Abstract
Summary
Evidence of the incidence and risk of osteonecrosis of the jaw (ONJ) in Asian osteoporosis populations receiving different osteoporosis medications is lacking. We found that there is no excess incidence of or risk for ONJ in osteoporosis patients >50 years old using alendronate as compared with patients using raloxifene or calcitonin under real-world conditions in Taiwan.
Introduction
To provide information on ONJ in Asian populations, this study compares the incidence and risk of ONJ between patients receiving alendronate and those receiving non-bisphosphonate osteoporosis medications in Taiwan.
Methods
Enrollees in the National Health Insurance Research Database (NHIRD) from 2003 to 2007, aged above 50 years, with vertebral/hip fracture, and new to osteoporosis therapy were recruited. Patients with Paget’s disease or cancer during the baseline period were excluded. Patients were classified into either the alendronate or the calcitonin/raloxifene (control) group according to their exposure during follow-up. Previously proposed possible ONJ diagnosis codes were adopted as potential ONJ cases, but qualifying cases also had a repeated ONJ diagnosis within 8 weeks of the first diagnosis and received one or more broad-spectrum oral antibiotics. Cox modeling compared the risk of ONJ between the alendronate and the control groups, which were matched using propensity scores. Results were examined in series sensitivity analyses, including different cumulative dose groups.
Results
We found 25 potential ONJ cases in the alendronate (N = 18,030) and 21 in the control groups (N = 25,615). Over the 6-year follow-up period, no increased risk of ONJ in the alendronate group in the original (hazard ratio (HR), 0.87; 95 % confidence interval (CI), 0.47–1.58) or propensity score-matched cohorts (HR, 0.86; 95 % CI, 0.44–1.69) was found. All comparison groups exhibited a similar incidence of ONJ, ranging from 6.9 to 8.2/10,000 person-years.
Conclusion
Under real-world conditions, there is no excess risk for ONJ in osteoporosis patients >50 years old using alendronate as compared with patients using raloxifene or calcitonin.
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References
Silverman SL, Landesberg R (2009) Osteonecrosis of the jaw and the role of bisphosphonates: a critical review. [Review] [60 refs]. Am J Med 122(2 Suppl):S33–S45
Khan AA, Sandor GK, Dore E, Morrison AD, Alsahli M, Amin F et al (2009) Bisphosphonate associated osteonecrosis of the jaw. [Review] [95 refs]. J Rheumatol 36(3):478–490
Marx RE (2003) Pamidronate (Aredia) and zoledronate (Zometa) induced avascular necrosis of the jaws: a growing epidemic. J Oral Maxillofac Surg 61(9):1115–1117
Woo SB, Hellstein JW, Kalmar JR (2006) Systematic review: bisphosphonates and osteonecrosis of the jaws. Ann Intern Med 144(10):753–761
Ruggiero SL, Mehrotra B, Rosenberg TJ, Engroff SL (2004) Osteonecrosis of the jaws associated with the use of bisphosphonates: a review of 63 cases. J Oral Maxillofac Surg 62(5):527–534
Marx RE, Sawatari Y, Fortin M, Broumand V (2005) Bisphosphonate-induced exposed bone (osteonecrosis/osteopetrosis) of the jaws: risk factors, recognition, prevention, and treatment. J Oral Maxillofac Surg 63(11):1567–1575
Solomon DH, Mercer E, Woo SB, Avorn J, Schneeweiss S, Treister N (2013) Defining the epidemiology of bisphosphonate-associated osteonecrosis of the jaw: prior work and current challenges. Osteoporos Int 24(1):237–244
Advisory Task Force on Bisphosphonate-Related Ostenonecrosis of the Jaws, American Association of Oral Maxillofacial, Surgeons (2007) Position paper on bisphosphonate-related osteonecrosis of the jaws. J Oral Maxillofac Surg 65(3):369–376
Wilkinson GS, Kuo YF, Freeman JL, Goodwin JS (2007) Intravenous bisphosphonate therapy and inflammatory conditions or surgery of the jaw: a population-based analysis. [see comment]. J Natl Cancer Inst 99(13):1016–1024
Cartsos VMZS, Zavras AI (2008) Bisphosphonate use and the risk of adverse jaw outcomes. J Am Dent Assoc 139:23–30
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(6):773–779
Black DM, Delmas PD, Eastell R, Reid IR, Boonen S, Cauley JA et al (2007) Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. [see comment]. N Engl J Med 356(18):1809–1822
NHIRD. National Health Insurance Research Database, Taiwan. http://www.nhri.org.tw/nhird/en/index.htm. Assessed Jan. 4th, 2011
Lin TC, Yang CY, Kao Yang YH, Lin SJ (2011) Alendronate adherence and its impact on hip-fracture risk in patients with established osteoporosis in Taiwan. Clin Pharmacol Ther 90(1):109–116
Hess LM, Jeter JM, Benham-Hutchins M, Alberts DS (2008) Factors associated with osteonecrosis of the jaw among bisphosphonate users. [Review] [57 refs]. Am J Med 121(6):475–483
Parsons LS. Reducing bias in a propensity score matched-pair sample using greedy matching techniques. http://www2.sas.com/proceedings/sugi26/p214-26.pdf. Assessed Jan. 4th, 2011
Shrank WH, Patrick AR, Brookhart MA (2011) Healthy user and related biases in observational studies of preventive interventions: a primer for physicians. J Gen Intern Med 26(5):546–550
Siris ES, Harris ST, Rosen CJ, Barr CE, Arvesen JN, Abbott TA et al (2006) Adherence to bisphosphonate therapy and fracture rates in osteoporotic women: relationship to vertebral and nonvertebral fractures from 2 US claims databases. [see comment]. Mayo Clin Proc 81(8):1013–1022
Hoff AO, Toth BB, Altundag K, Johnson MM, Warneke CL, Hu MM et al (2008) Frequency and risk factors associated with osteonecrosis of the jaw in cancer patients treated with intravenous bisphosphonates. J Bone Miner Res 23(6):826–836
Edwards BJ, Gounder M, McKoy JM, Boyd I, Farrugia M, Migliorati C et al (2008) Pharmacovigilance and reporting oversight in US FDA fast-track process: bisphosphonates and osteonecrosis of the jaw. [Review] [69 refs]. Lancet Oncol 9(12):1166–1172
Lo JC, O’Ryan FS, Gordon NP, Yang J, Hui RL, Martin D et al (2010) Prevalence of osteonecrosis of the jaw in patients with oral bisphosphonate exposure. J Oral Maxillofac Surg 68(2):243–253
Tennis P, Rothman KJ, Bohn RL, Tan H, Zavras A, Laskarides C et al (2012) Incidence of osteonecrosis of the jaw among users of bisphosphonates with selected cancers or osteoporosis. Pharmacoepidemiol Drug Saf 21(8):810–817
Van den Wyngaert T, Huizing MT, Vermorken JB (2007) Osteonecrosis of the jaw related to the use of bisphosphonates. [Review] [60 refs]. Curr Opin Oncol 19(4):315–322
Hong JW, Nam W, Cha IH, Chung SW, Choi HS, Kim KM et al (2010) Oral bisphosphonate-related osteonecrosis of the jaw: the first report in Asia. Osteoporos Int 21(5):847–853
King AE, Umland EM (2008) Osteonecrosis of the jaw in patients receiving intravenous or oral bisphosphonates. [Review] [71 refs]. Pharmacotherapy 28(5):667–677
Fellows JL, Rindal DB, Barasch A, Gullion CM, Rush W, Pihlstrom DJ et al (2011) ONJ in two dental practice-based research network regions. J Dent Res 90(4):433–438
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(10):1199–1206
Zavras AI, Zhu S (2006) Bisphosphonates are associated with increased risk for jaw surgery in medical claims data: is it osteonecrosis? [see comment]. J Oral Maxillofac Surg 64(6):917–923
American Association of Oral and Maxillofacial Surgeons (2007) Position paper on bisphosphonate-related osteonecrosis of the jaws. J Oral Maxillofac Surg 65(3):369–376
Kothawala P, Badamgarav E, Ryu S, Miller RM, Halbert RJ (2007) Systematic review and meta-analysis of real-world adherence to drug therapy for osteoporosis. [Review] [57 refs]. Mayo Clin Proc 82(12):1493–1501
Solomon DH, Avorn J, Katz JN, Finkelstein JS, Arnold M, Polinski JM et al (2005) Compliance with osteoporosis medications. Arch Intern Med 165(20):2414–2419
Acknowledgments
This study was supported in part by grants from the Department of Health, Executive Yuan, Taiwan and National Science Council, Taiwan (NSC 99-2320-B-006-016-MY3)
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Lin, TC., Yang, CY., Kao Yang, YH. et al. Incidence and risk of osteonecrosis of the jaw among the Taiwan osteoporosis population. Osteoporos Int 25, 1503–1511 (2014). https://doi.org/10.1007/s00198-014-2624-6
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DOI: https://doi.org/10.1007/s00198-014-2624-6