Bone resorbing activity

Horton JE, Raisz LG, Simmons HA, Oppenheim JJ, Mergenhagen SE (1972) Bone resorbing activity in supernatant fluid from cultured human peripheral blood leukocytes. Science 177 793-795... 

The bone resorbing activities of la,25(OH)2D2 and la,25(OH)2D4 were almost the same as for la,25(OH)2D3. It is positively related to binding affinity to VDR. The results clearly explain that the calcemic effects of la,25(OH)2D2 and la,25(OH)2D4 are comparable to that of la,25(OH)2D3 as expected from their binding affinity for VDR. Sato et al. reported that bone calcium mobilization of 24-epi-la,25(OH)2D2 and la,25(OH)2D7 in vitamin D deficient rats was about 50% of that by la,25(OH)2D3 by assessing serum calcium changes after intravenous administration [36]. The results of biological activities of la,25-(OH)2D analogues were shown in Table 1 in comparison with those of l,25(OH)2D3. 

Stern, P. H., C. L. Trommel, H. K. Schnoes, and H. F. DeLuca Bone Resorbing Activity of Vitamin D Metabolites and Congeners in vitro Influence of Hydroxyl Substituents in the A-Ring. Endocrin. 97, 1552 (1976). 

Bone metabolism comprises the processes of bone formation and bone resorption, the key actions by which skeletal mass, structure and quality are accrued and maintained throughout life. In the mature skeleton, anabolic and catabolic actions are mostly balanced due to the tight regulation of the activity of bone forming ( osteoblast) and bone resorbing ( osteoclast) cells through circulating osteotropic hormones and locally active cytokines. 

Abstract Compact bone is a well-organised, multi-level porous structure. Strain-derived fluid flow likely steers the activity of cells within the bone matrix, which in turn orchestrate the concerted activity of bone resorbing and bone forming cells at the surface. We present a model of the strain-driven bone remodelling proces, which could explain the mechanically optimised structure of compact bone. 

Contrary to the original assumption which linked the inhibition of bone resorption solely to physico-chemical adsorption of the BP onto the bone surface, there is new evidence indicating cellular mechanisms of BP action, although a prerequisite of the biological activity is still the adsorption. The bisphosphonates deposited on the bone surface poison the bone-resorbing osteoclasts after being internalized by them. 

Actions. These compounds are effective calcium chelators that rapidly target exposed bone mineral surfaces in vivo, where they can be released by bone-resorbing osteoclasts, resulting in inhibition of osteoclast function and osteoclast apoptosis. The bisphosphonates (alendronate, clodronate, etidronate, pamidronate, risedronate, tiludronate and zoledronate) inhibit the activation and function of osteoclasts and possibly directly stimulate formation of bone by the osteoblasts. They also bind strongly to hydroxyapatite crystals and, in high doses, can inhibit the mineralisation of bone. The doses at which effects on mineralisation occur are not related to antiresorptive efficacy. There is wide variation between these compoimds in terms of their capacity to inhibit... 

In vitro studies have shown that TRAcP 5b isoform remains intracellularly in macrophages and dendritic cells which only secrete the TRAcP 5a isoform [25]. Therefore, for clinical determinations it is assumed that the tartrate-resistant acid phosphatase activity associated with bone resorbing osteoclasts derives only from the TRAcP 5 b isoform. 

To clarify the mechanism of action of these diterpenoids on bone resorption, their effect on osteoclast-like cell formation was tested according to the method reported by Takahashi et al.[34]. As a result, both compounds dose-dependently inhibited PTH-induced tartrate resistant acid phosphatase-positive MNC formation. Especially, SDC showed complete inhbition at concentration over 0.1 pM. Next, the effect of SDB and SDC on resorbing activity of osteoclasts (pit forming activity of osteoclast-like cells) was assayed according to the method of Tamura et al. [35]. As indicated in Table 8, both compounds inhibited the pit-formation when osteoclasts obtained by the co-culture were placed on dentine slice in the presence of these compounds. Therefore, the inhibitory effect of... 

Osteopenia (i.e., loss of bone) and osteoporosis (i.e., porous, fragile bone) are noted owing to osteoclasts (i.e., bone-resorbing cells) that are more active than osteoblasts (i.e., bone depositing cells), resulting in decreased bone density and increased bone fragility... 

Pamidronate disodium is a bisphosphonate which binds irreversibly to hydroxyapatite in bone. It is a strong inhibitor of bone resorption, reducing osteoclast or osteoclast precursor activity. Bisphosphonates inhibit bone resorption by selective adsorption to mineral surfaces and subsequent internalization by bone-resorbing osteoclasts. 

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