[Bisphosphonates stimulate the production of basic fibroblast growth factor and the formation of bone marrow precursors of osteoblasts. New findings about their mechanism of action].
BACKGROUND
It has been recently shown that bisphosphonates may affect bone resorption either directly on osteoclast activity or through the mediation of osteoblasts activity. In this experimental study the potential effects of etidronate and alendronate on osteoblastic bone formation are investigated.


METHODS
The number of fibroblastic colony forming units (CFU-F) and mineralized nodules (CFU-OB) in murine and human bone marrow cultures, assessed. In addition, the basic-FGF production by human osteoblastic cells MG-63 measured.


RESULTS
In murine bone marrow cultures etidronate and alendronate stimulate CFU-F formation with a mean increases vs control of 106 +/- 17% at 10(-5) M and 78 +/- 5% at 10(-7) M respectively (p < 0.001). The formation of bone nodules is inhibited by bisphosphonates at high concentrations (> 10(-6) M) and stimulated at lower concentrations (from 10(-7) M to 10(-9) M for etidronate and from 10(-7) M to 10(-10) M for alendronate; p < 0.001). Similarly, in human bone marrow cultures alendronate increases CFU-F formation with a maximal effect at 10(-10) M (+161 +/- 12% vs control; p < 0.01) and the formation of CFU-OB with a maximal effect at 10(-10) M (+133 +/- 34%; p < 0.001). Finally, etidronate (from 10(-9) to 10(-11) M) and alendronate (from 10(-9) to 10(-12) M) stimulate the b-FGF production by human osteoblastic cells (p < 0.01).


CONCLUSIONS
In line with previous histomorphometric and clinical observations, the results obtained indicate that bisphosphonates directly affect osteoblastic cells with a positive effect on bone formation, probably via the stimulation of growth factors.
Giuliani
N
N
Istituto di Clinica Medica Generale e Terapia Medica, Università degli Studi, Parma.
Pedrazzoni
M
M
Passeri
G
G
Negri
G
G
Impicciatore
M
M
Girasole
G
G
D019386:Alendronate / Q000494:pharmacology*; D000818:Animals; D001853:Bone Marrow / Q000187:drug effects* / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D012968:Etidronic Acid / Q000494:pharmacology*; D016222:Fibroblast Growth Factor 2 / Q000096:biosynthesis*; D006801:Humans; D051379:Mice; D010006:Osteoblasts / Q000187:drug effects* / Q000502:physiology*; D013234:Stem Cells
D016222:Fibroblast Growth Factor 2; D012968:Etidronic Acid; D019386:Alendronate
I bisfosfonati stimolano la produzione di "basic fibroblast growth factor" e la formazione dei precursori midollari degli osteoblasti. Nuove acquisizioni sul meccanismo di azione.