These days, medicine is waxing optimistic about osteoporosis, announcing that there are more opportunities than ever before to make this crippling disorder a disease of the past. All that needs to be done is to overcome a few obstacles concerning treatment. But what these obstacles amount to are questions of basic safety and effectiveness - not least of which is whether some of the solutions to osteoporosis may actually cause the problem.
The most popular preventive medicine for osteoporosis - one of the great rationales for its use - is hormone replacement therapy (HRT). A number of studies indeed have shown that HRT retards bone loss in postmenopausal women. However, many of these results may be illusory. One early study puzzled HRT enthusiasts because it showed that women who'd used HRT lost bone faster that did untreated women once the hormone treatment was withdrawn (Lancet, 1979; ii:33.) But later research has demonstrated that you need to take HRT for at least seven years for a long-term protective effect on bone mineral, and even this may not be enough to protect women 75 years and older from fracture -t he age at which women are most at risk (N Engl J Med, October 14,1993).
What most people don't realize is that bone loss accelerates rapidly in women once they stop using estrogen, causing a 'catch-up' effect with those who'd never taken HRT. By age 80, women who had taken HRT for 10 years, starting soon after menopause, would lose 27 per cent of their initial bone density, while those never treated, about 30 per cent. The only solution would be to start on HRT once menopause began and to continue taking it for the rest of your life. This, of course, would have to be offset against your hugely increased risk of developing breast or endometrial cancer. It's well established that HRT increases the risk of breast and endometrial cancers, and that the longer a woman uses it, the greater the risk.
Contrary to what most doctors believe, estrogen only seems to have a temporary effect. Although it may decrease the rate at which old bone is torn down, formation of new bone eventually decreases in some three to five years, anyway. Indeed, one review of 31 studies on osteoporosis and estrogen concluded that estrogen did not have 'significant benefit' in slowing the onset of osteoporosis (Am J Med,1988; 85: 847-50).
A study comparing exercise alone with exercise plus calcium supplementation or exercise plus HRT in postmenopausal women with low bone mineral density (BMD) concluded that bone loss can be slowed or prevented by exercise plus calcium supplementation, or exercise plus HRT. Although the latter was more effective than the former in increasing bone mass, it also had more side effects. These included vaginal bleeding in 52 per cent of the women who hadn't had a hysterectomy, compared with less than a quarter of that in the exercise group and in the exercise-calcium group. Seven women in the exercise-HRT group needed a D & C. In addition, more than twice the women in the exercise-HRT group (47 per cent) had breast discomfort than the other two groups (N Engl J Med, Oct 24,1991).
Not all HRT studies have shown a positive effect. One study found that it didn't protect women with a history of osteoporosis even after 16 years of use (Ann Intern Med, 1995; 122: 9-16).
The other big question is whether estrogens or progestogens actually cause osteoporosis. Hormone replacement therapy usually consists of estrogen, or an estrogen-progestogen mixture, and there has been some concern over a possible link between progestogens and osteoporosis. One recent study found that women who had been using medroxyprogesterone as a contraceptive and then stopped increased their spinal bone density, whereas women who carried on using it, or who had never used it, did not (BMJ, Mar 12,1994).
Dr Kitty Little, an Oxford researcher, has spent many years studying the effects of hormones on bone marrow. In a number of experiments on animals, Dr Little observed that one effect of estrogen-progestogen combinations is to distort large cells in the bone, leading to a huge increase in abnormally sticky platelets, or tiny blood clots. These can interfere with the blood supply to the trabecular, spongy bone mainly found in the spinal vertebrae. Dr Little believes that HRT will eventually cause, rather than cure, osteoporosis because of these numbers of tiny blood clots in the bones (Bone Behaviour, Academic Press, London, 1973. See Sexual Chemistry by Dr Ellen Grant, Cedar, 1994).
Besides HRT, the drug of choice if you've already got osteoporosis is usually sodium etidronate, a non-hormonal, bisphosphonate drug which sticks to the bone surface and makes the osteoclasts (cells that break down bone) less effective. This supposedly allows the osteoblasts (cells that build up bone) to work more efficiently. Etidronate has yielded quite good results in the treatment of established spinal osteoporosis, which is the only form of osteoporosis it is licensed to treat. However, ironically, it can adversely affect bone mineralization, increasing bone pain and the risk of fractures if used in high doses or for prolonged periods. This is why it is only given on an intermittent, restricted dose basis for a maximum of three years.
Of the two main studies of etidronate with calcium (sold as Didronel PMO) (both supported by Norwich Eaton, the manufacturer of the drug), one discovered a significant increase in bone mass and a 50 per cent reduction in vertebral fractures in the etidronate-treated groups. There was an even greater reduction (two-thirds) in the fracture rate in patients with the lowest bone mass. However, one of the strange outcomes in this study was that the groups receiving etidronate had a slightly higher rate of non-vertebral fractures than the controls, leading two doctors from Tulane University Medical Center in New Orleans to argue that the drug is not as 'extraordinary' as the study would have us believe. The authors of the study countered that these were due to trauma rather than osteoporosis. Those not getting the drug also had a small increase in spinal bone density, when it was expected to decrease. The authors explained this as being due, in part, to calcium supplementation (N Engl J Med, July 12,1990).
According to the Drug and Therapeutics Bulletin (June 8, 1992), etidronate is supposed to be restricted to postmenopausal women (hence the initials 'PMO') and started only once a vertebral fracture has been detected and osteoporosis confirmed. (Ironically it noted that since this is unlikely until the patient is in her 70s or 80s, using the drug to prevent further breaks has 'less impact.') Nevertheless, the drug is licensed to be used by women - and men - of all ages, and some doctors have been known to prescribe this drug as a preventative in women before they have the disease.
Etidronate is also known to be retained in bone for a long period - to unknown effect. In at least one instance, it has been shown to interfere with radioisotopic bone scans (N Engl J Med, December 6, 1990) - a test for osteoporosis.
Another popular treatment is supplementing with fluoride. Any excess fluoride not excreted collects in the bones. Although fluoride does increase bone mass and density, it also seems to make bones more brittle. In one four-year clinical trial, fluoride (plus calcium) treatment not only did not reduce the rate of vertebral fractures, but caused twice as many hip fractures. Pain in the lower extremities was so severe in some patients they needed crutches (N Eng J Med, Mar 22,1990). Four other recent studies show a higher incidence of hip fractures in the elderly in areas where the water is fluoridated (see WDDTY vol 3 no 9).
Perhaps the most popular preventive medicine is megadosing with calcium. A study undertaken by the Department of Medicine, University of Auckland, New Zealand, corroborated what 26 earlier and less-controlled studies suggested - that taking calcium can slow or prevent osteoporosis. The average rate of loss of total body BMD was reduced by 43 per cent in the calcium group compared to the placebo group, with bone loss in the legs of the calcium group reduced by 35 per cent and eliminated altogether in the trunk (N Engl J Med, Feb 18,1993).
Nevertheless, other studies show that as much as 2 g per day of calcium supplements for two years didn't appreciably reduce bone loss in postmenopausal women (Sexual Chemistry). Nutritional researcher Dr Melvyn Werbach notes that many calcium studies showing a daily need of a gram or more have been criticized as being subject to inaccuracies. And calcium intake is disturbed by the high phosphorus content of the typical Western diet.
The solution is far more complicated than simply wolfing down glasses of milk or calcium pills, as most doctors now recommend. At Biolab in London, researcher Dr John McLaren Howard studied the nutritional profiles of a number of patients with osteoporosis and compared them with controls, menstruating women, postmenopausal women with no osteoporosis and postmenopausal women on HRT. His astounding conclusion: none of the women studied, whether they had osteoporosis or were taking HRT, had low calcium levels (Curr Res in L,dteo and Bone Mineral Meas II, British Institute Radiology, London, 1992).
Nevertheless, Biolab discovered that osteoporotic women were markedly low in many other nutrients associated with bone development and the bone enzyme alkaline phosphatase. This enzyme helps (with magnesium) to form calcium crystals in the bone and so is an indicator of whether new bone is being laid down. The lowest levels of alkaline phosphatase in Dr Howard's study were women with osteoporosis on HRT. Low levels were also observed of magnesium, zinc, manganese and vitamin C among the osteoporosis group, but were even lower in the HRT group. A vitamin C deficiency can cause osteoporosis (Br J Clin Prac,1963;17: 332-40), vitamin D is necessary for calcium absorption, and zinc and manganese are necessary for bone mineralization. Fluoride has also been found to inhibit alkaline phosphatase (Townsend Lett Docs, `r4/March 1985).
Dr Guy Abrahams, an American researcher who has also studied the nutritional profiles of women with osteoporosis, believes that magnesium, rather than calcium, deficiency is responsible for osteoporosis. Magnesium is necessary to activate alkaline phosphatase. He divided a group of women on HRT who'd undergone premature menopause and gave half magnesium. After nine months, the bone mineral density in the women taking the supplements had increased by 11 per cent, while there was no increase in the women taking HRT without nutritional supplements. Although 15 of the 19 women had a BMD below what is likely to cause spinal fracture, after a year, only half still had bones that were too thin (J Nutr Med, 1991; 2:165-78).
Interestingly, Dr Ellen Grant says that in her studies in the 60s of the Pill, the levels of this enzyme were also decreased by progestogen.
Deanne Pearson and Lynne McTaggart