A multicenter case registry study on medication-related osteonecrosis of the jaw in patients with advanced cancer

Morten Schiodt, Saroj Vadhan-Raj, Mark S Chambers, Ourania Nicolatou-Galitis, Constantinus Politis, Ruxandra Coropciuc, Stefano Fedele, Danielle Jandial, Jeffrey Zhang, Haijun Ma, Deborah P Saunders, Morten Schiodt, Saroj Vadhan-Raj, Mark S Chambers, Ourania Nicolatou-Galitis, Constantinus Politis, Ruxandra Coropciuc, Stefano Fedele, Danielle Jandial, Jeffrey Zhang, Haijun Ma, Deborah P Saunders

Abstract

Purpose: This observational case registry study was designed to describe the natural history of cancer patients with medication-related osteonecrosis of the jaw (ONJ) and evaluate the ONJ resolution rate.

Methods: Adults with a diagnosis of cancer and with a new diagnosis of ONJ were enrolled and evaluated by a dental specialist at baseline and every 3 months for 2 years and then every 6 months for 3 years until death, consent withdrawal, or loss to follow-up. The primary endpoint was the rate and time course of ONJ resolution. Secondary endpoints included frequency of incident ONJ risk factors, ONJ treatment patterns, and treatment patterns of antiresorptive agents for subsequent ONJ.

Results: Overall, 327 patients were enrolled; 207 (63%) were continuing on study at data cutoff. Up to 69% of evaluable patients with ONJ had resolution or improvement during the study. ONJ resolution (AAOMS ONJ staging criteria) was observed in 114 patients (35%); median (interquartile range) time from ONJ onset to resolution was 7.3 (4.5-11.4) months. Most patients (97%) had received antiresorptive medication before ONJ development, 9 patients (3%) had not; 68% had received zoledronic acid, 38% had received denosumab, and 10% had received pamidronate (56% had received bisphosphonates only, 18% had received denosumab only, and 21% had exposure to both).

Conclusions: These results are consistent with those observed in clinical trials evaluating skeletal-related events in patients with advanced malignancy involving bone. Longer follow-up will provide further information on ONJ recurrence and resolution rates between medically and surgically managed patients.

Keywords: Bisphosphonates; Denosumab; Osteonecrosis of the jaw; Outcomes; Risk factors; Treatment.

Conflict of interest statement

DPS is a global advisor and investigator for Amgen and has received honoraria from Pfizer. SV-R received honoraria and research funding from Amgen. MSC and RC have no disclosures. ON-G has received travel support from Novartis and travel support and honoraria from Amgen. CP has participated as an investigator in an Amgen trial. SF has received research funding and travel support and honoraria from Amgen and salary support from the National Institute for Health Research (NIHR). DJ, JZ, and HM are employees of and own stock in Amgen. MS has served as a consultant to and received honoraria from Amgen.

References

    1. Rosella D, Papi P, Giardino R, Cicalini E, Piccoli L, Pompa G. Medication-related osteonecrosis of the jaw: clinical and practical guidelines. J Int Soc Prev Community Dent. 2016;6(2):97–104. doi: 10.4103/2231-0762.178742.
    1. Ruggiero SL, Dodson TB, Assael LA, Landesberg R, Marx RE, Mehrotra B, American Association of Oral and Maxillofacial Surgeons American Association of Oral and Maxillofacial Surgeons position paper on bisphosphonate-related osteonecrosis of the jaws—2009 update. J Oral Maxillofac Surg. 2009;67(5 Suppl):2–12. doi: 10.1016/j.joms.2009.01.009.
    1. Khan A, Morrison A, Cheung A, Hashem W, Compston J. Osteonecrosis of the jaw (ONJ): diagnosis and management in 2015. Osteoporos Int. 2016;27(3):853–859. doi: 10.1007/s00198-015-3335-3.
    1. Khan AA, Morrison A, Hanley DA, Felsenberg D, McCauley LK, O'Ryan F, Reid IR, Ruggiero SL, Taguchi A, Tetradis S, Watts NB, Brandi ML, Peters E, Guise T, Eastell R, Cheung AM, Morin SN, Masri B, Cooper C, Morgan SL, Obermayer-Pietsch B, Langdahl BL, Al Dabagh R, Davison KS, Kendler DL, Sandor GK, Josse RG, Bhandari M, El Rabbany M, Pierroz DD, Sulimani R, Saunders DP, Brown JP, Compston J, International Task Force on Osteonecrosis of the Jaw Diagnosis and management of osteonecrosis of the jaw: a systematic review and international consensus. J Bone Miner Res. 2015;30(1):3–23. doi: 10.1002/jbmr.2405.
    1. El-Rabbany M, Sgro A, Lam DK, Shah PS, Azarpazhooh A (2017) Effectiveness of treatments for medication-related osteonecrosis of the jaw: a systematic review and meta-analysis. J Am Dent Assoc
    1. Kim KM, Rhee Y, Kwon YD, Kwon TG, Lee JK, Kim DY. Medication related osteonecrosis of the jaw: 2015 position statement of the Korean Society for Bone and Mineral Research and the Korean Association of Oral and Maxillofacial Surgeons. J Bone Metab. 2015;22(4):151–165. doi: 10.11005/jbm.2015.22.4.151.
    1. Svejda B, Muschitz C, Gruber R, Brandtner C, Svejda C, Gasser RW, Santler G, Dimai HP. Position paper on medication-related osteonecrosis of the jaw (MRONJ) Wien Med Wochenschr. 2016;166(1-2):68–74. doi: 10.1007/s10354-016-0437-2.
    1. Yoneda T, Hagino H, Sugimoto T, Ohta H, Takahashi S, Soen S, Taguchi A, Nagata T, Urade M, Shibahara T, Toyosawa S. Antiresorptive agent-related osteonecrosis of the jaw: position paper 2017 of the Japanese Allied Committee on Osteonecrosis of the Jaw. J Bone Miner Metab. 2017;35(1):6–19. doi: 10.1007/s00774-016-0810-7.
    1. Zhang X, Hamadeh IS, Song S, Katz J, Moreb JS, Langaee TY, Lesko LJ, Gong Y. Osteonecrosis of the jaw in the United States Food and Drug Administration’s Adverse Event Reporting System (FAERS) J Bone Miner Res. 2016;31(2):336–340. doi: 10.1002/jbmr.2693.
    1. Ruggiero SL, Dodson TB, Fantasia J, Goodday R, Aghaloo T, Mehrotra B, O'Ryan F, American Association of Oral and Maxillofacial Surgeons American Association of Oral and Maxillofacial Surgeons position paper on medication-related osteonecrosis of the jaw—2014 update. J Oral Maxillofac Surg. 2014;72:1938–1956. doi: 10.1016/j.joms.2014.04.031.
    1. Woo SB, Hellstein JW, Kalmar JR. Systematic review: bisphosphonates and osteonecrosis of the jaws. Ann Intern Med. 2006;144(10):753–761. doi: 10.7326/0003-4819-144-10-200605160-00009.
    1. 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. 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(10):1479–1491. doi: 10.1359/jbmr.0707onj.
    1. Fedele S, Bedogni G, Scoletta M, Favia G, Colella G, Agrillo A, Bettini G, Di Fede O, Oteri G, Fusco V, Gabriele M, Ottolenghi L, Valsecchi S, Porter S, Fung PP, Saia G, Campisi G, Bedogni A. Up to a quarter of patients with osteonecrosis of the jaw associated with antiresorptive agents remain undiagnosed. Br J Oral Maxillofac Surg. 2015;53(1):13–17. doi: 10.1016/j.bjoms.2014.09.001.
    1. Fedele S, Porter SR, D'Aiuto F, Aljohani S, Vescovi P, Manfredi M, Arduino PG, Broccoletti R, Musciotto A, Di Fede O, Lazarovici TS, Campisi G, Yarom N. Nonexposed variant of bisphosphonate-associated osteonecrosis of the jaw: a case series. Am J Med. 2010;123(11):1060–1064. doi: 10.1016/j.amjmed.2010.04.033.
    1. Schiodt M, Reibel J, Oturai P, Kofod T. Comparison of nonexposed and exposed bisphosphonate-induced osteonecrosis of the jaws: a retrospective analysis from the Copenhagen cohort and a proposal for an updated classification system. Oral Surg Oral Med Oral Pathol Oral Radiol. 2014;117(2):204–213. doi: 10.1016/j.oooo.2013.10.010.
    1. Marx RE, Sawatari Y, Fortin M, Broumand V. Bisphosphonate-induced exposed bone (osteonecrosis/osteopetrosis) of the jaws: risk factors, recognition, prevention, and treatment. J Oral Maxillofac Surg. 2005;63(11):1567–1575. doi: 10.1016/j.joms.2005.07.010.
    1. Dimopoulos MA, Kastritis E, Anagnostopoulos A, Melakopoulos I, Gika D, Moulopoulos LA, Bamia C, Terpos E, Tsionos K, Bamias A. Osteonecrosis of the jaw in patients with multiple myeloma treated with bisphosphonates: evidence of increased risk after treatment with zoledronic acid. Haematologica. 2006;91(7):968–971.
    1. Scagliotti GV, Hirsh V, Siena S, Henry DH, Woll PJ, Manegold C, Solal-Celigny P, Rodriguez G, Krzakowski M, Mehta ND, Lipton L, Garcia-Saenz JA, Pereira JR, Prabhash K, Ciuleanu TE, Kanarev V, Wang H, Balakumaran A, Jacobs I. Overall survival improvement in patients with lung cancer and bone metastases treated with denosumab versus zoledronic acid: subgroup analysis from a randomized phase 3 study. J Thorac Oncol. 2012;7(12):1823–1829. doi: 10.1097/JTO.0b013e31826aec2b.
    1. Papapoulos S, Chapurlat R, Libanati C, Brandi ML, Brown JP, Czerwinski E, Krieg MA, Man Z, Mellstrom D, Radominski SC, Reginster JY, Resch H, Roman Ivorra JA, Roux C, Vittinghoff E, Austin M, Daizadeh N, Bradley MN, Grauer A, Cummings SR, Bone HG. Five years of denosumab exposure in women with postmenopausal osteoporosis: results from the first two years of the FREEDOM extension. J Bone Miner Res. 2012;27(3):694–701. doi: 10.1002/jbmr.1479.
    1. Qi WX, Tang LN, He AN, Yao Y, Shen Z. Risk of osteonecrosis of the jaw in cancer patients receiving denosumab: a meta-analysis of seven randomized controlled trials. Int J Clin Oncol. 2014;19(2):403–410. doi: 10.1007/s10147-013-0561-6.
    1. Henry DH, Costa L, Goldwasser F, Hirsh V, Hungria V, Prausova J, Scagliotti GV, Sleeboom H, Spencer A, Vadhan-Raj S, von Moos R, Willenbacher W, Woll PJ, Wang J, Jiang Q, Jun S, Dansey R, Yeh H. Randomized, double-blind study of denosumab versus zoledronic acid in the treatment of bone metastases in patients with advanced cancer (excluding breast and prostate cancer) or multiple myeloma. J Clin Oncol. 2011;29(9):1125–1132. doi: 10.1200/JCO.2010.31.3304.
    1. Fizazi K, Carducci M, Smith M, Damiao R, Brown J, Karsh L, Milecki P, Shore N, Rader M, Wang H, Jiang Q, Tadros S, Dansey R, Goessl C. Denosumab versus zoledronic acid for treatment of bone metastases in men with castration-resistant prostate cancer: a randomised, double-blind study. Lancet. 2011;377(9768):813–822. doi: 10.1016/S0140-6736(10)62344-6.
    1. Lipton A, Balakumaran A. Denosumab for the treatment of cancer therapy-induced bone loss and prevention of skeletal-related events in patients with solid tumors. Expert Rev Clin Pharmacol. 2012;5(4):359–371. doi: 10.1586/ecp.12.35.
    1. Bamias A, Kastritis E, Bamia C, Moulopoulos LA, Melakopoulos I, Bozas G, Koutsoukou V, Gika D, Anagnostopoulos A, Papadimitriou C, Terpos E, Dimopoulos MA. Osteonecrosis of the jaw in cancer after treatment with bisphosphonates: incidence and risk factors. J Clin Oncol. 2005;23(34):8580–8587. doi: 10.1200/JCO.2005.02.8670.
    1. Saad F, Brown JE, Van Poznak C, Ibrahim T, Stemmer SM, Stopeck AT, Diel IJ, Takahashi S, Shore N, Henry DH, Barrios CH, Facon T, Senecal F, Fizazi K, Zhou L, Daniels A, Carriere P, Dansey R. Incidence, risk factors, and outcomes of osteonecrosis of the jaw: integrated analysis from three blinded active-controlled phase III trials in cancer patients with bone metastases. Ann Oncol. 2012;23(5):1341–1347. doi: 10.1093/annonc/mdr435.
    1. Brenson JR, Stopeck AT (2016) Medication-related osteonecrosis of the jaw in patients with cancer. Available at: . Accessed 2 Sep 2016
    1. XGEVA® (denosumab). Full Prescribing Information, Amgen Inc., Thousand Oaks, CA, 2016.
    1. Yamazaki T, Yamori M, Ishizaki T, Asai K, Goto K, Takahashi K, Nakayama T, Bessho K. Increased incidence of osteonecrosis of the jaw after tooth extraction in patients treated with bisphosphonates: a cohort study. Int J Oral Maxillofac Surg. 2012;41(11):1397–1403. doi: 10.1016/j.ijom.2012.06.020.
    1. Wessel JH, Dodson TB, Zavras AI. Zoledronate, smoking, and obesity are strong risk factors for osteonecrosis of the jaw: a case-control study. J Oral Maxillofac Surg. 2008;66(4):625–631. doi: 10.1016/j.joms.2007.11.032.
    1. Jacobsen C, Metzler P, Rossle M, Obwegeser J, Zemann W, Gratz KW. Osteopathology induced by bisphosphonates and dental implants: clinical observations. Clin Oral Investig. 2013;17(1):167–175. doi: 10.1007/s00784-012-0708-2.
    1. Vahtsevanos K, Kyrgidis A, Verrou E, Katodritou E, Triaridis S, Andreadis CG, Boukovinas I, Koloutsos GE, Teleioudis Z, Kitikidou K, Paraskevopoulos P, Zervas K, Antoniades K. Longitudinal cohort study of risk factors in cancer patients of bisphosphonate-related osteonecrosis of the jaw. J Clin Oncol. 2009;27(32):5356–5362. doi: 10.1200/JCO.2009.21.9584.
    1. Otto S, Troltzsch M, Jambrovic V, Panya S, Probst F, Ristow O, Ehrenfeld M, Pautke C. Tooth extraction in patients receiving oral or intravenous bisphosphonate administration: a trigger for BRONJ development? J Craniomaxillofac Surg. 2015;43(6):847–854. doi: 10.1016/j.jcms.2015.03.039.
    1. Giovannacci I, Meleti M, Manfredi M, Mortellaro C, Greco Lucchina A, Bonanini M, Vescovi P. Medication-related osteonecrosis of the jaw around dental implants: implant surgery-triggered or implant presence-triggered osteonecrosis? J Craniofac Surg. 2016;27(3):697–701. doi: 10.1097/SCS.0000000000002564.
    1. Hoff AO, Toth BB, Altundag K, Johnson MM, Warneke CL, Hu M, Nooka A, Sayegh G, Guarneri V, Desrouleaux K, Cui J, Adamus A, Gagel RF, Hortobagyi GN. Frequency and risk factors associated with osteonecrosis of the jaw in cancer patients treated with intravenous bisphosphonates. J Bone Miner Res. 2008;23(6):826–836. doi: 10.1359/jbmr.080205.
    1. Pazianas M, Miller P, Blumentals WA, Bernal M, Kothawala P. A review of the literature on osteonecrosis of the jaw in patients with osteoporosis treated with oral bisphosphonates: prevalence, risk factors, and clinical characteristics. Clin Ther. 2007;29(8):1548–1558. doi: 10.1016/j.clinthera.2007.08.008.
    1. Lopez-Cedrun JL, Sanroman JF, Garcia A, Penarrocha M, Feijoo JF, Limeres J, Diz P. Oral bisphosphonate-related osteonecrosis of the jaws in dental implant patients: a case series. Br J Oral Maxillofac Surg. 2013;51(8):874–879. doi: 10.1016/j.bjoms.2013.06.011.
    1. Yazdi PM, Schiodt M. Dentoalveolar trauma and minor trauma as precipitating factors for medication-related osteonecrosis of the jaw (ONJ): a retrospective study of 149 consecutive patients from the Copenhagen ONJ cohort. Oral Surg Oral Med Oral Pathol Oral Radiol. 2015;119(4):416–422. doi: 10.1016/j.oooo.2014.12.024.
    1. Serra E, Paolantonio M, Spoto G, Mastrangelo F, Tetè S, Dolci M. Bevacizumab-related osteneocrosis of the jaw. Int J Immunopathol Pharmacol. 2009;22(4):1121–1123. doi: 10.1177/039463200902200429.
    1. Pakosch D, Papadimas D, Munding J, Kawa D, Kriwalsky MS. Osteonecrosis of the mandible due to anti-angiogenic agent, bevacizumab. Oral Maxillofac Surg. 2013;17(4):303–306. doi: 10.1007/s10006-012-0379-9.
    1. Nicolatou-Galitis O, Migkou M, Psyrri A, Bamias A, Pectasides D, Economopoulos T, Raber-Durlacher JE, Dimitriadis G, Dimopoulos MA. Gingival bleeding and jaw bone necrosis in patients with metastatic renal cell carcinoma receiving sunitinib: report of 2 cases with clinical implications. Oral Surg Oral Med Oral Pathol Oral Radiol. 2012;113(2):234–238. doi: 10.1016/j.tripleo.2011.08.024.
    1. Koch FP, Walter C, Hansen T, Jager E, Wagner W. Osteonecrosis of the jaw related to sunitinib. Oral Maxillofac Surg. 2011;15(1):63–66. doi: 10.1007/s10006-010-0224-y.
    1. Garuti F, Camelli V, Spinardi L, Bucci L, Trevisani F (2016) Osteonecrosis of the jaw during sorafenib therapy for hepatocellular carcinoma. Tumori 0
    1. Marino R, Orlandi F, Arecco F, Gandolfo S, Pentenero M. Osteonecrosis of the jaw in a patient receiving cabozantinib. Aust Dent J. 2015;60(4):528–531. doi: 10.1111/adj.12254.
    1. Stopeck AT, Lipton A, Body JJ, Steger GG, Tonkin K, de Boer RH, Lichinitser M, Fujiwara Y, Yardley DA, Viniegra M, Fan M, Jiang Q, Dansey R, Jun S, Braun A. Denosumab compared with zoledronic acid for the treatment of bone metastases in patients with advanced breast cancer: a randomized, double-blind study. J Clin Oncol. 2010;28(35):5132–5139. doi: 10.1200/JCO.2010.29.7101.
    1. Weitzman R, Sauter N, Eriksen EF, Tarassoff PG, Lacerna LV, Dias R, Altmeyer A, Csermak-Renner K, McGrath L, Lantwicki L, Hohneker JA. Critical review: updated recommendations for the prevention, diagnosis, and treatment of osteonecrosis of the jaw in cancer patients—May 2006. Crit Rev Oncol Hematol. 2007;62(2):148–152. doi: 10.1016/j.critrevonc.2006.12.005.
    1. Stopeck AT, Fizazi K, Body J-J, Brown JE, Carducci M, Diel I, Fujiwara Y, Martín M, Paterson A, Tonkin K, Shore N, Sieber P, Kueppers F, Karsh L, Yardley D, Wang H, Maniar T, Arellano J, Braun A. Safety of long-term denosumab therapy: results from the open label extension phase of two phase 3 studies in patients with metastatic breast and prostate cancer. Support Care Cancer. 2016;24(1):447–455. doi: 10.1007/s00520-015-2904-5.
    1. Stopeck AT, Warner DJ (2016) Response to letter to the editors—safety of long-term denosumab therapy. Support Care Cancer 1–3
    1. Pichardo SE, van Merkesteyn JP. Bisphosphonate related osteonecrosis of the jaws: spontaneous or dental origin? Oral Surg Oral Med Oral Pathol Oral Radiol. 2013;116(3):287–292. doi: 10.1016/j.oooo.2013.05.005.
    1. Almazrooa SA, Woo SB. Bisphosphonate and nonbisphosphonate-associated osteonecrosis of the jaw: a review. J Am Dent Assoc. 2009;140(7):864–875. doi: 10.14219/jada.archive.2009.0280.
    1. Kwon TG, Lee CO, Park JW, Choi SY, Rijal G, Shin HI. Osteonecrosis associated with dental implants in patients undergoing bisphosphonate treatment. Clin Oral Implants Res. 2014;25(5):632–640. doi: 10.1111/clr.12088.

Source: PubMed

Спонсоры и соавторы

Заболевания

Медикаментозные вмешательства

Подписаться