A limited menu of medication

The menu of medications approved for the treatment of osteoporosis is slim.

There’s hormone replacement therapy (HRT) – estrogen and progesterone; there’s fluoride and calcitonin; and there are the recently arrived bisphosphonates, etidronate and alendronate (Fosomax). And that’s about it.

Everything after that, says Dr. Gillian Hawker, Research Director of the Multi Disciplinary Osteoporosis Program at Women’s College Hospital in Toronto, “is basically investigational,” meaning all other drugs or treatments in the pipeline – such as parathyroid hormones, which just started randomized trials – still have a way to go before they come to market, if ever they do. Raloxifene, for example, is the first in a new class of medications called SERMS (selective estrogen receptor modulators), which may offer some of the benefits of HRT – without the same risks. According to the October ’97 issue of the Mayo Clinic Health Letter, raloxifene hydrochloride is expected to receive FDA (American Food and Drug Administration) approval within the next year. Hawker is testing raloxifene in Canada, but it will be several years before it’s approved for use here — assuming it passes must with Hawker and her colleagues.

Fluoride, on the other hand – or sodium fluoride – has been available for years, though it’s used rarely. It got a bad rap in the mid to late ’80s, when it was given to test patients in a clinical trial in very high (80 mg) dosages. “Nobody uses 80 mg,” Hawker says. At that dosage, “you produce abnormal bone, so even though the density of the bone looked better, it actually was more brittle. We tend to use 20 mg (maximum 40 mg) but that study gave fluoride a very bad name, and no further studies have been launched.”

In the body, calcitonin is a natural antiresorptive agent (meaning it helps regulate bone loss) produced by the thyroid gland. It’s also available synthetically, in injectable and nasal spray formulations, though it’s not used often; physicians occasionally use it in patients with osteoporosis who can’t tolerate HRT or bisphosphonates.

The new kids on the block, the bisphosphonates, are creating a lot of noise, not only because they increase bone mass and reduce fractures, but because they provide an effective alternative to HRT. Only etidronate and alendronate have been approved here in Canada to date, but more bisphosphonates are on the horizon. Etidronate is given in two week cycles every three months, while alendronate is given daily.

As ICES (the Institute for Clinical and Evaluative Sciences in Ontario) reported in a supplement to its June 1997 issue of informed, bisphosphonates are clearly appropriate for someone who’s already had an osteoporosis induced fracture, though it’s not as clear whether patients who’ve not suffered one should receive prolonged bisphosphonate therapy to prevent future fractures.

Nor are bisphosphonates approved to prevent osteoporosis in menopausal women who’ve been diagnosed as having osteopenia (reduced bone mass, a precursor to osteoporosis); and patients over the age of 70, ICES suggested, “might be treated more conservatively with calcium and vitamin D supplements, followed up with repeated [bone density tests].”

Side effects – mostly gastrointestinal symptoms – are minimal, and, although there’s little clinical evidence as yet, most doctors believe bisphosphonates should be equally effective in treating osteoporosis in men.

Alendronate and etidronate are more or less equally effective, depending on the individual, though alendronate “probably does work faster,” Hawker says, “and it may be slightly more potent, i.e. have a better response over the long term. But we’ve never had a head to head comparison of the two drugs, so it’s a bit of a trade off — cost and side effects for a bit more potency.” In one form or another, etidronate is on provincial formularies right across the country; alendronate isn’t on a single one. That’s because new medications must prove they can offer distinct advantages over what’s already available before they’ll be put on a formulary; alendromate was turned down because it was too similar in its activity and effectiveness to etidronate and too expensive, Hawker says. But most private drug plans cover it. “I haven’t found one recently that hasn’t covered it,” she says.

Hormones (in patches, creams and oral formulations) are still first line therapy, not only because they have a good effect on bone, but because they also have a beneficial effect on the heart, and menopausal symptoms, such as hot flashes, thinning of the vagina wall and insomnia. (Bisphosphonates only affect bone.)

HRT is the single most important way for a woman to reduce her risk of developing osteoporosis during or after menopause. Although HRT can help to prevent bone loss at any time after menopause, best results are achieved by starting as soon after the onset of menopause as possible, and continuing for up to 10 years. Studies have shown that HRT not only prevents bone loss, but reduces the risk of spinal and hip fractures by some 50 per cent. In women who already have osteoporosis, HRT can help rebuild bone by as much as five per cent in the hip and up to 10 per cent in the spine.

What’s made HRT controversial is its association with breast cancer, a spectre that prevents many women from seeing the whole picture, says U.S. journalist Malcolm Gladwell. Writing in the June ’97 issue of The New Yorker, Gladwell noted that only a quarter of women who begin HRT after menopause stick with it for more than two years, one of the major reasons being “the persistent inclination of many women to overestimate their risks of getting breast cancer and underestimate their risks of developing heart disease.”

There has been research showing an increased risk of breast cancer in women taking HRT, but there have also been studies showing the opposite.

According to the Mayo Letter, “About half the studies of women taking estrogen replacement [HRT] found a slight increase in breast cancer, and half found a small decrease. The increase in risk occurred in long term use – longer than 10 years. Experts tend to agree that while there may be an increased risk of breast cancer from long term estrogen use, the benefits may offset the risks.”

“Because heart disease is so much more common than anything else, and because hormones definitely reduce the risk of fatal heart attacks and stroke – heart attacks for sure – hormones are always going to be first line,” Hawker says.

There are some important cautions, however: HRT’s not advisable for women who’ve already had breast or uterine cancer, and oral estrogen isn’t recommended for women with high blood pressure or a tendency to form blood clots. HRT can also cause fluid retention, sore, tender breasts and uterine bleeding in some women, though some symptoms can be reduced by careful management.

The bottom line? Before making any decision about HRT, talk to your doctor about your personal risks and benefits.