Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020438 (hypercalciuria)
 2,502 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study aimed to evaluate whether recombinant human growth hormone (rhGH) or insulin-like growth factor-I (rhIGF-I) can reverse or prevent further bone loss in aged osteopenic ovariectomized (OVX) rats and to compare their effects with those of 17 beta-estradiol (E2). Twelve-month-old rats were OVX, remained untreated for 8 weeks, and subsequently received daily subcutaneous (SC) injections of rhGH (75 micrograms/day), rhIGF-I (250 micrograms/day), E2 (1.5 micrograms/day), and their respective combinations during 8 weeks, and were then compared with sham-operated, pretreatment OVX, and saline-treated OVX rats. A single sc injection of rhGH resulted in peak hGH concentrations after 90 minutes, with a half-life of 124 minutes; the highest plasma IGF-I concentrations were reached 45 minutes after rhIGF-I injection (+57% vs. baseline) with a gradual decline thereafter. Measurements included: biochemical parameters of bone remodeling (plasma osteocalcin and urinary pyridinolines); histomorphometry of proximal tibial metaphysis; DXA of femur; biomechanical analysis of femur and fifth lumbar vertebra (L5); plasma 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), and calbindin-D9K in duodenal mucosa. Whereas all E2-treated OVX rats had much suppressed bone remodeling, rhGH or rhIGF-I had no effect on any biochemical or histomorphometrical parameter of remodeling. The bone mineral density (BMD) at the distal femoral metaphysis as well as parameters of strength at L5 were maintained at pretreatment values in OVX rats treated with E2, GH, or IGF-I, but not in saline-treated OVX rats; their effects were not additive, however. Trabecular bone volume in the tibial metaphysis was also higher in rats treated with these agents than in saline-treated rats, but this was more apparent at the primary than at the secondary spongiosa, suggesting that their mechanism of action is on primary spongiosa formation or breakdown. E2 alone was ineffective to augment the BMD at the femoral diaphysis; however, the diaphyseal BMD was 12-14% higher (p < 0.01) after 8 weeks of GH treatment than in pretreatment or saline-treated OVX rats and sham-operated rats, while IGF-I was less effective than GH, GH or IGF-I treatment had no effect on plasma 1,25(OH)2D3 or duodenal calbindin-D9K concentrations, but the combination of GH or IGF-I with E2 potentiated the effect of E2 to stimulate calbindin-D9K concentrations and urinary calcium excretion, indicating "hyperabsorption hypercalciuria." In conclusion, the administration of rhGH and rhIGF-I, like that of E2, into aged OVX rats prevents further loss of bone mass and strength at sites containing trabecular bone. In addition, rhGH increases cortical bone mass above pretreatment values.
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PMID:Effects of recombinant human growth hormone and insulin-like growth factor-I, with or without 17 beta-estradiol, on bone and mineral homeostasis of aged ovariectomized rats. 891 80

Both diabetes and fractures affect a large proportion of older adults. Recent cohort studies indicate that diabetes itself is associated with increased risk of fracture of the hip, proximal humerus, and foot. Observational studies and animal models suggest that decreased bone strength in diabetes may contribute to fracture risk but this remains a controversial issue. Type 1 diabetes is associated with modest reductions in bone mineral density (BMD) but type 2 diabetes is often characterized by elevated BMD. This paradox of higher BMD but increased fracture risk in type 2 diabetes may be explained by a combination of more frequent falls and poorer bone quality. Diabetes can impact bone through multiple pathways, some with contradictory effects, including obesity, changes in insulin levels, higher concentrations of advanced glycation end products in collagen, hypercalciuria associated with glycosuria, reduced renal function, lower insulin-like growth factor-I, microangiopathy, and inflammation. A better understanding of how diabetes metabolism and treatments affect bone would improve fracture prevention efforts in older diabetic adults.
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PMID:Diabetes Mellitus: Does it Affect Bone? 1451 15