Oral bisphosphonates increase osteomyelitis of the jaw

Bisphosphonates are medications such as Fosamax®, Actonel®, Aredia®, Didronel®, Reclast® and Zometa® that are given to increase bone density. They have received much attention for a severe side effect, osteonecrosis of the jaw (ONJ), when given intravenously as part of a chemotherapy regimen. (ONJ refers to pockets of dead bone in the upper jaw and facial bones that can be very painful and prone to infection. Even surgery is rarely remedial.) There is also evidence bisphosphonates cause 'brittle bones' with an increased risk of fracture after five years of oral use. The authors of a study just published in the journal Bone offer evidence that bisphosphonates taken orally can also cause osteonecrosis of the jaw. Oral bisphosphonates are frequently used...

"However, several studies have reported osteonecrosis of the jaw (ONJ), also known as osteomyelitis of the jaw (OMJ), as a side effect of these drugs...Here, we estimated risk of oral BPs for OMJ in osteoporosis patients taking oral BPs compared with other osteoporosis drugs."

They examined data on patients taking medications for osteoporosis between November 2000 and October 2010 to evaluate the relative risks of taking 4129 patients who were taking oral bisphosphonates for OMJ while 2794 subjects received other osteoporosis drugs. The data show that concern is justified:

"Absolute risk for OMJ was estimated to range from 0.46% to 0.99% (95% CIs: 0.25–0.66 to 0.69–1.2) among patients receiving oral BPs and 0.071% to 0.17% (95% CIs: 0–0.17 to 0.022–0.33) among patients receiving other osteoporosis drugs. The attributable risks of oral BPs for OMJ were estimated to range from 0.38% to 0.81% (95% CIs: 0.38–0.39 to 0.80–0.81). ORs (95% CIs) adjusted for confounding factors were 5.0 (1.9–12.9) to 6.0 (1.3–26.1) for confirmed cases only."

OMJ/ONJ is a particularly severe side effect of bisphosphonates. ONJ and increase in brittleness and fracture after extended use of bisphosphonates are not surprising since bisphosphonates are a kind of chemotherapy that kills the osteoclasts—the special cells that break down old bone making way for its replacement by fresh new bone. When this cycle of tearing down to build anew is interrupted bone may appear more dense on scans but lacks the shock-absorbing elasticity of healthy bone, hence the increase in fractures. Since bones of the jaw receive a lot of pressure with chewing they are subject to localized foci of collapse in those most vulnerable. The authors conclude:

"In terms of absolute and attributable risks, the risk of oral BPs for OMJ is considered to be less than 1% in patients with osteoporosis. However, oral BPs may increase the risk of OMJ compared with patients treated with other osteoporosis medications and the risk of side effects should be kept in mind."