Osteoporosis drugs Bisphosphonates and Calcitonin don’t work

Don’t take the heavily advertised Bisphosphonates (see Box 1), the mainstay of osteoporosis treatment because, among the available medications.  These include Fosamax, Actonel, Boniva, and Zoledronic acid; they don’t work.  They compared raw data given to the FDA and the cooked results submitted to journals for publication.  For primary prevent there was no benefit, and for secondary (already had a hip fracture) only one hip fracture per 100 women over five years entails that the drug is not worth its costs, side effects, and inconvenience.  At 10 years of usage there was no reduction.  Moreover, two recent studies have showed that the big PhARMA cooks the results.

Worst Pills, a division of Public Citizen, is the most respected consumer drug protection group in the U.S.  Their submissions to the FDA have lead to numerous publishing of black-box warnings on prescription drugs and other changes. 

Osteoporosis Fracture Prevention: What You Need to Know about Drugs and other Measures - Part 2

     Worst Pills Best Pills Newsletter article December, 2008
     at http://www.worstpills.org/member/newsletter.cfm?n_id=618

Last month in Worst Pills, Best Pills News we provided a guide to the sometimes overwhelming world of osteoporosis screening. In our article we explained that an osteoporosis diagnosis is usually made by evaluating bone mineral density (BMD), which reflects only bone quantity. Because low BMD is but one of many risk factors for fractures, BMD represents only part of a person’s fracture risk. Other conditions and diseases impact bone quality and quantity and are important risk factors for fractures. This month, we are following up with an overview of osteoporosis drugs. Our emphasis remains focused on the extent to which these drugs reduce the risk of fractures, not simply their effect on bone mineral density

Drugs for Osteoporosis

Several classes of drugs have been developed to treat osteoporosis. These vary in their effectiveness in reducing the risk of fractures.

Bisphosphonates (see Box 1) have become the mainstay of osteoporosis treatment because, among the available medications, they have the best risk-benefit profile. For example, older drugs for preventing fractures, such as estrogens, increase the risk of breast cancer as well as heart disease, and their risks outweigh their benefits. The bisphosphonates are also very heavily advertised.  {The warning concerning estrogens is misplaced.  They are cheap—off –patent—and were unfairly analyzed in one major study--jk.  “The most important risk factors for osteoporosis are advanced age (in both men and women) Estrogen deficiency following menopause is correlated with a rapid reduction in BMD, while in men a decrease in testosterone levels has a comparable (but less pronounced) effect.”—Wikipedia, Osteoporosis}

Bone is constantly being absorbed and reconstructed, a process called “remodeling.” Reconstruction predominates into our 20s, when bone quantity and quality peak. After that, the quantity and quality of our bones begins to decrease and the risk of fractures may therefore increase. In women, the decline becomes more pronounced after menopause.

Bisphosphonates work by interfering with cells that absorb bone.

When to Use a Bisphosphonate

Before beginning any medication, it is important to know how much you stand to benefit because you may be exposing yourself to dangerous side effects. (See the November 2008 issue of Worst Pills, Best Pills News for a review of ways of determining your risk of bone fractures.)

Bisphosphonates are intended to prevent fractures. But the benefit is not the same for all people. A straightforward way to think about how a bisphosphonate might benefit you is in terms of primary and secondary prevention of fractures — when used to prevent a first fracture from occurring, it is called primary prevention; when used to prevent a subsequent fracture from occurring in someone who has already sustained a fragility fracture, it is called secondary prevention.

Sometimes the existing data about a drug make it difficult to understand its effects in straightforward terms. Reflecting this difficulty, a recent analysis of all major clinical trials of alendronate using a slightly different (and technically confusing) definition of primary and secondary prevention, provides a relatively straightforward assessment of its benefits:

Patients taking alendronate for primary prevention (first fracture) had the same number of hip fractures as those taking a placebo; in other words, alendronate made no difference for the most serious type of fracture. Over five years, only two fewer patients out of 100 suffered a vertebral fracture if they took alendronate.

Risedronate (ACTONEL) did not decrease the risk of any fractures for primary prevention. Studies of primary prevention with ibandronate (BONIVA) and zolendronate (RECLAST) have yet to be performed.

When used for secondary prevention of fractures (subsequent fractures), the number of women who would need to be treated with alendronate for five years to prevent one hip fracture was 100. Six fewer patients per 100 sustained vertebral fractures if they took alendronate for five years; these findings are similar for the other bisphosphonates.

These results are not especially impressive. Moreover, little is known about the use of bisphosphonates for longer than five years. A 10-year study of alendronate concluded that patients receiving treatment beyond five years maintained an increased BMD compared to those who stopped at five years; however the number of hip fractures was not statistically different between the two groups. This means that although an indicator of osteoporosis (BMD) was improved, the outcome (the number of hip fractures) for the patients using alendronate was not better than for those who stopped using the drug after five years. Using risedronate for up to seven years maintained BMD, and vertebral fractures occurred at a rate similar to the previous year; however, there was no comparison group of patients who stopped risedronate after five years so there is no way to know if continuing is beneficial.

Serious Side Effects Associated With Bisphosphonates

Bisphosphonates, like all medications, have potential hazards.

Severe ulcers in the esophagus is a well-documented hazard. In order to decrease esophageal irritation and possible ulcers, bisphosphonates (alendronate, ibandronate and risedronate) must be taken with an empty stomach and a full glass of water.

You should remain in an upright position for at least 30 minutes after swallowing the medicine.

Osteonecrosis of the jaw (destruction of the jaw bone) is a very serious complication; it has most often occurred in cancer patients receiving intravenous bisphosphonates (ibandronate and zoledronate), but there are also many cases in people using drugs such as alendronate for treatment of osteoporosis. This side effect often occurs in the context of dental surgery/extractions...

Atrial fibrillation, an irregular and rapid heart beat, is a newly recognized risk being investigated by the Food and Drug Administration. Lastly, incapacitating bone, muscle and joint pain is another known hazardous side effect of bisphosphonates. Additionally, there is growing concern that prolonged interference with bone remodeling cells by long-term bisphosphonate use may actually lead to fractures. (See next month’s Worst Pills, Best Pills News for a more in-depth discussion of this topic.)

Non-Drug measures Can Decrease Fractures

Just as there are many factors that can lead to fractures, there are more options than just drugs for preventing osteoporosis-related fractures.

Falls are antecedent to most fractures. One’s risk of falling is a combination of intrinsic characteristics and extrinsic hazards, some of which can be modified. There are measures that decrease one’s risk of falling and can decrease fall-related injuries, including fractures (see Box 2).

In addition, smoking cigarettes and excessive alcohol consumption both negatively impact bone; quitting smoking and decreasing alcohol consumption can decrease fracture risk.

Bringing it together

Although osteoporosis is an important component of fracture risk, the single-minded focus on drugs for this condition risks neglecting other fracture-reducing interventions. We can achieve better application of limited health care resources with a more thoughtful approach to prevention, incorporating modifiable risks for falling and lifestyle modifications with prudent use of medications, like bisphosphonates, when evidence demonstrates a clinically important reduction in fractures.

Calcitonin (CALCIMAR, MIACALIN) for Osteoporosis - Value Uncertain After 30 Years

Worst Pills Best Pills Newsletter article May, 2002

At http://www.worstpills.org/member/newsletter.cfm?n_id=64

CONCLUSION:

After 30 years of clinical experience, calcitonin’s effect on fracture risk is uncertain. As the 40th anniversary of calcitonin’s discovery approaches, perhaps it is time for all interested parties to reassess this drug’s role in treatment of patients with osteoporosis.

Our conclusion would be more to the point: 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. First, physicians in their everyday medical practice cannot differentiate between a useful drug and one that only leads to increased cost without added benefit to patients. This is the case with calcitonin. It continues to be prescribed, causing economic harm to patients, despite the fact that there is no clear evidence that the drug provides them a meaningful benefit in terms of fracture risk. A second lesson is that when the FDA raises the bar for new drug approvals patients get better drugs. Requiring documentation of the efficacy of a drug in reducing fractures before being approved for the treatment of osteoporosis brought drugs that reduced fracture risk. Though this reduction in risk is very small with the new drugs, it is a large improvement over calcitonin. Unfortunately, the treatment of osteoporosis is one of the few areas where the FDA has raised the bar. Most drugs are still approved — with only the hope — not the proof that they will provide a meaningful outcome for patients.

Danny it isn’t what they say, but what they don’t say.  Goodman & Gilman at 1668 “Although the dug is approved only for the treating hypercalcemia of malignancy, a single injection of zoledronate (zometa) {what you call aclasta} decreased bone turnover markers for 90 days in patients with Paget’s disease.”  The left talk of the bio-mechanism, but not the clinical benefits.  Normally when they fail to, it indicates there isn’t any.  This is especially true for pharmacology text books, since they maintain a higher stander than medical journals.   Since you wanted treatment, you got it.  There isn’t an effective treatment to prevent bone loss, but for hormones.  Estrogen stops it, and the male hormones does the same (I don’t know which is more effective).  However, it seems that nothing reverses the process—except possible exercise. 

For how bad the journal articles are go to http://healthfully.org/index/id9.html

Hypercalcemia an abnormally large amount of calcium in the blood.