VIEWS & REVIEWS

h h rm n : p t nti I u in th Id rl

-Martin Harris-

Growth hormone (GH) may not be the panacea for aging or the fountain of youth, but it may have a role in cell protection. In this way, it could provide elderly patients with greater independence by protecting against osteoporosis, increasing muscle strength and possibly even reducing cholesterol levels. This was concluded at a symposium on the use of GH for preventing physical frailty in older persons, sponsored by the US National Institute on Aging. The symposium was held at the recent XVth Congress of the International Association of Gerontology in Budapest, Hungary.

The administration of GH to elderly people results in several changes that could help to prevent osteoporosis. For example: • urinary nitrogen and protein secretion are reduced • parathyroid hormone, osteocalcin and collagen

levels are increased • serum calcium levels remain constant while urinary

calcium levels are increased • serum phosphate levels are increased while urinary

phosphate levels are decreased. These changes suggest that GH acts anabolically

and aids bone remodelling. Normally, remodelling leads to a net loss of bone in older patients, due to reduced efficiency of osteoblasts relative to osteo­clasts. However, the efficiency of the process may be enhanced by GH, which through insulin-like growth facton (IGFt), stimulates the proliferation and differentiation of osteoblasts. Studies have shown that the loss of bone mineral density in Ward's triangle in elderly patients can be prevented by the administration of GH over 1 year. However, 1 year is not a long time when looking at changes in this parameter, so these results must still be considered preliminary. In addition, many of the changes noted have only been small.

Why should GH be useful in the elderly? GH has some direct properties on cells such as

osteocytes. However, most of the actions of GH are mediated through IGF) and the circulating binding proteins, of which IGF-BP3 is the most important in the production of the anabolic effects of GH.

With increasing age, there is a significant decline in the levels of circulating GH and IGF) . This may be due to reduced GH-releasing hormone levels or to increased levels of somatostatin (an inhibitor of GH release).

Both the number and the amplitude of GH pulses observed during a 24h period decline to almost un­detectable levels after the age of 40 years.

In addition, basal levels of IGF1 are reduced with increasing age, and there is also a decrease in the

amount of IGF) produced in response to exogenous GH administration.

Further evidence for the impairment of the GH axis with increasing age is provided by the effect of exercise on GH. In young people, exercise stim­ulates GH release, whereas no such increase was observed in old people after exercise involving 12 stations of Nautilus exercise machines.

Data point to role in osteoporosis In studies comparing patients with osteoporosis and those with osteoarthritis, patients with osteo­porosis had significantly reduced GH responses. In

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addition, elderly patients with osteoporosis have significantly lower levels of IGF) and IGF-BP3 than age-matched controls. This suggests that patients with osteoporosis have a relative GH deficiency.

These are just some of the data that point to a role for GH in the elderly. Other potential beneficial effects include: • an increase in lean body mass • a decrease in the percentage of body fat • an increase in vertebral bone density • a decrease in serum cholesterol levels (this has

been seen after just a few days of therapy, but such results have not been replicated in all studies)

• an increase in muscle strength • an increase in mobility • improved healing of fractures and leg ulcers • improved nitrogen balance resulting in better

prognosis after surgery or in patients with pulmonary disease.

Future cIirectiom The role of GH in diseases associated with aging

involves extremely complex interactions with other hormones, binding proteins, receptors and cell membranes. Longer-term studies of GH in combi­nation with estrogens in women and androgens in men for the prevention of osteoporosis are indicated.

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