Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0005940 (bone disease)
 7,459 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Childhood and adolescence are crucial times for the development of a healthy skeletal and cardiovascular system. Disordered mineral and bone metabolism accompany chronic kidney disease (CKD) and present significant obstacles to optimal bone strength, final adult height, and cardiovascular health. Decreased activity of renal 1 alpha hydroxylase results in decreased intestinal calcium absorption, increased serum parathyroid hormone levels, and high-turnover renal osteodystrophy, with subsequent growth failure. Simultaneously, phosphorus retention exacerbates secondary hyperparathyroidism, and elevated levels contribute to cardiovascular disease. Treatment of hyperphosphatemia and secondary hyperparathyroidism improves growth and high-turnover bone disease. However, target ranges for serum calcium, phosphorus, and parathyroid hormone (PTH) levels vary according to stage of CKD. Since over-treatment may result in adynamic bone disease, growth failure, hypercalcemia, and progression of cardiovascular calcifications, therapy must be carefully adjusted to maintain optimal serum biochemical parameters according to stage of CKD. Newer therapeutic agents, including calcium-free phosphate binding agents and new vitamin D analogues, effectively suppress serum PTH levels while limiting intestinal calcium absorption and may provide future therapeutic alternatives for children with CKD.
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PMID:Chronic kidney disease mineral and bone disorder in children. 1804 81

Decreased activity of osteoblasts (OBs) contributes to osteolytic lesions in multiple myeloma (MM). The production of the soluble Wnt inhibitor Dickkopf-1 (DKK1) by MM cells inhibits OB activity, and its serum level correlates with focal bone lesions in MM. Therefore, we have evaluated bone anabolic effects of a DKK1 neutralizing antibody (BHQ880) in MM. In vitro BHQ880 increased OB differentiation, neutralized the negative effect of MM cells on osteoblastogenesis, and reduced IL-6 secretion. In a severe combined immunodeficiency (SCID)-hu murine model of human MM, BHQ880 treatment led to a significant increase in OB number, serum human osteocalcin level, and trabecular bone. Although BHQ880 had no direct effect on MM cell growth, it significantly inhibited growth of MM cells in the presence of bone marrow stromal cells (BMSCs) in vitro. This effect was associated with inhibition of BMSC/MM cell adhesion and production of IL-6. In addition, BHQ880 up-regulated beta-catenin level while down-regulating nuclear factor-kappaB (NF-kappaB) activity in BMSC. Interestingly, we also observed in vivo inhibition of MM cell growth by BHQ880 treatment in the SCID-hu murine model. These results confirm DKK1 as an important therapeutic target in myeloma and provide the rationale for clinical evaluation of BHQ880 to improve bone disease and to inhibit MM growth.
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PMID:Anti-DKK1 mAb (BHQ880) as a potential therapeutic agent for multiple myeloma. 1941 13