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Bone health is a major lifelong concern in caring for women and girls with Turner syndrome (TS). There is an approximately 25% increase in fracture risk most of which is related to medium or high impact trauma. The long bones, especially of the forearm are predominantly affected. This fact may be due to a selective cortical bone deficiency in TS which is unrelated to hypogonadism. In addition, lack of adequate estrogen replacement can lead to trabecular bone deficiency and increase in vertebral compression fractures after age 45. Evaluation of bone density by dual X-ray absorptiometry (DEXA) is important, however, it should be used judiciously in TS in view of its inherent tendency to underestimate the bone density of people with short stature. Bone size-independent methods, such as QCT or volumetric transformation of DEXA data should be used in individuals shorter than 150 cm. Achieving optimal bone density is of critical importance for fracture prevention in TS, and should be pursued by timely introduction of hormone replacement therapy, adequate dose of estrogens during the young adult life, optimal calcium and vitamin D intake and regular physical exercise. In addition, other measures to prevent fall and trauma should be considered, including optimizing hearing and vision, avoiding contact sports and exercise to improve coordination.

Background: Many girls with Turner syndrome (TS) are treated with GH to increase adult height. In addition to promoting longitudinal bone growth, GH has effects on bone and body composition., Objective: The objective was to determine how GH treatment affects bone mineral density (BMD) and body composition in girls with TS., Method: In a cross-sectional study, we compared measures of body composition and BMD by dual energy x-ray absorptiometry, and phalangeal cortical thickness by hand radiography in 28 girls with TS who had never received GH and 39 girls who were treated with GH for at least 1 yr. All girls were participants in a National Institutes of Health (NIH) Clinical Research Center (CRC) protocol between 2001 and 2006., Results: The two groups were similar in age (12.3 yr, sd 2.9), bone age (11.5 yr, sd 2.6), and weight (42.8 kg, sd 16.6); but the GH-treated group was taller (134 vs. 137 cm, P = 0.001). The average duration of GH treatment was 4.2 (sd 3.2) yr (range 1-14 yr). After adjustment for size and bone age, there were no significant differences in BMD at L1-L4, 1/3 radius or cortical bone thickness measured at the second metacarpal. However, lean body mass percent was higher (P < 0.001), whereas body fat percent was lower (P < 0.001) in the GH-treated group. These effects were independent of estrogen exposure and were still apparent in girls that had finished GH treatment at least 1 yr previously., Conclusions: Although GH treatment has little effect on cortical or trabecular BMD in girls with TS, it is associated with increased lean body mass and reduced adiposity.

This review highlights recent developments in the detection and management of congenital heart disease and osteoporosis in patients with monosomy X, or Turner syndrome (TS). Magnetic resonance angiography (MRA) using gadolinium as a contrast agent demonstrates a higher prevalence and greater diversity of congenital cardiovascular defects than previously recognized in TS. Almost 50% of girls and women with TS have marked tortuosity or ectasia of the aortic arch, suggesting that these individuals may be at greater risk for aneurysm formation or dissection and therefore require closer monitoring. MRA also reveals that major venous anomalies are common in TS, with partial anomalous pulmonary venous return and persistent left superior vena cava each found in about 13% of patients. MR imaging even without contrast is a valuable complement to routine cardiac ultrasound in detecting abnormalities of the aortic valve. Abnormal electrocardiographic findings, including prolongation of the QTc interval, have recently been documented in many individuals with TS. Conduction and repolarization abnormalities have not been associated with congenital anatomic defects and are as common in young girls as adults. The clinical significance of these electrophysiological findings is unknown at present, but attention to the ECG in TS is important, particularly in monitoring the QTc when prescribing drugs associated with QT prolongation. Patients with TS are at high risk for osteoporosis as a result of premature ovarian failure and intrinsic bone abnormalities specific to the syndrome. Low cortical bone mineral density (BMD) is apparent in prepubertal girls, and it remains low in adults, independent of estrogen treatment and other hormonal factors. The low mineralization of cortical bone in TS may be associated with a small increased fracture risk, but no treatments are known to increase cortical bone mineral content in TS. Trabecular BMD is normal in TS women who have received continuous estrogen treatment from their mid-teens, although areal densitometry scores may be misleadingly low in very small patients. However, young women with ovarian failure who have not received estrogen treatment for extended periods of time are at high risk for osteoporosis of trabecular bone of the spine, with associated compression fractures and height loss. Therefore, judicious management of estrogen therapy to prevent osteoporosis while minimizing estrogen-associated adverse events is a challenging aspect of care for girls and women with TS.

In a previous report, preliminary data showed a significant reduction in cortical bone mineral density (BMD) in women with Turner syndrome that had been treated with GH compared with women with Turner syndrome that had not been treated. To clarify this point, we have investigated the effects of GH treatment at multiple sites in this case-control, cross-sectional study. There were 23 women per group, who were similar in age, height, body mass index, estrogen use, and ethnic makeup. Median age (range) at start and duration of GH treatment was 9 (3-17) and 5 (2-9) yr, respectively. GH-treated women had a slightly greater ( approximately 8%, P = 0.03) width of the radial shaft, but otherwise there were no significant differences between groups in bone dimensions or BMD at the distal radius, lumbar spine, or femoral neck. Furthermore, regression analysis in a linear model including independent variables of age, age at diagnosis, body mass index, presence of spontaneous puberty, and GH use confirmed that GH use did not contribute to variation in BMD.

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.

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.