Osteoporosis International

, Volume 24, Issue 1, pp 237–244 | Cite as

Defining the epidemiology of bisphosphonate-associated osteonecrosis of the jaw: prior work and current challenges

  • D. H. Solomon
  • E. Mercer
  • S. B. Woo
  • J. Avorn
  • S. Schneeweiss
  • N. Treister
Original Article



Bisphosphonate-related osteonecrosis of the jaw (BONJ) is an adverse effect of bisphosphonate use with a poorly described epidemiology in osteoporosis patients. We examined the literature and two new cohorts for BONJ. The literature suggests an incidence rate of 0.028 % to 4.3 %. Our cohort studies found an incidence of 0.02 % (95 % CI 0.004 %–0.11 %).


We examined the epidemiology of BONJ associated with osteoporosis dosing of bisphosphonates.


First, we systematically searched the literature about osteoporosis BONJ. Identified studies were abstracted by two authors. Second, we attempted to estimate the relative risk of BONJ among bisphosphonate users with osteoporosis. Two different large insurance databases, one from 2005–2007 and another from 2007–2010, combined with medical record review, were searched. The older dataset did not include the International Classification of Diagnoses (ICD) diagnosis code for osteonecrosis of the jaw (ONJ; ICD 733.45). Incidence rates and relative risks were estimated using Cox regression.


The literature review produced nine studies of varying quality. The incidence rates for BONJ among osteoporosis patients varied from 0.028 % to 4.3 %. Two prior studies estimated the relative risk of ONJ related to bisphosphonates and found odds ratios of 7.2 and 9.2. Our attempts to estimate the incidence rate of BONJ encompassed 41,957 in the dataset from 2005–2007 and 466,645 in a separate dataset from 2007–2010. From the older dataset, we found 51 potential cases of BONJ using a broad definition of possible ONJ. One case was confirmed by a dentist for a prevalence of 0.02 % (95 % CI 0.004 %–0.11 %) among bisphosphonate users. From the newer dataset, we found 13 possible cases, but none could be confirmed. Most subjects with the ONJ diagnosis code appeared to have had an osteoporosis-related fracture and not ONJ.


The literature suggests a broad range of possible values for the prevalence of BONJ; our estimate fell within the range from prior literature.


Bisphosphonate Epidemiology Osteonecrosis of the jaw Osteoporosis 

Supplementary material

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ESM 1(DOC 41 kb)


  1. 1.
    Drugs.com In http://www.drugs.com/top200_units_2009.html. Accessed 1 Jun 2012
  2. 2.
    Kolata G (2006) In: New York Times. New York. http://www.nytimes.com/2006/06/02/health/02jaw.html?scp=1&sq=osteonecrosis%20jaw%20kolata&st=cse. Accessed 1 Jun 2012
  3. 3.
    Yablonsky T (2006) Some drugs can lead to bone death. Chicago Tribune, ChicagoGoogle Scholar
  4. 4.
    Bilezikian JP (2006) Osteonecrosis of the jaw—do bisphosphonates pose a risk? N Engl J Med 355:2278–2281PubMedCrossRefGoogle Scholar
  5. 5.
    Marx RE (2008) Uncovering the cause of "phossy jaw" Circa 1858 to 1906: oral and maxillofacial surgery closed case files-case closed. J Oral Maxillofac Surg 66:2356–2363PubMedCrossRefGoogle Scholar
  6. 6.
    AAOMS (2007) American Association of Oral and Maxillofacial Surgeons position paper on bisphosphonate-related osteonecrosis of the jaws. J Oral Maxillofac Surg 65:369-376Google Scholar
  7. 7.
    Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gotzsche PC, Ioannidis JP, Clarke M, Devereaux PJ, Kleijnen J, Moher D (2009) The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. PLoS Med 6:e1000100PubMedCrossRefGoogle Scholar
  8. 8.
    Baillargeon J, Kuo YF, Lin YL, Wilkinson GS, Goodwin JS (2011) Osteonecrosis of the jaw in older osteoporosis patients treated with intravenous bisphosphonates. Ann Pharmacother 45:1199-1206Google Scholar
  9. 9.
    Pazianas M, Blumentals WA, Miller PD (2008) Lack of association between oral bisphosphonates and osteonecrosis using jaw surgery as a surrogate marker. Osteoporos Int 19:773–779PubMedCrossRefGoogle Scholar
  10. 10.
    Fellows JL, Rindal DB, Barasch A, Gullion CM, Rush W, Pihlstrom DJ, Richman J (2011) ONJ in two dental practice-based research network regions. J. Dent Res 90:433-438Google Scholar
  11. 11.
    Mavrokokki T, Cheng A, Stein B, Goss A (2007) Nature and frequency of bisphosphonate-associated osteonecrosis of the jaws in Australia. J Oral Maxillofac Surg 65:415–423PubMedCrossRefGoogle Scholar
  12. 12.
    Lo JC, O'Ryan FS, Gordon NP, Yang J, Hui RL, Martin D, Hutchinson M, Lathon PV, Sanchez G, Silver P, Chandra M, McCloskey CA, Staffa JA, Willy M, Selby JV, Go AS (2010) Prevalence of osteonecrosis of the jaw in patients with oral bisphosphonate exposure. J Oral Maxillofac Surg 68:243-253Google Scholar
  13. 13.
    Cartsos VM, Zhu S (1939) Zavras AI 2008 bisphosphonate use and the risk of adverse jaw outcomes: a medical claims study of 714,217 people. J Am Dent Assoc 139:23–30Google Scholar
  14. 14.
    Jeffcoat MK (2006) Safety of oral bisphosphonates: controlled studies on alveolar bone. Int J Oral Maxillofac Implants 21:349–353PubMedGoogle Scholar
  15. 15.
    Barasch A, Cunha-Cruz J, Curro FA, Hujoel P, Sung AH, Vena D, Voinea-Griffin AE, Beadnell S, Craig RG, DeRouen T, Desaranayake A, Gilbert A, Gilbert GH, Goldberg K, Hauley R, Hashimoto M, Holmes J, Latzke B, Leroux B, Lindblad A, Richman J, Safford M, Ship J, Thompson VP, Williams OD, Yin W (2011) Risk factors for osteonecrosis of the jaws: a case-control study from the CONDOR dental PBRN. J Dental Res 90:439-444Google Scholar
  16. 16.
    Sedghizadeh PP, Stanley K, Caligiuri M, Hofkes S, Lowry B (1939) Shuler CF 2009 oral bisphosphonate use and the prevalence of osteonecrosis of the jaw: an institutional inquiry. J Am Dent Assoc 140:61–66Google Scholar
  17. 17.
    Hong JW, Nam W, Cha IH, Chung SW, Choi HS, Kim KM, Kim KJ, Rhee Y, Lim SK (2010) Oral bisphosphonate-related osteonecrosis of the jaw: the first report in Asia. Osteoporos Int 21:847-853Google Scholar
  18. 18.
    Khosla S, Burr D, Cauley J, Dempster DW, Ebeling PR, Felsenberg D, Gagel RF, Gilsanz V, Guise T, Koka S, McCauley LK, McGowan J, McKee MD, Mohla S, Pendrys DG, Raisz LG, Ruggiero SL, Shafer DM, Shum L, Silverman SL, Van Poznak CH, Watts N, Woo SB, Shane E (2007) Bisphosphonate-associated osteonecrosis of the jaw: report of a task force of the American Society for Bone and Mineral Research. J Bone Miner Res 22:1479–1491PubMedCrossRefGoogle Scholar
  19. 19.
    Lazarovici TS, Mesilaty-Gross S, Vered I, Pariente C, Kanety H, Givol N, Yahalom R, Taicher S, Yarom N (2010) Serologic bone markers for predicting development of osteonecrosis of the jaw in patients receiving bisphosphonates. J Oral Maxillofac Surg 68:2241-2247Google Scholar
  20. 20.
    Fugazzotto PA, Lightfoot WS, Jaffin R, Kumar A (2007) Implant placement with or without simultaneous tooth extraction in patients taking oral bisphosphonates: postoperative healing, early follow-up, and the incidence of complications in two private practices. J Periodontol 78:1664–1669PubMedCrossRefGoogle Scholar
  21. 21.
    Grant BT, Amenedo C, Freeman K, Kraut RA (2008) Outcomes of placing dental implants in patients taking oral bisphosphonates: a review of 115 cases. J Oral Maxillofac Surg 66:223–230PubMedCrossRefGoogle Scholar
  22. 22.
    Lee CY, Suzuki JB (2009) CTX biochemical marker of bone metabolism. Is it a reliable predictor of bisphosphonate-associated osteonecrosis of the jaws after surgery? Part I: biological concepts with a review of the literature. Implant Dent 18:492–500PubMedCrossRefGoogle Scholar
  23. 23.
    Kunchur R, Need A, Hughes T, Goss A (2009) Clinical investigation of C-terminal cross-linking telopeptide test in prevention and management of bisphosphonate-associated osteonecrosis of the jaws. J Oral Maxillofac Surg 67:1167–1173PubMedCrossRefGoogle Scholar

Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2012

Authors and Affiliations

  • D. H. Solomon
    • 1
    • 2
  • E. Mercer
    • 2
  • S. B. Woo
    • 3
    • 4
  • J. Avorn
    • 1
  • S. Schneeweiss
    • 1
  • N. Treister
    • 3
    • 4
  1. 1.Division of PharmacoepidemiologyBrigham and Women’s HospitalBostonUSA
  2. 2.Division of RheumatologyBrigham and Women’s HospitalBostonUSA
  3. 3.Department of MedicineBrigham and Women’s HospitalBostonUSA
  4. 4.Department of Oral MedicineBrigham and Women’s HospitalBostonUSA

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