Abstract
Bisphosphonates are effective antiresorptive agents frequently used in the treatment of different bone disorders, as osteoporosis, Paget�s disease and tumours that cause osteolysis. A major concern related to bisphosphonates therapy is represented by osteonecrosis of jaw, a serious, debilitating, and mostly, a therapy-resistant disease, reported as a frequent side effect of bisphosphonates. The present study was aimed to assess and compare the effect of four commercially available bisphosphonates, very frequently used as oral (Fosamax - F and Actonel - A) and injectable (Ossica - O and Zoledronic acid - Z) therapy on primary human gingival fibroblasts - HGF viability. Alamar blue cell viability assay was performed to assess the effect of test compounds (1.5; 2.5; 5 and 10 mM) on gingival fibroblasts viability after a 24 h interval. In these experimental conditions, injectable bisphosphonates (O and Z) proved to be safe for HGF cells, whereas oral compounds (F and A) were cytotoxic even at low concentrations.
Highlights
Bisphosphonates are effective antiresorptive agents frequently used in the treatment of different bone disorders, as osteoporosis, Paget’s disease and tumours that cause osteolysis
Bisphosphonates are a class of pharmaceutics applied as treatment for several bone disorders and cancers, as: Paget’s disease, osteoporosis, multiple myeloma and hypercalcemia of malignancy, that act by suppressing osteoclast differentiation, impairing its activity and leading to early apoptosis
The test compounds from the class of bisphosphonates: Actonel, Fosamax (Alendronate sodium -70 mg tablets, Merck Sharp &Dohme, Romania), Ossica and Zoledronic acid (Actavis -4 mg/ 5 mL solution for parenteral use), were prepared as follows: Actonel and Fosamax were dissolved in DMSO, obtaining stock solutions of 10 mM, and Ossica and Zoledronic acid were diluted in culture medium
Summary
The cell line used in the present study was human primary gingival fibroblast - HGF (ATCC® PCS-201-018TM) purchased from ATCC (American Type Cell Collection) and received as frozen vial. These cells are adherent, bipolar and refractile, present a spindle-shape and were obtained from a Caucasian female. The test compounds from the class of bisphosphonates: Actonel (risedronic acid -75 mg tablets, Actavis, Islanda), Fosamax (Alendronate sodium -70 mg tablets, Merck Sharp &Dohme, Romania), Ossica (ibandronic acid -1 mg/ mL solution for i.v administration, Gedeon Richter, Hungary) and Zoledronic acid (Actavis -4 mg/ 5 mL solution for parenteral use), were prepared as follows: Actonel and Fosamax were dissolved in DMSO, obtaining stock solutions of 10 mM, and Ossica and Zoledronic acid were diluted in culture medium
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