Disease relevance of Bone Resorption

• We administered high doses of calcitriol (up to 32 micrograms per day) to an infant with malignant osteopetrosis, in an attempt to stimulate bone resorption [1].
• BACKGROUND: Alendronate, an aminobisphosphonate and a selective inhibitor of osteoclast-mediated bone resorption, is used to treat osteoporosis in postmenopausal women and Paget's disease of bone [2].
• Experiments were conducted to test the hypothesis that tumor-derived transforming growth factor-alpha (TGF-alpha) is responsible for the increased bone resorption and hypercalcemia seen in some malignant diseases [3].
• TNF-alpha together with IL-1alpha may play an important role in bone resorption of inflammatory bone diseases [4].
• Postmenopausal bone loss stems from the inability of osteoblastic activity to match the increase in osteoclastic bone resorption induced by estrogen deficiency [5].

Psychiatry related information on Bone Resorption

• Genes for carbonic anhydrase that are expressed at high levels in osteoclast are known to be involved in bone resorption and Id genes role in osteoblast-osteoclast differentiation reflects the genomic effect of Vitamin D on bones [6].
• The effect of the systemic administration of prostaglandin (PG) E(1) on physical activity and bone resorption was examined in patients with intermittent claudication (gait disturbance) [7].

High impact information on Bone Resorption

• A novel secreted glycoprotein that regulates bone resorption has been identified [8].
• Bisphosphonates such as pamidronate inhibit osteoclastic activity and reduce bone resorption [9].
• BACKGROUND: Bisphosphonates such as pamidronate disodium inhibit osteoclast-induced bone resorption associated with cancer that has metastasized to bone [10].
• Differences in spinal bone density between members of a pair were associated with differences in the serum concentrations of parathyroid hormone (P = 0.01) and calcium (P = 0.05) and urinary pyridinoline excretion (P = 0.06), a marker of bone resorption [11].
• There was a marginal decrease in bone resorption in the clodronate group and no change in bone accretion [12].

Chemical compound and disease context of Bone Resorption

• Prostaglandin mediation of collagenase-induced bone resorption [13].
• These effects were inhibited by cortisol but were not altered by hormones that normally stimulate osteoclastic bone resorption [14].
• Flurbiprofen: a potent inhibitor of alveolar bone resorption in beagles [15].
• MAIN OUTCOME MEASURES: Efficacy measures included spine, hip, and forearm BMD and biochemical markers of bone resorption (urinary hydroxyproline corrected for creatinine and urinary CrossLaps [Osteometer Biotech, Herlev, Denmark] corrected for creatinine), assessed every 6 months [16].
• An essential role of cytosolic phospholipase A2alpha in prostaglandin E2-mediated bone resorption associated with inflammation [17].

Biological context of Bone Resorption

• Histomorphometric studies done before and after ovariectomy showed that the absence of osteocalcin leads to an increase in bone formation without impairing bone resorption [18].
• Interestingly, GH treatment to GHD adults initially results in increased bone resorption with an increased number of bone-remodeling units and more newly produced unmineralized bone, resulting in an apparent low or unchanged bone mass [19].
• Our data suggest that apart from the established role of M-CSF in the provision of precursors for osteoclastic induction, a major role for M-CSF in bone resorption is to enhance osteoclastic survival, migration, and chemotaxis [20].
• We conclude that during lactation mammary epithelial cells are a source of circulating PTHrP that promotes bone loss by increasing rates of bone resorption [21].
• Since the stimulation by parathyroid hormone of both cytokine production and bone resorption depends on the same signal transduction pathway, we hypothesized that IL-6 might be a downstream effector of parathyroid hormone [22].

Anatomical context of Bone Resorption

• Our study shows that there is cross-talk between the tumour necrosis factor and IFN families of cytokines, through which IFN-gamma provides a negative link between T-cell activation and bone resorption [23].
• Using a recently developed technique for isolation of highly purified mammalian osteoclasts, we showed that 17 beta-estradiol (E2) was able to directly inhibit osteoclastic bone resorption [24].
• These results indicate that IL-1 stimulates bone resorption through a primary action on osteoblasts, which are induced by IL-1 to transmit a short-range signal that stimulates osteoclastic bone resorption [25].
• Osteoclasts formed in the presence of IL-11 were capable of bone resorption, as evidenced by the formation of resorption pits, as well as the release of 45Ca from prelabeled murine calvaria [26].
• Src family tyrosine kinases are implicated in various intracellular signaling pathways, including mitogenic response to growth factors in fibroblasts, activation of lymphocytes, and osteoclastic bone resorption [27].

Gene context of Bone Resorption

• c-Cbl is downstream of c-Src in a signalling pathway necessary for bone resorption [28].
• These results indicate that c-Cbl may act downstream of c-Src in a signalling pathway that is required for bone resorption [28].
• Vav3-deficient mice have increased bone mass and are protected from bone loss induced by systemic bone resorption stimuli such as parathyroid hormone or RANKL [29].
• Moreover, osteoblast-mediated stimulation of bone resorption was abrogated by soluble TRANCE receptor and by the soluble decoy receptor osteoprotegerin (OPG), and stimulation of isolated osteoclasts by TRANCE was neutralized by OPG [30].
• These results demonstrate that M-CSF and VEGF have overlapping functions in the support of osteoclastic bone resorption [31].

Analytical, diagnostic and therapeutic context of Bone Resorption

• We examined the effects of herbimycin A on the formation of bone resorbing osteoclasts in mouse long-term marrow cultures, on isolated rodent osteoclasts and on bone resorption in organ cultures of fetal rat long bones stimulated by parathyroid hormone [32].
• Urinary markers of bone resorption, pyridinoline and deoxypyridinoline were measured before and at 4 weeks after radiotherapy for metastatic bone pain [33].
• Blockade of NF-kappaB signaling in MDA-MB-231 cells by the mutant IkappaB decreased in vitro cell proliferation, expression of the proinflammatory, bone-resorbing cytokine interleukin-6, and in vitro bone resorption by tumor/osteoclast cocultures while reciprocally up-regulating production of the proapoptotic enzyme caspase-3 [34].
• NF-kappaB signaling in breast cancer cells therefore promotes bone tumor burden and tumor-mediated osteolysis through combined control of tumor proliferation, cell survival, and bone resorption [34].
• CONCLUSION: IL-1 appears to be of major importance in mediating the bone resorption that occurs in rat adjuvant arthritis, but is less important in the pathogenesis of periarticular inflammation in this disease [35].

References