International Journal of Medical Sciences

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20 April 2019

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Int J Med Sci 2019; 16(1):23-32. doi:10.7150/ijms.27470

Research Paper

Nitrogen Containing Bisphosphonates Impair the Release of Bone Homeostasis Mediators and Matrix Production by Human Primary Pre-Osteoblasts

Chiara Giannasi1,2, Stefania Niada2, Davide Farronato3, Giovanni Lombardi2, Barbara Manfredi1, Giampietro Farronato1,4, Anna Teresa Brini1,2✉

1. Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy.
2. IRCCS Istituto Ortopedico Galeazzi, Milan, Italy.
3. Department of Medicine and Surgery, Insubria University, Varese, Italy.
4. IRCCS Fondazione Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.


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.

Keywords: bisphosphonates, human primary pre-osteoblasts, bone formation

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license ( See for full terms and conditions.
How to cite this article:
Giannasi C, Niada S, Farronato D, Lombardi G, Manfredi B, Farronato G, Brini AT. Nitrogen Containing Bisphosphonates Impair the Release of Bone Homeostasis Mediators and Matrix Production by Human Primary Pre-Osteoblasts. Int J Med Sci 2019; 16(1):23-32. doi:10.7150/ijms.27470. Available from