Birth and Death of Bone Cells: Basic Regulatory Mechanisms and Implications for the Pathogenesis and Treatment of Osteoporosis1
Stavros C. Manolagas
Division of Endocrinology & Metabolism, Center for Osteoporosis &
Metabolic Bone Diseases, University of Arkansas for Medical Sciences,
and the Central Arkansas Veterans Healthcare System, Little Rock,
Arkansas 72205, USA
The adult skeleton regenerates by temporary cellular structuresthat
comprise teams of juxtaposed osteoclasts and osteoblastsand replace
periodically old bone with new. A considerable bodyof evidence
accumulated during the last decade has shown thatthe rate of genesis
of these two highly specialized cell types,as well as the prevalence
of their apoptosis, is essential forthe maintenance of bone
homeostasis; and that common metabolicbone disorders such as
osteoporosis result largely from a derangementin the birth or death of
these cells. The purpose of this articleis 3-fold: 1) to review the
role and the molecular mechanismof action of regulatory molecules,
such as cytokines and hormones,in osteoclast and osteoblast birth and
apoptosis; 2) to reviewthe evidence for the contribution of changes in
bone cell birthor death to the pathogenesis of the most common forms
of osteoporosis;and 3) to highlight the implications of bone cell
birth anddeath for a better understanding of the mechanism of action
andefficacy of present and future pharmacotherapeutic agents for
osteoporosis.
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