Bisphosphonate-induced exposed bone (osteonecrosis/osteopetrosis) of the jaws: risk factors, recognition, prevention, and treatment.
OBJECTIVE
Bisphosphonates inhibit bone resorption and thus bone renewal by suppressing the recruitment and activity of osteoclasts thus shortening their life span. Recently three bisphosphonates, Pamidronate (Aredia; Novartis Pharmaceuticals, East Haven, NJ), Zoledronate (Zometa; Novartis Pharmaceuticals), and Alendronate (Fosamax; Merck Co, West Point, VA) have been linked to painful refractory bone exposures in the jaws.


METHODS
One hundred-nineteen total cases of bisphosphonate-related bone exposure were reviewed.


RESULTS
Thirty-two of 119 patients (26%) received Aredia, 48 (40.3%) received Zometa, 36 (30.2%) received Aredia later changed to Zometa, and 3 (2.5%) received Fosamax. The mean induction time for clinical bone exposure and symptoms was 14.3 months for those who received Aredia, 12.1 months for those who received both, 9.4 months for those who received Zometa, and 3 years for those who received Fosamax. Sixty-two (52.1%) were treated for multiple myeloma, 50 (42%) for metastatic breast cancer, 4 (3.4%) for metastatic prostate cancer and 3 (2.5%) for osteoporosis. Presenting findings in addition to exposed bone were 37 (31.1%) asymptomatic, 82 (68.9%) with pain, 28 (23.5%) mobile teeth, and 21 (17.6%) with nonhealing fistulas. Eighty-one (68.1%) bone exposures occurred in the mandible alone, 33 (27.7%) in the maxilla, and 5 (4.2%) occurred in both jaws. Medical comorbidities included the malignancy itself 97.5%, previous and/or maintenance chemotherapy 97.5%, Dexamethasone 59.7%. Dental comorbidities included the presence of periodontitis 84%, dental caries 28.6%, abscessed teeth 13.4% root canal treatments 10.9%, and the presence of mandibular tori 9.2%. The precipitating event that produced the bone exposures were spontaneous 25.2%, tooth removals 37.8%, advanced periodontitis 28.6%, periodontal surgery 11.2%, dental implants 3.4% and root canal surgery 0.8%.


CONCLUSIONS
Complete prevention of this complication in not currently possible. However, pre-therapy dental care reduces this incidence, and non-surgical dental procedures can prevent new cases. For those who present with painful exposed bone, effective control to a pain free state without resolution of the exposed bone is 90.1% effective using a regimen of antibiotics along with 0.12% chlorohexidine antiseptic mouth.
Marx
Robert E
RE
Miller School of Medicine, Division of Oral and Maxillofacial Surgery, University of Miami, 9380 SW 150th Street, Miami, FL 33157, USA. rmarx@med.miami.edu
Sawatari
Yoh
Y
Fortin
Michel
M
Broumand
Vishtasb
V
D000038:Abscess / Q000150:complications / Q000628:therapy; D019386:Alendronate / Q000009:adverse effects; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D050071:Bone Density Conservation Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000150:complications / Q000188:drug therapy / Q000556:secondary; D001943:Breast Neoplasms / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D003731:Dental Caries / Q000150:complications / Q000628:therapy; D003907:Dexamethasone / Q000009:adverse effects / Q000627:therapeutic use; D004164:Diphosphonates / Q000009:adverse effects* / Q000627:therapeutic use; D004347:Drug Interactions; D005260:Female; D006801:Humans; D015576:Hyperostosis / Q000150:complications / Q000628:therapy; D007093:Imidazoles / Q000009:adverse effects; D007571:Jaw Diseases / Q000139:chemically induced* / Q000175:diagnosis / Q000628:therapy; D008297:Male; D009101:Multiple Myeloma / Q000150:complications / Q000188:drug therapy; D010020:Osteonecrosis / Q000139:chemically induced* / Q000175:diagnosis / Q000628:therapy; D010022:Osteopetrosis / Q000139:chemically induced* / Q000175:diagnosis / Q000628:therapy; D010024:Osteoporosis / Q000188:drug therapy; D000077268:Pamidronate; D010518:Periodontitis / Q000150:complications* / Q000628:therapy; D011471:Prostatic Neoplasms / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D012307:Risk Factors; D014081:Tooth Extraction / Q000009:adverse effects; D000077211:Zoledronic Acid
D000970:Antineoplastic Agents; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid; D003907:Dexamethasone; D000077268:Pamidronate; D019386:Alendronate