Top

Clinical Oral Investigations

Published in:

01-01-2017 | Original Article

Primary wound closure after tooth extraction for prevention of medication-related osteonecrosis of the jaw in patients under denosumab

Authors: Akihiko Matsumoto, Masanori Sasaki, Rainer Schmelzeisen, Yukiko Oyama, Yoshihide Mori, Pit Jacob Voss

Published in: Clinical Oral Investigations | Issue 1/2017

Abstract

Objectives

Some recent reports have indicated that local infection causes osteonecrosis of the jaw and described that tooth extraction may not be a direct cause of developing medication-related osteonecrosis of the jaw (MRONJ) in patients receiving antiresorptive medications. Tooth extraction and elimination of the source of infection are expected to reduce the risk of developing MRONJ. However, there is no data regarding prevention for developing osteonecrosis of the jaw in patients receiving denosumab. Therefore, the aim of this study was to investigate the outcome of tooth extractions with proper wound closure in patients receiving denosumab.

Patients and methods

Forty teeth in 19 patients treated with denosumab therapy were extracted under preoperative intravenous antibiotics. Patients who had already developed MRONJ in the extraction sites or who had a history of radiation therapy were excluded. During surgery, bone edges were smoothed and all wounds were closed using the double-layered technique.

Results

Thirty-seven extraction sites (92.5 %) in 17 out of 19 patients (89.5 %) were healed. However, three extraction sites in two patients had complications; one patient had exposed bone and developed MRONJ (stage 1) and the other developed a mucosa fistula. Additional surgical procedures were performed and all wounds were completely healed.

Conclusions

Tooth extractions in patients receiving denosumab can be performed in an appropriate manner and result in good outcomes.

Clinical relevance

This study indicated that tooth extraction with proper wound closure to avoid secondary infection may be effective for the prevention of MRONJ even in high-risk patients.

Cummings SR, San Martin J, McClung MR, Siris ES, Eastell R, Reid IR, Delmas P, Zoog HB, Austin M, Wang A (2009) Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med 361(8):756–765CrossRefPubMed

Silva I, Branco JC (2011) Rank/Rankl/opg: literature review. Acta Reumatologica Portuguesa 36(3):209–218PubMed

Stopeck AT, Lipton A, Body JJ, Steger GG, Tonkin K, de Boer RH, Lichinitser M, Fujiwara Y, Yardley DA, Viniegra M (2010) 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 Off J Am Soc Clin Oncol 28(35):5132–5139CrossRef

Ruggiero SL, Dodson TB, Fantasia J, Goodday R, Aghaloo T, Mehrotra B, O'Ryan F (2014) American Association of Oral and Maxillofacial Surgeons position paper on medication-related osteonecrosis of the jaw–2014 update. J Oral Craniomaxillofac Surg Off J Am Assoc Oral Craniomaxillofac Surgeons 72(10):1938–1956CrossRef

Brown JP, Fortier M, Frame H, Lalonde A, Papaioannou A, Senikas V, Yuen CK (2006) Canadian consensus conference on osteoporosis, 2006 update. J Obstet Gynaecol Can JOGC J d'obstetrique et gynecologie du CanadaJOGC 28(2 Suppl 1):S95–112

Lipton A (2007) Efficacy and safety of intravenous bisphosphonates in patients with bone metastases caused by metastatic breast cancer. Clin Breast Cancer 7(Suppl 1):S14–S20CrossRefPubMed

Lipton A, Steger GG, Figueroa J, Alvarado C, Solal-Celigny P, Body JJ, de Boer R, Berardi R, Gascon P, Tonkin KS (2008) Extended efficacy and safety of denosumab in breast cancer patients with bone metastases not receiving prior bisphosphonate therapy. Clin Cancer Res Off J Am Assoc Cancer Res 14(20):6690–6696CrossRef

Yee AJ, Raje NS (2012) Denosumab, a RANK ligand inhibitor, for the management of bone loss in cancer patients. Clin Interv Aging 7:331–338PubMedPubMedCentral

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 8:295–306CrossRefPubMedPubMedCentral

10.

Marx RE (2003) Pamidronate (Aredia) and zoledronate (Zometa) induced avascular necrosis of the jaws: a growing epidemic. J Oral Maxillofac Surg Off J Am Assoc Oral Maxillofac Surgeons 61(9):1115–1117CrossRef

11.

Rustemeyer J, Bremerich A (2010) Bisphosphonate-associated osteonecrosis of the jaw: what do we currently know? A survey of knowledge given in the recent literature. Clin Oral Investig 14(1):59–64CrossRefPubMed

12.

Aghaloo TL, Felsenfeld AL, Tetradis S (2010) Osteonecrosis of the jaw in a patient on Denosumab. J Oral Maxillofac Surg Off J Am Assoc Oral Maxillofac Surgeons 68(5):959–963CrossRef

13.

Saad F, Brown JE, Van Poznak C, Ibrahim T, Stemmer SM, Stopeck AT, Diel IJ, Takahashi S, Shore N, Henry DH (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 Off J Eur Soc Med Oncol/ESMO 23(5):1341–1347CrossRef

14.

Khan AA, Sandor GK, Dore E, Morrison AD, Alsahli M, Amin F, Peters E, Hanley DA, Chaudry SR, Dempster DW (2008) Canadian consensus practice guidelines for bisphosphonate associated osteonecrosis of the jaw. J Rheumatol 35(7):1391–1397PubMed

15.

Ripamonti CI, Maniezzo M, Campa T, Fagnoni E, Brunelli C, Saibene G, Bareggi C, Ascani L, Cislaghi E (2009) Decreased occurrence of osteonecrosis of the jaw after implementation of dental preventive measures in solid tumour patients with bone metastases treated with bisphosphonates. The experience of the National Cancer Institute of Milan. Ann Oncol Off J Eur Soc Med Oncol/ESMO 20(1):137–145CrossRef

16.

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 jaw - 2009 update. Aust Endod J J Aust Soc Endodontol Inc 35(3):119–130CrossRef

17.

Kyrgidis A, Vahtsevanos K, Koloutsos G, Andreadis C, Boukovinas I, Teleioudis Z, Patrikidou A, Triaridis S (2008) Bisphosphonate-related osteonecrosis of the jaws: a case-control study of risk factors in breast cancer patients. J Clin Oncol Off J Am Soc Clin Oncol 26(28):4634–4638CrossRef

18.

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 Off J Am Assoc Oral Maxillofac Surgeons 71(8):1360–1366CrossRef

19.

Felsenberg D (2006) Osteonecrosis of the jaw—a potential adverse effect of bisphosphonate treatment. Nat Clin Pract Endocrinol Metab 2(12):662–663CrossRefPubMed

20.

Vahtsevanos K, Kyrgidis A, Verrou E, Katodritou E, Triaridis S, Andreadis CG, Boukovinas I, Koloutsos GE, Teleioudis Z, Kitikidou K (2009) Longitudinal cohort study of risk factors in cancer patients of bisphosphonate-related osteonecrosis of the jaw. J Clin Oncol Off J Am Soc Clin Oncol 27(32):5356–5362CrossRef

21.

Heufelder MJ, Hendricks J, Remmerbach T, Frerich B, Hemprich A, Wilde F (2014) Principles of oral surgery for prevention of bisphosphonate-related osteonecrosis of the jaw. Oral Surg Oral Med Oral Pathol Oral Radiol 117(6):e429–e435CrossRefPubMed

22.

Mozzati M, Arata V, Gallesio G (2013) Tooth extraction in osteoporotic patients taking oral bisphosphonates. Osteoporos Int J Established Result Cooperation Between Eur Found Osteoporos Nat Osteoporos Found USA 24(5):1707–1712CrossRef

23.

Otto S, Troltzsch M, Jambrovic V, Panya S, Probst F, Ristow O, Ehrenfeld M, Pautke C (2015) Tooth extraction in patients receiving oral or intravenous bisphosphonate administration: a trigger for BRONJ development? J Craniomaxillofac Surg Off Publ Eur Assoc Craniomaxillofac Surg 43(6):847–854

24.

Groetz KA, Piesold J-U, Al-Nawas B (2012) Bisphosphonat-assoziierte Kiefernekrose (BPONJ) und andere Medikamenten-assoziierte Kiefernekrosen. http://www.awmf.org; In AWMF online:

25.

Saad F, Gleason DM, Murray R, Tchekmedyian S, Venner P, Lacombe L, Chin JL, Vinholes JJ, Goas JA, Chen B (2009) A randomized, placebo-controlled trial of zoledronic acid in patients with hormone-refractory metastatic prostate carcinoma. J Natl Cancer Inst 94(19):1458–1468CrossRef

26.

Bonacina R, Mariani U, Villa F, Villa A (2011) Preventive strategies and clinical implications for bisphosphonate-related osteonecrosis of the jaw: a review of 282 patients. J Can Dent Assoc 77:b147PubMed

27.

Vandone AM, Donadio M, Mozzati M, Ardine M, Polimeni MA, Beatrice S, Ciuffreda L, Scoletta M (2012) Impact of dental care in the prevention of bisphosphonate-associated osteonecrosis of the jaw: a single-center clinical experience. Ann Oncol Off J Eur Soc Med Oncol/ESMO 23(1):193–200CrossRef

28.

Lodi G, Sardella A, Salis A, Demarosi F, Tarozzi M, Carrassi A (2010) Tooth extraction in patients taking intravenous bisphosphonates: a preventive protocol and case series. J Oral Maxillofac Surg Off J Am Assoc Oral Maxillofac Surgeons 68(1):107–110CrossRef

29.

Scoletta M, Arata V, Arduino PG, Lerda E, Chiecchio A, Gallesio G, Scully C, Mozzati M (2013) Tooth extractions in intravenous bisphosphonate-treated patients: a refined protocol. J Oral Maxillofac Surg Off J Am Assoc Oral Maxillofac Surgeons 71(6):994–999CrossRef

30.

Mozzati M, Arata V, Gallesio G (2012) Tooth extraction in patients on zoledronic acid therapy. Oral Oncol 48(9):817–821CrossRefPubMed

31.

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(11):1397–1403CrossRefPubMed

32.

Saia G, Blandamura S, Bettini G, Tronchet A, Totola A, Bedogni G, Ferronato G, Nocini PF, Bedogni A (2010) Occurrence of bisphosphonate-related osteonecrosis of the jaw after surgical tooth extraction. J Oral Maxillofac Surg Off J Am Assoc Oral Maxillofac Surgeons 68(4):797–804CrossRef

33.

Otto S, Pautke C, Opelz C, Westphal I, Drosse I, Schwager J, Bauss F, Ehrenfeld M, Schieker M (2010) Osteonecrosis of the jaw: effect of bisphosphonate type, local concentration, and acidic milieu on the pathomechanism. J Oral Maxillofac Surg Off J Am Assoc Oral Maxillofac Surgeons 68(11):2837–2845CrossRef

34.

Lopez-Jornet P, Camacho-Alonso F, Martinez-Canovas A, Molina-Minano F, Gomez-Garcia F, Vicente-Ortega V (2011) Perioperative antibiotic regimen in rats treated with pamidronate plus dexamethasone and subjected to dental extraction: a study of the changes in the jaws. J Oral Maxillofac Surg Off J Am Assoc Oral Maxillofac Surgeons 69(10):2488–2493CrossRef

35.

Aguirre JI, Akhter MP, Kimmel DB, Pingel JE, Williams A, Jorgensen M, Kesavalu L, Wronski TJ (2012) Oncologic doses of zoledronic acid induce osteonecrosis of the jaw-like lesions in rice rats (Oryzomys palustris) with periodontitis. J Bone Miner Res Off J Am Soc Bone Miner Res 27(10):2130–2143CrossRef

36.

Kang B, Cheong S, Chaichanasakul T, Bezouglaia O, Atti E, Dry SM, Pirih FQ, Aghaloo TL, Tetradis S (2013) Periapical disease and bisphosphonates induce osteonecrosis of the jaws in mice. J Bone Miner Res Off J Am Soc Bone Miner Res 28(7):1631–1640CrossRef

37.

Lemound J, Eckardt A, Kokemuller H, von See C, Voss PJ, Tavassol F, Rucker M, Rana M, Gellrich NC (2012) Bisphosphonate-associated osteonecrosis of the mandible: reliable soft tissue reconstruction using a local myofascial flap. Clin Oral Investig 16(4):1143–1152CrossRefPubMed

38.

Wilde F, Hendricks J, Riese C, Pausch NC, Schramm A, Heufelder M (2011) Bone regeneration without bone grafting after resection of a segment of the mandible to treat bisphosphonate-related osteonecrosis of the jaw. J Oral Maxillofac Surg Off J Am Assoc Oral Maxillofac Surgeons 69(10):2657–2662CrossRef

39.

Voss PJ, Joshi Oshero J, Kovalova-Muller A, Veigel Merino EA, Sauerbier S, Al-Jamali J, Lemound J, Metzger MC, Schmelzeisen R (2012) Surgical treatment of bisphosphonate-associated osteonecrosis of the jaw: technical report and follow up of 21 patients. J Craniomaxillofac Surg Off Publ Eur Assoc Craniomaxillofac Surg 40(8):719–725

40.

Ruggiero SL, Mehrotra B, Rosenberg TJ, Engroff SL (2004) Osteonecrosis of the jaws associated with the use of bisphosphonates: a review of 63 cases. J Oral Craniomaxillofac Surg Off J Am Assoc Oral Craniomaxillofac Surgeons 62(5):527–534CrossRef

41.

Marx RE, Sawatari Y, Fortin M, Broumand V (2005) Bisphosphonate-induced exposed bone (osteonecrosis/osteopetrosis) of the jaws: risk factors, recognition, prevention, and treatment. J Oral Craniomaxillofac Surg Off J Am Assoc Oral Craniomaxillofac Surgeons 63(11):1567–1575CrossRef

42.

Bartl R (2007) Practical guidelines for the management of osteoporosis–evidence-based and cost-effective. Deutsche Medizinische Wochenschrift (1946) 132(18):995–999CrossRef

43.

Otto S, Baumann S, Ehrenfeld M, Pautke C (2013) Successful surgical management of osteonecrosis of the jaw due to RANK-ligand inhibitor treatment using fluorescence guided bone resection. J Oral Craniomaxillofac Surg Off J Am Assoc Oral Craniomaxillofac Surgeons 41(7):694–698

44.

Abu-Id MH, Warnke PH, Gottschalk J, Springer I, Wiltfang J, Acil Y, Russo PA, Kreusch T (2008) “Bis-phossy jaws”—high and low risk factors for bisphosphonate-induced osteonecrosis of the jaw. J Oral Craniomaxillofac Surg Off J Am Assoc Oral Craniomaxillofac Surgeons 36(2):95–103

45.

Otto S, Abu-Id MH, Fedele S, Warnke PH, Becker ST, Kolk A, Mucke T, Mast G, Kohnke R, Volkmer E (2011) Osteoporosis and bisphosphonates-related osteonecrosis of the jaw: not just a sporadic coincidence—a multi-centre study. J Oral Craniomaxillofac Surg Off J Am Assoc Oral Craniomaxillofac Surgeons 39(4):272–277

46.

Stanton DC, Balasanian E (2009) Outcome of surgical management of bisphosphonate-related osteonecrosis of the jaws: review of 33 surgical cases. J Oral Craniomaxillofac Surg Off J Am Assoc Oral Craniomaxillofac Surgeons 67(5):943–950CrossRef

Title: Primary wound closure after tooth extraction for prevention of medication-related osteonecrosis of the jaw in patients under denosumab
Authors: Akihiko Matsumoto
Masanori Sasaki
Rainer Schmelzeisen
Yukiko Oyama
Yoshihide Mori
Pit Jacob Voss
Publication date: 01-01-2017
Publisher: Springer Berlin Heidelberg
Published in: Clinical Oral Investigations / Issue 1/2017
Print ISSN: 1432-6981
Electronic ISSN: 1436-3771
DOI: https://doi.org/10.1007/s00784-016-1762-y

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Primary wound closure after tooth extraction for prevention of medication-related osteonecrosis of the jaw in patients under denosumab

Abstract

Objectives

Patients and methods

Results

Conclusions

Clinical relevance

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Objectives

Patients and methods

Results

Conclusions

Clinical relevance

Please log in to get access to this content

Other articles of this Issue 1/2017

Anatomical relationship between mental foramen, mandibular teeth and risk of nerve injury with endodontic treatment

Effect of body shape and inflammation on tooth loss in men and women

Postoperative socket irrigation with drinking tap water reduces the risk of inflammatory complications following surgical removal of third molars: a multicenter randomized trial

Effect of hyperbaric oxygen therapy on tooth extraction sites in rats subjected to bisphosphonate therapy—histomorphometric and immunohistochemical analysis

Dentifrices for children differentially affect cell viability in vitro

Serum antibody levels against Porphyromonas gingivalis in patients with and without rheumatoid arthritis – a systematic review and meta-analysis