Osteoporosis Medication Warning(s)

[Harrison]

Esophageal cancer linked to osteoporosis drug use

January 2009

The popular osteoporosis drug Fosamax (alendronate sodium, Merck) and other similar drugs may carry a risk for esophageal cancer, a Food and Drug Administration official said last week.

Diane Wysowski of the FDA’s division of drug risk assessment said researchers should check into potential links between so called bisphosphonate drugs and cancer, according to a press release.

In a letter in the New England Journal of Medicine, Wysowski said that since the initial marketing of Fosamax in 1995, the FDA has received 23 reports of patients who developed esophageal tumors after taking the drug. Typically, 2 years lapsed between the time patients started taking the drug and the onset of esophageal cancer. Eight patients died, according to her report.

In Europe and Japan, physicians logged 21 cases involving esophageal cancer and Fosamax use, with another six instances where Procter & Gamble’s Actonel (risedronate) and Didronel (etidronate) and Roche’s Boniva (ibandronate) may have been involved. Six of those patients died, according to the release.

Esophagitis — an inflammation of the lining of the esophagus — is one side effect of the drugs, which is why patients are instructed to remain upright for at least 30 minutes after taking them, she said.

In her letter, Wysowski also recommended that doctors should avoid prescribing the drugs to people with Barrett’s esophagus, which is a change in the lining that leads to the stomach. It is often found in people with acid reflux disease and itself increases the risk of cancer, according to the press release.

Also last week, researchers at the University of Southern California School of Dentistry released clinical data linking alendronate sodium to an increased incidence of jaw necrosis. The study is among the first to acknowledge that even short-term use of common oral osteoporosis drugs may leave the jaw vulnerable to devastating necrosis, according to the report in the Jan. 1 issue of the Journal of the American Dental Association.

Courtesy of OrthoSupersite, Slack, Inc.

[CindyLou]

Oh, great. One more thing for me to worry about. Bummer. I'm not on Fosamax (was). But my mother is, and I am on Actinol (sp?). Thank-you Rich, for the warning. I will forward this information to my Mom for sure.

Cindylou

[sahuaro]

These findings are a grim reminder to be vigilant about taking biophosphanates with a full 8 oz of water, as well as remaining upright for the full 30 minutes, as directed.

[Harrison]

Bisphosphonate use may affect mechanical properties of bone

BALTIMORE — A study of bone biopsies taken from like-aged postmenopausal women undergoing internal fixation for femoral fractures has found that the women who had taken bisphosphonate treatments for osteoporosis had narrower pattern of aged bone matrix, perhaps indicating a loss of mechanical integrity.

“Osteoporosis is the most common cause of fragility fractures and bisphosphonates have emerged as a cornerstone of osteoporosis treatment,” Brian J. Rebolledo, said at the 2010 Annual Meeting of the Orthopaedic Trauma Association. “The reason for this being, they prevent bone loss and reduce fracture risk. However, recent concerns have been raised about long-term bisphosphonate treatment in the development of atypical femoral fractures.”

Rebolledo presented research conducted at Hospital for Special Surgery and Weill Cornell Medical College that assessed and compared the parameters of bone quality in women who took bisphosphonate therapy and those who did not.

Core biopsies

The researchers enrolled postmenopausal women with proximal femoral fractures treated with internal fixation using intertrochanteric nails. During the surgical procedure, a 1-cm diameter core reamer was used to remove a cylindrical piece of corticocancellous bone prior to the insertion of the helical blade, from the lateral cortex of the femur.

These biopsies were than categorized into bisphosphonate treatment or nontreatment groups. Overall, there were 17 patients in the bisphosphonate group and 15 in the group who never took bisphosphonate therapy.

Race, age and body mass index were recorded and no differences were seen between the groups.

Analysis

The specimens were analyzed by micro-CT to assess bone volume fraction, trabecular number, trabecular thickness, trabecular separation and trabecular connectivity. Histomorphometry was then used to measure the ratio of unmineralized to mineralized bone surface of the trabecular and cortical bone.

Lastly, they were analyzed with Fourier transform infrared imaging (FTIRI) to assess the properties of cortical and trabecular bone in terms of mineral-matrix ratio; carbonate-phosphate ratio; collagen crosslinking maturity and mineral crystallinity.

“The width of these values is representative of the heterogeneity of the samples,” Rebolledo said. “Heterogeneity is important to consider because bone is normally a heterogeneous material due to the constant remodeling and the differing mineralization at time points. And it has also been shown that a high mineral content can lead to brittle bones.

“Therefore a narrower distribution of these parameters can lead to reduced bone toughness,” he said.

The researchers found that the cortical tissue mineral properties “indicated a narrower distribution in the bisphosphonate-treated group.” The mean cortical and trabecular values of all the FTIRI analyses were similar.

“Although bisphosphonates may be the cornerstone treatment, we really don’t know what the long-term effects are on bone quality,” Rebolledo said. “Our data show that the proximal femoral fracture patients treated with bisphosphonates had a narrower distribution of bone compositional parameters, but no change in the tissue microarchitecture. Therefore this raises concerns that long-term bisphosphonate therapy could affect bone quality and may affect some mechanical properties by the loss of heterogeneity.”

Reference:

Rebolledo BJ, Donnelly E, Lorich DG, et al. Altered bone quality in bisphosphonate-related femoral fractures of postmenopausal women. Paper #38. Presented at the 2010 Annual Meeting of the Orthopaedic Trauma Association. Oct. 13-16, 2010. Baltimore.

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Please note: we covered some of these issues last year in our on-camera interview with Dr. Tom Webster, see this topic and follow the links to the video interviews:

Video Interview with Dr. Thomas Webster

[Harrison]

Another story on the same subject:

Doctors suggest that women hit pause button on osteoporosis drugs

Many patients have taken medications that include bisphosphonates for years. Doctors are debating how long people should take them. Recent studies point to health risks and problems linked to long-term use.

By Shari Roan, Los Angeles Times

November 8, 2010

With the launch of the first prescription osteoporosis medication 15 years ago, millions of Americans with the bone-thinning disease began taking the drugs and never looked back.

But now many bone-health doctors are looking back and becoming increasingly uneasy.

In the last few years, evidence has emerged that long-term use of osteoporosis drugs — particularly the oldest class of drugs, the bisphosphonates — may do more harm than good. Some doctors are starting to tell at least some of their patients to stop taking the drugs for a time — in other words, to take a "drug holiday."

That strategy is a tough sell for consumers who have been bombarded with osteoporosis medication advertisements for years.

When osteoporosis drugs first came out, "people thought, this is a recurring disease, like high blood pressure. So why wouldn't you treat it for the rest of their lives?" said Dr. Richard Eastell, an expert in bone metabolism at the University of Sheffield in Britain who spoke about the issue last month at the annual meeting of the American Society for Bone and Mineral Research. "But there are now some anxieties with long-term use."

Full story here:

Doctors suggest that women hit pause button on osteoporosis drugs - latimes.com