Bisphosphonates


Bisphosphonates are one of the most commonly prescribed classes of drugs today. Most of these drugs have been associated with a risk of osteonecrosis of the jaws. All drugs in this class slow down bone turnover by inhibiting osteoclast activity, therefore helping to prevent a net negative bone turnover. The accumulation of these drugs has been proven to cause bisphosphonates related osteonecrosis of the jaws (BRONJ). Although the chance of this occurring is low, the disease can be devastating. Prevention is the best option, because there are few treatment choices. This disease is most common in the jaws secondary to the increased turnover rate as compared to the other bones in the body. Alveolar bone has the greatest risk. Below is a list of the medications in this class.

  • Oral Fosamax (Alendronate)
  • Oral Actonel (Risedronate)
  • Oral Boniva (Ibandronate)
  • IV Aredia (Pamidronate)
  • IV Zometa (Zoledronate, Reclast)
  • IV Ostac (Clordonate, Bonefos)
  • * Didronel (Etidronate)
  • * Skelid (Tiludronate)

* No risk of Osteonecrosis

Note that there is no risk with Didronel and Skelid due to a slightly different chemical structure. Patients on the IV forms of bisphosphonates are at an increased risk to develop BRONJ as compared to the oral forms. These patients are considered to be at high risk for osteonecrosis after only 4 doses, the risk then increases with increased number of doses. Bone availability is 140 times higher with IV administration compared to the oral route, hence the higher risk. The risk is generally accepted to be between 1-4% after the 4th dose. Patients with bone wasting malignancies (breast cancer, multiple myeloma, and prostate cancer) are most commonly those on IV forms of these medications.

Patients on oral bisphosphonates are considered to be safe if they have been taking these medicines for less than 3 years. If they have been on one for greater than five years they are considered to be at risk. Between three and five years is a grey area. It is suggested to handle them as if they are in the at risk class. The risk is .01– .1% for patients on oral bisphosphonate for longer than five years.

It has recently become possible to assess a patient’s theoretical risk for developing BRONJ by a lab test called a CTx test. This test name is short for serum C-terminal telopeptide test and measures bone metabolism. C-terminal is a by-product of normal bone metabolism and normally runs > 250pg/ml. When a patient’s telopeptide value is under 100pg/ml they are considered high risk, if greater than 150pg/ml their risk is considered minimal, if between 100-150pg/ml their risk is moderate. When in the moderate or high risk categories discontinuing the medication (a drug holiday) will normally lead to an increase in CTx levels of approximately 25pg/ml a month. Also note that patients with a bone wasting malignancy will have falsely elevated CTx values. Finally, realize that a CTx level is a guideline to help with treatment decisions. A normal value does not guarantee that the patient will not have a problem. Those patients who have had a drug holiday for low CTx values should remain off the bisphosphonates for three months after the procedure before restarting the medicine.

In addition, the following factors are thought to be risk factors for bisphosphonate-related osteonecrosis of the jaw (BRONJ):

  • Corticosteroid therapy
  • Diabetes
  • Smoking
  • Alcohol use
  • Poor oral hygiene
  • Chemotherapeutic drugs

Patients on bisphosphonates who have one or more of the above risk factors should be treated as high risk.