Vitamin D is ineffective in prevention of osteoporosis in postmenopausal women

Abstract

The effects of vitamin D (VitD) and estrogen therapy (HRT) on bone mineral density (BMD) were studied in postmenopausal women in a 2.5 year follow-up. The study population was a subgroup of the Kuopio Osteoporosis Study(n=13100). 464 women (mean age 52.7• mean duration of menopause 1.1• yr) were randomized into 4 groups: I.HRT; a sequential combination: 2mg E 2 valerate and img cyproterone acetate (E2V/CPA) (=Climen R) n=83; 2.VitD(cholecalsiferol 3001U/day;not June-August) n=104; 3. E;V/CPA +VitD n=92; 4. Calcium lactate (93mg Ca 2.) as a placebo n=109. Spinal (L2-4) and femoral neck BMD were determined by dual X-ray absorptiometry (DXA) before and after 2.5 years' treatment. Student's T-test for paired data was used. The groups were statistically equal at the baseline.After 2.5 years, lumbar BMD had increased by 1.7% in the E2V/CPA (p=0.000) and by 1.3% in the E2V/CPA +VitD group (p=0.002), Lumbar BMD decreased by -3.5% in the VitD (p=0.000) and by -3.7% in the placebo group (p=0.000). Femoral BMD decreased by -2.5% in the VitD (p=0.000) and by -3.7% in the placebo group (p=0.000) but, the decrease was non-significant in the E2V/CPA and E2V/CPA +VitD groups.Our results confirm the beneficial effect of HRT On spinal BMD. Vitamin D appears to be ineffective in prevention of osteoporosis in postmenopausal women and HRT and vitamin D is not more effective than HRT alone.Several attempts have been undertaken in the past, to design antagonists of PTH and PTHrP. Here we describe a novel type of antagonists based on position-10-modified analogues of hPTHrP. /n vitro, SDZ 161 (Naphthyl(2)-acetyl-[3-naphthyl(2)-alanine1~ SDZ 162 (Naphthyl(2)acetyl-[3-naphthyl(2)-alaninet~ )-NHs) and SDZ 219 (Succinyl-[phes, naphthyl(2)-alanine~~ inhibited binding of [r~I-Tyr'~JchPTHrP-(1-36)-NH2 in OK-1 cells with pKo values of 8.3, 7.9 and 8.4, respectively. The analogues were devoid of intrinsic activity on adenylate cyclase in vitro. They were full competitive antagonists versus hPTH-(1-34)-stimulated cAMP production in UMR-t 06-06 cells with pA~ values of 10.3, 9.7, and 9.3, respectively. In vivo, infusion of the antagonists alone (45 nmolkg 4 h -1) for 4 h had no effect on urinary phosphate (Pi) and cAMP excretion nor on plasma calcium levels in TPTX rats. When hPTH-1 1 (1-34) (0.9 nmol kg h, for 4 h) and the respective antagonist (45 nmol kg 1 h -1 for 5 h, starting 1 h before the agonist) were infused i.v., SDZ 161 and SDZ 219 blocked PTH mediated increases of Pj and cAMP completely for about 2 h, thereafter only partially. Under the same experimental conditions, rryr~]bPTH-(7-34)-NH=, which had been described as a potent PTH antagonist in vivo (Hoduchi N et el. (1983), Science, 220:1053-1055"), or SDZ 162 showed only minimal inhibition of PTH-mediated responses. Conclusion: SDZ 161 and SDZ 219 are very potent PTH antagonists in vitro. In vivo, they are devoid of intrinsic activity and able to inhibit PTH-mediated effects in the kidney. Although being considerably more potent as antagonists than [Tyr~bPTH-(7-34)-NH=, they failed ...