Nitrogen Containing Bisphosphonates Impair the Release of Bone Homeostasis Mediators and Matrix Production by Human Primary Pre-Osteoblasts.
Bisphosphonates (BPs) represent the first-line treatment for a wide array of bone disorders. Despite their well-known action on osteoclasts, the effects they induce on osteoblasts are still unclear. In order to shed light on this aspect we evaluated the impact of two nitrogen containing bisphosphonates, Alendronate (ALN) and Zoledronate (ZOL), on human primary pre-osteoblasts. At first, we showed an inhibitory effect on cell viability and alkaline phosphatase activity starting from µM concentrations of both drugs. In addition, an inhibitory trend on mineralized nodules deposition was observed. Then low doses of both ALN and ZOL rapidly increased the release of the pro-inflammatory mediators TNFα and IL-1β, while increased DKK-1 and Sclerostin, both inhibitors of osteoblastogenesis. Finally, ALN and 10-7M ZOL decreased the expression of type I Collagen and Osteopontin, while both drugs slightly stimulated SPARC production. With these results, we would like to suggest a direct inhibitory action on bone-forming cells by nitrogen containing bisphosphonates.
['Giannasi|Chiara|C|', 'Niada|Stefania|S|', 'Farronato|Davide|D|', 'Lombardi|Giovanni|G|', 'Manfredi|Barbara|B|', 'Farronato|Giampietro|G|', 'Brini|Anna Teresa|AT|']
D019386:Alendronate D000469:Alkaline Phosphatase D015415:Biomarkers D050071:Bone Density Conservation Agents D001847:Bone Diseases D002113:Calcification, Physiologic D002454:Cell Differentiation D002470:Cell Survival D002478:Cells, Cultured D024042:Collagen Type I D016207:Cytokines D006801:Humans D010006:Osteoblasts D053495:Osteopontin D000077211:Zoledronic Acid
bisphosphonates human primary pre-osteoblasts bone formation