nach oben

Erschienen in:

17.05.2021 | Original Article

Denosumab-related osteonecrosis of the jaw after tooth extraction and the effects of a short drug holiday in cancer patients: a multicenter retrospective study

verfasst von: T. Hasegawa, N. Ueda, SI. Yamada, S. Kato, E. Iwata, S. Hayashida, Y. Kojima, M. Shinohara, I. Tojo, H. Nakahara, T. Yamaguchi, T. Kirita, H. Kurita, Y. Shibuya, S. Soutome, M. Akashi, Japanese Study Group of Co-operative Dentistry with Medicine (JCDM)

Erschienen in: Osteoporosis International | Ausgabe 11/2021

Einloggen, um Zugang zu erhalten

Abstract

Summary

Pre-existing inflammation, corticosteroid therapy, periapical periodontitis, longer duration of denosumab therapy, and female sex were significantly associated with an increased risk of denosumab-related osteonecrosis of the jaw after tooth extraction in patients with cancer on oncologic doses of denosumab. A short drug holiday did not protect against this complication.

Introduction

This study retrospectively investigated the relationship between various risk factors, including brief discontinuation of denosumab, and development of denosumab-related osteonecrosis of the jaw (DRONJ) after tooth extraction in patients with cancer who were receiving oncologic doses of this agent.

Methods

Data were collected on demographic characteristics, duration of denosumab therapy, whether or not denosumab was discontinued before tooth extraction (drug holiday), duration of discontinuation, presence of pre-existing inflammation, and whether or not additional surgical procedures were performed. Risk factors for DRONJ after tooth extraction were evaluated by univariate and multivariate analyses.

Results

A total of 136 dental extractions were performed in 72 patients (31 men, 41 women) with cancer who were receiving oncologic doses of denosumab. Post-extraction DRONJ was diagnosed in 39 teeth (28.7%) in 25 patients. Tooth extraction was significantly associated with development of DRONJ only in patients with pre-existing inflammation (odds ratio [OR] 243.77), those on corticosteroid therapy (OR 73.50), those with periapical periodontitis (OR 14.13), those who had been taking oncologic doses of denosumab for a longer period (OR 4.69), and in women (OR 1.04). There was no significant difference in the occurrence of DRONJ between patients who had a drug holiday before tooth extraction and those who did not.

Conclusions

These findings suggest that inflamed teeth should be extracted immediately in patients with cancer who are receiving oncologic doses of denosumab. Drug holidays have no significant impact on the risk of DRONJ.

Ruggiero SL, Dodson TB, Fantasia J, Goodday R, Aghaloo T, Mehrotra B, O’Ryan F, American Association of Oral and Maxillofacial Surgeons (2014) American Association of Oral and Maxillofacial Surgeons position paper on medication-related osteonecrosis of the jaw--2014 update. J Oral Maxillofac Surg 72:1938–1956PubMed

Otto S, Pautke C, Van den Wyngaert T, Niepel D, Schiødt M (2018) Medication-related osteonecrosis of the jaw: prevention, diagnosis and management in patients with cancer and bone metastases. Cancer Treat Rev 69:177–187PubMed

Berenson JR, Rajdev L, Broder M (2006) Treatment strategies for skeletal complications of cancer. Cancer Biol Ther 5:1074–1077PubMed

Fizazi K, Carducci M, Smith M, Damião R, Brown J, Karsh L, Milecki P, Shore N, Rader M, Wang H, Jiang Q, Tadros S, Dansey R, Goessl C (2011) Denosumab versus zoledronic acid for treatment of bone metastases in men with castration-resistant prostate cancer: a randomised, double-blind study. Lancet 377:813–822PubMedPubMedCentral

Marx RE (2003) Pamidronate (Aredia) and zoledronate (Zometa) induced avascular necrosis of the jaws: a growing epidemic. J Oral Maxillofac Surg 61:1115–1117PubMed

Migliorati CA (2003) Bisphosphonates and oral cavity avascular bone necrosis. J Clin Oncol 21(22):4253–4254PubMed

Yoshimura H, Ohba S, Yoshida H, Saito K, Inui K, Yasui R, Ichikawa D, Aiki M, Kobayashi J, Matsuda S, Imamura Y, Sano K (2017) Denosumab-related osteonecrosis of the jaw in a patient with bone metastases of prostate cancer: a case report and literature review. Oncol Lett 14:127–136PubMedPubMedCentral

Mavrokokki T, Cheng A, Stein B, Goss A (2007) Nature and frequency of bisphosphonate-associated osteonecrosis of the jaws in Australia. J Oral Maxillofac Surg 65:415–423PubMed

Kunchur R, Need A, Hughes T, Goss A (2009) Clinical investigation of C-terminal cross-linking telopeptide test in prevention and management of bisphosphonate-associated osteonecrosis of the jaws. J Oral Maxillofac Surg 67:1167–1173PubMed

10.

Hasegawa T, Kawakita A, Ueda N, Funahara R, Tachibana A, Kobayashi M, Kondou E, Takeda D, Kojima Y, Sato S, Yanamoto S, Komatsubara H, Umeda M, Kirita T, Kurita H, Shibuya Y, Komori T, Japanese Study Group of Cooperative Dentistry with Medicine (JCDM) (2017) A multicenter retrospective study of the risk factors associated with medication-related osteonecrosis of the jaw after tooth extraction in patients receiving oral bisphosphonate therapy: can primary wound closure and a drug holiday really prevent MRONJ? Osteoporos Int 28:2465–2473PubMed

11.

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 (2008) Frequency and risk factors associated with osteonecrosis of the jaw in cancer patients treated with intravenous bisphosphonates. J Bone Miner Res 23:826–836PubMed

12.

Hasegawa T, Hayashida S, Kondo E, Takeda Y, Miyamoto H, Kawaoka Y, Ueda N, Iwata E, Nakahara H, Kobayashi M, Soutome S, Yamada SI, Tojyo I, Kojima Y, Umeda M, Fujita S, Kurita H, Shibuya Y, Kirita T, Komori T, Japanese Study Group of Co-operative Dentistry with Medicine (JCDM) (2019) Medication-related osteonecrosis of the jaw after tooth extraction in cancer patients: a multicenter retrospective study. Osteoporos Int 30(1):231–239PubMed

13.

Brown JP, Fortier M, Frame H, Lalonde A, Papaioannou A, Senikas V, Yuen CK, Osteoporosis Guidelines Committee (2006) Canadian Consensus Conference on osteoporosis, 2006 update. J Obstet Gynaecol Can 28(2 Suppl 1):S95–S112PubMedPubMedCentral

14.

Lipton A, Steger GG, Figueroa J, Alvarado C, Solal-Celigny P, Body JJ, de Boer R, Berardi R, Gascon P, Tonkin KS, Coleman RE, Paterson AH, Gao GM, Kinsey AC, Peterson MC, Jun S (2008) Extended efficacy and safety of denosumab in breast cancer patients with bone metastases not receiving prior bisphosphonate therapy. Clin Cancer Res 14(20):6690–6696PubMed

15.

Anastasilakis AD, Toulis KA, Polyzos SA, Anastasilakis CD, Makras P (2012) Long-term treatment of osteoporosis: safety and efficacy appraisal of denosumab. Ther Clin Risk Manag 8:295–306PubMedPubMedCentral

16.

Amgen, Inc. Prolia (denosumab) prescribing information. 2010 updated 2014

17.

Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, Carbone PP (1982) Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol 5(6):649–655PubMed

18.

Fizazi K, Lipton A, Mariette X, Body JJ, Rahim Y, Gralow JR, Gao G, Wu L, Sohn W, Jun S (2009) Randomized phase II trial of denosumab in patients with bone metastases from prostate cancer, breast cancer, or other neoplasms after intravenous bisphosphonates. J Clin Oncol 27(10):1564–1571PubMed

19.

Lipton A, Steger GG, Figueroa J, Alvarado C, Solal-Celigny P, Body JJ, de Boer R, Berardi R, Gascon P, Tonkin KS, Coleman R, Paterson AH, Peterson MC, Fan M, Kinsey A, Jun S (2007) Randomized active-controlled phase II study of denosumab efficacy and safety in patients with breast cancer-related bone metastases. J Clin Oncol 25(28):4431–4437PubMed

20.

Smith MR, Egerdie B, Hernández Toriz N, Feldman R, Tammela TL, Saad F, Heracek J, Szwedowski M, Ke C, Kupic A, Leder BZ, Goessl C, Denosumab HALT Prostate Cancer Study Group (2009) Denosumab in men receiving androgen-deprivation therapy for prostate cancer. N Engl J Med 361(8):745–755PubMedPubMedCentral

21.

Smith MR, Saad F, Coleman R, Shore N, Fizazi K, Tombal B, Miller K, Sieber P, Karsh L, Damião R, Tammela TL, Egerdie B, Van Poppel H, Chin J, Morote J, Gómez-Veiga F, Borkowski T, Ye Z, Kupic A, Dansey R, Goessl C (2012) Denosumab and bone-metastasis-free survival in men with castration-resistant prostate cancer: results of a phase 3, randomised, placebo-controlled trial. Lancet 379(9810):39–46PubMed

22.

Okuma S, Matsuda Y, Nariai Y, Karino M, Suzuki R, Kanno T (2020) A retrospective observational study of risk factors for denosumab-related osteonecrosis of the jaw in patients with bone metastases from solid cancers. Cancers (Basel) 12(5):1209PubMed

23.

Limones A, Sáez-Alcaide LM, Díaz-Parreño SA, Helm A, Bornstein MM, Molinero-Mourelle P (2020) Medication-related osteonecrosis of the jaws (MRONJ) in cancer patients treated with denosumab vs. zoledronic acid: a systematic review and meta-analysis. Med Oral Patol Oral Cir Bucal 25(3):e326–e336PubMedPubMedCentral

24.

Ueda N, Nakashima C, Aoki K, Shimotsuji H, Nakaue K, Yoshioka H, Kurokawa S, Imai Y, Kirita T (2020) Does inflammatory dental disease affect the development of medication-related osteonecrosis of the jaw in patients using high-dose bone-modifying agents? Clin Oral Investig [Online ahead of print]

25.

Matsumoto A, Sasaki M, Schmelzeisen R, Oyama Y, Mori Y, Voss PJ (2017) Primary wound closure after tooth extraction for prevention of medication-related osteonecrosis of the jaw in patients under denosumab. Clin Oral Investig 21(1):127–134PubMed

26.

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, Carrière P, Dansey R (2012) 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 23:1341–1347PubMed

27.

Yamazaki T, Yamori M, Ishizaki T, Asai K, Goto K, Takahashi K, Nakayama T, Bessho K (2012) Increased incidence of osteonecrosis of the jaw after tooth extraction in patients treated with bisphosphonates: a cohort study. Int J Oral Maxillofac Surg 41:1397–1403PubMed

28.

Soutome S, Hayashida S, Funahara M, Sakamoto Y, Kojima Y, Yanamoto S, Umeda M (2018) Factors affecting development of medication-related osteonecrosis of the jaw in cancer patients receiving high-dose bisphosphonate or denosumab therapy: is tooth extraction a risk factor? PLoS One 13(7):e0201343PubMedPubMedCentral

29.

Schwartz S, Joseph C, Iera D, Vu DD (2008) Bisphosphonates, osteonecrosis, osteogenesis imperfecta and dental extractions: a case series. J Can Dent Assoc 74(6):537–542PubMed

30.

Chahine C, Cheung MS, Head TW, Schwartz S, Glorieux FH, Rauch F (2008) Tooth extraction socket healing in pediatric patients treated with intravenous pamidronate. J Pediatr 153(5):719–720PubMed

31.

Guilbeau JM (2002 Sep) (2002) Delayed wound healing with sirolimus after liver transplant. Ann Pharmacother 36(9):1391–1395PubMed

32.

Cavalli RC, Tambara Filho R, Gomes Rde P, Veronez DA, Slongo J, Rd F (2014) Analysis of the histology of the scar bladder and biochemical parameters of rats with a solitary kidney undergoing immunosuppression with tacrolimus. Acta Cir Bras 29(8):508–514PubMed

33.

Weinstein RS (2012) Glucocorticoid-induced osteonecrosis. Endocrine 41(2):183–190PubMed

34.

Weinstein RS (2012) Glucocorticoid-induced osteoporosis and osteonecrosis. Endocrinol Metab Clin N Am 41(3):595–611

35.

Takano-Murakami R, Tokunaga K, Kondo N, Ito T, Kitahara H, Ito M, Endo N (2009) Glucocorticoid inhibits bone regeneration after osteonecrosis of the femoral head in aged female rats. Tohoku J Exp Med 217(1):51–58PubMed

36.

Aljohani S, Gaudin R, Weiser J, Tröltzsch M, Ehrenfeld M, Kaeppler G, Smeets R, Otto S (2018) Osteonecrosis of the jaw in patients treated with denosumab: a multicenter case series. J Craniomaxillofac Surg 46(9):1515–1525PubMed

37.

Wong LS, Tay KK, Cheing YL (2015) Osteonecrosis of mandible: a rare complication of long-term steroid use. J Oral Maxillofac Surg Med Pathol 27:255–257

38.

Hoefert S, Yuan A, Munz A, Grimm M, Elayouti A, Reinert S (2017) Clinical course and therapeutic outcomes of operatively and non-operatively managed patients with denosumab-related osteonecrosis of the jaw (DRONJ). J Craniomaxillofac Surg 45(4):570–578PubMed

39.

Bone HG, Bolognese MA, Yuen CK, Kendler DL, Miller PD, Yang YC, Grazette L, San Martin J, Gallagher JC (2011) Effects of denosumab treatment and discontinuation on BMD and bone turnover markers in postmenopausal women with low bone mass. J Clin Endocrinol Metab 96(4):972–980PubMed

40.

Miller PD, Bolognese MA, Lewiecki EM, MR MC, Ding B, Austin M, Liu Y, San Martin J, Amg Bone Loss Study Group (2008) Effect of denosumab on BMD and turnover in postmenopausal women with low bone mass after long-term continued, discontinued, and restarting of therapy: a randomized blinded phase 2 clinical trial. Bone 43(2):222–229PubMed

41.

Malan J, Ettinger K, Naumann E, Beirne OR (2012) The relationship of denosumab pharmacology and osteonecrosis of the jaws. Oral Surg Oral Med Oral Pathol Oral Radiol 114(6):671–676PubMed

42.

Taylor KH, Middlefell LS, Mizen KD (2010) Osteonecrosis of the jaws induced by anti-RANK ligand therapy. Br J Oral Maxillofac Surg 48(3):221–223PubMed

43.

Hayashida S, Yanamoto S, Fujita S, Hasegawa T, Komori T, Kojima Y, Miyamoto H, Shibuya Y, Ueda N, Kirita T, Nakahara H, Shinohara M, Kondo E, Kurita H, Umeda M (2020) Drug holiday clinical relevance verification for antiresorptive agents in medication-related osteonecrosis cases of the jaw. J Bone Miner Metab 38(1):126–134PubMed

44.

McClung MR (2016) Cancel the denosumab holiday. Osteoporos Int 27(5):1677–1682PubMed

Titel: Denosumab-related osteonecrosis of the jaw after tooth extraction and the effects of a short drug holiday in cancer patients: a multicenter retrospective study
verfasst von: T. Hasegawa
N. Ueda
SI. Yamada
S. Kato
E. Iwata
S. Hayashida
Y. Kojima
M. Shinohara
I. Tojo
H. Nakahara
T. Yamaguchi
T. Kirita
H. Kurita
Y. Shibuya
S. Soutome
M. Akashi
Japanese Study Group of Co-operative Dentistry with Medicine (JCDM)
Publikationsdatum: 17.05.2021
Verlag: Springer London
Erschienen in: Osteoporosis International / Ausgabe 11/2021
Print ISSN: 0937-941X
Elektronische ISSN: 1433-2965
DOI: https://doi.org/10.1007/s00198-021-05995-3

Arthropedia

Grundlagenwissen der Arthroskopie und Gelenkchirurgie. Erweitert durch Fallbeispiele, Videos und Abbildungen.
» Jetzt entdecken

Neu im Fachgebiet Orthopädie und Unfallchirurgie

Notfall-TEP der Hüfte ist auch bei 90-Jährigen machbar

26.04.2024 Hüft-TEP Nachrichten

Ob bei einer Notfalloperation nach Schenkelhalsfraktur eine Hemiarthroplastik oder eine totale Endoprothese (TEP) eingebaut wird, sollte nicht allein vom Alter der Patientinnen und Patienten abhängen. Auch über 90-Jährige können von der TEP profitieren.

Arthroskopie kann Knieprothese nicht hinauszögern

25.04.2024 Gonarthrose Nachrichten

Ein arthroskopischer Eingriff bei Kniearthrose macht im Hinblick darauf, ob und wann ein Gelenkersatz fällig wird, offenbar keinen Unterschied.

Therapiestart mit Blutdrucksenkern erhöht Frakturrisiko

25.04.2024 Hypertonie Nachrichten

Beginnen ältere Männer im Pflegeheim eine Antihypertensiva-Therapie, dann ist die Frakturrate in den folgenden 30 Tagen mehr als verdoppelt. Besonders häufig stürzen Demenzkranke und Männer, die erstmals Blutdrucksenker nehmen. Dafür spricht eine Analyse unter US-Veteranen.

Ärztliche Empathie hilft gegen Rückenschmerzen

23.04.2024 Leitsymptom Rückenschmerzen Nachrichten

Personen mit chronischen Rückenschmerzen, die von einfühlsamen Ärzten und Ärztinnen betreut werden, berichten über weniger Beschwerden und eine bessere Lebensqualität.

Update Orthopädie und Unfallchirurgie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

Abstract

Summary

Introduction

Methods

Results

Conclusions

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 11/2021

Bone biomechanical properties and tissue-scale bone quality in a genetic mouse model of familial dysautonomia

Fracture risk in hypoparathyroidism: a systematic review and meta-analysis

A randomized, controlled trial of once-weekly teriparatide injection versus alendronate in patients at high risk of osteoporotic fracture: primary results of the Japanese Osteoporosis Intervention Trial-05

The role of diet quality and dietary patterns in predicting muscle mass and function in men over a 15-year period

Long-term effects of lifestyle and metformin interventions in DPP on bone density

Bone turnover markers as determinants of bone density and fracture in men with distal forearm fractures: the pathogenesis examined in the Mr F study