Actonel

The osteoporosis drug Fosamax has been on the market for ten years now. Merck promoted it heavily for the last decade by selling women the fear of a disabling hip fracture and the necessity of regular bone-density measurement tests. Merck's initial ad campaign directed at physicians featured a slender woman in her 40s, thus conveying the erroneous idea that testing was appropriate for this age group.

Estrogen used to be an option for fracture prevention--that is, until the Women's Health Initiative trial found, in 2002, that it posed more risks than benefits. Now Fosamax is the dominant drug for low bone density. Along with two newer osteoporosis medicines Actonel and Didronel, Fosamax is in a drug class known as bisphosphonates. These drugs improve bone density, but where it concerns the more important issue of fracture prevention, their benefit is modest--in fact, very modest.

Some osteoporosis researchers are concerned that this drug, when taken for more than ten years, will make the bones more brittle and more susceptible to fracture. One such researcher is Susan M. Ott, MD, of the University of Washington. In a 2004 letter to Annals of Internal Medicine, she wrote, "Many people believe that these drugs are 'bone builders,' but the evidence shows they are actually bone hardeners."

An expert in bone physiology, Dr. Ott offered this caution, "The drugs deposit in the skeleton for many years, depressing the bone resorption rate as well as the bone formation rate. The bisphosphonates seem safe enough for the first 10 years, but there are theoretical reasons why these drugs might not prevent fractures 20 years into the future: the bones could become brittle with long-term accumulation." These unknowns are one reason why most osteoporosis guidelines committees do not recommend bone-density measurement prior to the age of 60. Also, a woman's risk of a hip fracture under the age of 65 years is low--1%.

Anyone taking a drug for 10 to 20 years should know how effective it is in reducing the fracture rate. While hip fracture is the most serious consequence of osteoporosis, this risk is small and so is the protective effect of Fosamax. In a three-year study of older women with osteoporosis and at least one previous fracture, 2% of the women taking a placebo had a subsequent hip fracture, as compared to 1% of the women on Fosamax. There is no information about the benefit of Fosamax to postmenopausal women who have never experienced a fracture. And not much is known about its effect on men because few studies have included them.

Safe (So Far) But Not Very Effective

An extension of the above-mentioned three-year trial was published last year in the New England Journal of Medicine. The study participants who had been taking a placebo went on Fosamax. For the rest of this ten-year study, all participants were on varying doses of Fosamax. The research team led by Henry Bone, MD, concluded that the drug is safe. Results showed that discontinuation of Fosamax resulted in a gradual loss of bone density. The number of participants was too small, however, to determine Fosamax's effect on the ultimate goal--reducing the fracture rate. The study was financed by Merck with two Merck researchers listed as coauthors.

In the editorial that accompanied this study, Gordon J. Strewler, MD, raised a long list of questions remaining about Fosamax. Among them are: What is the optimal dose and optimal duration of treatment? Is there an eventual point at which the benefit of treatment with regard to protection from fractures will diminish? How rapidly does the risk of fracture increase after Fosamax is discontinued? Could Fosamax be stopped after 10 or more years with continued protection against fractures?

Fosamax is frequently prescribed to people whose bone loss was caused by long-term use of prescribed steroids, such as prednisone. This is a major concern to people with auto-immune diseases, such as asthma, rheumatoid arthritis, and lupus, who are frequently treated with steroids. In their best-selling book, Worse Pills, Best Pills, the authors from Public Citizen's Health Research Group warn against the use of bisphosphonates for people with steroid-induced osteoporosis. Fosamax increases bone mineral density, they wrote, but it also increases fractures of the foot, pelvis, ankle, and hip.

What else is there?

Another osteoporosis drug, Evista, has been proven only to reduce the rate of the less-serious spinal, or vertebral, fractures that often do not produce symptoms. The studies of this drug have lasted eight years. Evista is a selective estrogen receptor modulator. As with estrogen, Evista increases the risk of blood clots.

Calcitonin nasal spray is the safest bone drug, according to Dr. Ott, who cites studies that showed some reduction in vertebral fractures--though less so than the other drugs. Worst Pills, Best Pills strongly disagree, "After 30 years of clinical experience, there is no clear evidence that calcitonin reduces the risk of fracture. In the absence of such evidence, calcitonin should no longer be prescribed for the treatment of patients with osteoporosis."

Weight-bearing exercises are widely regarded as the best way to prevent osteoporosis, and as a result, walking is the most popular form of regular exercise among older women. But it might not provide the preventive benefit we've been led to believe, according to a study published recently in The Lancet. The research team led by Paul M. Mayhew found that walking does not sufficiently load the portion of the bone implicated in a sideways fall--the most likely way older women break their hips.

The researchers concentrated on the top of the thigh bone where it joins the hip socket. Using scanning machines and X-rays, they studied 77 thigh bones from people, aged 20-95 years, who had died suddenly. The researchers zeroed in on the importance of elasticity of the bone tissue in this small portion of the upper femur. "In many societies in which sitting near ground level is usual, hip fracture is rare, even when most women older than 65 years have osteoporosis, as in Gambia. This paradox might be due to the beneficial loading effect on the upper femur of regular standing up from squatting or of subsistence farming," wrote Dr. Mayhew and colleagues.

Based on their findings Dr. Mayhew and colleagues identified sculling, cycling, gymnastics and weights as exercises that should be investigated further for hip fracture prevention because they involve extension of the flexed femur. In the meantime, get rid of the scatter rugs and watch out for certain prescription drugs implicated in falling. Worst Pills, Best Pills contains a long list of prescription drugs that can cause falls and hip fracture. Daily supplements of 1000 mg calcium and 800 I.U. vitamin D3 decrease the likelihood of a first hip fracture, according to a 2005 JAMA review of relevant trials. This is a lower amount of calcium and a higher amount of vitamin D than the longstanding recommendations.

Something to think about

Merck's ads directed to women sell the idea of bone-density measurement ("Ask your doctor"). The pharmaceutical industry has long been aware that screening itself creates customers for its drugs. Years ago, Merck entered a financial arrangement with a company that makes bone-density measuring equipment in order to get these machines in as many doctors' offices as possible. Since the drugs for preventing hip fracture are only marginally effective, give careful thought to undergoing this test. As consumer advocate Barbara Mintzes once put it in the British medical journal, BMJ, "Bone mineral density testing is a poor predictor of future fractures, but an excellent predictor of the start of drug use." And, finally, a little history.

In the not-so-distant past, one would not have been diagnosed with osteoporosis until a fracture occurred. In 1992, the World Health Organization held a conference to see if osteoporosis could be diagnosed before this happened, thus preventing fractures. Co-sponsored with pharmaceutical and medical equipment companies, the WHO committee constructed a new definition of osteoporosis. First, normal was identified as the bone density of a 30-year-old woman, the age at which bone mass peaks. Anyone with a spinal fracture or a -2.5 T-score or worse now had osteoporosis. The -2.5 T score means that the bones are about 32% less dense than those of the average 30-year-old woman.

In time another diagnosis was created called osteopenia, or low bone mass--a T score between -1 and -2.4. One prominent osteoporosis researcher Steven Cummings, MD, University of California School Of Medicine, San Francisco, has stated that there is no medical basis for using that number. In the May 3, 2005 Annals of Internal Medicine, Michael R. McClung, MD, Oregon Osteoporosis Center, wrote, "It is time to abandon the diagnosis of osteopenia based on bone mineral density values and give the term back to radiologists to describe decreased bone mineralization on radiographs." Some osteoporosis researchers have stated that osteopenia rarely requires drug therapy, especially in women under age 65.

For more information

Dr. Ott has an excellent Web site called "Osteoporosis and Bone Physiology." http://courses.washington.edu/ bonephys/ It is aimed at physicians and the general public. She deals with everything from the importance of good nutrition to providing a risk chart so women can put their odds of having a hip fracture in perspective. For example, a 70-year-old woman with osteoporosis and a vertebral fracture has a 3% chance of having a hip fracture in the next five years.

COPYRIGHT 2005 Center for Medical Consumers, Inc.
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