Stimulation of bone resorption

TOBE H, KOMIYAMA o, KOMIYAMA Y and MARUYAMA H B (1997) Daidzein stimulation of bone resorption in pit formation assay. Biosci Biotechnol Biochem 61, 370-71. 

The purified product is presented as a solution and contains sodium citrate, EDTA, sodium chloride and polysorbate 80 as excipients. A daily (s.c.) injection of 100 mg is recommended for patients with rheumatoid arthritis. This inflammatory condition is (not surprisingly) characterized by the presence of high levels of IL-1 in the synovial fluid of affected joints. In addition to its pro-inflammatory properties, IL-1 also mediates additional negative influences on the joint/bone, including promoting cartilage degradation and stimulation of bone resorption. 

Tumor necrosis factor a (TNF-a) is a multifunctional cytokine produced by activated monocytes-macrophages. TNF-a is one of the most potent osteoclastogenic cytokines produced in inflammation, and, in addition, TNF-a induces IL-1 synthesis. Like the other known stimulators of bone resorption, it acts through osteoblastic cells however, it has been demonstrated that TNF-a is able to induce osteoclast formation from stromal-depleted macrophages, with potency similar to that of RANKL (Kobayashi et al. 2000). TNF-a is able to induce bone resorption in vitro (Thomson et al. 1987) as well as in vivo (Koning et al. 1988). Osteoclasts induced by TNF-a have the capacity to form resorption pits on dentine slices only in the presence of IL-la. TNF-a, together with IL-1, plays an important role in bone resorption in inflammatory diseases (Kobayashi et al. 2000). Inhibition of TNF by TNF binding protein (TNFbp) completely prevents bone loss and osteoclast formation (Kimble et al. 1997). 

During the 1970s data on the expression of receptors for known stimulators of bone resorption, like PTH and vitamin D3, demonstrated that these receptors were not present on osteoclasts or their precursor cells, but were on osteoblasts (Rodan et al. 1981). Moreover, cellular interactions between stromal/OB cells... 

Deal C, Omizo M, Schwartz EN, Eriksen EF, Cantor P, Wang J, et al. (2004) Raloxifene in combination with teriparatide reduces teriparatide-induced stimulation of bone resorption but not formation in postmenopausal women with osteoporosis. J Bone Min Res 19(Suppl 1) 1169... 

Prostaglandins are abundant in skeletal tissue and are produced by osteoblasts and adjacent hematopoietic cells. The major effect of prostaglandins (especially PGE2, acting on EP4) in vivo is to increase bone turnover, ie, stimulation of bone resorption and formation. EP4 receptor deletion in mice results in an imbalance between bone resorption and formation, leading to a negative... 

Vitamin D has been known for more than half a century to be a powerful antirachitic agent, necessary for the development of normal bone. However, and oddly enough, its primary and most direct effect in this tissue is the stimulation of bone resorption [36] leading to an increase in the circulating levels of calcium and phos-... 

In this in vivo model, stimulation of bone resorption was induced in thyroparathyroidectomized rats by the infusion of parathyroid hormone. The changes in bone resorption were monitored by measuring the serum calcium concentration, which is directly related to the extent of bone resorption. 

The osteoblast and osteoclast can be considered to be the basic multicellular units of bone. The osteoblast plays an important role in mediating local osteoclast activity through the release of chemical messengers. The principal factors responsible for stimulation of bone resorption, such as parathyroid hormone, interleukin-1 (Il-l), and IL-6, have minimal effects on osteoclasts, but osteoblasts have receptors for these substances. 

The effects of PTH on bone are complex, as evidenced by its stimulation of bone resorption or bone formation, depending on the concentration of PTH and the duration of exposure. Chronic exposure to high concentrations of PTH leads to increased bone resorption. PTH acts directly by altering the activity or numbers of osteoblasts and indirectly on osteoclasts. Bone resorption, a prompt effect, is important for the maintenance of calcium homeostasis, whereas... 

An increase in trabecular bone mass by as much as 50% has been demonstrated in patients treated with low doses of PTH, but it comes at the expense of the cortical bone (1,11,25). Treatment with high doses of PTH is correlated with stimulation of bone resorption (20). Cyclical therapy with PTH and calcitonin has been shown to improve BMD in the spine without adverse effects in the cortical bone (11). When given in combination with estrogen, PTH promoted the formation of well-mineralized trabecular bone. 

Some conflicting statements have been made concerning the relative potencies of compounds possessing of the 24 R)- and 24(iS)-configuration in the vitamin D3 side chains. DeLuca (185) claims that both synthetically derived 24-hydroxyvitamin D3 isomers stimulate intestinal calcium transport almost equally well in the rat and has shown that the 24(S)-isomer has little or no activity in bone calcium resorption or in bone formation, whereas the 24(/ )-isomer is almost as active as 25-hydroxyvitamin D3 in these in vivo tests. However, Atkins (7) claims that both diastereo-isomers of 24,25-dihydroxyvitamin D3 are potent stimulators of bone resorption in tissue culture and there is no significant difference between the (R)- and (5)-forms. Boris (24) recently also showed that both 24 R)-and 24(/S)-isomers of la,24,25-trihydroxyvitamin D3 promote bone mineralization almost equally well in cockerels. Whether the differentiation of the 24(i )- and 24(5)-diastereoisomers in bone formation and resorption occurs only in the absence of the la- and the 25-hydroxy substituents is not known at this time, but it seems unlikely. 

---