title: Effects of risedronate, alendronate, and etidronate on the viability and activity of rat bone marrow stromal cells in vitro.
abstract: 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.
authors.affiliation: Child Health, University of Sheffield Medical School, Western Bank, Sheffield S10 2TH, UK.
authors.forename: K
authors.initials: K
authors.lastname: Still
authors.forename: R J
authors.initials: RJ
authors.lastname: Phipps
authors.forename: A
authors.initials: A
authors.lastname: Scutt
mesh_terms: 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
chemical_list: D004164:Diphosphonates; D004224:Diterpenes; D005204:Farnesol; C017338:geranylgeraniol; D000068296:Risedronic Acid; D012968:Etidronic Acid; D019386:Alendronate