Recombinant human OPG-Fc recognizes RANKL from multiple species and reduced bone resorption and increased bone volume, density, and strength in a number of rodent models of bone disease.
Recently, sclerostin and Dickkopf-related protein 1 were suggested to play a significant role in CKD-related bone disease as they are known inhibitors of the Wnt pathway, thus preventing bone formation.
Many types of cells express RANKL to support osteoclastogenesis depending on the biological context and the dysregulation of RANKL signaling leads to bone diseases such as osteoporosis and osteopetrosis.
Thus, our studies define a novel role of Runx2 in up-regulating the vicious cycle of metastatic bone disease, in addition to Runx2 regulation of genes related to progression of tumor metastasis.
Our results suggest that circulating inflammatory monocytes from advanced CKD or HD patients trans differentiate into OCs in vitro and play a relevant role in mineral bone disorders and that LIGHT and RANKL represent new potential therapeutic targets in these settings.
DKK-1 may also play a role in osteoarthritis, metabolic bone disease (osteoporosis and Paget's disease), as well as multiple myeloma-associated bone disease and prostate cancer bone metastases.
These transcriptional activators converge on IL-11 as a result of Runx2-Smad and Runx2-c-Jun interactions to amplify IL-11 gene expression that, together with Runx2, supports the osteolytic pathology of cancer induced bone disease.
Together, these results indicated that Macf1 plays a significant role in bone formation and osteoblast differentiation by regulating Bmp2/Smad/Runx2 pathway, suggesting that Macf1 might be a therapeutic target for bone disease.
Additional studies that correlate the diagnosis and management of CKD mineral and bone disorders with bone histomorphometric findings are needed to determine whether bio-intact PTH assay results are better surrogate markers in these early stages of CKD.
Osteoclast activity factors (in particular MIP1alpha) and imbalances between RANKL and osteoprotegerin are major factors for the development of myeloma bone disease.
These data open new avenues for the treatment of bone disease in MM and highlight the promising therapeutical interest of RANKL inhibitors (OPG and RANK-Fc) and MIP-1 inhibitors in the management of myeloma-associated osteolysis, besides bisphosphonates.
Therefore, considering its ability to inhibit RANKL-mediated osteoclastogenesis and the underlying mechanisms, astilbin might be a potential candidate for treating osteolytic bone diseases.
Clarifications of the role of FGF-23 has improved our understanding of posttransplant bone disease in addition to the known roles of hyperparathyroidism and vitamin D. The mechanisms of renal electrolyte wasting by immunosuppressive agents give insight into potential treatment options for hyperkalemia and hypomagnesemia.
Mineral and bone disorder management in hemodialysis patients: comparing PTH control practices in Japan with Europe and North America: the Dialysis Outcomes and Practice Patterns Study (DOPPS).
These findings provide evidence that Izb may be used to improve the therapeutic efficacy of PTH for the treatment of osteoporosis and other resorptive bone diseases.
There are two well-described syndromes caused by tumor production of parathyroid hormone-related peptide (PTHrP), namely osteolytic bone disease associated with breast cancer and humoral hypercalcemia of malignancy (HHM) that occurs with or without bone metastasis.
Microarray analysis of the DUSP1 mRNA levels in patients with pathological bone diseases also showed that the downregulated <i>DUSP1</i> expression leads to increased expression of RANKL and consequently to the destruction of the bone observed in these patients.