IV bisphosphonates greatly increase the risk for major facial bone problems

It seems the drugs used to treat osteoporosis can also erode the facial bones of those being treated for cancer. Intravenous doses of the bisphosphonates pamidronate and/or zoledronic acid increase the risk for inflammatory conditions or osteomyelitis of the jaw by more than 11 times (HR 11.48; 95% CI, 6.49–20.33) and increase the risk for jaw or facial bone surgery more than three times (HR 3.15; 95% CI, 1.86–5.32), according to a population-based study involving more than 16,000 cancer patients.

Using data from the Surveillance, Epidemiology, and End Results (SEER) program linked to Medicare claims, the authors of the study calculated the absolute risk at 6 years for any jaw toxicity to be 5.48 events per 100 patients using IV bisphosphonates and 0.30 events per 100 patients not using such agents. Risk increased along with cumulative dose, so, for example, four to eight infusions were associated with an HR of 3.63 for operations on the jaw and facial bones (95% CI, 0.77–17.08). More than 21 infusions had an HR of 9.18 (95% CI, 1.74–48.53).

The authors of the study conclude that the increased risks uncovered in this analysis may indicate an increased risk for osteonecrosis of the jaw. But they also emphasize that the toxicity of the drugs must be balanced against their effectiveness. IV bisphosphonates substantially reduce bone loss and fractures among cancer patients who have had bone metastases.

The authors of the editorial conclude that the sheer number of cases that have been reported to date and the mode of actions of these drugs make it all too likely that there is a causal relationship. Numerous studies are underway to identify risk factors and biomarkers for osteonecrosis and methods for early diagnosis.

Wilkinson GS, Kuo YF, Freeman JL, et al. Intravenous bisphosphonate therapy and inflammatory conditions or surgery of the jaw: a population-based analysis. J Natl Cancer Inst. 2007;99:1016-1024.

Woo SB, Solomon DH. Bisphosphonate therapy for cancer and prevalence of inflammatory jaw conditions. J Natl Cancer Inst. 2007;99:986-987.