Identification of early postmenopausal women with no bone response to HRT:Results of a five-year clinical trial

Hormone replacement therapy (HRT) prevents postmenopausal bone loss and fra ctures. However, the occurrence of women with no bone response to HRT has n ot been widely examined. We identified the densitometric nonresponders to l ong-term HRT and investigated some characteristics and biochemical variable s as possible predictors of densitometric nonresponse in postmenopausal wom en. The study population was a subsample of the Kuopio Osteoporosis Study ( n = 14 220. A total of 464 early postmenopausal women were randomized into four treatment groups: (1) HRT (sequential combination of 2 mg estradiol va lerate and 1 mg cyproterone acetate); (2) vitamin D-3; (3) HRT + Vitamin D- 3 combined; and (4) placebo. In this study, the data from HRT and placebo g roups were analyzed. Lumbar (L2-4) and femoral neck bone mineral density (B MD) were determined by dual-energy X-ray absorptiometry (DXA) at baseline a nd after 5 years of treatment. A densitometric nonresponder was defined as a woman whose 5-year BMD change was similar to the mean BMD change (+ 95% C I) of the placebo group or worse. Altogether, 74 women in the HRT group and 104 women in the placebo group complied with the treatment. According to s pinal BMD analysis, 11% of the women were classified as densitometric nonre sponders; the corresponding proportion for femoral BMD analysis was 26%. Bo th smoking (p = 0.003) and low body weight (P = 0.028) were significant ris k factors for densitometric nonresponse to HRT. After 6 months of treatment the densitometric nonresponders (hip) had a significantly higher mean seru m follicle stimulating hormone (FSH) level (p = 0.038) and lower increases in serum estradiol levels (p = 0.006) than the densitometric responders. Th e mean changes in serum FSH and alkaline phosphatase levels were significan tly lower among the densitometric nonresponders (spine) than responders (p = 0.043 and 0.017, respectively). In conclusion, this prospective study sho ws that especially current smokers and women with low body weight are at in creased risk of poor bone response to HRT. Repeated serum FSH, estradiol an d alkaline phosphatase measurements during the first months of long-term HR T may be helpful in identifying the women with no bone response to HRT.