Effects of an Oral Bisphosphonate and Three Intravenous Bisphosphonates on Several Cell Types in Vitro

Overview

Journal Clin Oral Investig

Specialty Dentistry

Date 2018 Feb 2

PMID 29388023

Citations 22

Authors

Junho Jung

Jung Soo Park

Leonardo Righesso

Andreas Max Pabst

Bilal Al-Nawas

Yong-Dae Kwon

Christian Walter

Affiliations

Soon will be listed here.

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.

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References

Amin D, Cornell S, Gustafson S, Needle S, Ullrich J, Bilder G . Bisphosphonates used for the treatment of bone disorders inhibit squalene synthase and cholesterol biosynthesis. J Lipid Res. 1992; 33(11):1657-63. View

Tamura T, Shomori K, Nakabayashi M, Fujii N, Ryoke K, Ito H . Zoledronic acid, a third-generation bisphosphonate, inhibits cellular growth and induces apoptosis in oral carcinoma cell lines. Oncol Rep. 2011; 25(4):1139-43. DOI: 10.3892/or.2011.1152. View

Martins C, Leyhausen G, Volk J, Geurtsen W . Effects of alendronate on osteoclast formation and activity in vitro. J Endod. 2014; 41(1):45-9. DOI: 10.1016/j.joen.2014.07.010. View

Marx R . Pamidronate (Aredia) and zoledronate (Zometa) induced avascular necrosis of the jaws: a growing epidemic. J Oral Maxillofac Surg. 2003; 61(9):1115-7. DOI: 10.1016/s0278-2391(03)00720-1. View

Kwon J, Park E, Jung S, Sohn H, Ryu H, Suh H . 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. 2015; 94(9 Suppl):212S-9S. DOI: 10.1177/0022034515587862. View

Dimopoulos M, Kastritis E, Anagnostopoulos A, Melakopoulos I, Gika D, Moulopoulos L . 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):968-71. View

Walter C, Pabst A, Ziebart T, Klein M, Al-Nawas B . Bisphosphonates affect migration ability and cell viability of HUVEC, fibroblasts and osteoblasts in vitro. Oral Dis. 2010; 17(2):194-9. DOI: 10.1111/j.1601-0825.2010.01720.x. View

Rogers M, Crockett J, Coxon F, Monkkonen J . Biochemical and molecular mechanisms of action of bisphosphonates. Bone. 2010; 49(1):34-41. DOI: 10.1016/j.bone.2010.11.008. View

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

10.

Misso G, Porru M, Stoppacciaro A, Castellano M, De Cicco F, Leonetti C . Evaluation of the in vitro and in vivo antiangiogenic effects of denosumab and zoledronic acid. Cancer Biol Ther. 2012; 13(14):1491-500. PMC: 3542241. DOI: 10.4161/cbt.22274. View

11.

. Dental management of patients receiving oral bisphosphonate therapy: expert panel recommendations. J Am Dent Assoc. 2006; 137(8):1144-50. DOI: 10.14219/jada.archive.2006.0355. View

12.

Gertz B, Holland S, Kline W, Matuszewski B, Freeman A, Quan H . Studies of the oral bioavailability of alendronate. Clin Pharmacol Ther. 1995; 58(3):288-98. DOI: 10.1016/0009-9236(95)90245-7. View

13.

Hoff A, Toth B, Altundag K, Johnson M, Warneke C, Hu M . Frequency and risk factors associated with osteonecrosis of the jaw in cancer patients treated with intravenous bisphosphonates. J Bone Miner Res. 2008; 23(6):826-36. PMC: 2677083. DOI: 10.1359/jbmr.080205. View

14.

Walter C, Sagheb K, Bitzer J, Rahimi-Nedjat R, Taylor K . Analysis of reasons for osteonecrosis of the jaws. Clin Oral Investig. 2014; 18(9):2221-6. DOI: 10.1007/s00784-014-1205-6. View

15.

Terpos E, Kleber M, Engelhardt M, Zweegman S, Gay F, Kastritis E . European Myeloma Network guidelines for the management of multiple myeloma-related complications. Haematologica. 2015; 100(10):1254-66. PMC: 4591757. DOI: 10.3324/haematol.2014.117176. View

16.

Wysowski D, Greene P . Trends in osteoporosis treatment with oral and intravenous bisphosphonates in the United States, 2002-2012. Bone. 2013; 57(2):423-8. DOI: 10.1016/j.bone.2013.09.008. View

17.

Fisher J, Rosenberg E, Santora A, Reszka A . 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. 2013; 92(6):531-8. DOI: 10.1007/s00223-013-9711-0. View

18.

Rogers M, Russell R, Blackburn G, Williamson M, Watts D . Metabolism of halogenated bisphosphonates by the cellular slime mould Dictyostelium discoideum. Biochem Biophys Res Commun. 1992; 189(1):414-23. DOI: 10.1016/0006-291x(92)91574-a. View

19.

Otto S, Pautke C, Opelz C, Westphal I, Drosse I, Schwager J . Osteonecrosis of the jaw: effect of bisphosphonate type, local concentration, and acidic milieu on the pathomechanism. J Oral Maxillofac Surg. 2010; 68(11):2837-45. DOI: 10.1016/j.joms.2010.07.017. View

20.

Kos M . Incidence and risk predictors for osteonecrosis of the jaw in cancer patients treated with intravenous bisphosphonates. Arch Med Sci. 2015; 11(2):319-24. PMC: 4424249. DOI: 10.5114/aoms.2015.50964. View