Femur Fractures Bisphosphonate Treatment

WOMEN'S MEDICAL ISSUES, WOMEN'S HEALTH

Femur Fractures Bisphosphonate Treatment

I just added this before becasue bisphosphonates are worse than thought. They improve bone density by being absorbed long-term by the bones. They do not promote calcium absorption, and not being calcium they fail to signficantly reduce bone fractures based on journal articles--which always must be considered biased.

FDA: Possible increased risk of thigh bone fracture with bisphosphonates

http://www.fiercepharma.com/press_releases/fda-possible-increased-risk-thigh-bone-fracture-bisphosphonates-0

FDA: Possible increased risk of thigh bone fracture with bisphosphonates
Labeling change adds warning about possible risks of long-term use of osteoporosis drugs

The U.S. Food and Drug Administration today warned patients and health care providers about the possible risk of atypical thigh bone (femoral) fracture in patients who take bisphosphonates, a class of drugs used to prevent and treat osteoporosis. A labeling change and Medication Guide will reflect this risk.

Bisphosphonates inhibit the loss of bone mass in people with osteoporosis. Bisphosphonates have been shown to reduce the rate of osteoporotic fractures -- fractures that can result in pain, hospitalization, and surgery-- in people with osteoporosis. While it is not clear whether bisphosphonates are the cause, atypical femur fractures, a rare but serious type of thigh bone fracture, have been predominantly reported in patients taking bisphosphonates. The optimal duration of bisphosphonate use for osteoporosis is unknown, and the FDA is highlighting this uncertainty because these fractures may be related to use of bisphosphonates for longer than five years.

The labeling changes and Medication Guide will affect only those bisphosphonates approved for osteoporosis, including oral bisphosphonates such as Fosamax, Fosamax Plus D, Actonel, Actonel with Calcium, Boniva, Atelvia, and their generic products, as well as injectable bisphosphonates such as Reclast and Boniva.

Labeling changes and the Medication Guide will not apply to bisphosphonates used for Paget's disease or cancer/hypercalcemia such as Didronel, Zometa, Skelid, and their generic products.

"The FDA is continuing to evaluate data about the safety and effectiveness of bisphosphonates when used long-term for osteoporosis treatment," said RADM Sandra Kweder, M.D., deputy director, Office of New Drugs in the FDA's Center for Drug Evaluation and Research. "In the interim, it's important for patients and health care professionals to have all the safety information available when determining the best course of treatment for osteoporosis."

Today's warning follows a March 10, 2010, Drug Safety Communication announcing the FDA's ongoing safety review of bisphosphonate use and the occurrence of atypical femur fractures. The FDA has since reviewed all available data on bisphosphonate use, including data summarized in the American Society for Bone Mineral Research Task Force report. The report recommended additional product labeling, better identification and tracking of patients experiencing these breaks, and more research to determine whether and how these drugs cause the serious but uncommon fractures.

Based on the FDA's review, the Warnings and Precautions section of all bisphosphonate products for osteoporosis will be revised, and the FDA will require the inclusion of a Medication Guide to better inform patients of the possible increased fracture risk.

The FDA recommends that health care professionals be aware of the possible risk in patients taking bisphosphonates and consider periodic reevaluation of the need for continued bisphosphonate therapy for patients who have been on bisphosphonates for longer than five years.

Patients taking bisphosphonates for osteoporosis should not stop using their medication unless told to do so by their health care professional. Those taking bisphosphonates also should report any new thigh or groin pain to their health care provider and be evaluated for a possible femur fracture. Patients and health care professionals should report side effects with the use of bisphosphonates to the FDA's MedWatch Adverse Event Reporting program at www.fda.gov/MedWatch or by calling (800) 332-1088.

Worst Pill.org

The Medical Letter On Drugs and Therapeutics, known for its independence from drug company influence, reviewed ibandronate (BONIVA) in its August 14, 2006, issue. The publication noted that the oral form of this osteoporosis drug had been shown to decrease vertebral fractures, which involve the bones that make up the spine, or vertebrae. The drug did not show any decrease in nonvertebral fractures, such as hip fractures, in postmenopausal women.

As oft repeated the journal articles are a proven unreliable source, for they do not see the raw data, and when such has been examined the typical positive bias is over 25%--jk.

Alendronate (FOSAMAX)

Alendronate has been shown to reduce the risk of hip fracture by 1 percent in women who had previously experienced at least one vertebral fracture: 2 percent of women on placebo had hip fractures versus 1 percent of women on alendronate, a 50 percent relative reduction. We are still waiting for the results of a study evaluating the effects of alendronate on hip fracture in postmenopausal women who have never experienced a vertebral fracture. Most (over 85 percent) of the women who took the placebo in three-year clinical trials did not have a fracture of any type. Fewer studies have been done on men taking alendronate.

A study looking at patients using alendronate for up to 10 years has left many questions unanswered. Three groups of postmenopausal women were studied:

those who had been on alendronate for five years and been discontinued for five years;

those who had been on five milligrams per day for 10 years; and

those who had been on 10 milligrams per day for 10 years.

The main study endpoint was bone mineral density (BMD) at the lumbar spine, not fractures — although fractures were also studied.⁵

Although there were increases in BMD with the larger, 10 milligram dose, this increase was not related to fracture rate. The five milligram group had eight times the increase in BMD of the spine of the discontinued group but twice the number of new vertebral fractures as the discontinued group.

Women who had discontinued the drug for five years had about the same number of vertebral fractures as those taking 10 milligrams for five years. (New “fractures” were defined by examining radiographs and measuring loss of height of the vertebrae.) The loss in height was only very slightly less in the 10 milligram group than in the discontinuation group (less than 0.1 inch less loss over the five year period). As noted in the drug profile for raloxifene (EVISTA), improvement in BMD and fracture reduction are not clearly related; that appears here as well. Yet, women are often treated based on BMD alone.

An accompanying commentary to the 10-year trial raised concerns about what happens to bone structure with continuing increases in BMD. There is evidence from animal studies that with prolonged alendronate use, bones become more brittle and susceptible to fracture. Unfortunately, it is currently unknown at what point that occurs in people. The commentary stated that it was not clearly known how long women should stay on alendronate as well as how long benefits might last after the drug is stopped.⁶

A more recent study concluded that for many women, discontinuation of alendronate after five years for up to five more years does not significantly increase fracture risk, but women at high risk of clinical vertebral fractures, such as those with vertebral fracture or very low BMD, may benefit by continuing beyond. ⁷

Risedronate (ACTONEL)

A published study sponsored by risedronate manufacturer Procter & Gamble suggests that risedronate may reduce the risk of hip fracture, the most serious consequence of osteoporosis, in elderly women with low bone mineral density by about 1 percent (the same result as alendronate).⁹ However, this study has been criticized on a number of grounds, including the fact that follow-up information was not available for 3,324 of the 9,331 women in the study.¹⁰ This could have biased the results in favor of risedronate by leaving out women who had fractures.

A review of medical literature shows there have been hundreds of reported cases of osteonecrosis of the jaw linked to drugs commonly used to treat osteoporosis. According to the review, osteonecrosis was more common in the lower jaw than the upper jaw. More than half of all cases (60 percent) occurred after dentoalveolar surgery (such as tooth extraction) to treat infections, and the remaining 40 percent are probably related to infection, denture trauma or other physical traum

Another Big PhARMA profit ploy that is counter to our health. Bisphosphonates don’t work, and this is in a study which they manipulated the data to make it seem as an effective treatment.

http://www.worstpills.org/member/newsletter.cfm?n_id=618

Worst Pills (by Public Citizen) is a site which using the available scientific information in a far and balanced way exposes the drugs that don’t work and their risks.

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

(part 1 was about bone mineral density screening—published here)

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.

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.

Box 1. Bisphosphonates Approved for Prevention and/or Treatment of Osteoporosis

• Alendronate (FOSAMAX)
• Risedronate (ACTONEL)
• Ibandronate (BONIVA)
• Zoledronic acid (RECLAST)

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.

Box 2: Strategies to Decrease Falls:

Strength and balance training decrease fall-induced injuries, such as fractures.
Additional strategies that may decrease falls include:
Reducing medications that cause sedation
Treating heart conditions that may cause fainting (slow heart rate, orthostatic hypotension, etc)
Home hazard reduction (removing loose rugs and clutter, adequate lighting, keeping wires behind furniture, etc.)
Treating poor vision (cataract surgery)
Strategies to decrease the force of impact, such as hip protecting pads, in patients that are prone to fall can decrease fractures.

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.

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