title: HRT and Vit D in prevention of non-vertebral fractures in postmenopausal women; a 5 year randomized trial.
abstract: OBJECTIVE
  We investigated the incidence of new non-vertebral fractures during HRT or low-dose vitamin (Vit) D3 supplementation in a 5-year prospective trial.
  
  
  METHODS
  A total of 464 early postmenopausal women, (a subgroup of the Kuopio Osteoporosis Study, n = 13,100) were randomized to four groups: (1) HRT, a sequential combination of 2 mg estradiol valerate and 1 mg cyproterone acetate; (2) Vit D (300 IU/day and 100 IU/day during the fifth years); (3) HRT + Vit D; and (4) placebo. Lumbar (L2-4) and femoral neck bone mineral densities (BMD) were determined by dual X-ray absorptiometry (DXA) at baseline, after 2.5 and 5 years of treatment. All new symptomatic non-vertebral, radiographically defined fractures were recorded.
  
  
  RESULTS
  Altogether, 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 non-vertebral fractures was significant in women with HRT alone (P = 0.032) when adjusted by baseline BMD and previous fractures; observed also with the 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 non-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 femoral BMD and previous fractures).
  
  
  CONCLUSIONS
  This study is the first prospective trial confirming the beneficial effect of HRT on prevention of peripheral fractures in non-osteoporotic postmenopausal women. The effect of low-dose Vit D remains to be proved.
authors: Department of Obstetrics and Gynecology, Kuopio University Hospital, Finland. mkomulai@uku.fi
authors: M H
authors: MH
authors: Komulainen
authors: H
authors: H
authors: Kröger
authors: M T
authors: MT
authors: Tuppurainen
authors: A M
authors: AM
authors: Heikkinen
authors: E
authors: E
authors: Alhava
authors: R
authors: R
authors: Honkanen
authors: S
authors: S
authors: Saarikoski
mesh_terms: D015519:Bone Density; D005260:Female; D050723:Fractures, Bone / Q000517:prevention & control*; D020249:Hormone Replacement Therapy; D006801:Humans; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000517:prevention & control*; D011446:Prospective Studies; D016896:Treatment Outcome; D014807:Vitamin D / Q000627:therapeutic use*
chemical_list: D014807:Vitamin D