Normal bone anatomy and physiology

Abstract

This review describes normal bone anatomy and physiology as an introduction to the subsequent articles in this section that discuss clinical applications of iliac crest bone biopsy. The normal anatomy and functions of the skeleton are reviewed first, followed by a general description of the processes of bone modeling and remodeling. The bone remodeling process regulates the gain and loss of bone mineral density in the adult skeleton and directly influences bone strength. Thorough understanding of the bone remodeling process is critical to appreciation of the value of and interpretation of the results of iliac crest bone histomorphometry. Osteoclast recruitment, activation, and bone resorption is discussed in some detail, followed by a review of osteoblast recruitment and the process of new bone formation. Next, the collagenous and noncollagenous protein components and function of bone extracellular matrix are summarized, followed by a description of the process of mineralization of newly formed bone matrix. The actions of biomechanical forces on bone are sensed by the osteocyte syncytium within bone via the canalicular network and intercellular gap junctions. Finally, concepts regarding bone remodeling, osteoclast and osteoblast function, extracellular matrix, matrix mineralization, and osteocyte function are synthesized in a summary of the currently understood functional determinants of bone strength. This information lays the groundwork for understanding the utility and clinical applications of iliac crest bone biopsy.

Figure 1.

Regulation of osteoclastogenesis by receptor activator of NF-κB ligand (RANKL) and osteoprotegerin (OPG): Colony-stimulating factor 1 (CSF-1) normally stimulates osteoclast recruitment. Two forms of RANKL are produced by osteoblasts and osteoblast precursors to stimulate osteoclast recruitment and activation. The membrane-bound form directly interacts with membrane-bound RANK molecules on adjacent osteoclast precursors. The soluble form is released from osteoblasts or osteoblast precursors to diffuse through the intercellular space and interact with membrane-bound RANK molecules on nearby osteoclast precursors. OPG acts as a decoy receptor to prevent RANKL or sRANKL from interacting with RANK. The ratio between RANKL and OPG produced by osteoblasts and osteoblast precursors controls RANKL-stimulated osteoclastogenesis.

Figure 2.

Multinucleated osteoclasts resorb bone to form resorption pits known as Howship's lacunae.

Figure 3.

Osteoblasts synthesize proteinaceous matrix, composed mostly of type I collagen, to fill in resorption pits. The proteinaceous matrix is gradually mineralized to form new bone.