Raloxifene inhibits bone loss and improves bone strength through an Opg-independent mechanism

Endocrine. 2010 Feb;37(1):55-61. doi: 10.1007/s12020-009-9267-y. Epub 2009 Nov 6.

Abstract

The osteoblast-derived paracrine factor osteoprotegerin (OPG) is considered to play a key role in inhibition of osteoclast formation and activity. Recently, raloxifene, a nonsteroidal benzothiophene, was found to exert anti-resorptive effects via modulating OPG expression in osteoblasts. To explore whether raloxifene regulates bone metabolism via an OPG-dependant pathway in vivo, we investigated the effects of raloxifene on bone loss in Opg-deficient mice. The results show that bone mineral density and bone strength are increased in mice deficient for Opg after treatment with raloxifene for 30 days. Histomorphometric analysis shows that raloxifene can increase bone trabecular area and decrease the number of osteoclasts in Opg (-/-) mice. Moreover, raloxifene reduces Rankl transcription and serum level of Rankl, which is dramatically increased in Opg knockout mice. These results suggest that raloxifene-induced inhibition of bone resorption may be independent of Opg pathway in mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Density / drug effects
  • Bone Density Conservation Agents / pharmacology*
  • Bone Density Conservation Agents / therapeutic use*
  • Bone Resorption / blood
  • Bone Resorption / metabolism
  • Bone Resorption / pathology
  • Bone Resorption / prevention & control*
  • Bone and Bones / chemistry
  • Bone and Bones / drug effects*
  • Bone and Bones / pathology
  • Cell Count
  • Elastic Modulus
  • Female
  • Femur / chemistry
  • Femur / drug effects
  • Femur / pathology
  • Gene Expression Regulation / drug effects
  • Lumbar Vertebrae / chemistry
  • Lumbar Vertebrae / drug effects
  • Lumbar Vertebrae / pathology
  • Mechanical Phenomena
  • Mice
  • Mice, Knockout
  • Osteoclasts / drug effects
  • Osteoclasts / pathology
  • Osteoprotegerin / blood
  • Osteoprotegerin / genetics
  • Osteoprotegerin / metabolism*
  • RANK Ligand / blood
  • RANK Ligand / genetics
  • RANK Ligand / metabolism
  • RNA, Messenger / metabolism
  • Raloxifene Hydrochloride / pharmacology*
  • Raloxifene Hydrochloride / therapeutic use*
  • Random Allocation

Substances

  • Bone Density Conservation Agents
  • Osteoprotegerin
  • RANK Ligand
  • RNA, Messenger
  • Tnfrsf11b protein, mouse
  • Tnfsf11 protein, mouse
  • Raloxifene Hydrochloride