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J Oral Maxillofac Surg. 2007 Dec;65(12):2397-410.

Oral bisphosphonate-induced osteonecrosis: risk factors, prediction of risk using serum CTX testing, prevention, and treatment.

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Division of Oral and Maxillofacial Surgery, University of Miami Miller School of Medicine, Miami, FL, USA.



To assess the risk and time course of oral bisphosphonate-induced osteonecrosis of the jaws.


Detailed data from 30 consecutive cases were compared with 116 cases due to intravenous aminobisphosphonates.


Results in part noted a higher incidence related to alendronate (Fosamax; Merck, Whitehouse Station, NJ), a 94.7% predilection for the posterior mandible, and a 50% occurrence spontaneously, with the remaining 50% resulting from an oral surgical procedure, mostly tooth removals. Just over 53% of patients were taking their oral bisphosphonate for osteopenia, 33.3% for documented osteoporosis, and 13.4% for steroid-induced osteoporosis related to 4 or more years of prednisone therapy for an autoimmune condition. There was a direct exponential relationship between the size of the exposed bone and the duration of oral bisphosphonate use. There was also a direct correlation between reports of pain and clinical evidence of infection. The morning fasting serum C-terminal telopeptide (CTX) test results were observed to correlate to the duration of oral bisphosphonate use and could indicate a recovery of bone remodeling with increased values if the oral bisphosphonate was discontinued. A stratification of relative risk was seen as CTX values less than 100 pg/mL representing high risk, CTX values between 100 pg/mL and 150 pg/mL representing moderate risk, and CTX values above 150 pg/mL representing minimal risk. The CTX values were noted to increase between 25.9 pg/mL to 26.4 pg/mL for each month of a drug holiday indicating a recovery of bone remodeling and a guideline as to when oral surgical procedures can be accomplished with the least risk. In addition, drug holidays associated with CTX values rising above the 150 pg/mL threshold were observed to correlate to either spontaneous bone healing or a complete healing response after an office-based debridement procedure.


Oral bisphosphonate-induced osteonecrosis is a rare but real entity that is less frequent, less severe, more predictable, and more responsive to treatment than intravenous bisphosphonate-induced osteonecrosis. The morning fasting serum C-terminal telopeptide bone suppression marker is a useful tool for the clinician to assess risks and guide treatment decisions.

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