Recent evidence for an extraskeletal origin of osteoelasts and the historical record of the genesis of osteoelasts are examined critically. Reviews of the structure, function and development of osteoelasts from mononuclear precursors, the local regulation of bone resorption and the coupling of bone formation to preceding resorption are presented as a background for discussing the clinical implications for management of osteolytic bone diseases. The roles of osteoelasts and macrophages as phagocytes are compared and contrasted, and recent evidence for macrophage heterogeneity resulting from site-specific monoblastic precursors is reviewed. The implications of these recent developments in macrophage biology are extrapolated to osteoelasts and the existence of site-specific, extraskeletal tsteoclast precursors is proposed. Finally, the investigative challenges inherent in these perspectives are discussed.

We conclude that the metaphyseal plate of the growing rat offers an optimal model to study vasculogenesis. Capillary sprouts can be readily identified, measured, and counted because they are located within a plane bordering against avascular cartilage. In addition, by using microvascular corrosion casting in SEM not only capillary sprouting per se but also different stages of neovascularization, indicated by differently sized nodular projections at the tip of vascular loops, can be studied in the growing long bone.

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Osteopetrosis in laboratory animals is a metabolic bone disease characterized by increased skeletal mass. It is inherited as an autosomal recessive and results from a defect in the development and/or function of osteoclasts. We studied two enzymes essential for bone resorption, carbonic anhydrase II isoenzyme (CA II) and H+ -ATPase, in osteoclasts from four osteopetrotic mutations in the rat; namely incisors-absent (ia), osteopetrosis (op), toothless (tl), and microphthalmia (mib), to test the hypothesis that reduced bone resorption in one or more of these mutations results from defects in the synthesis or activity of one of these enzymes. CA II was present in most osteoclasts from normal, tl, op, and mib littermates and was homogeneously distributed in cytoplasm. CA II staining in ia osteoclasts was more variable and less intense than in the other mutations. H+-ATPase was also present in osteoclasts from normal animals and mutants and immunostaining showed clear polarization to the ruffled border region in all normal rats and mutants except ia, which showed diffuse distribution of staining in the cytoplasm. H+-ATPase activity (proton transport) in a related tissue, kidney, was normal in tl and ia rats but increased in op and mib rats compared to their normal littermates. These results suggest that the osteoclasts in osteopetrotic rat mutations are not abnormal with respect to the distribution of CA II and H+ -ATPase and that the function of these enzymes in the skeleton, while likely normal, needs to be tested directly in bone.