Osteoporosis International

, Volume 25, Issue 5, pp 1625–1632

Distinctive role of 6-month teriparatide treatment on intractable bisphosphonate-related osteonecrosis of the jaw

Original Article



The administration of teriparatide (TPTD) in conjunction with periodontal care could provide faster and more favorable clinical outcomes in previously refractory bisphosphonate-related osteonecrosis of the jaws (BRONJ) cases compared to conventional dental care, combination of surgery and antimicrobial treatment. We also found that underlying vitamin D levels might influence the response to TPTD treatment.


Treatment of BRONJ is quite challenging and there are no standard treatment modalities. In this retrospective, longitudinal study, we examined whether additional TPTD administration could be beneficial for the resolution of BRONJ lesions compared to conservative management, such as antimicrobial treatment with or without surgery, and also studied the factors influencing the response to TPTD.


Twenty-four cases of intractable BRONJ were included: 15 subjects were assigned to the TPTD group and the other 9 subjects, who refused TPTD administration, were assigned to the non-TPTD group. All subjects in both groups continued calcium and vitamin D supplementation and the TPTD group additionally received a daily subcutaneous injection of 20 μg TPTD for 6 months.


While 60.0 % of the non-TPTD group showed one stage of improvement in BRONJ, 40.0 % of the group did not show any improvement in disease status. In the TPTD group, 62.5 % of the treated subjects showed one stage of improvement and the other 37.5 % demonstrated a marked improvement, including two stages of improvement or complete healing, and there was not a single case that did not improve. The clinical improvement of BRONJ was statistically better in the TPTD group after the 6-month treatment (p < 0.05). Moreover, patients with higher baseline serum 25(OH)D levels showed better clinical therapeutic outcomes with TPTD.


We observed the beneficial effects of TPTD on BRONJ, and subjects with optimal serum vitamin D concentrations seemed to reap the maximum therapeutic effects of TPTD. A prospective, randomized, controlled trial should be needed to further evaluate the therapeutic efficacy of TPTD in the resolution of BRONJ.


Bisphosphonate Jaw Osteonecrosis Teriparatide Vitamin D 



Bisphosphonate-related osteonecrosis of the jaws


Bone mineral density


Body mass index




C-telopeptide of type I collagen




Parathyroid hormone


25-Hydroxyvitamin D


  1. 1.
    Cauley JA (2011) Defining ethnic and racial differences in osteoporosis and fragility fractures. Clin Orthop Relat Res 469:1891–1899PubMedCentralPubMedCrossRefGoogle Scholar
  2. 2.
    Haentjens P, Magaziner J, Colon-Emeric CS, Vanderschueren D, Milisen K, Velkeniers B, Boonen S (2010) Meta-analysis: excess mortality after hip fracture among older women and men. Ann Intern Med 152:380–390PubMedCentralPubMedCrossRefGoogle Scholar
  3. 3.
    Ruggiero SL (2011) Bisphosphonate-related osteonecrosis of the jaw: an overview. Ann N Y Acad Sci 1218:38–46PubMedCrossRefGoogle Scholar
  4. 4.
    Bilezikian JP (2009) Efficacy of bisphosphonates in reducing fracture risk in postmenopausal osteoporosis. Am J Med 122:S14–S21PubMedCrossRefGoogle Scholar
  5. 5.
    Urade M, Tanaka N, Furusawa K, Shimada J, Shibata T, Kirita T, Yamamoto T, Ikebe T, Kitagawa Y, Fukuta J (2011) Nationwide survey for bisphosphonate-related osteonecrosis of the jaws in Japan. J Oral Maxillofac Surg 69:e364–e371PubMedCrossRefGoogle Scholar
  6. 6.
    Khosla S, Burr D, Cauley J et al (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
  7. 7.
    Marx RE (2003) Pamidronate (Aredia) and zoledronate (Zometa) induced avascular necrosis of the jaws: a growing epidemic. J Oral Maxillofac Surg 61:1115–1117PubMedCrossRefGoogle Scholar
  8. 8.
    Ruggiero SL, Dodson TB, Assael LA, Landesberg R, Marx RE, Mehrotra B (2009) American Association of Oral and Maxillofacial Surgeons position paper on bisphosphonate-related osteonecrosis of the jaws-2009 update. J Oral Maxillofac Surg 67:2–12PubMedGoogle Scholar
  9. 9.
    Stepaniuk K (2011) Bisphosphonate related osteonecrosis of the jaws: a review. J Vet Dent 28:277–281PubMedGoogle Scholar
  10. 10.
    Rubin MR, Bilezikian JP (2003) The anabolic effects of parathyroid hormone therapy. Clin Geriatr Med 19:415–432PubMedCrossRefGoogle Scholar
  11. 11.
    Bashutski JD, Eber RM, Kinney JS, Benavides E, Maitra S, Braun TM, Giannobile WV, McCauley LK (2010) Teriparatide and osseous regeneration in the oral cavity. N Engl J Med 363:2396–2405PubMedCrossRefGoogle Scholar
  12. 12.
    Lee JJ, Cheng SJ, Jeng JH, Chiang CP, Lau HP, Kok SH (2011) Successful treatment of advanced bisphosphonate-related osteonecrosis of the mandible with adjunctive teriparatide therapy. Head Neck 33:1366–1371PubMedCrossRefGoogle Scholar
  13. 13.
    Narongroeknawin P, Danila MI, Humphreys LG Jr, Barasch A, Curtis JR (2010) Bisphosphonate-associated osteonecrosis of the jaw, with healing after teriparatide: a review of the literature and a case report. Spec Care Dentist 30:77–82PubMedCrossRefGoogle Scholar
  14. 14.
    Cheung A, Seeman E (2010) Teriparatide therapy for alendronate-associated osteonecrosis of the jaw. N Engl J Med 363:2473–2474PubMedCrossRefGoogle Scholar
  15. 15.
    Mashiba T, Hirano T, Turner CH, Forwood MR, Johnston CC, Burr DB (2000) Suppressed bone turnover by bisphosphonates increases microdamage accumulation and reduces some biomechanical properties in dog rib. J Bone Miner Res 15:613–620PubMedCrossRefGoogle Scholar
  16. 16.
    Wutzl A, Biedermann E, Wanschitz F, Seemann R, Klug C, Baumann A, Watzinger F, Schicho K, Ewers R, Millesi G (2008) Treatment results of bisphosphonate-related osteonecrosis of the jaws. Head Neck 30:1224–1230PubMedCrossRefGoogle Scholar
  17. 17.
    Wutzl A, Pohl S, Sulzbacher I, Seemann R, Lauer G, Ewers R, Drach J, Klug C (2012) Factors influencing surgical treatment of bisphosphonate-related osteonecrosis of the jaws. Head Neck 34:194–200PubMedCrossRefGoogle Scholar
  18. 18.
    Marx RE, Cillo JE Jr, Ulloa JJ (2007) Oral bisphosphonate-induced osteonecrosis: risk factors, prediction of risk using serum CTX testing, prevention, and treatment. J Oral Maxillofac Surg 65:2397–2410PubMedCrossRefGoogle Scholar
  19. 19.
    Quattrocchi E, Kourlas H (2004) Teriparatide: a review. Clin Ther 26:841–854PubMedCrossRefGoogle Scholar
  20. 20.
    McClung MR, San Martin J, Miller PD, Civitelli R, Bandeira F, Omizo M, Donley DW, Dalsky GP, Eriksen EF (2005) Opposite bone remodeling effects of teriparatide and alendronate in increasing bone mass. Arch Intern Med 165:1762–1768PubMedCrossRefGoogle Scholar
  21. 21.
    Chen P, Satterwhite JH, Licata AA, Lewiecki EM, Sipos AA, Misurski DM, Wagman RB (2005) Early changes in biochemical markers of bone formation predict BMD response to teriparatide in postmenopausal women with osteoporosis. J Bone Miner Res 20:962–970PubMedCrossRefGoogle Scholar
  22. 22.
    Lindsay R, Cosman F, Zhou H, Bostrom MP, Shen VW, Cruz JD, Nieves JW, Dempster DW (2006) A novel tetracycline labeling schedule for longitudinal evaluation of the short-term effects of anabolic therapy with a single iliac crest bone biopsy: early actions of teriparatide. J Bone Miner Res 21:366–373PubMedCrossRefGoogle Scholar
  23. 23.
    Ettinger B, San Martin J, Crans G, Pavo I (2004) Differential effects of teriparatide on BMD after treatment with raloxifene or alendronate. J Bone Miner Res 19:745–751PubMedCrossRefGoogle Scholar
  24. 24.
    Ma YL, Bryant HU, Zeng Q, Schmidt A, Hoover J, Cole HW, Yao W, Jee WS, Sato M (2003) 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 144:2008–2015PubMedCrossRefGoogle Scholar
  25. 25.
    Andreassen TT, Cacciafesta V (2004) Intermittent parathyroid hormone treatment enhances guided bone regeneration in rat calvarial bone defects. J Craniofac Surg 15:424–427, discussion 428–429PubMedCrossRefGoogle Scholar
  26. 26.
    Jung RE, Cochran DL, Domken O, Seibl R, Jones AA, Buser D, Hammerle CH (2007) The effect of matrix bound parathyroid hormone on bone regeneration. Clin Oral Implants Res 18:319–325PubMedCrossRefGoogle Scholar
  27. 27.
    Aspenberg P, Genant HK, Johansson T et al (2010) Teriparatide for acceleration of fracture repair in humans: a prospective, randomized, double-blind study of 102 postmenopausal women with distal radial fractures. J Bone Miner Res 25:404–414PubMedCrossRefGoogle Scholar
  28. 28.
    Gomberg SJ, Wustrack RL, Napoli N, Arnaud CD, Black DM (2011) Teriparatide, vitamin D, and calcium healed bilateral subtrochanteric stress fractures in a postmenopausal woman with a 13-year history of continuous alendronate therapy. J Clin Endocrinol Metab 96:1627–1632PubMedCrossRefGoogle Scholar
  29. 29.
    Hewitt C, Farah CS (2007) Bisphosphonate-related osteonecrosis of the jaws: a comprehensive review. J Oral Pathol Med 36:319–328PubMedCrossRefGoogle Scholar
  30. 30.
    Green JR (2004) Bisphosphonates: preclinical review. Oncologist 9(Suppl 4):3–13PubMedCrossRefGoogle Scholar
  31. 31.
    Wood J, Bonjean K, Ruetz S, Bellahcene A, Devy L, Foidart JM, Castronovo V, Green JR (2002) Novel antiangiogenic effects of the bisphosphonate compound zoledronic acid. J Pharmacol Exp Ther 302:1055–1061PubMedCrossRefGoogle Scholar
  32. 32.
    Estilo CL, Fornier M, Farooki A, Carlson D, Bohle G 3rd, Huryn JM (2008) Osteonecrosis of the jaw related to bevacizumab. J Clin Oncol 26:4037–4038PubMedCrossRefGoogle Scholar
  33. 33.
    Dhillon RS, Xie C, Tyler W, Calvi LM, Awad HA, Zuscik MJ, O'Keefe RJ, Schwarz EM (2013) PTH-enhanced structural allograft healing is associated with decreased angiopoietin-2-mediated arteriogenesis, mast cell accumulation, and fibrosis. J Bone Miner Res 28:586–597PubMedCentralPubMedCrossRefGoogle Scholar
  34. 34.
    Priemel M, von Domarus C, Klatte TO et al (2010) Bone mineralization defects and vitamin D deficiency: histomorphometric analysis of iliac crest bone biopsies and circulating 25-hydroxyvitamin D in 675 patients. J Bone Miner Res 25:305–312PubMedCrossRefGoogle Scholar
  35. 35.
    Holick MF (2007) Vitamin D deficiency. N Engl J Med 357:266–281PubMedCrossRefGoogle Scholar
  36. 36.
    Dietrich T, Nunn M, Dawson-Hughes B, Bischoff-Ferrari HA (2005) Association between serum concentrations of 25-hydroxyvitamin D and gingival inflammation. Am J Clin Nutr 82:575–580PubMedGoogle Scholar
  37. 37.
    Krall EA, Wehler C, Garcia RI, Harris SS, Dawson-Hughes B (2001) Calcium and vitamin D supplements reduce tooth loss in the elderly. Am J Med 111:452–456PubMedCrossRefGoogle Scholar
  38. 38.
    Bashutski JD, Eber RM, Kinney JS, Benavides E, Maitra S, Braun TM, Giannobile WV, McCauley LK (2011) The impact of vitamin D status on periodontal surgery outcomes. J Dent Res 90:1007–1012PubMedCentralPubMedCrossRefGoogle Scholar
  39. 39.
    Tsao C, Darby I, Ebeling PR, Walsh K, O'Brien-Simpson N, Reynolds E, Borromeo G (2013) Oral health risk factors for bisphosphonate-associated jaw osteonecrosis. J Oral Maxillofac Surg 71:1360–1366PubMedCrossRefGoogle Scholar

Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2014

Authors and Affiliations

  1. 1.Department of Internal MedicineSeoul National University Bundang HospitalSeongnamSouth Korea
  2. 2.Department of Advanced General Dentistry, Severance Dental HospitalYonsei University College of DentistrySeoulSouth Korea
  3. 3.Department of Oral and Maxillofacial Surgery, Severance Dental HospitalYonsei University College of DentistrySeoulSouth Korea
  4. 4.Department of Internal Medicine, Severance Hospital, Endocrine Research Institute, Brain Korea 21 Project for Medical ScienceYonsei University College of MedicineSeoulSouth Korea

Personalised recommendations