Dosage of estradiol, bone and body composition in Turner syndrome: a 5-year randomized controlled clinical trial.

OBJECTIVE: Reduced bone mineral density (BMD) is seen in Turner syndrome (TS) with an increased risk of fractures, and body composition is characterized by increased body fat and decreased lean body mass. To evaluate the effect of two different doses of oral 17B-estradiol in young TS women on bone mineral density (BMD), biochemical markers of bone turnover and body composition with the hypothesis of a positive effect of the higher dose. DESIGN: A double-blind 5-year randomized controlled clinical trial. 20 young TS women participated. Inclusion criteria were diagnosis of TS, age 15-25 years and current treatment with 2 mg oral estradiol daily. METHODS: The low-dose (LD) group was administered 2 mg 17B-estradiol/day orally and placebo, the high-dose (HD) group was administered 2 + 2 mg 17B-estradiol/day orally. Main outcome measures were whole body and regional bone mineral density (BMD), lean body mass (LBM), fat mass (FM) measured yearly by DXA scan and resorptive and formative bone markers in serum. RESULTS: BMD, whole body and regional, increased over time with an attenuation toward the end of the study, and bone turnover markers decreased over time, both with no differences between the treatment groups (P = 0.2-0.9). LBM increased significantly more in the HD group (P = 0.02). FM remained stable in both groups. CONCLUSIONS: A steady increase in BMD over time in TS was found similar to healthy young women. The higher estrogen dose did not differentially affect BMD or bone markers. The positive effect on body composition may have long-ranging health benefits in TS.

Normal tempo of bone formation in Turner syndrome despite signs of accelerated bone resorption.

AIMS: To evaluate area bone mineral density (aBMD) and volumetric BMD (vBMD) by dual-energy X-ray absorptiometry, and relations to bone markers and hormones in adolescent women with Turner syndrome (TS). METHODS: Cross-sectional study in TS patients (n = 37, 16.7 ± 3.4 years) and control group (n = 49), assessed by dual-energy X-ray absorptiometry, bone markers and hormones. TS patients were divided into a young group receiving ('ongoing') GH (n = 15) and an older group previously receiving ('previous') GH (n = 22). RESULTS: vBMD(spine) was similar in 'ongoing GH' TS, but higher in 'previous GH' TS, compared to controls. vBMD(hip) was lower in 'ongoing GH' TS, but similar in 'previous GH'. z scores for aBMD were uniformly reduced in 'ongoing TS', but near-normalized in 'previous GH' TS. Bone formation and resorption markers were increased in 'ongoing GH' TS, while 'previous GH' TS had elevated bone resorption markers. CONCLUSION: BMD increased in parallel with age in TS patients receiving optimal estradiol replacement therapy and GH according to consensus guidelines, and in controls. Young TS undergoing pubertal induction and still receiving GH have lower z score BMD than older TS patients receiving hormonal replacement therapy, where a near-normalization of BMD was achieved. TS patients previously receiving GH showed signs of increased bone resorption.