Oral and maxillofacial surgery
Bisphosphonates and osteonecrosis of the jaws: Science and rationale

https://doi.org/10.1016/j.tripleo.2006.12.004Get rights and content

Bisphosphonates as a group of drugs were introduced for the management of various conditions such as osteoporosis, Paget’s disease, multiple myeloma, hypercalcemia of malignancy, breast cancer, prostate cancer, and other tumors. This group of drugs has improved the quality of life in many patients with proven efficacy in limiting pain and skeletal-related events. The controversy of osteonecrosis of the jaws and bisphosphonates is a recent and growing problem. Osteonecrosis of the jaws is recognized as a serious complication of bisphosphonate therapy, more commonly with the intravenous form of the drugs. However, there is limited scientific understanding about the association between osteonecrosis of the jaws and bisphosphonates. In the present article we discuss various mechanisms of action of bisphosphonates, the rationale for occurrence of osteonecrosis in the jaws, and treatment guidelines for the condition.

Section snippets

Discovery of Bisphosphonates as Inhibitors of Bone Resorption

In the early 1960s Fleisch proved that inorganic pyrophosphates (PPi) prevent body fluid calcification by binding to hydroxyapatite crystals.6 They also revealed that the oral forms of PPi were inactivated by the phosphatases secreted by the gastrointestinal brush border.7 In an attempt to find stable analogs of PPi, diphosphonates (now called bisphosphonates) were among some of the drugs that were investigated during that time.7 The BPs tolerated the oral route very well without being

BP and ONJ

Every year, an estimated 30 million BP prescriptions are written in the U.S. alone. It is estimated that pamidronate and zoledronate have been used in over 2.5 million patients worldwide.48 The first case report in oral and maxillofacial surgery on BP was the failure of osseointegrated dental implants.49 The exact incidence of ONJ is unknown. However, some reports have estimated it to be about 1 in 10,000.50 A single-center study has reported 11% incidence of ONJ in patients with multiple

Can We Design Safer Compounds?

It is possible to design BPs with activity against selective GTPases excluding the Rho and Ras groups of proteins. This will prevent the disruption of isoprenylation of the mevalonate pathway, thus sparing the osteoclastic activity. Based on the evidence that BPs act as inhibitors of farsenyldiphosphate and geranylgeranyldiphosphate, a later-generation aminobisphosphonate, NE10790, was developed. This has the specific ability to inhibit the activity of other proteins than the Ras and Rho

Conclusion

It is important that all health professionals, especially dentists, oncologists, and oral surgeons, be aware of the possibility that patients being considered for dental extractions or other oral surgery may be undergoing BP therapy. Most medical practitioners are unaware of this serious and potentially permanent complication. Also, patients should be informed of the risk of ONJ, so that they have the opportunity to assess their need for dental treatment before starting therapy. All patients

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