Acetate inhibition of chick bone cell proliferation and bone growth in vitro

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Abstract
A hypothesis has been advanced that parenteral solutions as commonly formulated for use in clinical practice have a toxic effect on cell metabolism. A specific component of these solutions, sodium acetate, has been suggested to disrupt normal bone turnover and therefore to contribute to the osteopenia observed in patients receiving hemodialysis and parenteral nutrition (PN). We developed an in vitro model to test the hypothesis that sodium acetate at concentrations that are infused in PN solutions has a deleterious effect on bone metabolism. Osteoblasts and preosteoblasts from 16- to 17-day-old embryonic chick calvaria, and tibiae and femora from 10-day-old embryonic chicks were grown in BGJb medium (control) or in BGJb medium plus sodium acetate (5, 10, or 20 mM). Calvarial cell proliferation was quantified by direct cell counts as well as by incorporation of [3H]TdR into DNA as an index of cell proliferation. Calvarial cell alkaline phosphatase activity was quantified by the ability of extracts of the cultured cells to hydrolyze p-nitrophenyl phosphate to p-nitrophenol, and bone growth was determined by measuring final dry weight. Calvarial cell counts as well as DNA synthesis showed a dose-dependent decrease in the presence of sodium acetate (5–20 mM) compared with controls. [3H]TdR incorporation was decreased a mean 19% with 5 mM, 38% with 10 mM, and 63% with 20 mM acetate. Alkaline phosphatase activity per cell increased 48% with 5 mM, 140% with 10 mM, and 355% with 20 mM acetate. Cell viability as assessed by trypan blue exclusion was identical for test and control media (>95%). Long bone dry weight was decreased 6% with 5 mM acetate, 15% with 10 mM, and 33% with 20 mM acetate compared with controls. These effects were independent of the presence or absence of fetal bovine serum in the culture medium and could not be accounted for by pH differences between the test and control media. We conclude that sodium acetate inhibits the proliferation of chick osteoblasts and preosteoblasts as well as the growth of chick long bones in vitro and that the potential role of sodium acetate in parenteral solutions as a contributor to abnormal bone metabolism merits further investigation.
Funding Information
  • Caremark Homecare
  • Clinical Nutrition Research Unit ((#DK 35816))
  • University of Washingtion
  • NIH (68-5986)
  • NIH (AM 35816)
  • NIH (AM 35496)