EFFECT OF ALENDRONATE ON CULTURED NORMAL HUMAN OSTEOBLASTS

Alendronate is an aminobisphosphonate with a potent antireabsorptive a ction that does not appear to interfere with bone mineralization, and is even able to increase bone mineral density in osteoporotic postmeno pausal women through a still not fully understood mechanism, This stud y was conducted to assess the direct effect of alendronate on diverse aspects of normal human osteoblast physiology, For that purpose, the i n vitro effect of a wide range of concentrations (from 10(-1) to 10(-1 2) mol/L) of alendronate on cell viability, proliferation, collagen sy nthesis, and the mineral-depositing capacity of normal human osteoblas ts was tested. Alendronate effects were examined at 48 and 96 h of cul ture in the presence or absence of fetal calf serum, In vitro alendron ate affected osteoblast viability at concentrations equal to or higher than 10(-4) mol/L, At concentrations equal to or higher than 10(-3) m ol/L, no viable cells were observed in cultures, In vitro alendronate at concentrations between 10(-5) and 10(-12) mol/L did not have any ef fect on the proliferative capacity of normal human osteoblasts determi ned by two different techniques: (1) tritiated thymidine incorporation to DNA and (2) cell counting, Collagen synthesis by normal human oste oblasts showed a tendency to decrease following incubation with alendr onate supplemented with fetal calf serum, This decrease was only stati stically significant after 96 h of culture; however, a dose-response e ffect could not he documented, Finally, no effect of alendronate was o bserved on calcium deposition in vitro by normal human osteoblasts at concentrations equal to or lower than 10(-5) mol/L, In conclusion, the present study shows that alendronate in vitro does not affect viabili ty, proliferation, and mineral deposit capacity of normal human osteob lasts at the concentration at which it inhibits by 50 % the resorptive capacity of osteoclasts that for this drug has been reported as 2 x 1 0(-9) mol/L, (C) 1998 by Elsevier Science Inc. All rights reserved.