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Teriparatide therapy for severe, refractory osteoradionecrosis of the jaw

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Abstract

Although osteoradionecrosis (ORN) is a serious complication of craniofacial radiotherapy, the current management methods remain suboptimal. Teriparatide (TPTD), a recombinant human parathyroid hormone (1–34), has shown beneficial effects on osseous regeneration in medication-related osteonecrosis of the jaw or periodontitis. However, TPTD therapy in irradiated bones has not been indicated yet because of the theoretical risk of osteosarcoma seen in rat models. Hence, we first report here two patients with tongue cancer with late-emerging ORN who were successfully treated with TPTD for 4–6 months with serum calcium and vitamin D supplementation. In contrast to the usual progress of ORN, the bone defect regenerated well and bone turnover markers including serum C-terminal telopeptide of type 1 collagen and osteocalcin were restored with TPTD therapy. Our experience might suggest that TPTD therapy with careful monitoring can provide an effective treatment option for patients with ORN in select refractory cases, with the benefits outweighing the potential risks.

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References

  1. Marx RE (1983) Osteoradionecrosis: a new concept of its pathophysiology. J Oral Maxillofac Surg 41(5):283–288. https://doi.org/10.1016/0278-2391(83)90294-X

    Article  CAS  PubMed  Google Scholar 

  2. Reuther T, Schuster T, Mende U, Kubler A (2003) Osteoradionecrosis of the jaws as a side effect of radiotherapy of head and neck tumour patients—a report of a thirty year retrospective review. Int J Oral Maxillofac Surg 32(3):289–295. https://doi.org/10.1054/ijom.2002.0332

    Article  CAS  PubMed  Google Scholar 

  3. Mendenhall WM (2004) Mandibular osteoradionecrosis. J Clin Oncol 22(24):4867–4868. https://doi.org/10.1200/JCO.2004.09.959

    Article  PubMed  Google Scholar 

  4. Peterson DE, Doerr W, Hovan A, Pinto A, Saunders D, Elting LS, Spijkervet FKL, Brennan MT (2010) Osteoradionecrosis in cancer patients: the evidence base for treatment-dependent frequency, current management strategies, and future studies. Support Care Cancer 18(8):1089–1098. https://doi.org/10.1007/s00520-010-0898-6

    Article  PubMed  Google Scholar 

  5. Pitak-Arnnop P, Sader R, Dhanuthai K, Masaratana P, Bertolus C, Chaine A, Bertrand JC, Hemprich A (2008) Management of osteoradionecrosis of the jaws: an analysis of evidence. Eur J Surg Oncol 34(10):1123–1134. https://doi.org/10.1016/j.ejso.2008.03.014

    Article  CAS  PubMed  Google Scholar 

  6. Lyons A, Ghazali N (2008) Osteoradionecrosis of the jaws: current understanding of its pathophysiology and treatment. Br J Oral Maxillofac Surg 46(8):653–660. https://doi.org/10.1016/j.bjoms.2008.04.006

    Article  PubMed  Google Scholar 

  7. Khan A, Morrison A, Cheung A, Hashem W, Compston J (2016) Osteonecrosis of the jaw (ONJ): diagnosis and management in 2015. Osteoporos Int 27(3):853–859. https://doi.org/10.1007/s00198-015-3335-3

    Article  CAS  PubMed  Google Scholar 

  8. Lau AN, Adachi JD (2009) Resolution of osteonecrosis of the jaw after teriparatide [recombinant human PTH-(1-34)] therapy. J Rheumatol 36(8):1835–1837. https://doi.org/10.3899/jrheum.081176

    Article  CAS  PubMed  Google Scholar 

  9. 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(25):2396–2405. https://doi.org/10.1056/NEJMoa1005361

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Chandra A, Lin T, Zhu J, Tong W, Huo Y, Jia H, Zhang Y, Liu XS, Cengel K, Xia B, Qin L (2015) PTH1-34 blocks radiation-induced osteoblast apoptosis by enhancing DNA repair through canonical Wnt pathway. J Biol Chem 290(1):157–167. https://doi.org/10.1074/jbc.M114.608158

    Article  CAS  PubMed  Google Scholar 

  11. Kang SY, Deshpande SS, Donneys A, Rodriguez JJ, Nelson NS, Felice PA, Chepeha DB, Buchman SR (2013) Parathyroid hormone reverses radiation induced hypovascularity in a murine model of distraction osteogenesis. Bone 56(1):9–15. https://doi.org/10.1016/j.bone.2013.04.022

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Oest ME, Gong B, Esmonde-White K, Mann KA, Zimmerman ND, Damron TA, Morris MD (2016) Parathyroid hormone attenuates radiation-induced increases in collagen crosslink ratio at periosteal surfaces of mouse tibia. Bone 86:91–97. https://doi.org/10.1016/j.bone.2016.03.003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Delanian S, Lefaix JL (2004) The radiation-induced fibroatrophic process: therapeutic perspective via the antioxidant pathway. Radiother Oncol 73(2):119–131. https://doi.org/10.1016/j.radonc.2004.08.021

    Article  PubMed  Google Scholar 

  14. Gallagher KK, Deshpande S, Tchanque-Fossuo CN, Donneys A, Sarhaddi D, Nelson NS, Chepeha DB, Buchman SR (2013) Role of parathyroid hormone therapy in reversing radiation-induced nonunion and normalization of radiomorphometrics in a murine mandibular model of distraction osteogenesis. Head Neck 35(12):1732–1737. https://doi.org/10.1002/hed.23216

    Article  PubMed  PubMed Central  Google Scholar 

  15. Deshpande SS, Gallagher KK, Donneys A, Tchanque-Fossuo CN, Sarhaddi D, Nelson NS, Chepeha DB, Buchman SR (2013) Parathyroid hormone therapy mollifies radiation-induced biomechanical degradation in murine distraction osteogenesis. Plast Reconstr Surg 132(1):91e–100e. https://doi.org/10.1097/PRS.0b013e3182910ae7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Subbiah V, Madsen VS, Raymond AK, Benjamin RS, Ludwig JA (2010) Of mice and men: divergent risks of teriparatide-induced osteosarcoma. Osteoporos Int 21(6):1041–1045. https://doi.org/10.1007/s00198-009-1004-0

    Article  CAS  PubMed  Google Scholar 

  17. Gold DT, Pantos BS, Masica DN, Misurski DA, Marcus R (2006) Initial experience with teriparatide in the United States. Curr Med Res Opin 22(4):703–708. https://doi.org/10.1185/030079906X100159

    Article  CAS  PubMed  Google Scholar 

  18. Vahle JL, Long GG, Sandusky G, Westmore M, Ma YL, Sato M (2004) Bone neoplasms in F344 rats given teriparatide [rhPTH(1-34)] are dependent on duration of treatment and dose. Toxicol Pathol 32(4):426–438. https://doi.org/10.1080/01926230490462138

    Article  CAS  PubMed  Google Scholar 

  19. Harper KD, Krege JH, Marcus R, Mitlak BH (2007) Osteosarcoma and teriparatide? J Bone Miner Res 22:334

    Article  PubMed  Google Scholar 

  20. Harper KD, Krege JH, Marcus R, Mitlak BH (2006) Comments on Initial experience with teriparatide in the United States. Curr Med Res Opin 22(10):1927–1927. https://doi.org/10.1185/030079906X132578

    Article  PubMed  Google Scholar 

  21. Fatayerji D, Eastell R (1999) Age-related changes in bone turnover in men. J Bone Miner Res 14(7):1203–1210. https://doi.org/10.1359/jbmr.1999.14.7.1203

    Article  CAS  PubMed  Google Scholar 

  22. Ebeling PR, Atley LM, Guthrie JR, Burger HG, Dennerstein L, Hopper JL, Wark JD (1996) Bone turnover markers and bone density across the menopausal transition. J Clin Endocrinol Metab 81(9):3366–3371. https://doi.org/10.1210/jcem.81.9.8784098

    CAS  PubMed  Google Scholar 

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Funding

This work was supported by a National Research Foundation of Korea (NRF) grant funded by the Korean government (Ministry of Science, ICT and Future Planning) (NRF-2016R1D1A1B03934296).

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Author notes

  1. Y. H. Cha and N. Hong contributed equally to this work.

Authors and Affiliations

  1. Department of Oral and Maxillofacial Surgery, Yonsei University College of Dentistry, 50-1 Yonsei-ro, Seodaemoon-gu, Seoul, 03722, Korea

    Y. H. Cha & I.-H. Cha

  2. Department of Internal Medicine, Severance Hospital, Endocrine Research Institute, Yonsei University College of Medicine, Seoul, Korea

    N. Hong & Y. Rhee

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  1. Y. H. Cha
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  2. N. Hong
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  3. Y. Rhee
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  4. I.-H. Cha
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Contributions

Drafting the manuscript and data analysis: YHC and NH. Revising the manuscript: YR and IC. Approving the final version of the manuscript: all authors.

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Correspondence to I.-H. Cha.

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Cha, Y.H., Hong, N., Rhee, Y. et al. Teriparatide therapy for severe, refractory osteoradionecrosis of the jaw. Osteoporos Int 29, 987–992 (2018). https://doi.org/10.1007/s00198-017-4343-2

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  • DOI: https://doi.org/10.1007/s00198-017-4343-2

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