A bisphosphonate that does not affect osteoclasts prevents osteoblast and osteocyte apoptosis and the loss of bone strength induced by glucocorticoids in mice

L. I. Plotkin, Nicoletta Bivi, T. Bellido

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53 Scopus citations

Abstract

Although a major effect of bisphosphonates on bone is inhibition of resorption resulting from their ability to interfere with osteoclast function, these agents also prevent osteoblast and osteocyte apoptosis in vitro and in vivo. However, the contribution of the latter property to the overall beneficial effects of the drugs on bone remains unknown. We compared herein the action on glucocorticoid-induced bone disease of the classical bisphosphonate alendronate with that of IG9402, a bisphosphonate analog that preserves osteoblast and osteocyte viability but does not induce osteoclast apoptosis in vitro. The bisphosphonates were injected daily (2.3 μmol/kg) to 5-month-old Swiss Webster mice (6-11 per group), starting 3. days before implantation of pellets releasing the glucocorticoid prednisolone (2.1. mg/kg/day). IG9402 did not affect levels of circulating C-telopeptide or osteocalcin, markers of resorption and formation, respectively, nor did it decrease mRNA levels of osteocalcin or collagen 1a1 in bone. On the other hand, alendronate decreased all these parameters. Moreover, IG9402 did not reduce cancellous mineralizing surface, mineral apposition rate, or bone formation rate, whereas alendronate induced a decrease in each of these bone formation measures. These findings demonstrate that, in contrast to alendronate, IG9402 does not inhibit bone turnover. Both alendronate and IG9402, on the other hand, activated survival kinase signaling in vivo, as evidenced by induction of ERK phosphorylation in bone. Furthermore, both bisphosphonates prevented the increase in osteoblast and osteocyte apoptosis as well as the decrease in vertebral bone mass and strength induced by glucocorticoids. We conclude that a bisphosphonate that does not affect osteoclasts prevents osteoblast and osteocyte apoptosis and the loss of bone strength induced by glucocorticoids in mice.

Original languageEnglish (US)
Pages (from-to)122-127
Number of pages6
JournalBone
Volume49
Issue number1
DOIs
StatePublished - Jul 1 2011

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Keywords

  • Apoptosis
  • Bisphosphonate
  • Bone strength
  • Glucocorticoid
  • Osteoblast
  • Osteocyte

ASJC Scopus subject areas

  • Physiology
  • Endocrinology, Diabetes and Metabolism
  • Histology

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