The authors state that they have no conflicts of interest.
Version of Record online: 29 MAY 2007
Copyright © 2007 ASBMR
Journal of Bone and Mineral Research
Volume 22, Issue 10, pages 1492–1501, October 2007
How to Cite
Jilka, R. L., Weinstein, R. S., Parfitt, A. M. and Manolagas, S. C. (2007), Perspective: Quantifying Osteoblast and Osteocyte Apoptosis: Challenges and Rewards. J Bone Miner Res, 22: 1492–1501. doi: 10.1359/jbmr.070518
Published online on May 29, 2007
- Issue online: 4 DEC 2009
- Version of Record online: 29 MAY 2007
- Manuscript Accepted: 24 MAY 2007
- Manuscript Revised: 16 MAY 2007
- Manuscript Received: 17 APR 2007
- bone formation
Since the initial demonstration of the phenomenon in murine and human bone sections ∼10 yr ago, appreciation of the biologic significance of osteoblast apoptosis has contributed greatly not only to understanding the regulation of osteoblast number during physiologic bone remodeling, but also the pathogenesis of metabolic bone diseases and the pharmacology of some of the drugs used for their treatment. It is now appreciated that all major regulators of bone metabolism including bone morphogenetic proteins (BMPs), Wnts, other growth factors and cytokines, integrins, estrogens, androgens, glucocorticoids, PTH and PTH-related protein (PTHrP), immobilization, and the oxidative stress associated with aging contribute to the regulation of osteoblast and osteocyte life span by modulating apoptosis. Moreover, osteocyte apoptosis has emerged as an important regulator of remodeling on the bone surface and a critical determinant of bone strength, independently of bone mass. The detection of apoptotic osteoblasts in bone sections remains challenging because apoptosis represents only a tiny fraction of the life span of osteoblasts, not unlike a 6-mo -long terminal illness in the life of a 75-yr -old human. Importantly, the phenomenon is 50 times less common in human bone biopsies because human osteoblasts live longer and are fewer in number. Be that as it may, well-controlled assays of apoptosis can yield accurate and reproducible estimates of the prevalence of the event, particularly in rodents where there is an abundance of osteoblasts for inspection. In this perspective, we focus on the biological significance of the phenomenon for understanding basic bone biology and the pathogenesis and treatment of metabolic bone diseases and discuss limitations of existing techniques for quantifying osteoblast apoptosis in human biopsies and their methodologic pitfalls.