New cures for brittle bones

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Hip-hip-hooray! Pardon the pun ... but today our hips and wrists and spines--our most breakable bones--really do have something to cheer about. The U.S. Food and Drug Administration (FDA) recently approved two new medicines (and currently is considering a third) to treat osteoporosis, the brittle bone condition that strikes half of all women age 50 and older.

If you scored low on your bone-density test (see Prevention's "Size Up Your Bones ... Now!" February 1996, for screening guidelines)--or if you've already broken a bone due to osteoporosis--this could be welcome news. But before you ask your doctor for a prescription, there's much you should know--and consider.

Still First Choice
HORMONE REPLACEMENT

Among the nation's top osteoporosis experts we interviewed there was unanimous agreement: Despite the new drugs on the block, hormone replacement therapy (HRT) remains the osteoporosis treatment of choice for most women past menopause. For two simple reasons. First, it's tried and true. Lifestyle factors (like consuming adequate calcium and getting regular weight-bearing exercise), while important, are usually not enough to stem the bone drain that occurs after menopause. But estrogen replacement can. The bone-strengthening effect of estrogen replacement on postmenopausal women has been documented over many years of research, longer than any other osteoporosis drug out there. In fact, a major study of nearly 10,000 women 65 and older who started estrogen within five years of menopause and continued taking it found risk of hip fracture less than a third of that in women who never used estrogen (Annals of Internal Medicine, January 1, 1995).

Second, hormone replacement therapy is the only bone-protecting medication that also delivers multiple health benefits. For example, HRT cuts in half the risk of death from heart disease, the leading cause of death among women when all ages are combined. No wonder doctors continue to urge every woman to consider HRT at menopause--or any time after menopause--when low bone density threatens her health.
NOT YOUR CHOICE?

But HRT isn't for every woman--or for every woman's bones. In a small percentage of cases, bones don't respond adequately to the standard bone-protecting dose of estrogen, explains David Baylink, M.D., distinguished professor of medicine at Loma Linda University and chief, mineral metabolism laboratory at the Jerry L. Pettis Veterans Administration Hospital in Loma Linda, California. More often, however, HRT is ruled out because other health conditions prohibit its use or because a woman makes a decision not to take it.

Certainly if you have active breast cancer or liver disease, you absolutely should not take estrogen. If you've had migraines or deep-vein blood clots--both of which can be aggravated by HRT--you may opt against it. Or maybe you're reluctant to commit to HRT because of potential side effects like continued menstrual bleeding or uncertainties about breast-cancer risk. (Some studies show a slightly increased risk of breast cancer from estrogen use; other studies do not.)

Whatever your reason, the point is this: Without hormone replacement, you had no truly effective way to stop the downward slide in bone density after menopause. Until now. Today you have two new FDA-approved alternatives to HRT: alendronate (trade name Fosamax) and nasal spray calcitonin (trade name Miacalcin), formerly available in injectable form only. Plus, slow-release sodium fluoride--potentially an even more powerful weapon against osteoporosis--is being reviewed by the FDA. (Final FDA approval is likely, though not assured.)

While our experts say it's too soon to give absolutes as to which patient should use which drug, they offered recommendations to help us all "bone up" on the new possibilities.

Your Second Choice
ALENDRONATE

You are an ideal candidate for alendronate if you are five-plus years past menopause with borderline or low bone density (as determined by a bone-density test) and you can't take estrogen. "I think alendronate should be considered the first-line osteoporosis therapy for any woman who's not taking estrogen," says Ethel Siris, M.D., director of osteoporosis programs for the Women's Health Center at New York's Columbia Presbyterian Medical Center. So far alendronate has been tested and approved only for women five or more years past menopause. In a three-year study of women five-plus years past menopause, daily alendronate combined with a 500 milligram calcium supplement (from calcium carbonate) resulted in an average gain of nearly 9 percent bone mass in the spine and nearly 6 percent in the hip. This uptick in density may sound puny, but small increases in bone mass can mean significant reduction in fractures. In fact, in this study, alendronate cut fractures of the spine in half! (New England Journal of Medicine, November 30, 1995).

Alendronate is worth considering even if less than five years have passed since your menopause but you have borderline or low bone density and you can't take estrogen. While this is considered prescribing "off label" because the drug is still being tested on younger menopausal women, the doctors we consulted considered it a reasonable option. After all, if you can't take estrogen, your only other alternative is to rely completely on a bone-healthy lifestyle, which has its limitations after menopause. So while alendronate's benefits to you haven't yet been established, it's probably worth trying. "I can't guarantee alendronate will have the same effect as it does in older postmenopausal women," says Dr. Siris. "The studies haven't been published yet showing that." Keep in mind, too, that side effects on younger women are not fully known either.

... or if you are premenopausal with very low bone density (or you've already broken a bone due to osteoporosis) and you can't use estrogen.

Of course, the same caveats pertain as above--but in premenopausal women, the unknowns regarding side effects must be weighed very, very carefully. Of particular concern is the effect this medication might have on a developing fetus.

... or if after six months on HRT at the standard estrogen dose of 0.625 mg. your rate of bone loss hasn't been reduced (as determined by blood or urine tests).

If, however, estrogen's heart or other health benefits are important to you, your doctor may prescribe a combination of estrogen and alendronate. "It's not recommended in the package insert to take them together. That's because it hasn't been studied, although studies are now under way," explains Robert Recker, M.D., an alendronate researcher and director of the osteoporosis research center at Creighton University School of Medicine in Omaha, Nebraska. "The combination of penicillin and digitalis hasn't been studied either, yet if someone on digitalis needs penicillin, doctors prescribe it anyway. This is the same thing."

How it works Like estrogen, alendronate works by stopping bone loss. Though we think of our bones as unchanging, like the girders in a skyscraper, the truth is, they're continuously undergoing change. At any given time, 5 to 10 percent of our bone mass is being eaten away by special cells whose job is to come along and dig holes in old bone.

For a short while, these holes lie dormant. Then, special bone-building cells show up to fill existing holes with fresh new bone. Start to finish, the whole cycle takes about three months--but depending on your age and other factors, the bone you remove isn't always completely replaced by new bone. That's how osteoporosis happens. Too much bone digging or too little bone building ... and you've got trouble. Alendronate fights osteoporosis by stopping the bone-digging process. A mixture of phosphorus and carbon, it adheres to bone surfaces, preventing bone loss. You see a small increase in total bone density--even though alendronate works by halting bone removal --as a result of existing holes being filled with new bone.

Yet to be determined One concern is that alendronate attaches so well to bone it may remain there forever. Since experience with alendronate is limited, physicians don't really know what the results of that might be. It's known that alendronate slows or stops bone loss in the first year of treatment. But "what isn't certain is what's happening during years two and three," says Dr. Recker. "The study we did showed a continuing increase in bone mass after year one. We would like to think that shows that alendronate increased bone building and also slowed bone loss. We're all anxiously awaiting data from further studies."

Potential side effects and precautions There's a small possibility of minor GI complaints, such as bloating or heartburn (if you have an ulcer, alendronate may not be for you). Alendronate should not be taken by people with low blood calcium, severe kidney disease, or pregnant and nursing women.

For best results You'll need to follow specific instructions when you take alendronate, since it's very poorly absorbed--only 2 to 3 percent of each dose. You must take it on an empty stomach, first thing in the morning, with a glass of water only. Then wait 30 minutes before eating or drinking anything else; Dr. Recker says waiting one hour is better. Don't lie down during this time if GI irritation is a problem. And don't forget to get your calcium--though not at the same time you take your alendronate.

Your Third Choice
NASAL SPRAY CALCITONIN

You are an ideal candidate for nasal spray calcitonin if you're over age 65, have lost height due to compression fractures of the spine or have broken any bone due to osteoporosis, and you can't take estrogen or alendronate. Studies indicate that calcitonin may not be as effective as estrogen or alendronate at bolstering bones. But it is a good option for some women with osteoporosis who are unable to take the other drugs and seems to work especially well in women 65 and older, says Dr. Baylink, who has conducted research on this drug.

Without doubt, ease of use is one of nasal spray calcitonin's great advantages. (It comes in glass bottles, ready to spray.) "If I have an older woman who's just had a fracture and for whom estrogen seems unrealistic and perhaps who isn't happy with the way she'd have to take alendronate and maybe had an ulcer five years ago, a squirt of calcitonin in the nose once a day is very easy," Dr. Baylink explains. Moreover, calcitonin's best effect may be on the bone of the spine. It has been shown to increase spinal bone density by two to three percent, which means fewer fractures. A recent study found that women who used nasal spray calcitonin for two years had a 60 percent reduction in the number of new spinal fractures (Calcified Tissue International, March 1995).

Another plus: Calcitonin often helps relieve the pain that accompanies fractures of the spine.

Nasal spray calcitonin is worth considering even if you haven't celebrated your sixty-fifth birthday but you're past menopause, have low bone density and can't take estrogen or alendronate.

... or if you are premenopausal with very low bone density (or you've already broken a bone due to osteoporosis) and you can't use estrogen or alendronate.

This would be considered an "off label" use of nasal calcitonin, since it hasn't been studied. "But in my mind there is potentially a lot to gain and very little to lose in applying nasal calcitonin to this group of women," says Dr. Baylink.

... or if, after six months on HRT at the standard estrogen dose of 0.625 mg., your rate of bone loss hasn't been reduced (as determined by blood and urine tests) and you are not a good candidate for alendronate.

If, however, estrogen's heart or other health benefits are important to you, your doctor may prescribe the off-label combination of estrogen and nasal calcitonin. The two drugs actually complement each other in their action to decrease bone loss, in Dr. Baylink's opinion. In fact, he sometimes prescribes a lower dose of estrogen (0.325 mg.) to ease menopausal symptoms along with nasal calcitonin to slow bone loss.

How it works Calcitonin is a hormone manufactured in the human body. Sometimes you'll see this drug identified as salmon calcitonin. That's because nasal-spray calcitonin is a synthetic version of the calcitonin manufactured by salmon, closely related to human calcitonin but 50 times more powerful. Like estrogen and alendronate, calcitonin works by inhibiting bone loss. Calcitonin attaches to the cells that chew up bone and slows them down. It also drops the number of these cells. But, unlike alendronate, calcitonin is rapidly processed and eliminated from the body once it has done its work.

Possible side effects and precautions Luckily, not much to report. A few users have minor nasal irritation that usually goes away in a week or two.

For best results Again, adequate calcium and vitamin D intake are essential.

Coming Soon?
SODIUM FLUORIDE

If slow-release sodium fluoride is approved by the FDA, it may jump to the top of the "anti-osteoporosis medication" list because it's the first medication that works by revving up bone-building cells to stimulate substantial new bone growth.

Studies show increases in spinal bone density from taking slow-release sodium fluoride of 4.8 percent a year for four years--a whopping total of almost 20 percent! Hip-bone density (tougher to build than the spine) increased almost 10 percent! That may be enough to protect even high-risk women with very low bone densities (Annals of Internal Medicine, September 15, 1995). "This is an exciting time," says Dr. Baylink.

"We can't regenerate an ailing heart or liver," he says, "but if sodium fluoride is approved, we can tap into the body's ability to regenerate lost bone." It's possible that someday you may take sodium fluoride even if you have only moderate bone loss.

Dr. Siris notes that slow-release sodium fluoride may work best of all in such women. "It may be that you still have to have some bone there on which to grow new bone. If your bone is a bunch of holes, there's no tree to put leaves on."

Potential drawbacks: resolved Early studies using a rapid-release fluoride at much higher doses were less than successful--causing stomach ulcers and generating weak, fracture-prone bone. The new formulation of slow-release sodium fluoride seems to have solved those problems. A wax honeycomb structure keeps the fluoride from being released until it reaches the small intestine, protecting the stomach.

The weak bone in previous studies probably came about because the dose of sodium fluoride was too high. Bone was made so fast that subjects couldn't take in enough calcium to build strong bone, says Khashayar Sakhaee, M.D., professor of medicine, Center for Mineral Metabolism and Clinical Research at the University of Texas Southwestern Medical Center, Dallas. Dr. Sakhaee helped develop the lower-dose slow-release sodium fluoride.

Recent studies with slow-release sodium fluoride (plus 800 mg. calcium from calcium citrate supplements daily) have found that new-built bone is quite strong. Rates of new spinal fractures were reduced by 70 percent (Annals of Internal Medicine, September 15, 1995).

Another potential advantage You may not need to take slow-release sodium fluoride for life in order to enjoy the benefits. (Other osteoporosis drugs appear to stop protecting your bones if you stop taking them.) "At this point, it looks like seven years of treatment with sodium fluoride may deliver life-long protection from osteoporosis," Dr. Sakhaee says.

Until this is confirmed, however, slow-release sodium fluoride will be prescribed with calcium for 12-month cycles, followed by 2 months on calcium alone. During treatment, Dr. Sakhaee says it's essential to monitor blood-fluoride levels (a simple lab test) and urinary calcium excretion (to make sure patients are taking and absorbing enough calcium to make strong new bone with). Bone-density tests are essential as well, so treatment can be discontinued when new bone growth is sufficient. The bottom line? Today, thanks to bone-density tests, we can detect when bones are getting into trouble. And thanks to these brand-new osteoporosis-fighting drugs plus HRT, we can do something about it before bones break.

"We can stop osteoporosis from happening," says Dr. Siris. That's news worth boning up on.

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--by Holly McCord, R.D., with Toby Hanlon

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