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PHYSIOLOGY OF BONE METABOLISM

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The Skeleton

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The skeleton is a highly vascularized and cellular tissue that serves as an ion reservoir of calcium, phosphate, and (to a lesser extent) magnesium; the exquisitely orchestrated balance between creating and removing bone tissue defines the process of bone remodeling that enables the adult skeleton to maintain its integrity and strength. The pediatric skeleton also demonstrates bone modeling, which permits bones to grow and reshape according to both genetic and environmental influences. Integrated with this activity is the ability to respond to external signaling in order to regulate calcium and phosphorus homeostasis. The complexity of the intimate and intricate interactions performed by the cellular elements of bone throughout the life of an individual is only recently becoming appreciated, and much about it remains to be elucidated.

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Osteoblasts, Osteocytes, and Osteoclasts
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The two fundamental processes occurring in bone are 1) modeling, which occurs during growth and results in the enlargement and reshaping of the skeleton to assume the final adult dimensions, and 2) remodeling, which occurs throughout life and involves removal for homeostatic needs, in response to changes in physical stress, and for replacement with no net change in bone mass. Three cells are central to these processes. The osteoblast secretes bone matrix and initiates bone formation, the osteocyte is an aged osteoblast that has become entombed within the newly created bone and maintains a network of communication throughout the bone, and the osteoclast is responsible for bone resorption (Figure 40-1). The osteoblast and osteoclast are both derived from embryonic progenitors within the bone marrow, but from distinctly different stem cell lines. Hence the initiating factors for differentiation of one or the other cell type, as well as cellular responsiveness to extracellular messengers, differ. Moreover, it appears that the osteoblast regulates osteoclastic activity through cell–cell interactions, thus coordinating the creative and destructive activities that ensure the development and maintenance of the necessary shapes of specific bones of the skeleton.

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FIGURE 40-1.

Developmental stages of osteoblast and osteoclast production. Each type of bone cell arises from distinct embryonic cell lines, which underscores the distinct nature of their functions. The osteoblast derives from bone marrow multipotent mesenchymal stem cells (MMSCs), acted on by a family of cytokines factors called bone morphogenetic proteins (BMPs) to become converted into a precursor osteoblast (POB). The mature, or active, osteoblast (O) migrates to the bone surface, where it secretes the bone matrix materials. With continued secretion and bone remodeling, some osteoblasts are trapped within the matrix and are entombed, becoming osteocytes (OCs) and communicating with the surface osteoblasts by means of syncytial processes extending through the canaliculi. The osteoclast, in contrast, emerges from the hematopoietic stem cell (HSC), a process initiated by macrophage colony-stimulating factor (M-CSF) as a precursor osteoclast (POC). Under the direction of many stimulating factors, especially RANK-L produced by the precursor osteoblast, the POC is converted ...

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