Other agerelated endocrine abnormalities

Although decreases in serum sex steroids and increases in serum PTH are by far the most important endocrine abnormalities causing age-related bone loss, there are other abnormalities that contribute variably. The two most important of these are those of the vitamin D—endocrine system and the growth hormone—IGF1 system. Reduced serum concentrations of both the active vitamin D metabolites — 25-hydroxyvitamin D (25[OH]D and 1,25-dihydroxyvitamin D (1,25[OH]2D)—have been demonstrated in both genders with ageing. Serum 25(OH)D is an indicator of vitamin D nutrition. Several population based studies have shown that 25(OH)D decreases by 30—60% with ageing in both genders (Tsai et al 1987). This may contribute to the secondary hyperparathyroidism of ageing because these decreases correlate inversely with serum PTH levels (Khosla et al 1998). Elderly, housebound persons with inadequate exposure to ultraviolet radiation and poor nutrition are particularly prone to vitamin D deficiency which, unless severe, is manifested by osteoporosis, rather than osteomalacia. This is particularly likely in populations living in higher latitudes, such as Great Britain and France, that do not fortify milk products with vitamin D. Indeed, Chapuy et al (1992) have demonstrated that supplementing the diet of elderly, house-bound women from Lyon, France with 800 U/day of vitamin D and 1000mg/day of calcium for 18 months decreased the incidence of hip fracture by 43% over the following 18 months. Also, serum levels of the physiologically active vitamin D metabolite, 1,25(OH)2D decrease with ageing (Manolagas et al 1983), at least relative to the concomitant increases in serum PTH (Eastell et al 1991). Because infusions with the trophic hormone, PTH, result in a blunting of the increase in serum 1,25(OH)2D levels relative to young adults (Tsai et al 1984), ageing may result in a primary deficiency in the renal enzyme, 25(OH)D 1a-hydroxylase, that is responsible for the conversion of 25(OH)D to 1,25(OH)2D, and this may also contribute to the secondary hyperparathyroidism and increased bone resorption with ageing.

There is indisputable evidence that ageing decreases the amplitude and frequency of growth hormone secretion (Thorner & Vance 1988). There is also a 60% decrease in serum IGF1 levels with ageing and a smaller decrease in serum IGF2 levels (Bennett et al 1984). Whether the decreased serum IGF1 levels are due to a decreased production of hepatic or skeletal IGF1 production or increased plasma clearance is still unclear. Nonetheless, these abnormalities may contribute to the decreases in osteoblastic function in elderly men and women. They may also contribute to the progressive, age-related increases in serum SHBG levels in men which is a major cause of their decreases in serum bioavailable sex steroids and, thus, to their slow phase of bone loss.

Other changes in endocrine function with ageing appear to make smaller contributions to bone loss. There are decreases of almost 70% in serum dehydroepiandrosterone (DHEA) and DHEA sulfate in elderly women and men (Meikle et al 1991). However, this is a relatively weak adrenal androgen and, its importance, if any, in bone loss is problematic. In contrast to the decrease in bioavailable anticatabolic sex steroids with ageing, the concentration of plasmafree cortisol, a catabolic steroid, increases by 20—50% (Van Cauter et al 1996). Thus, the increased catabolic/anti-catabolic ratio of circulating steroid hormones with ageing could contribute to bone loss.

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