Skip to main content
SpringerLink
Log in

Osteoporosis therapy in patients with inflammatory rheumatic diseases and osteonecrosis of the jaw

Osteoporosetherapie bei Patienten mit entzündlich-rheumatischen Erkrankungen und Kieferosteonekrosen

  • Originalien
  • Published:
Zeitschrift für Rheumatologie Aims and scope Submit manuscript

Abstract

Background and objectives

The aim of the present study was to assess the prevalence of medication-related osteonecrosis of the jaw (MRONJ) in osteoporosis patients suffering from inflammatory rheumatic diseases, as well as to assess the prevalence of relevant dental, behavioral, and medical risk factors for MRONJ.

Materials and methods

A total of 198 patients with inflammatory rheumatic diseases and osteoporosis therapy were recruited from a tertiary rheumatological/immunological referral center between June 2015 and September 2016. They were assessed using a structured interview. A maxillofacial surgeon later examined patients complaining of possible symptoms of osteonecrosis. In cases of osteonecrosis, dental records were obtained and evaluated. Preventive measures taken and dental as well as other clinical risk factors were evaluated.

Results

Of the 198 patients, three suffered from osteonecrosis of the jaw, none of whom had any history of malignant disease or radiation therapy, resulting in a prevalence of 1.5%. Of these three patients, only one was given bisphosphonates intravenously (i.v.), whereas all three had been treated orally. All three diagnoses of MRONJ had been previously known to the patients and their maxillofacial surgeons. Two of the patients had rheumatoid arthritis, and one patient suffered from large vessel vasculitis. Long anti-osteoporotic treatment duration, low functional status, and low bone density of the femur were significantly associated with MRONJ development.

Conclusion

Inflammatory rheumatic diseases constitute a risk factor for MRONJ in patients treated with bisphosphonates for osteoporosis. Patients should be counseled accordingly and should be offered dental screening and regular dental check-ups.

Zusammenfassung

Hintergrund und Fragestellung

In der vorliegenden Studie wurde die Prävalenz medikamentenassoziierter Kieferosteonekrosen (MRONJ) bei Osteoporosepatienten erhoben, die an einer entzündlich-rheumatischen Erkrankung leiden. Zusätzlich wurden dentale, verhaltensbezogene und medizinische Risikofaktoren analysiert.

Material und Methoden

Zwischen Juni 2015 und September 2016 wurden 198 Patienten mit entzündlich-rheumatischen Erkrankungen und medikamentöser Osteoporosetherapie in einem tertiären Rheumatologie‑/Immunologiezentrum rekrutiert. Sie wurden mittels eines strukturierten Telefoninterviews befragt. Ein Mund-Kiefer-Gesichts-Chirurg untersuchte Patienten, die beim Interview über mögliche Symptome einer Osteonekrose klagten. Von den betroffenen Patienten wurden zahnärztliche Unterlagen angefordert und ausgewertet. Zusätzlich wurden präventive Maßnahmen sowie dentale und andere medizinische Risikofaktoren erhoben.

Ergebnisse

Von 198 Patienten litten 3 an einer MRONJ. Daraus ergibt sich eine Prävalenz von 1,5 %. Keine der betroffenen Patientinnen wies in der Anamnese ein Malignom oder eine Radiatio auf. Bisphosphonate (BP) i.v. hatte nur eine der Betroffenen erhalten, orale BP jedoch alle. Die MRONJ-Diagnose waren allen 3 Patientinnen und ihren Zahnärzten bekannt. Bei 2 Patientinnen lag eine rheumatoide Arthritis, bei einer eine Großgefäßvaskulitis vor. Eine langdauernde antiosteoporotische Therapie, niedriger Funktionsstatus und niedrige am Femur gemessene Knochendichte waren signifikant mit dem Auftreten einer MRONJ assoziiert.

Schlussfolgerung

Entzündlich-rheumatische Erkrankungen stellen einen MRONJ-Risikofaktor bei Patienten dar, die wegen Osteoporose mit BP behandelt werden. Die Patienten sollten entsprechend beraten werden und regelmäßige zahnärztliche Kontrollen wahrnehmen.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Ruggiero SL, Dodson TB, Fantasia J, Goodday R, Aghaloo T, Mehrotra B et al (2014) American Association of Oral and Maxillofacial Surgeons position paper on medication-related osteonecrosis of the jaw—2014 update. J Oral Maxillofac Surg 72:1938–1956

    Article  Google Scholar 

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

    Article  Google Scholar 

  3. Landesberg R, Woo V, Cremers S, Cozin M, Marolt D, Vunjak-Novakovic G et al (2011) Potential pathophysiological mechanisms in osteonecrosis of the jaw. Ann N Y Acad Sci 1218:62–79

    Article  CAS  Google Scholar 

  4. Hong SO, Lee CY, Jung J, Kim DY, Walter C, Kwon YD (2016) A retrospective study of osteomyelitis and osteonecrosis of the jaws and its etiologic implication of bisphosphonate in Asians. Clin Oral Investig 21:1905–1911

    Article  Google Scholar 

  5. Jarnbring F, Kashani A, Bjork A, Hoffman T, Krawiec K, Ljungman P et al (2015) Role of intravenous dosage regimens of bisphosphonates in relation to other aetiological factors in the development of osteonecrosis of the jaws in patients with myeloma. Br J Oral Maxillofac Surg 53:1007–1011

    Article  Google Scholar 

  6. Jeong HG, Hwang JJ, Lee JH, Kim YH, Na JY, Han SS (2017) Risk factors of osteonecrosis of the jaw after tooth extraction in osteoporotic patients on oral bisphosphonates. Imaging Sci Dent 47:45–50

    Article  Google Scholar 

  7. Kos M, Kuebler JF, Luczak K, Engelke W (2010) Bisphosphonate-related osteonecrosis of the jaws: a review of 34 cases and evaluation of risk. J Craniomaxillofac Surg 38:255–259

    Article  Google Scholar 

  8. Vahtsevanos K, Kyrgidis A, Verrou E, Katodritou E, Triaridis S, Andreadis CG et al (2009) Longitudinal cohort study of risk factors in cancer patients of bisphosphonate-related osteonecrosis of the jaw. J Clin Oncol 27:5356–5362

    Article  CAS  Google Scholar 

  9. Allen MR, Burr DB (2009) The pathogenesis of bisphosphonate-related osteonecrosis of the jaw: so many hypotheses, so few data. J Oral Maxillofac Surg 67:61–70

    Article  Google Scholar 

  10. Bamias A, Kastritis E, Bamia C, Moulopoulos LA, Melakopoulos I, Bozas G et al (2005) Osteonecrosis of the jaw in cancer after treatment with bisphosphonates: incidence and risk factors. J Clin Oncol 23:8580–8587

    Article  Google Scholar 

  11. Bonomi M, Nortilli R, Molino A, Sava T, Santo A, Caldara A et al (2010) Renal toxicity and osteonecrosis of the jaw in cancer patients treated with bisphosphonates: a long-term retrospective analysis. Med Oncol 27:224–229

    Article  CAS  Google Scholar 

  12. Lo JC, O’ryan FS, Gordon NP, Yang J, Hui RL, Martin D et al (2010) Prevalence of osteonecrosis of the jaw in patients with oral bisphosphonate exposure. J Oral Maxillofac Surg 68:243–253

    Article  Google Scholar 

  13. Walter C, Al-Nawas B, Frickhofen N, Gamm H, Beck J, Reinsch L et al (2010) Prevalence of bisphosphonate associated osteonecrosis of the jaws in multiple myeloma patients. Head Face Med 6:11

    Article  Google Scholar 

  14. Advisory Task Force on Bisphosphonate-Related Ostenonecrosis of the Jaws, American Association of Oral and Maxillofacial Surgeons (2007) American Association of Oral and Maxillofacial Surgeons position paper on bisphosphonate-related osteonecrosis of the jaws. J Oral Maxillofac Surg 65:369–376

    Article  Google Scholar 

  15. Monkkonen H, Ottewell PD, Kuokkanen J, Monkkonen J, Auriola S, Holen I (2007) Zoledronic acid-induced IPP/ApppI production in vivo. Life Sci 81:1066–1070

    Article  Google Scholar 

  16. Raikkonen J, Crockett JC, Rogers MJ, Monkkonen H, Auriola S, Monkkonen J (2009) Zoledronic acid induces formation of a pro-apoptotic ATP analogue and isopentenyl pyrophosphate in osteoclasts in vivo and in MCF-7 cells in vitro. Br J Pharmacol 157:427–435

    Article  CAS  Google Scholar 

  17. Plotkin LI, Aguirre JI, Kousteni S, Manolagas SC, Bellido T (2005) Bisphosphonates and estrogens inhibit osteocyte apoptosis via distinct molecular mechanisms downstream of extracellular signal-regulated kinase activation. J Biol Chem 280:7317–7325

    Article  CAS  Google Scholar 

  18. Jansen JP, Bergman GJ, Huels J, Olson M (2011) The efficacy of bisphosphonates in the prevention of vertebral, hip, and nonvertebral-nonhip fractures in osteoporosis: a network meta-analysis. Semin Arthritis Rheum 40:275–284e1–2

    Article  CAS  Google Scholar 

  19. Poxleitner P, Engelhardt M, Schmelzeisen R, Voss P (2017) The Prevention of medication-related Osteonecrosis of the jaw. Dtsch Arztebl Int 114:63–69

    PubMed  PubMed Central  Google Scholar 

  20. Reginster JY, Burlet N (2006) Osteoporosis: a still increasing prevalence. Bone 38:4–9

    Article  Google Scholar 

  21. Ringe JD, Doherty JG (2010) Absolute risk reduction in osteoporosis: assessing treatment efficacy by number needed to treat. Rheumatol Int 30:863–869

    Article  CAS  Google Scholar 

  22. Dougados M (2016) Comorbidities in rheumatoid arthritis. Curr Opin Rheumatol 28:282–288

    Article  Google Scholar 

  23. Bieniek J, Wilczynski K, Szewieczek J (2016) Fried frailty phenotype assessment components as applied to geriatric inpatients. Clin Interv Aging 11:453–459

    PubMed  PubMed Central  Google Scholar 

  24. Listing J, Gerhold K, Zink A (2013) The risk of infections associated with rheumatoid arthritis, with its comorbidity and treatment. Rheumatology 52:53–61

    Article  CAS  Google Scholar 

  25. Richter A, Listing J, Schneider M, Klopsch T, Kapelle A, Kaufmann J et al (2016) Impact of treatment with biologic DMARDs on the risk of sepsis or mortality after serious infection in patients with rheumatoid arthritis. Ann Rheum Dis 75:1667–1673

    Article  CAS  Google Scholar 

  26. Smitten AL, Simon TA, Hochberg MC, Suissa S (2008) A meta-analysis of the incidence of malignancy in adult patients with rheumatoid arthritis. Arthritis Res Ther 10:45

    Article  Google Scholar 

  27. Dougados M, Soubrier M, Antunez A, Balint P, Balsa A, Buch MH et al (2014) Prevalence of comorbidities in rheumatoid arthritis and evaluation of their monitoring: results of an international, cross-sectional study (COMORA). Ann Rheum Dis 73:62–68

    Article  Google Scholar 

  28. Pischon N, Hoedke D, Kurth S, Lee P, Dommisch H, Steinbrecher A et al (2016) Increased periodontal attachment loss in patients with systemic sclerosis. J Periodontol 87:763–771

    Article  Google Scholar 

  29. Rogers SN, Palmer NO, Lowe D, Randall C (2015) United Kingdom nationwide study of avascular necrosis of the jaws including bisphosphonate-related necrosis. Br J Oral Maxillofac Surg 53:176–182

    Article  CAS  Google Scholar 

  30. Di Fede O, Bedogni A, Giancola F, Saia G, Bettini G, Toia F et al (2016) BRONJ in patients with rheumatoid arthritis: a multicenter case series. Oral Dis 22:543–548

    Article  Google Scholar 

  31. Fleisher KE, Jolly A, Venkata UD, Norman RG, Saxena D, Glickman RS (2013) Osteonecrosis of the jaw onset times are based on the route of bisphosphonate therapy. J Oral Maxillofac Surg 71:513–519

    Article  Google Scholar 

  32. Wang CC, Lu HT, Dusetzina SB, Wu CH (2016) The association between long-term bisphosphonate use and the risk of fracture among women aged 50 or older with osteoporosis. J Womens Health (larchmt) 25:738–746

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Rheumatology and Immunology (Head: H.-P. Tony), University Hospital Würzburg, Oberdürrbacher Straße 6, 97080, Würzburg, Germany

    E. C. Schwaneck, A. Streit, O. Gadeholt, M. Schmalzing & H.-P. Tony

  2. Institute for Hygiene and Microbiology, University of Wuerzburg, Josef-Schneider-Straße 2, 97080, Würzburg, Germany

    M. Krone

  3. Department of Oral and Maxillofacial Plastic Surgery (Head: A.C. Kübler), University Hospital Würzburg, Pleicherwall 2, 97070, Würzburg, Germany

    S. Hartmann, U. Müller-Richter, A. C. Kübler & R. C. Brands

Authors
  1. E. C. Schwaneck
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. Streit
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M. Krone
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. S. Hartmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. U. Müller-Richter
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. A. C. Kübler
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. O. Gadeholt
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. M. Schmalzing
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. H.-P. Tony
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. R. C. Brands
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to E. C. Schwaneck.

Ethics declarations

Conflict of interest

E.C. Schwaneck, O. Gadeholt, M. Schmalzing, and H.‑P. Tony have received speaker’s fees, travel grants, research funding, or compensation for consultations or board memberships from Roche, Chugai, MSD, UCB, Baxalta (Shire/Takeda), CSL Behring, AbbVie, Janssen, Lilly, Pfizer, Celgene, and Novartis. A. Streit, M. Krone, S. Hartmann, U. Müller-Richter, A. C. Kübler, and R. C. Brands declare that they have no competing interests.

This article does not contain any studies with human participants or animals performed by any of the authors.

Additional information

Redaktion

U. Müller-Ladner, Bad Nauheim

U. Lange, Bad Nauheim

Caption Electronic Supplementary Material

393_2019_606_MOESM1_ESM.pdf

Questionnaire. To identify any undocumented cases of MRONJ, a telephone interview was performed using a structured questionnaire developed in cooperation with the Department of Oral and Maxillofacial Plastic Surgery of the University Hospital Würzburg.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Schwaneck, E.C., Streit, A., Krone, M. et al. Osteoporosis therapy in patients with inflammatory rheumatic diseases and osteonecrosis of the jaw. Z Rheumatol 79, 203–209 (2020). https://doi.org/10.1007/s00393-019-0606-y

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00393-019-0606-y

Keywords

Schlüsselwörter

Search

Navigation