title: Oral bisphosphonate-induced osteonecrosis: risk factors, prediction of risk using serum CTX testing, prevention, and treatment.
abstract: OBJECTIVE
  To assess the risk and time course of oral bisphosphonate-induced osteonecrosis of the jaws.
  
  
  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.
authors.affiliation: Division of Oral and Maxillofacial Surgery, University of Miami Miller School of Medicine, Miami, FL, USA.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Marx
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Cillo
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Ulloa
mesh_terms: D019386:Alendronate / Q000009:adverse effects; D015415:Biomarkers / Q000097:blood; D050071:Bone Density Conservation Agents / Q000009:adverse effects*; D024042:Collagen Type I / Q000097:blood*; D004164:Diphosphonates / Q000009:adverse effects*; D012968:Etidronic Acid / Q000009:adverse effects / Q000031:analogs & derivatives; D005260:Female; D006801:Humans; D007571:Jaw Diseases / Q000097:blood / Q000139:chemically induced / Q000628:therapy; D008875:Middle Aged; D010020:Osteonecrosis / Q000097:blood* / Q000139:chemically induced / Q000628:therapy; D010455:Peptides / Q000097:blood*; D011446:Prospective Studies; D000068296:Risedronic Acid; D013997:Time Factors
chemical_list: D015415:Biomarkers; D050071:Bone Density Conservation Agents; D024042:Collagen Type I; D004164:Diphosphonates; D010455:Peptides; C052929:collagen type I trimeric cross-linked peptide; D000068296:Risedronic Acid; D012968:Etidronic Acid; D019386:Alendronate