Abstract
Summary
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 %).
Introduction
We examined the epidemiology of BONJ associated with osteoporosis dosing of bisphosphonates.
Methods
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.
Results
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.
Conclusions
The literature suggests a broad range of possible values for the prevalence of BONJ; our estimate fell within the range from prior literature.
Similar content being viewed by others
References
Drugs.com In http://www.drugs.com/top200_units_2009.html. Accessed 1 Jun 2012
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
Yablonsky T (2006) Some drugs can lead to bone death. Chicago Tribune, Chicago
Bilezikian JP (2006) Osteonecrosis of the jaw—do bisphosphonates pose a risk? N Engl J Med 355:2278–2281
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 66:2356–2363
AAOMS (2007) American Association of Oral and Maxillofacial Surgeons position paper on bisphosphonate-related osteonecrosis of the jaws. J Oral Maxillofac Surg 65:369-376
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:e1000100
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 45:1199-1206
Pazianas M, Blumentals WA, Miller PD (2008) Lack of association between oral bisphosphonates and osteonecrosis using jaw surgery as a surrogate marker. Osteoporos Int 19:773–779
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 90:433-438
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 65:415–423
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 68:243-253
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 139:23–30
Jeffcoat MK (2006) Safety of oral bisphosphonates: controlled studies on alveolar bone. Int J Oral Maxillofac Implants 21:349–353
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 90:439-444
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 140:61–66
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 21:847-853
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 22:1479–1491
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 68:2241-2247
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 78:1664–1669
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 66:223–230
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 18:492–500
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 67:1167–1173
Conflicts of interest
Dr. Solomon receives research support from Amgen and Lilly.
Author information
Authors and Affiliations
Corresponding author
Additional information
Support: NIH-DE-R21018750
Electronic supplementary material
Below is the link to the electronic supplementary material.
ESM 1
(DOC 41 kb)
Appendix 1
Appendix 1
Possible diagnosis codes for osteonecrosis of the jaw
Rights and permissions
About this article
Cite this article
Solomon, D.H., Mercer, E., Woo, S.B. et al. Defining the epidemiology of bisphosphonate-associated osteonecrosis of the jaw: prior work and current challenges. Osteoporos Int 24, 237–244 (2013). https://doi.org/10.1007/s00198-012-2042-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00198-012-2042-6