Abstract
Introduction: Bisphosphonates are effective for treating osteoporosis, Paget's disease of bone, and malignancy-associated bone diseases. Bisphosphonate-associated osteonecrosis of the jaw (ONJ) is a rare but serious adverse effect of bisphosphonate therapy. Due to inhibitory actions on bone turnover, bisphosphonate therapy may result in the accumulation of microdamage.
Case summary: A 74-year-old Korean woman (height, 150 cm; weight, 51 kg) was referred to the Department of Endocrinology and Metabolism, Ajou University School of Medicine, Suwon, South Korea, for evaluation of pain and persistent abnormal exposure of jaw bone after extraction of teeth. She had been receiving weekly oral alendronate treatment for osteoporosis for ~5 years. The patient had the clinical features of bisphosphonate-associated osteonecrosis of the mandible, which was precipitated by teeth extraction ~14 months prior to the outpatient referral visit. At her clinical baseline visit, serum hormone concentrations and bone turnover markers were as follows: thyroid-stimulating hormone, 0.88 μIU/mL (reference range, 0.25–5.00 μIU/mL); 25-hydroxyvitamin D3, 20.9 (9.0–37.6) ng/mL; parathyroid hormone (PTH), 57 (11–62) pg/mL; serum osteocalcin, 8.7 (12.9–55.9) ng/mL; and urine N-telopeptide 21 (26–124) nM/mM creatinine. She had multiple systemic risk factors for ONJ, including older age, type 2 diabetes mellitus, and long duration of bisphosphonate therapy. There was no mandibular lesion improvement despite repeated surgical procedures performed within a 14-month period. Bisphosphonate therapy was discontinued and PTH therapy was started. After 2 months, exposed oral mucosa had healed. After 4 months of treatment, the pain had completely subsided, and after 6 months the patient's eating and drinking habits returned. The serum concentration of osteocalcin, a bone formation marker, which was initially suppressed (8.7 ng/mL), increased 174% (15.1 ng/mL) from baseline after 6 months of treatment with PTH.
Conclusions: Here we report a probable case of oral bisphosphonate-associated ONJ featuring suppressed bone turnover. Treatment with the bone formation-stimulating agent PTH was beneficial.
Key words: osteonecrosis of the jaw, bisphosphonate, alendronate, osteoporosis, parathyroid hormone treatment
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References
- 1.Lam DK, Sándor GK, Holmes HI. A review of bisphosphonate-associated osteonecrosis of the jaws and its management. J Can Dent Assoc. 2007;73:417–422. [PubMed] [Google Scholar]
- 2.Mashiba T, Mori S, Burr DB. The effects of suppressed bone remodeling by bisphosphonates on microdamage accumulation and degree of mineralization in the cortical bone of dog rib. J Bone Miner Metab. 2005;23(Suppl):36–42. doi: 10.1007/BF03026321. [DOI] [PubMed] [Google Scholar]
- 3.Odvina CV, Zerwekh JE, Rao DS. Severely suppressed bone turnover: A potential complication of alendronate therapy. J Clin Endocrinol Metab. 2005;90:1294–1301. doi: 10.1210/jc.2004-0952. [DOI] [PubMed] [Google Scholar]
- 4.Wang J, Goodger NM, Pogrel MA. Osteonecrosis of the jaws associated with cancer chemotherapy. J Oral Maxillofac Surg. 2003;61:1104–1107. doi: 10.1016/s0278-2391(03)00328-8. [DOI] [PubMed] [Google Scholar]
- 5.Marx RE. Pamidronate (Aredia) and zoledronate (Zometa) induced avascular necrosis of the jaws: A growing epidemic. J Oral Maxillofac Surg. 2003;61:1115–1117. doi: 10.1016/s0278-2391(03)00720-1. [DOI] [PubMed] [Google Scholar]
- 6.Migliorati CA. Bisphosphonates and oral cavity avascular bone necrosis. J Clin Oncol. 2003;21:4253–4254. doi: 10.1200/JCO.2003.99.132. [DOI] [PubMed] [Google Scholar]
- 7.Yarom N, Yahalom R, Shoshani Y. Osteonecrosis of the jaw induced by orally administered bisphosphonates: Incidence, clinical features, predisposing factors and treatment outcome. Osteoporos Int. 2007;18:1363–1370. doi: 10.1007/s00198-007-0384-2. [DOI] [PubMed] [Google Scholar]
- 8.Mavrokokki T, Cheng A, Stein B, Gross A. Nature and frequency of bisphosphonate-associated osteonecrosis of the jaws in Australia. J Oral Maxillofac Surg. 2007;65:415–423. doi: 10.1016/j.joms.2006.10.061. [DOI] [PubMed] [Google Scholar]
- 9.The Advisory Task Force on Bisphosphonate-Related Osteonecrosis of the Jaws and the American Association of Oral and Maxillofacial Surgeons American Association of Oral and Maxillofacial Surgeons position paper on bisphosphonate-related osteonecrosis of the jaws. J Oral Maxillofac Surg. 2007;65:369–376. doi: 10.1016/j.joms.2006.11.003. [DOI] [PubMed] [Google Scholar]
- 10.Khosla S, Burr D, Cauley J, American Society for Bone and Mineral Research Bisphosphonate-associated osteonecrosis of the jaw: Report of a task force of the American Society for Bone and Mineral Research. J Bone Miner Res. 2007;22:1479–1491. doi: 10.1359/jbmr.0707onj. [DOI] [PubMed] [Google Scholar]
- 11.Naranjo CA, Busto O, Sellers EM. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther. 1981;30:239–245. doi: 10.1038/clpt.1981.154. [DOI] [PubMed] [Google Scholar]
- 12.Harper RP, Fung E. Resolution of bisphosphonate-associated osteonecrosis of the mandible: Possible application for intermittent low-dose parathyroid hormone (rhPTH[1–34]) J Oral Maxillofac Surg. J Oral Maxillofac Surg. 2007;2007;6565:573–580. 1059. doi: 10.1016/j.joms.2006.10.076. [published correction appears in. ] [DOI] [PubMed] [Google Scholar]
- 13.Gasser JA, Kneissel M, Thomsen JS, Mosekilde L. PTH and interactions with bisphosphonates. J Musculoskelet Neuronal Interact. 2000;1:53–56. [PubMed] [Google Scholar]
- 14.Lecart MP, Bruyere O, Reginster JY. Combination/sequential therapy in osteoporosis. Curr Osteoporos Rep. 2004;2:123–130. doi: 10.1007/s11914-996-0011-8. [DOI] [PubMed] [Google Scholar]
- 15.Ma YL, Bryant HU, Zeng Q. New bone formation with teriparatide (human parathyroid hormone-[1–34]) is not retarded by long-term pretreatment with alendronate, estrogen, or raloxifene in ovariectomized rats. Endocrinology. 2003;144:2008–2015. doi: 10.1210/en.2002-221061. [DOI] [PubMed] [Google Scholar]