Bisphosphonate-associated osteomyelitis of the jaw: guidelines for practicing clinicians.
OBJECTIVE
To evaluate the literature and discuss the risk factors, mechanisms, pathophysiologic aspects, and recommended management of bisphosphonate-associated osteomyelitis of the jaw (BAOMJ).


METHODS
More than 350 published articles, case reports mentioning BAOMJ, and independent histology slides from BAOMJ lesions were reviewed critically. The most pertinent publications are cited and discussed.


RESULTS
The incidence of BAOMJ increases after extraction of teeth, dentoalveolar surgical procedures, or recent oral trauma leading to exposed maxillary or mandibular bone. Contributory factors include poor oral hygiene, oral infections, periodontal disease; recent or ongoing corticosteroid administration or chemotherapy; compromised immune status; diabetes or vascular insufficiency; old age; chronic diseases; and malignancies. On average, 1 of every 100,000 patients treated with bisphosphonates orally for osteoporosis or Paget disease of bone may develop BAOMJ-like lesions. Patients with cancer often receive bisphosphonate doses 10 times or higher, and also more frequently, than those used in patients with osteoporosis or Paget disease of bone. Therefore, greater frequency of administration of bisphosphonates, higher dosages, and prolonged use (that is, for more than 2 years) are likely to be factors triggering BAOMJ.


CONCLUSIONS
The association of bisphosphonate therapy with BAOMJ is rare in noncancer patients and is likely to be a class effect that may occur with use of any bisphosphonate. Whether patients with cancer require such a high frequency of intravenously administered bisphosphonates needs to be investigated. Following established guidelines can decrease the risks of BAOMJ in vulnerable patients. Rather than necrotic bone, current evidence supports an infectious and perhaps immunologic underlying cause for BAOMJ. The estimated incidence of BAOMJ among noncancer patients receiving bisphosphonates is about 0.001%, whereas among patients with cancer receiving intravenous bisphosphonate therapy the incidence is between 0.5% and 4%, depending on the dose, frequency, and duration of therapy (on average, approximately 2%). Nevertheless, the benefits of bisphosphonates far outweigh the risks.
Wimalawansa
Sunil J
SJ
Division of Endocrinology, Metabolism & Nutrition, Department of Medicine, Robert Wood Johnson Medical School, University of Medicine & Dentistry of New Jersey, New Brunswick, New Jersey 08903-0019, USA. wimalasu@umdnj.edu
D020533:Angiogenesis Inhibitors / Q000009:adverse effects; D050071:Bone Density Conservation Agents / Q000009:adverse effects; D004164:Diphosphonates / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D007571:Jaw Diseases / Q000139:chemically induced* / Q000175:diagnosis / Q000453:epidemiology / Q000517:prevention & control; D008954:Models, Biological; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010019:Osteomyelitis / Q000139:chemically induced* / Q000175:diagnosis / Q000453:epidemiology / Q000517:prevention & control; D010024:Osteoporosis / Q000150:complications / Q000188:drug therapy; D017410:Practice Guidelines as Topic; D014945:Wound Healing / Q000187:drug effects
D020533:Angiogenesis Inhibitors; D050071:Bone Density Conservation Agents; D004164:Diphosphonates