Mechanisms of action of antiresorptive therapies of postmenopausal osteoporosis

Jan J. Stepan, F. Alenfeld, G. Boivin, J. H M Feyen, P. Lakatos

Research output: Contribution to journalArticle

82 Citations (Scopus)

Abstract

In the treatment of osteoporosis, the aim of the antiresorptive therapy is to restore bone density by decreasing bone remodeling. The process of bone remodeling plays a role in plasma calcium homeostasis and serves to modify bone architecture in order to meet changing mechanical needs, to maintain osteocyte viability, and to repair microdamage in bone matrix. Estrogen deficiency results in a number of detrimental effects on bone, including suppression of osteocyte survival as well as impairment of osteoblast response to mechanical stimuli and repair of ageing bone. In this review, effects of available antiresorptive therapies on endocrine regulations of bone metabolism in postmenopausal osteoporosis are compared. The aim of antiresorptive treatment is to ensure adequate bone remodeling, reparation of microdamage of bone, and increased bone strength. Ideally, this effect should be maintained long-term. Several agents are approved for the treatment of osteoporosis. Calcitonin transiently inhibits osteoclast activity without decreasing osteoblast collagen synthesis. Aminobisphosphonates decrease bone remodeling by decreasing osteoclast activity and by inducing osteoclast apoptosis. This allows more time for secondary mineralization to proceed to completion in the existing bone tissue mass, so increasing the mechanical resistance of bone to loading. Estrogens and raloxifene (a selective estrogen receptor modulator that acts as an estrogen agonist in bone) suppress bone remodeling to the premenopausal range, maintaining the function of osteoblasts and osteocytes. In the placebo-controlled osteoporosis treatment trials, all the above treatments reduced the risk of fractures. Raloxifene therapy was also associated with a favorable or neutral effect in the cardiovascular system, and a reduced incidence of breast cancer. Selection of appropriate drug for treatment of postmenopausal osteoporosis should take into account the long-term effect of the antiresorptive agent on bone. Moreover, the effects on other tissues ++should also be considered, and this encompasses both safety concerns, as well as the potentially beneficial effects on other tissues. Further investigation is needed to evaluate the different modes of action of these agents, and their long-term effects on bone and other tissues.

Original languageEnglish
Pages (from-to)225-238
Number of pages14
JournalEndocrine Regulations
Volume37
Issue number4
Publication statusPublished - Dec 2003

Fingerprint

Postmenopausal Osteoporosis
Bone and Bones
Bone Remodeling
Osteocytes
Osteoclasts
Osteoblasts
Osteoporosis
Therapeutics
Estrogens
Bone Density Conservation Agents
Selective Estrogen Receptor Modulators
Bone Matrix
Calcitonin
Cardiovascular System
Bone Density
Homeostasis
Collagen
Placebos
Apoptosis
Breast Neoplasms

Keywords

  • Apoptosis
  • Bisphosphonates
  • Calcitonin
  • Cytokines
  • Estrogen
  • Osteoblasts
  • Osteoclasts
  • Raloxifene
  • SERM

ASJC Scopus subject areas

  • Endocrinology

Cite this

Stepan, J. J., Alenfeld, F., Boivin, G., Feyen, J. H. M., & Lakatos, P. (2003). Mechanisms of action of antiresorptive therapies of postmenopausal osteoporosis. Endocrine Regulations, 37(4), 225-238.

Mechanisms of action of antiresorptive therapies of postmenopausal osteoporosis. / Stepan, Jan J.; Alenfeld, F.; Boivin, G.; Feyen, J. H M; Lakatos, P.

In: Endocrine Regulations, Vol. 37, No. 4, 12.2003, p. 225-238.

Research output: Contribution to journalArticle

Stepan, JJ, Alenfeld, F, Boivin, G, Feyen, JHM & Lakatos, P 2003, 'Mechanisms of action of antiresorptive therapies of postmenopausal osteoporosis', Endocrine Regulations, vol. 37, no. 4, pp. 225-238.
Stepan, Jan J. ; Alenfeld, F. ; Boivin, G. ; Feyen, J. H M ; Lakatos, P. / Mechanisms of action of antiresorptive therapies of postmenopausal osteoporosis. In: Endocrine Regulations. 2003 ; Vol. 37, No. 4. pp. 225-238.
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