Treatment of osteoporosis with vitamin D

Abstract

There are probably few more controversial areas in the pathophysiology and therapeutics of osteoporosis than that concerning the role of vitamin D and its derivatives. It has been argued that osteoporosis is in part related to defective production of calcitriol, and low values for calcitriol have been reported in postmenopausal women [1]. It is suggested that this gives rise to intestinal malabsorption of calcium, secondary hyperparathyroidism which accelerates bone turnover and thereby induces skeletal losses. Since oestrogens may stimulate the synthesis of calcitriol, at least in vitro, oestrogen withdrawal has been considered to be the signal for decreased production of calcitriol. This is, however, not the sole merchanism that could account for calcium malabsorption. It is equally plausible that oestrogen deficiency directly causes bone loss which in turn infuses the extracellular fluid with calcium, and that this in turn decreases the secretion of parathyroid hormone (PTH) and the synthesis of calcitriol. Thus, the intestinal malabsorption is a consequence of bone loss and not its cause [2].A more convincing role of disturbed metabolism of vitamin D arises in the elderly. With advancing years low values for calcitriol and increased secretion of PTH are consistently reported [1,3]. The administration of physiologically appropriate doses of parent vitamin D reverses these abnormalities [3,4]. For this reason it is probable that hyperparathyroidism is in part due to inadequacies in the nutriitional status of the elderly. Although florid osteomalacia due to vitamin D deficiency is rare [5], milder vitamin D insufficiency may be common, particularly in the institutionalized elderly. Over and above there is circumstantial evidence that abnormalities in the production of calcitriol occur due to the decline in renal function that occurs with age, which would also induce secondary hyperparathyroidism [6].In view of these uncertainties, the role of vitamin D, its analogues and metabolites in therapeutics cannot be argued from considerations of pathophysiology, but must Correspondence and offprint requsts to: Professor J. A. Kanis, WHO be judged from a pharmacodynamic perspective. From this viewpoint the principal action of vitamin D and related compounds is to increase intestinal absorption of calcium irrespective of the underlying pathophysiology and thereby to increase serum calcium, suppress PTH, suppress the turnover of bone and thus to decrease the rate of bone loss in bone-losing states [2]. Whether vitamin D has additional anabolic effects on the formation of bone is uncertain. Even if not, vitamin D treatment could be viewed as a means for the sustained delivery of calcium.The agents most widely used are the parent vitamins, calcitriol and alfacalcidol. Alfacalcidol is a synthetic .analogue of calcitriol that is metabolized to calcitriol by its 25-hydroxylation in the liver. Dihydrotachysterol (DHT) has a similar structural configuration with a pseudo-Iz-hydroxyl in the 3ß position ot the A ring. Like alfacalc...

Calcium Absorption in Postmenopausal Osteoporosis: Benefit of HRT Plus Calcitriol, but not HRT Alone, in both Malabsorbers and Normal Absorbers

“…Treatment with calcitriol has been shown to improve spinal bone density [34] and to reduce the rate of fractures in some [13,35] but not all [22,36] studies of postmenopausal osteoporotic women. Studies in progress on the patients in our trial will show whether those with initially good calcium absorption go on to develop these other favorable responses to HRT and calcitriol, or whether these bone improvements are limited to those patients in whom malabsorption has been corrected with concomitant calcitriol.…”

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“…The reduced absorption of calcium and phosphorus through the intestine also leads to poor skeletal integrity. In children, vitamin D deficiency results in rickets, a bone disease characterized by bowed legs and deformed ribs; in adults, vitamin D deficiency results in osteoporosis (Kanis, 1997; Kanis, McCloskey et al, 1997).…”

Effects of Calcitriol or Calcium on Bone Mineral Density, Bone Turnover, and Fractures in Men with Primary Osteoporosis: A Two-Year Randomized, Double Blind, Double Placebo Study

“…However, there was no evidence of increased bone resorption in the calcitriol group in our study. It is also possible that there is a narrow therapeutic window for calcitriol, and the response to a fixed dose in a population is heterogeneous (30), or that there are gender differences in its effects on bone and mineral metabolism, including bone turnover. In women treated with calcitriol, bone turnover is decreased, and this may partially result from suppression of the activation of bone turnover by PTH.…”