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By the way, doctor: Should I stop taking bisphosphonates?

By the way, doctor

Should I stop taking bisphosphonates?

Q. I'm hearing more and more about deterioration of the jawbone associated with bisphosphonate drugs. I've been taking Fosamax for over six years for osteoporosis. What should I do?

A. Bisphosphonates are widely prescribed for osteoporosis. They are also used to treat bone pain and other complications in cancer patients who have bone involvement. Besides alendronate (Fosamax), these drugs include risedronate (Actonel), ibandronate (Boniva), tiludronate (Skelid) and etidronate (Didronel), which are taken by mouth, and the more potent zoledronate (Zometa), pamidronate (Aredia), and clodronate (Bonefos), which are given intravenously.

Media reports have fueled concerns about a connection between bisphosphonates and the death of bone tissue (osteonecrosis) in the jaw. Since we last wrote about this problem, more cases of osteonecrosis have been reported. Most have occurred among cancer patients taking intravenous bisphosphonates, but a handful have involved otherwise healthy women taking oral forms of these drugs for osteoporosis prevention or treatment.

Scientists still don't know why these patients are developing osteonecrosis of the jaw. Many factors probably contribute, especially in cancer patients, who take multiple medications. But there are good reasons to suspect that bisphosphonates have a role. These drugs decrease bone breakdown — one of the steps in normal bone remodeling (see box). This increases bone density in the short run but in the long run may impair new bone formation, thereby reducing the jawbone's capacity to heal after traumas, such as dental extractions or implants.

Bone remodeling Healthy bone continually goes through a process of resorption (breakdown) and formation. Cells called osteoclasts bind to the surface of the bone and break it down. Bone-forming cells called osteoblasts then move in and help form new bone. Osteoporosis occurs when this remodeling cycle is out of balance, so that formation fails to keep up with resorption. Bisphosphonates inhibit osteoclasts and reduce resorption — one mechanism by which they modestly increase bone density and reduce fracture risk in women with osteoporosis.

Compared to the millions of women taking bisphosphonates, the number of osteonecrosis cases is still negligible. The American Dental Association estimates the prevalence to be only about 0.7 cases per 100,000 person years. That translates to 7 cases per year for every one million people taking oral bisphosphonates. The risk is mostly among cancer patients taking zoledronate or pamidronate. To further investigate the extent of the problem among otherwise healthy women taking bisphosphonates, researchers at the Harvard School of Dental Medicine are examining medical insurance claims for jaw surgery. Also, the National Institute of Dental Research plans to study the development of the condition in bisphosphonate-takers.

For now, we can't predict who will develop osteonecrosis of the jaw. Anyone taking a bisphosphonate should be aware of the symptoms, which include pain, swelling, and numbness at the site of an extraction, dental implant, or other oral surgery. The area may become infected, and teeth may feel loose. A dental specialist may treat it with antibiotics, clean out the affected area, or remove the dead parts of the jawbone.

The best treatment is prevention. Practice good oral hygiene. Before starting a bisphosphonate, get a dental exam and consider having any extractions or implants done first. If you're already taking a bisphosphonate, let your dentist know so that she or he can consider it in planning your treatment. For example, your dentist might choose a root canal rather than an extraction or implant to preserve a tooth. Some clinicians advise their patients to stop taking bisphosphonates for a few weeks before and after dental surgery. According to the American Society for Bone and Mineral Research, it's not clear whether this will reduce the already low risk of developing osteonecrosis of the jaw. On the other hand, there's no downside to this practice. Bisphosphonates remain active in bone for years, so taking a break is unlikely to adversely affect osteoporosis therapy.

As far as we know, the benefits of bisphosphonates still outweigh the risks when they are used appropriately. But we still don't know much about their long-term effects. So be sure you're taking a bisphosphonate for the right reason and at the correct dose. Know your bone mineral density and your risks for osteoporosis. Use the risk-free strategies first: Take 1,200–1,500 mg a day of calcium; if you aren't in the sun much, take 400–800 IU a day of vitamin D; get regular weight-bearing and resistance exercise; and if you smoke, do everything you can to stop.

— Celeste Robb-Nicholson, M.D. Editor in Chief, Harvard Women's Health Watch

Last updated:	September 05, 2008