Relationship to the development of senile osteopenia

The effects of aging on calcium and bone metabolism have not been systematically examinedin men. To identify age-related alterations in vitamin D and PTH physiologyand to assess their impact on skeletal health, we studied 62 normal men, aged 30-92 yr. The men were in excellent health, and none had any evidence of metabolic bone disease and/or known risk factors for osteopenia. Serum 25-hydroxyvitamin D (25OHD) concentrations declined steadily with advancing age (r = −0.47; P < 0.001), and there was a corresponding decline in serum 24,25-dihydroxyvitamin D [24,25-(OH)₂D] levels (r = −0.41; P < 0.001). Serum 1,25-(OH)₂D concentrations, however, did not vary over this age range (r = −0.07; P = NS). Plasma PTH levels increased with aging (r = −0.24; P < 0.001), and there was a concomitant increase in urinary cAMP excretion (r = 0.38; P < 0.001). Renal function (creatinine clearance) clearly declined with increasing age (r = −0.71; P < 0.001). In conjunction with thesechanges in calcium metabolism, radial and vertebral bone mineral content declined. Whereas the fall in radial bone mineral content (single photon absorptiometry) at both proximal and distal siteswas slight, there was a marked decrease invertebral bone mineral content, as measured by quantitative computed tomography (r = −0.72; P < 0.0001). The fall in vertebral bone mineral content correlated well with the declines in serum 25OHD and 24,25-(OH)₂D concentrations(r = 0.47; P < 0.001 and r = 0.51; P <0.001, respectively) and with the decline in renal function (r = 0.46; P < 0.001). Multiple regression analysis revealed that the effects of aging on bone mineral content could be accounted for in large part by concomitant changes in mineral metabolism. Both the decline in renal function and the fall in serum 24,25-(OH)₂D levels were closely associated with the fall in bone mineral content. These results indicate that a decline in renal function and alterations in vitamin D metabolism occur with aging in normal men. These changes contribute to, if not cause, the associated decline in skeletal mineral content in aging men.