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11 Bone Remodeling: Cellular and Molecular Events

T. John Martin, Natalie A. Sims


Bone remodeling refers to the renewal process whereby small packets of old trabecular and cortical bone, dispersed throughout the skeleton and separated from others geographically as well as chronologically, are replaced by new bone throughout adult life. A major feature of bone remodeling is that it does not occur uniformly throughout the skeleton, but takes place asynchronously in focal or discrete sites known as basic multicellular units (BMUs) of bone turnover (Frost 1964; Parfitt 1996). The BMU describes the cells within a packet of bone that is resorbed and then fully rebuilt. The resorption activity in a BMU in human bone takes approximately 3 weeks and the formation response takes 3–4 months. The process is such that remodeling replaces about 5%–10% of the skeleton each year, with the entire adult human skeleton replaced in 10 years. Understanding the tightly-controlled processes of bone resorption and formation that take place in individual BMUs throughout the skeleton requires appreciation of the many pathways that control cells of the osteoblast and osteoclast lineage and how they communicate among themselves.

Cancellous bone remodeling starts on the bone surface, initiated by any of several possible stimuli. Among these are pressure changes sensed by osteocytes, resulting in signals delivered to surface cells, and damage in the form of microcracks in bone that lead to osteocyte stimulation, or even apoptosis, and the release from other nearby bone cells of signals, some of which are likely to be...

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