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

The plethora of actions attributed to 1,25(OH)2D3 throughout the body have suggested potential therapeutic applications for the treatment of hyperproliferative diseases, immune dysfunction, endocrine disorders, and metabolic bone disease. However, the potent calcemic activity of the natural vitamin D hormone has precluded its use in most cases. New vitamin D analogues are under development that display greater specificity, in most cases, by retaining the therapeutic properties of 1,25(OH)2D3, but with lower calcemic activity. Two analogues have been approved for use in patients: calcipotriol (Dovonex from Leo Pharmaceuticals, Copenhagen, Denmark) for the treatment of psoriasis; and 19-nor-1,25(OH)2D2 (Zemplar from Abbott Laboratories, Abbott Park, IL) for secondary hyperparathyroidism. Many others analogues are currently being tested in preclinical and clinical trials for the treatment of various types of cancer and osteoporosis, and for immunosuppression. The selectivity of the analogues can be attributed to the combined interactions with four proteins: the vitamin D receptor (VDR), the serum vitamin D binding protein (DBP), the vitamin D-24-hydroxylase and to a newly described membrane receptor. Low DBP affinity has been shown to be responsible for the reduced calcemic actions of calcipotriol and 22-oxacalcitriol (OCT), which is being tested for secondary hyperparathyroidism. However, the low calcemic activity of other analogues, including 19-nor-1,25(OH)2D2, involves other, as yet undefined, mechanisms. Understanding of the molecular basis for the selectivity of the vitamin D analogues will allow the design of more effective and safer vitamin D compounds for the treatment of a wide range of clinical disorders.
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PMID:Vitamin D analogues. 980 41

Paricalcitol [Zemplar: Abbott Laboratories, Abbott Park, IL, U.S.A.] is efficient for treating secondary hyperparathyroidism in patients on maintenance hemodialysis (HD). Zemplar is thought to be more potent than calcitriol and has been reported to cause less hypercalcemia and hyperphosphatemia. Here, we report a 1-year follow-up on patients from one inner-city dialysis unit. We reviewed the charts of 100 patients and collected data for 1 year. Patients were stratified into four groups depending upon their intact parathormone (iPTH) levels. Hemoglobin (Hb) and erythropoietin (EPO) doses were determined. More than 50% of patients had iPTH levels greater than 300 pg/mL. Mean Ca and PO4 levels were not significantly different, but Zemplar doses were significantly different in all groups. None of the patients had symptomatic bone disease. Seven patients were changed to low-Ca dialysate (1.0 mEq/L) secondary to hypercalcemia (Ca > 11.5 mg/dL) and severe secondary hyperparathyroidism. Interestingly, patients with low iPTH (< 100 pg/microL) showed relative EPO resistance, and patients with high iPTH (> 600 pg/microL) required smaller EPO doses. An inverse relationship was observed between Zemplar and EPO dose. The effect of Zemplar on EPO responsiveness needs to be confirmed in a larger study. Our data suggest that severe secondary hyperparathyroidism is frequent despite aggressive paricalcitol therapy in our inner-city HD population. To control severe secondary hyperparathyroidism in these patients, dietary and medication compliance may need to be supplemented with more effective non-calcium phosphate binders or calcimimetic agents, or both.
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PMID:Severe hyperparathyroidism despite paricalcitol therapy: one-year follow-up. 1476 69