HRT and Vit D in prevention of non-vertebral fractures in postmenopausal women; a 5 year randomized trial

Objectives: We investigated the incidence of new non-vertebral fractures du ring HRT or low-dose vitamin (Vit) D-3 supplementation in a 5-year prospect ive trial. Methods: A total of 464 early postmenopausal women, (a subgroup of the Kuopio Osteoporosis Study, n = 13100) were randomized to four groups : (1) HRT, a sequential combination of 2 mg estradiol valerate and 1 mg cyp roterone acetate; (2) Vit D (300 IU/day and 100 IU/day during the fifth yea r); (3) HRT + Vit D; and (4) placebo. Lumbar (L2-4) and femoral neck bone m ineral densities (BMD) were determined by dual X-ray absorptiometry (DXA) a t baseline, after 2.5 and 5 years of treatment. All new symptomatic non-ver tebral, radiographically defined fractures were recorded. Results: Altogeth er, 368 women (79%) completed the 5 year treatment. In all, 32 women had 39 non-vertebral fractures during a mean of 4.3 year follow-up (HRT 4, Vit D 10, HRT + Vit D 8 and placebo 17). The reduction in the incidence of new no n-verterbral fractures was significant in women with HRT alone (P = 0.032) when adjusted by baseline BMD and previous fractures; observed also with th e intention-to-treat principle (P = 0.048). When the HRT groups were pooled , HRT showed a significantly lower incidence of new non-vertebral fractures (P = 0.042) than women receiving placebo and also after adjusting as above (P = 0.016); both in valid-case and in the intention-to-treat analysis. In the Vit D group, the fracture incidence was non-significantly decreased (P = 0.229) in comparison with the placebo group. The estimated risk of new n on-vertebral fractures among women treated with HRT alone was 0.29 (95% CI, 0.10-0.90) and with Vit D 0.47 (95% CI, 0.20-1.14) and with HRT + Vit D 0. 44 (95% CI, 0.17-1.15), in comparison with the placebo group (adjusted by f emoral BMD and previous fractures). Conclusions: This study is the first pr ospective trial confirming the beneficial effect of HRT on prevention of pe ripheral fractures in non-osteoporotic postmenopausal women. The effect of low-dose Vit D remains to be proved. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.