Effects of risedronate, alendronate, and etidronate on the viability and activity of rat bone marrow stromal cells in vitro.
The effects of risedronate, alendronate, and etidronate were assessed in calcifying fibroblastic colony-forming unit (CFU-f) cultures of rat bone marrow cells in vitro. Biphasic effects on the formation of bone-like colonies were observed. Treatment with high concentrations (10(-5)-10(-4)M) of alendronate and risedronate caused a total inhibition of colony formation whereas etidronate had relatively little effect. It was also found that intermediate concentrations (10(-6)M) of alendronate and risedronate decreased the formation of colonies displaying osteoblastic characteristics such as alkaline phosphatase expression, collagen accumulation, and calcification. At lower concentrations (10(-9)-10(-7)M), risedronate and alendronate increased the formation of fibroblastic colonies, suggesting a mild anabolic effect, however, the formation of colonies with osteoblastic properties was not affected. Treating the cells with a combination of bisphosphonate and 1 mM geranylgeraniol could to some extent abrogate the cytotoxic effects of alendronate or risedronate, suggesting the involvement of the mevalonate pathway. The colony-stimulating activity of these bisphosphonates was, however, unaffected.
Still
K
K
Child Health, University of Sheffield Medical School, Western Bank, Sheffield S10 2TH, UK.
Phipps
R J
RJ
Scutt
A
A
D019386:Alendronate / Q000494:pharmacology*; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D001842:Bone and Bones / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects; D004164:Diphosphonates / Q000378:metabolism; D004224:Diterpenes / Q000037:antagonists & inhibitors; D012968:Etidronic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology*; D005204:Farnesol / Q000037:antagonists & inhibitors; D005347:Fibroblasts / Q000502:physiology; D023421:Models, Animal; D051381:Rats; D017208:Rats, Wistar; D000068296:Risedronic Acid; D017154:Stromal Cells / Q000187:drug effects* / Q000502:physiology
D004164:Diphosphonates; D004224:Diterpenes; D005204:Farnesol; C017338:geranylgeraniol; D000068296:Risedronic Acid; D012968:Etidronic Acid; D019386:Alendronate