Bone and renal responsiveness to parathyroid hormone with aging

Abstract

It is well established that parathyroid hormone (PTH) plays a key regulatory role in calcium metabolism primarily through its action on kidney and bone. In the kidney PTH stimulates the 1-α-hydroxylase enzyme leading to an increased conversion of calcidiol to calcitriol. In the skeleton PTH represents the major systemic regulator of bone resorption. A large body of evidence indicates that circulating levels and bioactivity of different forms of PTH increase with age. Some, but not all, studies have shown that this phenomenon is usually paralleled by a significant decrease of calcitriol circulating levels with advancing age. To further elucidate the effects of increased PTH bioactivity on bone and kidney in the elderly, we performed two studies in young and elderly subjects and in postmenopausal osteoporotic (PMO) patients with normal renal function. The PTH infusion test showed that the renal calcitriol production was lower and the indexes of bone turnover were more increased in the elderly compared to younger subjects. In patients with PMO, 1 year treatment with estrogens determined a faster response of calcitriol renal production and a less pronounced increase of bone biomarkers compared to untreated patients. Taken all together, the results obtained in our studies suggest that aging is associated with an enhanced skeletal sensitivity and a reduced renal responsivity to PTH. Moreover, in patients with PMO, these combined effects of aging and estrogen depletion can be reversed by hormone replacement therapy.