nach oben

Erschienen in:

01.02.2018 | Original Article

Effects of an oral bisphosphonate and three intravenous bisphosphonates on several cell types in vitro

verfasst von: Junho Jung, Jung Soo Park, Leonardo Righesso, Andreas Max Pabst, Bilal Al-Nawas, Yong-Dae Kwon, Christian Walter

Erschienen in: Clinical Oral Investigations | Ausgabe 7/2018

Einloggen, um Zugang zu erhalten

Abstract

Objective

To analyze the influence of an oral bisphosphonate and compare the potency to intravenous bisphosphonates on various cell types as regards the rarity of bisphosphonate-associated osteonecrosis of the jaw (BP-ONJ) caused by oral bisphosphonate.

Materials and methods

A viability assay (MTT), a migration assay (Boyden chamber), and an apoptosis assay (Caspase-Glo® 3/7) were performed to analyze the effect of bisphosphonates on human fibroblasts, umbilical vein endothelial cells (HUVEC), and osteoblasts.

Results

Alendronate and intravenous bisphosphonates suppressed cell viability and migration, and induced apoptosis in all tested cell types. Alendronate had a greater impact than ibandronate on the characteristics in fibroblasts and osteoblasts but not as strong as zoledronate.

Conclusions

The incidence of BP-ONJ in oral bisphosphonate treatment is reported to be much lower than that in intravenous bisphosphonates. However, the influences of alendronate on human cells were at least as strong as ibandronate, although it was lower than zoledronate.

Clinical relevance

Alendronate showed strong enough effects to suppress human somatic cells and was comparable to certain intravenous bisphosphonates in potency. This study suggests that the lower incidence of BP-ONJ in alendronate treatment is not originated by its potency, but might be due to the low bioavailability of alendronate, lower dosing on a daily basis, and having no additional therapies.

Black DM, Bauer DC, Schwartz AV, Cummings SR, Rosen CJ (2012) Continuing bisphosphonate treatment for osteoporosis—for whom and for how long? N Engl J Med 366(22):2051–2053. https://doi.org/10.1056/NEJMp1202623 CrossRefPubMedPubMedCentral

Terpos E, Kleber M, Engelhardt M, Zweegman S, Gay F, Kastritis E, van de Donk NW, Bruno B, Sezer O, Broijl A, Bringhen S, Beksac M, Larocca A, Hajek R, Musto P, Johnsen HE, Morabito F, Ludwig H, Cavo M, Einsele H, Sonneveld P, Dimopoulos MA, Palumbo A, European Myeloma N (2015) European Myeloma Network guidelines for the management of multiple myeloma-related complications. Haematologica 100(10):1254–1266. https://doi.org/10.3324/haematol.2014.117176 CrossRefPubMedPubMedCentral

Hald JD, Evangelou E, Langdahl BL, Ralston SH (2015) Bisphosphonates for the prevention of fractures in osteogenesis imperfecta: meta-analysis of placebo-controlled trials. J Bone Miner Res 30(5):929–933. https://doi.org/10.1002/jbmr.2410 CrossRefPubMed

Van Acker HH, Anguille S, Willemen Y, Smits EL, Van Tendeloo VF (2016) Bisphosphonates for cancer treatment: mechanisms of action and lessons from clinical trials. Pharmacol Ther 158:15824–15840. https://doi.org/10.1016/j.pharmthera.2015.11.008

Choi WS, Lee JI, Yoon HJ, Min CK, Lee SH (2017) Medication-related osteonecrosis of the jaw: a preliminary retrospective study of 130 patients with multiple myeloma. Maxillofac Plast Reconstr Surg 39(1):1. https://doi.org/10.1186/s40902-016-0099-4 CrossRefPubMedPubMedCentral

Green J, Lipton A (2010) Anticancer properties of zoledronic acid. Cancer Investig 28(9):944–957. https://doi.org/10.3109/07357907.2010.512598 CrossRef

Tamura T, Shomori K, Nakabayashi M, Fujii N, Ryoke K, Ito H (2011) Zoledronic acid, a third-generation bisphosphonate, inhibits cellular growth and induces apoptosis in oral carcinoma cell lines. Oncol Rep 25(4):1139–1143. https://doi.org/10.3892/or.2011.1152 CrossRefPubMed

Stresing V, Fournier PG, Bellahcene A, Benzaid I, Monkkonen H, Colombel M, Ebetino FH, Castronovo V, Clezardin P (2011) Nitrogen-containing bisphosphonates can inhibit angiogenesis in vivo without the involvement of farnesyl pyrophosphate synthase. Bone 48(2):259–266. https://doi.org/10.1016/j.bone.2010.09.035 CrossRefPubMed

Wysowski DK, Greene P (2013) Trends in osteoporosis treatment with oral and intravenous bisphosphonates in the United States, 2002-2012. Bone 57(2):423–428. https://doi.org/10.1016/j.bone.2013.09.008 CrossRefPubMed

10.

Diel IJ, Bergner R, Grotz KA (2007) Adverse effects of bisphosphonates: current issues. J Support Oncol 5(10):475–482PubMed

11.

Marx RE (2003) Pamidronate (Aredia) and zoledronate (Zometa) induced avascular necrosis of the jaws: a growing epidemic. J Oral Maxillofac Surg 61(9):1115–1117. https://doi.org/10.1016/S0278-2391(03)00720-1 CrossRefPubMed

12.

Acil Y, Moller B, Niehoff P, Rachko K, Gassling V, Wiltfang J, Simon MJ (2012) The cytotoxic effects of three different bisphosphonates in-vitro on human gingival fibroblasts, osteoblasts and osteogenic sarcoma cells. J Craniomaxillofac Surg 40(8):e229–e235. https://doi.org/10.1016/j.jcms.2011.10.024 CrossRefPubMed

13.

Marolt D, Cozin M, Vunjak-Novakovic G, Cremers S, Landesberg R (2012) Effects of pamidronate on human alveolar osteoblasts in vitro. J Oral Maxillofac Surg 70(5):1081–1092. https://doi.org/10.1016/j.joms.2011.05.002 CrossRefPubMedPubMedCentral

14.

McLeod NM, Moutasim KA, Brennan PA, Thomas G, Jenei V (2014) In vitro effect of bisphosphonates on oral keratinocytes and fibroblasts. J Oral Maxillofac Surg 72(3):503–509. https://doi.org/10.1016/j.joms.2013.08.007 CrossRefPubMed

15.

Amin D, Cornell SA, Gustafson SK, Needle SJ, Ullrich JW, Bilder GE, Perrone MH (1992) Bisphosphonates used for the treatment of bone disorders inhibit squalene synthase and cholesterol biosynthesis. J Lipid Res 33(11):1657–1663PubMed

16.

Rogers MJ, Russell RG, Blackburn GM, Williamson MP, Watts DJ (1992) Metabolism of halogenated bisphosphonates by the cellular slime mould Dictyostelium discoideum. Biochem Biophys Res Commun 189(1):414–423. https://doi.org/10.1016/0006-291X(92)91574-A CrossRefPubMed

17.

Rogers MJ, Crockett JC, Coxon FP, Monkkonen J (2011) Biochemical and molecular mechanisms of action of bisphosphonates. Bone 49(1):34–41. https://doi.org/10.1016/j.bone.2010.11.008 CrossRefPubMed

18.

Kyle RA, Yee GC, Somerfield MR, Flynn PJ, Halabi S, Jagannath S, Orlowski RZ, Roodman DG, Twilde P, Anderson K, American Society of Clinical O (2007) American Society of Clinical Oncology 2007 clinical practice guideline update on the role of bisphosphonates in multiple myeloma. J Clin Oncol 25(17):2464–2472. https://doi.org/10.1200/JCO.2007.12.1269 CrossRefPubMed

19.

Boonyapakorn T, Schirmer I, Reichart PA, Sturm I, Massenkeil G (2008) Bisphosphonate-induced osteonecrosis of the jaws: prospective study of 80 patients with multiple myeloma and other malignancies. Oral Oncol 44(9):857–869. https://doi.org/10.1016/j.oraloncology.2007.11.012 CrossRefPubMed

20.

Walter C, Al-Nawas B, Grotz KA, Thomas C, Thuroff JW, Zinser V, Gamm H, Beck J, Wagner W (2008) Prevalence and risk factors of bisphosphonate-associated osteonecrosis of the jaw in prostate cancer patients with advanced disease treated with zoledronate. Eur Urol 54(5):1066–1072. https://doi.org/10.1016/j.eururo.2008.06.070 CrossRefPubMed

21.

Kos M (2015) Incidence and risk predictors for osteonecrosis of the jaw in cancer patients treated with intravenous bisphosphonates. Arch Med Sci 11(2):319–324. https://doi.org/10.5114/aoms.2015.50964 CrossRefPubMedPubMedCentral

22.

Bamias A, Kastritis E, Bamia C, Moulopoulos LA, Melakopoulos I, Bozas G, Koutsoukou V, Gika D, Anagnostopoulos A, Papadimitriou C, Terpos E, Dimopoulos MA (2005) Osteonecrosis of the jaw in cancer after treatment with bisphosphonates: incidence and risk factors. J Clin Oncol 23(34):8580–8587. https://doi.org/10.1200/JCO.2005.02.8670 CrossRefPubMed

23.

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(6):826–836. https://doi.org/10.1359/jbmr.080205 CrossRefPubMed

24.

Dimopoulos MA, Kastritis E, Anagnostopoulos A, Melakopoulos I, Gika D, Moulopoulos LA, Bamia C, Terpos E, Tsionos K, Bamias A (2006) Osteonecrosis of the jaw in patients with multiple myeloma treated with bisphosphonates: evidence of increased risk after treatment with zoledronic acid. Haematologica 91(7):968–971PubMed

25.

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(3):415–423. https://doi.org/10.1016/j.joms.2006.10.061 CrossRefPubMed

26.

Ulmner M, Jarnbring F, Torring O (2014) Osteonecrosis of the jaw in Sweden associated with the oral use of bisphosphonate. J Oral Maxillofac Surg 72(1):76–82. https://doi.org/10.1016/j.joms.2013.06.221 CrossRefPubMed

27.

American Dental Association Council on Scientific A (2006) Dental management of patients receiving oral bisphosphonate therapy: expert panel recommendations. J Am Dent Assoc 137(8):1144–1150CrossRef

28.

Kwon JW, Park EJ, Jung SY, Sohn HS, Ryu H, Suh HS (2015) A large national cohort study of the association between bisphosphonates and osteonecrosis of the jaw in patients with osteoporosis: a nested case-control study. J Dent Res 94(9 Suppl):212S–219S. https://doi.org/10.1177/0022034515587862 CrossRefPubMed

29.

Walter C, Pabst A, Ziebart T, Klein M, Al-Nawas B (2011) Bisphosphonates affect migration ability and cell viability of HUVEC, fibroblasts and osteoblasts in vitro. Oral Dis 17(2):194–199. https://doi.org/10.1111/j.1601-0825.2010.01720.x CrossRefPubMed

30.

Misso G, Porru M, Stoppacciaro A, Castellano M, De Cicco F, Leonetti C, Santini D, Caraglia M (2012) Evaluation of the in vitro and in vivo antiangiogenic effects of denosumab and zoledronic acid. Cancer Biol Ther 13(14):1491–1500. https://doi.org/10.4161/cbt.22274 CrossRefPubMedPubMedCentral

31.

Manzano-Moreno FJ, Ramos-Torrecillas J, De Luna-Bertos E, Ruiz C, Garcia-Martinez O (2015) High doses of bisphosphonates reduce osteoblast-like cell proliferation by arresting the cell cycle and inducing apoptosis. J Craniomaxillofac Surg 43(3):396–401. https://doi.org/10.1016/j.jcms.2014.12.008 CrossRefPubMed

32.

Schwabe UPD (2012) Arzneiverordnungs-Report 2012: Aktuelle Daten, Kosten, Trends und Kommentare. Springer, Heidelberg. https://doi.org/10.1007/978-3-642-29242-2 CrossRef

33.

Walter C, Sagheb K, Bitzer J, Rahimi-Nedjat R, Taylor KJ (2014) Analysis of reasons for osteonecrosis of the jaws. Clin Oral Investig 18(9):2221–2226. https://doi.org/10.1007/s00784-014-1205-6 CrossRefPubMed

34.

Fisher JE, Rosenberg E, Santora AC, Reszka AA (2013) In vitro and in vivo responses to high and low doses of nitrogen-containing bisphosphonates suggest engagement of different mechanisms for inhibition of osteoclastic bone resorption. Calcif Tissue Int 92(6):531–538. https://doi.org/10.1007/s00223-013-9711-0 CrossRefPubMed

35.

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 68(11):2837–2845. https://doi.org/10.1016/j.joms.2010.07.017 CrossRefPubMed

36.

Martins CA, Leyhausen G, Volk J, Geurtsen W (2015) Effects of alendronate on osteoclast formation and activity in vitro. J Endod 41(1):45–49. https://doi.org/10.1016/j.joen.2014.07.010 CrossRefPubMed

37.

Gertz BJ, Holland SD, Kline WF, Matuszewski BK, Freeman A, Quan H, Lasseter KC, Mucklow JC, Porras AG (1995) Studies of the oral bioavailability of alendronate. Clin Pharmacol Ther 58(3):288–298. https://doi.org/10.1016/0009-9236(95)90245-7 CrossRefPubMed

Titel: Effects of an oral bisphosphonate and three intravenous bisphosphonates on several cell types in vitro
verfasst von: Junho Jung
Jung Soo Park
Leonardo Righesso
Andreas Max Pabst
Bilal Al-Nawas
Yong-Dae Kwon
Christian Walter
Publikationsdatum: 01.02.2018
Verlag: Springer Berlin Heidelberg
Erschienen in: Clinical Oral Investigations / Ausgabe 7/2018
Print ISSN: 1432-6981
Elektronische ISSN: 1436-3771
DOI: https://doi.org/10.1007/s00784-018-2349-6

Neu im Fachgebiet Zahnmedizin

Parodontalbehandlung verbessert Prognose bei Katheterablation

19.04.2024 Vorhofflimmern Nachrichten

Werden Personen mit Vorhofflimmern in der Blanking-Periode nach einer Katheterablation gegen eine bestehende Parodontitis behandelt, verbessert dies die Erfolgsaussichten. Dafür sprechen die Resultate einer prospektiven Untersuchung.

Invasive Zahnbehandlung: Wann eine Antibiotikaprophylaxe vor infektiöser Endokarditis schützt

11.04.2024 Endokarditis Nachrichten

Bei welchen Personen eine Antibiotikaprophylaxe zur Prävention einer infektiösen Endokarditis nach invasiven zahnärztlichen Eingriffen sinnvoll ist, wird diskutiert. Neue Daten stehen im Einklang mit den europäischen Leitlinienempfehlungen.

Zell-Organisatoren unter Druck: Mechanismen des embryonalen Zahnwachstums aufgedeckt

08.04.2024 Zahnmedizin Nachrichten

Der Aufbau von Geweben und Organen während der Embryonalentwicklung wird von den Zellen bemerkenswert choreografiert. Für diesen Prozess braucht es spezielle sogenannte „Organisatoren“. In einer aktuellen Veröffentlichung im Fachjournal Nature Cell Biology berichten Forschende durch welchen Vorgang diese Organisatoren im Gewebe entstehen und wie sie dann die Bildung von Zähnen orchestrieren.

Die Oralprophylaxe & Kinderzahnheilkunde umbenannt

11.03.2024 Kinderzahnmedizin Nachrichten

Infolge der Umbenennung der Deutschen Gesellschaft für Kinderzahnheilkunde in Deutsche Gesellschaft für Kinderzahnmedizin (DGKiZ) wird deren Mitgliederzeitschrift Oralprophylaxe & Kinderzahnheilkunde in Oralprophylaxe & Kinderzahnmedizin umbenannt. Aus diesem Grunde trägt die erste Ausgabe in 2024 erstmalig den neuen Titel.

Bestellen Sie unseren kostenlosen Newsletter Update Zahnmedizin und bleiben Sie gut informiert – ganz bequem per eMail.

Newsletter bestellen

Springer Medizin

Abstract

Objective

Materials and methods

Results

Conclusions

Clinical relevance

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

Weitere Artikel der Ausgabe 7/2018

Stability of maxillary protraction therapy in children with Class III malocclusion: a systematic review and meta-analysis

Cyclic fatigue using severely curved canals and torsional resistance of thermally treated reciprocating instruments

Lactobacillus rhamnosus intake can prevent the development of Candidiasis

Clinical periodontal variables in patients with and without dementia—a systematic review and meta-analysis

Sensitivity of caries pathogens to antimicrobial peptides related to caries risk

Treatment of symptomatic benign migratory glossitis: a systematic review

Neu im Fachgebiet Zahnmedizin

Parodontalbehandlung verbessert Prognose bei Katheterablation

Invasive Zahnbehandlung: Wann eine Antibiotikaprophylaxe vor infektiöser Endokarditis schützt

Zell-Organisatoren unter Druck: Mechanismen des embryonalen Zahnwachstums aufgedeckt

Die Oralprophylaxe & Kinderzahnheilkunde umbenannt

Newsletter