TL;DR: Osteopetrotic mutants have provided a wealth of information about the genes that regulate the differentiation of osteoclasts and their capacity to resorb bone.
Abstract: Osteoporosis, a disease endemic in Western society, typically reflects an imbalance in skeletal turnover so that bone resorption exceeds bone formation. Bone resorption is the unique function of the osteoclast, and anti-osteoporosis therapy to date has targeted this cell. The osteoclast is a specialized macrophage polykaryon whose differentiation is principally regulated by macrophage colony-stimulating factor, RANK ligand, and osteoprotegerin. Reflecting integrin-mediated signals, the osteoclast develops a specialized cytoskeleton that permits it to establish an isolated microenvironment between itself and bone, wherein matrix degradation occurs by a process involving proton transport. Osteopetrotic mutants have provided a wealth of information about the genes that regulate the differentiation of osteoclasts and their capacity to resorb bone.
TL;DR: The role and the molecular mechanism of action of regulatory molecules, such as cytokines and hormones, in osteoclast and osteoblast birth and apoptosis are reviewed to review the evidence for the contribution of changes in bone cell birth or death to the pathogenesis of the most common forms of osteoporosis.
Abstract: The adult skeleton regenerates by temporary cellular structures that comprise teams of juxtaposed osteoclasts and osteoblasts and replace periodically old bone with new. A considerable body of evidence accumulated during the last decade has shown that the rate of genesis of these two highly specialized cell types, as well as the prevalence of their apoptosis, is essential for the maintenance of bone homeostasis; and that common metabolic bone disorders such as osteoporosis result largely from a derangement in the birth or death of these cells. The purpose of this article is 3-fold: 1) to review the role and the molecular mechanism of action of regulatory molecules, such as cytokines and hormones, in osteoclast and osteoblast birth and apoptosis; 2) to review the evidence for the contribution of changes in bone cell birth or death to the pathogenesis of the most common forms of osteoporosis; and 3) to highlight the implications of bone cell birth and death for a better understanding of the mechanism of action and efficacy of present and future pharmacotherapeutic agents for osteoporosis.
TL;DR: There is a strong rationale that in this research model, high magnesium ion concentration could lead to bone cell activation, and metallic implants made of magnesium alloys degrade in vivo depending on the composition of the alloying elements.
TL;DR: A discussion is presented of the interrelationship between determinated osteogenic precursor cells (preosteoblasts) and hematopoietic stem cells (or their descendants) in which osteogenesis is inducible.
Abstract: In semisyngeneic heterotopic bone marrow transplants the donor or recipient origin of cells of osteogenic and hematopoietic tissues was identified by chromosome markers (T6) and by reverse transplantation into the initial donor line. In syngeneic and semisyngeneic grafts of bone marrow under the renal capsule bone and bone marrow are formed. In allogeneic grafts only bone is formed; this bone is subsequently resorbed. In 14-month semisyngeneic transplants the bone marrow consists of recipient cells. This is true for both the proliferating pool and the stem cells of hematopoietic tissue. At the same time, osteogenic precursor cells and bone tissue in these transplants are of donor origin. A discussion is presented of the interrelationship between determinated osteogenic precursor cells (preosteoblasts) and hematopoietic stem cells (or their descendants) in which osteogenesis is inducible.
TL;DR: 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.
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.