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Oral Bisphosphonate-Induced Osteonecrosis

Oral Bisphosphonate-Induced Osteonecrosis: Risk Factors, Prediction of Risk Using Serum CTX Testing, Prevention, and Treatment Robert E. Marx DDS, , , Attending Surgeon, Oral and Maxillofacial Surgery, Alleghany General Hospital, Pittsburgh, PA. Joseph E. Cillo Jr DDS Fellow in Tumor and Reconstructive Surgery, Division of Oral and Maxillofacial Surgery, University of Miami Miller School of Medicine, Miami, FL. Juan J. Ulloa DDS Professor of Surgery and Chief, Division of Oral and Maxillofacial Surgery, University of Miami Miller School of Medicine, Miami, FL. Purpose To assess the risk and time course of oral bisphosphonate-induced osteonecrosis of the jaws. Materials and Methods Detailed data from 30 consecutive cases were compared with 116 cases due to intravenous aminobisphosphonates. Results 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. Conclusions 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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Ahmad Tehrani
Fred Barnett
Glenn Van As
Marga Ree
Mark Dreyer
Noemi Pascual
Sashi Nallapati
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Winfried Zeppenfeld

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