Selective reduction in cortical bone mineral density in turner syndrome independent of ovarian hormone deficiency.

Women with Turner syndrome (TS) are at risk for osteoporosis from ovarian failure and possibly from haploinsufficiency for bone-related X-chromosome genes. To establish whether cortical or trabecular bone is predominantly affected, and to control for the ovarian failure, we studied forearm bone mineral density (BMD) in 41 women with TS ages 18-45 yr and in 35 age-matched women with karyotypically normal premature ovarian failure (POF). We measured BMD at the 1/3 distal radius (D-Rad(1/3); predominantly cortical bone) and at the ultradistal radius (UD-Rad; predominantly trabecular bone) by dual x-ray absorptiometry. Women with TS had lower cortical BMD compared with POF (D-Rad(1/3) Z-score = -1.5 +/- 0.8 for TS and 0.08 +/- 0.7 for POF; P < 0.0001). In contrast, the primarily trabecular UD-Rad BMD was normal in TS and not significantly different from POF (Z-score = -0.62 +/- 1.1 for TS and -0.34 +/- 1.0 for POF; P = 0.26). The difference in cortical BMD remained after adjustment for height, age of puberty, lifetime estrogen exposure, and serum 25-hydroxyvitamin D (P = 0.0013). Cortical BMD was independent of serum IGF-I and -II, PTH, and testosterone in TS. We conclude that there is a selective deficiency in forearm cortical bone in TS that appears independent of ovarian hormone exposure and is probably related to X-chromosome gene(s) haploinsufficiency.

Bone mineral density and fractures in Turner syndrome.

PURPOSE: To determine whether women with Turner syndrome who were treated with estrogen were more likely to have osteoporosis and fractures. METHODS: Areal bone density at the lumbar spine and femoral neck was measured in 40 adult women with Turner syndrome and 43 age-matched healthy women using dual-energy X-ray absorptiometry. Histories of estrogen treatment and fractures were obtained by structured personal interviews. RESULTS: Mean (+/- SD) areal bone density was significantly lower at the lumbar spine (0.87 +/- 0.11 g/cm(2) vs. 0.98 +/- 0.10 g/cm(2), P <0.001) and femoral neck (0.68 +/- 0.07 g/ cm(2) vs. 0.83 +/- 0.08 g/cm(2), P <0.001) in women with Turner syndrome than in controls. The diagnostic criterion for osteoporosis (T-score <-2.5) was met by 8 women with Turner syndrome (20%) with scores at the lumbar spine and by 3 (8%) with scores at the femoral neck. All women diagnosed with osteoporosis were less than 150 cm in height. Areal bone density correlated significantly with height (lumbar spine: R(2) = 0.3, P <0.001; femoral neck: R(2) = 0.4, P <0.001). Adjustments for skeletal size reduced the differences between the groups as well as the number of women diagnosed with osteoporosis (e.g., from 8 to 2 women based on lumbar spine scores). The prevalence and type of fractures were similar in the two groups. CONCLUSIONS: The prevalence of osteoporosis and bone fractures is not increased significantly in women with Turner syndrome who are treated with standard estrogen therapy. Women less than 150 cm in height are likely to be misdiagnosed with osteoporosis when areal bone density is measured, unless adjustments for body size are made.

The importance of estrogen replacement in young women with Turner syndrome.

BACKGROUND: Most girls with Turner syndrome (TS) need estrogen replacement treatment (ERT) to induce and maintain feminization and prevent osteoporosis. There is abundant information on ERT use in postmenopausal women, but there is little information on this issue in women with TS. We aimed to determine the level of ERT use in women with TS living in the United States and assess the effects of ERT adherence vs. nonadherence on bone mineral density (BMD). METHODS: Fifty women with TS aged 30-59 years had ERT history obtained by structured interviews and BMD assessed at the lumbar spine by dual x-ray absorptiometry (DXA) and quantitative computed tomography (QCT). RESULTS: Thirty-four of the 50 women with TS had received ERT according to current recommendations, and the rest did not either because of physician failure to prescribe (5 of 50) or because of nonadherence to prescribed ERT (11 of 50). The mean duration of ERT was 25 +/- 2 years for the standard of care group vs. 8 +/- 2 years for the others (p < 0.0001). The major factor promoting adherence to ERT was education on the importance of ERT for bone health (p < 0.001). As expected, lumbar spine BMD was significantly reduced in women not taking ERT according to current guidelines (e.g., a reduction of 20% by QCT, p < 0.001) with 6 of 16 of these women having osteoporosis and 3 of 16 having vertebral compression fractures compared with 0 of 34 in the ERT adherent group. CONCLUSIONS: Approximately 70% of women with TS in this sample of highly educated women in the United States are taking ERT as currently recommended and appear to be protected from osteoporosis of the spine, whereas those women using ERT less than 75% of the time are at grave risk for osteoporosis. In a time of new reservations about postmenopausal ERT, it is important to emphasize to young women with TS and their caregivers that ERT is critical for bone health.