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Objective: To determine the effects of HRT with or without clodronate on bone mineral density (BMD) change and bone turnover markers., Design: Prospective, partly randomized trial., Setting: Kuopio University Hospital, Finland., Population: 167 osteoporotic women (61+/-2.7 years; T-score

Objectives: Bone mineral density (BMD) and development of osteoporosis are partly determined by genetic factors. The associations between one of suggested candidate, apolipoprotein E (apo E) genotype to bone mineral density (BMD) and bone biochemical markers was studied in 464 subjects recruited from a population-based group of early postmenopausal women (n = 13100). Additionally, the influence of apo E genotype on BMD changes during a 5-year follow-up with or without hormone replacement therapy (HRT) was investigated., Methods: Participants were randomized into two treatment groups: HRT group: Sequential combination of 2 mg estradiol valerate and 1 mg cyproterone acetate with or without vitamin D3, 100-300 IU/day + calcium lactate, 500 mg/day (n = 232), and the non-HRT group: Calcium lactate, 500 mg/day alone or in combination with vitamin D3, 100-300 IU/day (n = 232). BMD was measured from the lumbar spine and proximal femur at baseline and after 5 years of treatment (n = 352). In a subgroup (n = 59), the serum concentrations of bone biochemical markers (intact osteocalcin (OC), bone-specific alkaline phosphatase (BAP) and type I collagen carboxy-terminal telopeptide (ICTP)) were measured at baseline and after 1 year of follow-up., Results: At baseline, the BMDs were similar between the five apo E genotype groups (2/3, 2/4, 3/3, 3/4, 4/4). No significant differences in lumbar or femoral neck BMDs of women with the apo E4 allele were found compared with those without it. There was a statistically significant difference in 5-year BMD changes between the HRT and non-HRT groups. After 5 years, the BMD of the femoral neck had remained constant and the mean lumbar spine BMD had increased by 1.5% in the HRT group, whereas both BMDs had decreased by 4-5% in the non-HRT group. However, the apo E genotype did not modify the changes in BMD in either group. Additionally, the baseline concentrations of bone metabolic markers and their 1-year changes showed no genotype-related associations., Conclusions: The results of our population-based study indicate that apo E genotype does not modify lumbar or femoral neck BMDs or serum bone biochemical markers or their response to HRT in early postmenopausal Caucasian women.

Objectives: 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.

Objectives: Oxidative modification of low-density lipoprotein (oxLDL) has been suggested to play an important role in the pathogenesis of atherosclerosis, and autoantibodies against oxLDL have recently found to reflect this process. The antioxidant effect and inhibition of LDL oxidation may be one of the cardioprotective mechanisms of postmenopausal estrogen therapy., Methods: The effects of postmenopausal hormone replacement therapy (HRT) on the concentrations of serum lipids and oxLDL autoantibodies were studied in a population-based prospective 1-year study with 64 early postmenopausal women (mean age 52.2 +/- 0.4 (S.E.M.) years). The participants were randomized into two treatment groups: HRT-group: Sequential combination of 2 mg estradiol valerate and 1 mg cyproterone acetate alone or in combination with vitamin D3, 300 IU/day + calcium lactate, 500 mg/day (n = 31) and the non-HRT-group: Calcium lactate, 500 mg/day alone or in combination with vitamin D3, 300 IU/day (n = 33). The groups were well matched regarding age, body mass index and baseline serum lipid concentrations., Results: The serum concentrations of total cholesterol and LDL-cholesterol decreased in the HRT-group (4.1%, P = 0.05 and 6.4%, P = 0.03, respectively, paired t-test) but did not change in the non-HRT-group. No changes in the serum concentrations of HDL-cholesterol or triglycerides were observed. Additionally, no changes in oxLDL autoantibody concentrations were observed in either group., Conclusions: Although 1-year HRT lowered serum total- and LDL-cholesterol levels, it did not influence oxLDL antibody titers. On the basis of the present results we cannot question the possibility of there being beneficial effects of HRT on the oxidative modification of LDL. However, this effect is not reflected in the levels of oxLDL autoantibodies.