Fosamax Induced Fractures, More Bad News by Jeffrey Dach MD
Posted Mar 14 2010 5:41am
Fosamax Induced Fractures, More Bad News
by Jeffrey Dach MD
As if Fosamax didn't have enough problems, another nail was hammered into the coffin at the 2010 AAOS Meeting . Two more studies came out showing Fosamax disturbs bone formation, and implicates Fosamax in spontaneous mid-femur fractures (without trauma). These reports came from the Hospital for Special Surgery (HSS) and Columbia University Medical Center.
Right image: Xray of mid-femur fracture caused by Fosamax Fosamax Induced Femur Fractures
This is not the first time fosamax induced fracture has been reported. The number of reported cases has increased over the past few years. (see right image)
Reports of Spontaneous Mid Femur Fracture on Fosamax
Dr. Goh, a doctor in Singapore, identified nine more cases in his 2007 report of subtrochanteric femur fractures with minimal trauma in women on long term Fosamax.
Joseph M Lane MD reported 15 cases of spontaneous femur fracture in women on Fosamax (Alendronate). His report appeared in the New England Journal March 20, 2008.
Lane found that "ten of the 15 patients were found to share a unique radiographicpattern, defined as a simple transverse or oblique (30°)fracture with beaking of the cortex and diffuse cortical thickeningof the proximal femoral shaft."
The entire bisphosphonate class of osteoporosis drugs is implicated. This includes all of the drugs for osteoporosis such as Boniva, Actonel, Reclast, Fosamax, etc.
Problems with Fosamax From the Beginning
The Fosamax (Alendronate) study done for FDA approval failed to show any benefit for the majority of the worried well, which is the osteopenia group defined as T score greater than -2.5. This Osteopenia Group actually had higher fracture rates than placebo. This was published by Cummings in JAMA in 1998 . This is exactly the group that is targeted for treatment by the Sally Fields Boniva drug ads.
Bisphosphonate drugs like Fosamax have severe adverse side effects of jaw necrosis (OJN), spontaneous mid-femur fracture, heart rhythm disturbances, and severe bone and joint pain.
The spontaneous mid femur fractures are especially troubling, since these are spontaneous fractures without any trauma. Subtrochanteric fractures are pathological fractures, indicating the underlying bone matrix is abnormal. This abnormal weakening and brittleness is directly caused by the bisphosphonate drug.
Bottom Line: These are BAD drugs that actually make the bones weaker not stronger, and they should be banned by the FDA . However, knowing the FDA which is in the pocket of the drug companies, no action will be taken until many more women victims suffer from these drugs, and many more cases work their way through drug litigation court.
Watch this news video on Fosamax Induced Femur Fractures
Merck Defends Fosamax with Falsehoods
The Merck spokesman Ron Rogers denies that Fosamax could be causing fractures: Ron Rogers was quoted as saying: "In clinical studies, Fosamax has not been associated with increased fracture risk at any skeletal site,"
This defensive statement by Merck's spokesman Ron Rogers is directly contrary to the results of the Fracture Intervention Trial reported in 1998 JAMA by Cummings: For women with T scores greater than -2.5, Fosamax doubled the risk of hip fracture from 6 to 11.
This FIT Cummings trial reported increased overall fracture risk for women with T scores above -2.5. There were 27 fractures in the fosamax group and only 20 in the placebo group. This is highly significant and was ignored by the FDA who approved the drug anyway.
Here is a quote from the Cummings FIT paper . (JAMA. 1998;280:2077-2082) "Similarly, we observed no reduction in risk among women with T scores of -2.0 to -2.5: 20 (2.8%) in the placebo group vs 27 (3.7%) in the alendronate group (RH, 1.33; 95% CI, 0.75-2.4).
Among those whose femoral neck T scores were more than -2.0, more fractures occurred in the treatment group (n = 22, 3.3%) than in the placebo group (n = 12, 1.7%; RH, 1.9; 95% CI, 1.0-4.0; placebo-treatment difference, 1.6%). " end quote.
Alendronate doubled the risk of hip fractures in women with a femoral neck T score greater than -2.5: 6 hip fractures (0.4%) in the placebo group vs 11 fractures (0.8%) in the alendronate -Fosamax group (RH, 1.84; 95% CI, 0.70-5.36).
The FDA Sends Warning
on Possible Risk of Femur Fractures
This week, the FDA issued a safety announcement which recommended that healthcare professionals be aware of a "possible risk" of atypical subtrochanteric femur fractures in patients taking oral bisphosphonates. In my opinion, these drugs are bad drugs and the FDA should ban them. However, it may take a protest march from a thousand women in wheel chairs with femur fractures gathering on the Capitol steps before the FDA finally takes action.
At stake: A Ton of Money for the Drug Companies
In 2008, bisphosphonate drugs like fosamax generated 37 million prescriptions and $3.5 billion in sales, according to IMS Health.
Litigation Lining UP
Fosamax maker, Merck is facing 900 lawsuits by patients who claim Fosamax caused jaw bone disintegration, OJN, osteonecrosis of the jaw.
Above First Femur Fracture Xray courtesy of Joseph Lane MD , unique radiographic pattern of Fosamax induced fracture of femur. Above Second Fracture Xray, Spontaneous Femur Fracture Induced by Long Term Fosamax Courtesy of Jennifer Schneider MD .
Quantity vs. Quality: Long-Term Use of Bone-Building Osteoporosis Drugs May Affect Quality and Structural Integrity of Bone. Studies find possible links between prolonged bisphosphonate treatments and atypical fractures in post-menopausal women
NEW ORLEANS, LA - Bisphosphonate treatments, proven to enhance bone density and reduce fracture incidence in post-menopausal women, may adversely affect bone quality and increase risk of atypical fractures of the femur when used for four or more years, according to preliminary research presented today at the 2010 Annual Meeting of the American Academy of Orthopaedic Surgeons (AAOS).
Bisphosphonates are designed to slow or stop the bone loss that occurs during the body’s bone remodeling cycle, or the natural process that involves removal and replacement of bone tissue.
Two separate studies by researchers from Hospital for Special Surgery (HSS) and Columbia University Medical Center revealed data suggesting that long-term suppression of bone remodeling by bisphosphonate treatments may alter the material properties of bone, potentially affecting the bone’s mechanical integrity and potentially contributing to the risk of atypical fractures.
“Although bisphosphonates have demonstrated an improvement in bone quantity, little if anything is known about the effects of these drugs on bone quality,” said Brian Gladnick, BS, representing a team of investigators at HSS in New York.
Researchers at Columbia evaluated the bone structure of 111 postmenopausal women with primary osteoporosis, 61 of whom had been taking bisphosphonates for a minimum of four years and 50 controls taking calcium and vitamin D supplements.
This study found that bisphosphonate use improved structural integrity early in the course of treatment, but those gains were diminished with long-term treatment.
“In the early treatment period, patients using bisphosphonates experienced improvements in all parameters, including decreased buckling ratio and increased cross-sectional area,” said Melvin Rosenwasser, MD, orthopaedic surgeon for Columbia University Medical Center. “However, after four years of use, these trends reversed, revealing an association between prolonged therapy and declining cortical bone structural integrity.”
Scientists at both institutions noted that the culprit behind the diminishing results may be the fact that bisphosphonates suppress the body’s natural process of remodeling bone. “Recent research suggests that suppressed bone remodeling from long-term bisphosphonate use might result in brittle bone that is prone to atypical fractures,” said Gladnick.
The investigators added that more research is needed to determine the true efficacy of the long-term clinical use of bisphosphonates for the treatment of osteoporosis, and that the results of their studies will not likely affect clinical practice in the near future.
“Bisphosphonate use still is a very effective solution that prevents bone loss in most patients and no one is recommending that physicians avoid prescribing these,” said Dr. Rosenwasser. “However, as baby boomers age and continue to remain active, it is important that we conduct more research and develop sustainable, safe and effective treatments for osteoporosis.”
In a second unrelated prospective pilot study, conducted at HSS and funded in part by the NIH, researchers evaluated the bone composition of 21 post-menopausal women who were treated for femoral fractures. Of these, 12 patients had a history of bisphosphonate treatment for an average of 8.5 years, while nine had not had bisphosphonate treatment.
Samples of bone were removed from each patient’s femur during surgical placement of a femoral nail. Both micro-architecture and material properties of the bone were analyzed.
The study found that, although there were no differences in bone micro-architecture between groups, the material properties of bone in bisphosphonate-treated patients displayed reduced bone tissue heterogeneity, which may be associated with reduced strength and potentially may contribute to the presentation of atypical fractures.
“Patients who had been treated with bisphosphonates showed a reduction in tissue heterogeneity, specifically with mineral content and crystal size compared with the control group,” Gladnick said. “This tells us that there may be some measurable differences in bone quality parameters in patients on long-term bisphosphonate therapy, which might contribute to the development of atypical fractures.”
Disclosures: The HSS study was supported by NIH grant AR041325 to Dr. Adele Boskey. Dr. Rossenwasser and his co-authors received no compensation for their research.
The U.S. Food and Drug Administration issued its statement Wednesday following the publication of case reports of atypical subtrochanteric femur fractures — or fractures in the bone just below the hip joint — in women with osteoporosis using oral bisphosphonates.
In January, a Manhattan federal judge refused to dismiss a lawsuit alleging that Fosamax caused jaw damage to a woman during the nearly eight years she took the pill.
Merck faces a slew of lawsuits involving almost 900 cases by patients who say Fosamax caused osteonecrosis of the jaw, or death of jaw bone tissue.
"In clinical studies, Fosamax has not been associated with increased fracture risk at any skeletal site," Merck spokesman Ron Rogers said in a statement.
"Low energy femoral shaft and subtrochanteric fractures have been reported in the medical literature as occurring in non-bisphosphonate users," Rogers noted, adding that Merck is currently conducting studies "to further investigate the issue of low energy femoral shaft and subtrochanteric fractures."
The FDA recommended patients keep taking their medication unless told not to by their doctor. It also recommended that healthcare professionals be aware of a "possible risk" of atypical subtrochanteric femur fractures in patients taking oral bisphosphonates.
http://jama.ama-assn.org/cgi/content/full/280/24/2077 Effect of Alendronate on Risk of Fracture in Women With Low Bone Density but Without Vertebral Fractures Results From the Fracture Intervention Trial Steven R. Cummings, MD; Dennis M. Black, PhD; Desmond E. Thompson, PhD; William B. Applegate, MD; Elizabeth Barrett-Connor, MD; Thomas A. Musliner, MD; Lisa Palermo, MA; Ronald Prineas, MD; Susan M. Rubin, MA; Jean C. Scott, PhD; Thomas Vogt, MD, MPH; Robert Wallace, MD; A. John Yates, MD; Andrea Z. LaCroix, PhD; for the Fracture Intervention Trial Research Group JAMA. 1998;280:2077-2082.
quote from article:"Similarly, we observed no reduction in risk among women with T scores of -2.0 to -2.5: 20 (2.8%) in the placebo group vs 27 (3.7%) in the alendronate group (RH, 1.33; 95% CI, 0.75-2.4). Among those whose femoral neck T scores were more than -2.0, more fractures occurred in the treatment group (n = 22, 3.3%) than in the placebo group (n = 12, 1.7%; RH, 1.9; 95% CI, 1.0-4.0; placebo-treatment difference, 1.6%). "
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