Nicole De Wolf

Effect of strontium on PTHrP, OPG and RANKL mRNA expression in osteoblastic like cells UMR 106.1

Long-term aromatase inhibitors use causes bone loss and increase fracture risk secondary to induced estrogen deficiency. We postulated that alfacalcidol (vitamin D3 analog) could prevent the letrozole induced bone mineral loss. Fifty intact 1 month old female rats were randomly divided into five groups with 10 rat each; basal group (B) was sacrificed at start of the experiment; age matched control group (C); letrozole group (L) oral administration of 2 mg/kg per day; alfacalcidol group (A): oral administration of 0.1 ug/kg per day; group L+A: letrozole 2 mg/kg + Alfacalcidol 0.1 ug/kg per day for a period of 8 weeks. When animal sacrificed, serum estrone (E1), estradiol (E2), testosterone (T), LH, FSH, IGF-1 were measured and femoral bone mineral density were scanned by DEXA. Data was analyzed by One-Way ANOVA with group comparison. Eight weeks administration of Letrozole resulted in a significant increase in body weight, tibial and femoral bone length and a significant decrease in the ovary+utrus horn weight as compared to the non-treated groups with or without alfacalcidol. Letrozole administration increased serum T, LH, FSH, IGF-1 and suppressed E1 and E2 significantly. None of those parameters were affected by Alfacalcidol treatment. The result of DEXA shows that Letrozole increased femoral bone area (1.8±0.09cm vs C; 1.64±0.07cm (mean±S.D.), P<0.05) without a significant effect on the bone mineral content (0.39±0.02g vs C; 0.38±0.02g). Therefore, the BMD (217.8±4.4mg/cm) was significantly lower than that of the control group (229.8±4.9mg/cm, P<0.05). Alfacalcidol increased the bone area (1.78±0.07cm, P<0.05), bone mineral content (0.44±0.03g, P<0.05) and BMD (249.8±5.9mg/cm, P<0.05) as compared to the C group. L+A combine intervention resulted in a significant increase in the bone area (1.91±0.09cm, P<0.05 vs C, L and A groups), bone mineral content (0.46±0.03g, P<0.05 vs C and L groups) and BMD (236.8±8.0mg/cm, P<0.05 vs C and L groups). This study demonstrates that Letrozole treatment to the young growing female rats enhances body weight and bone elongation due to elevation of both T and IGF-I with the suppression of E1 and E2. However, the bone density decreased significantly. We believe that Letrozole induced reduction in BMD was secondary to increase bone volume without corresponding increase in mineral deposition. Increased mineral deposition to the growing bone by Alfacalcidol demonstrates that it has theraputical value in preventing Letrozole induced bone osteopenia.

Cationized serum albumin enhances basal and stimulated adenylate cyclase activity in canine renal membranes

We examined the effects of cationized serum albumin on the canine renal membrane adenylate cyclase in the basal state and when stimulated with guanylyl-imidodiphosphate, PTH or NaF. Human albumin was cationized to an isoelectric point greater than 9.5 by the addition of hexamethylene diamine. Cationized albumin increased basal and stimulated cAMP production by the membranes and increased the sensitivity of the system to low doses of PTH (0.25 pmol/l), being usually inactive in buffer alone or in human serum albumin. These observations are comparable to those previously reported on thyroid membranes and cells from adrenal tumours and confirm that positively charged macromolecules can increase adenylate cyclase activity. A decrease in non-specific binding of PTH is only partly responsible for the increased sensitivity to the hormone. Though this increase in sensitivity is small, it could nevertheless be useful in the detection of biologically active PTH after extraction from the serum.