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Objective: To investigate the effects of compound nylestriol tablet (CNT), containing nylestriol and levonorgestrel with a ratio of 1:0.3) and its components on the osteoporotic rat model induced by retinoic acid (RA) and ovariectomy (OVX)., Methods: We randomly divided 144 female SD rats (aged 7-month-old) into 12 groups (12 in each). In addition, 120 female SD rats aged 4-month were randomly divided into 10 groups (10 in each). Three dosage levels of CNT (0.039, 0.117 and 0.39 mg/kg body weight, daily), nylestriol (NYL, 0.30, 0.09 and 0.03 mg/kg body weight, daily) and levonorgestrel (LEV, 0.09, 0.027 and 0.009 mg/kg body weight, daily) were designed to prevent the bone loss of the osteoporotic rat model induced by RA and OVX respectively. Serum total calcium (Ca), phosphate (Pi), ALP, triglyceride (TG), total cholesterol (TC), HDL-C, total body BMD, isolated left femoral BMD and femoral Ca, and Pi after ashing were determined., Results: Osteoporotic models could be induced by RA (70 mg/kg body weightdaily given intragastrically for 14 days) or by ovariectomy; CNT and its components had the preventive effects on bone loss in both models; The preventive effect of CNT was dose-dependent and stronger than its components; Many observed markers showed us the levels of high and moderate CNT given to be the strongest, corresponding to an optimal choice of the moderate dose CNT about one tablet per week in adult women., Conclusions: CNT therapy can prevent the bone loss of RA-induced and OVX-induced osteoporotic rats, and its therapeutic and preventive effect is better than its components used alone.

Objective: To study the effects of progesterone (P) and 18-methyl levonorgestrel (LNG) on the expression of P receptors (PRA and PRB), c-fos, c-jun, and osteocalcin in the human osteosarcoma cell line MG-63 and human normal osteoblasts in order to understand the mechanism of progestin action on the proliferation and differentiation of osteoblasts., Methods: Cell proliferation was tested by MTT assay. The expression of PR, c-fos, c-jun, and osteocalcin was measured by semi-quantitative RT-PCR, Western immunoblot or immunocytochemistry., Results: Progesterone and LNG (10(-10)-10(-6)M) stimulated cell proliferation in a dose-dependent manner. Progesterone and LNG did not affect the expression of PRA and PRB mRNA and protein, but c-fos and c-jun mRNA and protein were upregulated in a dose-dependent manner. The expression of osteocalcin mRNA was also increased in human osteoblasts in a dose and time-dependent manner with greater effects of LNG than P, while the expression of osteocalcin mRNA in MG-63 cells was not changed by P or LNG., Conclusion: Progesterone and LNG promote osteocalcin gene transcription by stimulating the expression of c-fos and c-jun, and result in osteoblast proliferation and differentiation.

Objective: Recently our studies have shown that nylestriol in combination with levonorgestrel prevented bone loss, decreased bone turnover rate and increased the maximal loading of bone without obvious side effects in retinoic acid (RA) induced osteoporotic rats. In addition to the animal experiments, we evaluate the effect of Compound Nylestriol Tablet (CNT) on bone mineral density (BMD) in women with postmenopausal osteoporosis. Compound Nylestriol Tablet, which contains 0.5 mg of nylestriol (cyclopentylethinyl estriol) and 0.15 mg of levonorgestrel per tablet, was authorized as a new anti-osteoporotic agent for clinical trial in postmenopausal osteoporosis., Methods: One year's clinical observation was performed in 191 eligible patients who were randomly divided into two groups (A and B). In group A, 119 patients were treated for one year with CNT (one tablet per week) and in group B, 72 patients with placebo. Bone mineral density of lumbar antero-posterior spine (L1-L4), lateral spine, total hip and total forearm positions including radius+ulna at the ultra distal areas, mid areas, and one-third areas, were measured before and after treatment. Biochemical parameters and effects of CNT on uterus, and breast were observed., Results: We found that patients treated with CNT had a significant decrease of bone loss in total forearm, including radius+ulna at the ultra distal, mid, and 1/3 areas compared with control subjects (all P < 0.05). An improved BMD tendency could be seen at the lumbar spine. There were no differences in the observed biochemical variables. No side-effects on uterus, or mammary glands observed. None of the patients had uterine bleeding or vertebral fractures during one year's CNT treatment., Conclusion: These data suggested that CNT is effective, safe and convenient in treating postmenopausal osteoporosis.

Objective. To determine an optimal dosage combination for a nylestriol/levonorgestrel (NYL/LNG) regimen in the treatment of female Sprague-Dawley (SD) rats with retinoic acid (RA)-induced osteoporosis in order to examine the rationale of NYL/LNG use for postmenopausal women. Methods: This study included two sets of experiments; one was designed to confirm the success of the RA-induced osteoporosis model involving 48 SD rats, and the other to determine the optimal dosage combination of NYL/LNG. In the second set of experiments, a total of 160 female SD rats at 7 months of age were randomly divided according to their basal body weights into 16 groups (10 in each). Treatment dosages of NYL and LNG were arrayed in a 2 factor-4 level (2[sup 4]) factorial design, i.e., NYL level I (N1 0.015 mg/kg), level II (N2 0.05 mg/kg), level III (N3 0.15 mg/kg) and level IV (N4 0.5 mg/kg) and LNG level I (L1 0.005 mg/kg), level II (L2 0.015 mg/kg), level III (L3 0.05 mg/kg) and level IV (L4 0.15 mg/kg). For 14 d, 70 mg/kg/d RA was given intragastrically to establish the osteoporofic model and NYL and LNG were then administered in different dosages on alternate days over a 3 wk period. Subsequently, body weight, uterine weight, endometrial status, Bone mineral density (BMD), bone turnover, and morphometry as well as parameters of biomechanics, serum sex hormones and lipids and estrogen receptor-α expression were determined for these rats. Results. Uterine weights at L2, L3, and L4 dosage levels were significantly lower than those at L1 (P < 0.05). Serum estradiol at N4 and progesterone at N2, N3, and N4 had decreased. Bone mineral density at distal tibiae (R5) in L3 and L4, and at proximal femora (R3) in L4 had increased. The peak loading of lumbar vertebrae at N3 was higher than that at N1, N2, and N4 dosage levels and that of femora higher at N3 than that at N1 and N4. Serum alkaline phosphatase (ALP) levels at N3, N4, L2, L3, and L4 dosage levels were lower than those at... [ABSTRACT FROM AUTHOR]