Bone mineral density and fractures in Turner syndrome

doi:10.1016/S0002-9343(03)00364-4

The American Journal of Medicine

Volume 115, Issue 4, September 2003, Pages 259-264

https://doi.org/10.1016/S0002-9343(03)00364-4 Get rights and content

Abstract

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/cm² vs. 0.98 ± 0.10 g/cm², P <0.001) and femoral neck (0.68 ± 0.07 g/ cm² vs. 0.83 ± 0.08 g/cm², 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: R² = 0.3, P <0.001; femoral neck: R² = 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.

Conclusion

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.

Section snippets

Subjects

Study subjects comprised 40 women with Turner syndrome who were participants in an observational study of genotype and phenotype interaction that was conducted at the National Institute of Child Health and Human Development and approved by the Institutional Review Board. Participants were recruited through nationwide advertising. Women with known causes of osteoporosis or bone disease, or prior use of medications known to affect bone density, were excluded. Most women had been diagnosed at or

Results

Women with Turner syndrome were similar in age to controls (mean [± SD], 34 ± 11 years vs. 32 ± 8 years, P = 0.55). However, they were shorter (146 ± 7 cm vs. 164 ± 6 cm, P <0.0001) and had a higher body mass index (median [range], 26 [18 to 43] years vs. 23 [18-31] years, P = 0.002). The karyotypes in women with Turner syndrome were similar to those reported previously (24). These women had timely diagnoses and reported a high compliance rate with estrogen therapy; 39 of the 40 women took

Discussion

In our study of bone density in women with Turner syndrome who had undergone estrogen therapy and age-matched, healthy controls, uncorrected areal bone density measurements suggested that lumbar spine areal bone density was significantly lower, and osteoporosis was significantly more common, in women with Turner syndrome. However, these values were influenced by height and bone size, with the shortest women with Turner syndrome subject to misdiagnosis. Correction of areal bone mineral density

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There is no need to measure bone mineral density during childhood or adolescence unless there is an unusual clinical concern-for example, a low-impact or atraumatic fracture. Short stature is associated with the underestimation of bone mineral density obtained by DXA and results need to be normalized for bone size [113]. Size-adjusted vertebral bone mineral density is usually normal in adults with Turner syndrome that have received routine hormone replacement treatment, but it may decline dramatically with the discontinuation of treatment [114].
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However, for young premenopausal women, bone mass should preferably assessed by Z-score, which is a comparison to the age- and gender-matched normal, with a Z-score ≤ -2.0 defining the low threshold for bone mass [22]. It also must be considered that dual-energy x-ray absorptiometry (DXA), which is used for the BMD estimation, assess the area rather than the volume, thus underestimating BMD for individuals shorter than 150 cm, unless adjustments for body size are made [23]. The prevalence of osteopenia/osteoporosis among these women is estimated to be around 5564%, according to two large cohort studies [24,25].
Turner syndrome is one of the most common sex chromosomal anomalies, characterized by the complete or partial loss of one X chromosome. Females with Turner syndrome are characterized by skeletal abnormalities, short stature and primary ovarian insufficiency. The aim of this narrative review was to identify the underlying mechanisms of osteoporosis in Turner syndrome, summarize its clinical manifestations and provide suggestions regarding the management of osteoporosis. Girls and women with Turner syndrome have lower bone mineral density and a higher fracture rate than healthy individuals. The most important risk factors for osteoporosis are inadequately treated primary ovarian insufficiency, followed by intrinsic bone abnormalities. Comorbidities that further increase the risk of osteoporosis include vitamin D deficiency, celiac disease and inflammatory bowel disease. In addition, hearing problems can predispose to falls. Early initiation of hormone replacement therapy (HRT) at the age of 11-13 years, prompt titration to the adult dose after 2 years and long-term follow-up to ensure compliance with HRT are the cornerstones of osteoporosis prevention in women with Turner syndrome.
The Efficacy of Long-Term Estrogen Replacement Therapy in Turner Syndrome Women with Premature Ovarian Insufficiency
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To evaluate the efficacy of long-term estrogen replacement therapy (ERT) in uterine development and bone mineral density (BMD) of Turner syndrome (TS) women with premature ovarian insufficiency (POI).
Retrospective study.
Thirty-seven TS women grouped according to ovarian function status: TS women with POI (n = 32), aged 11-26 years, and those with intact ovarian function (IOF; n = 5), aged 13-17 years. TS women with POI underwent ERT.
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In TS women with POI, uterine length, AP fundal diameter, and BMD significantly increased after ERT (P < .001). TS women with POI were subdivided into classic (n = 11) and variant (n = 21) types, and there were no significant differences in uterine development and BMD according to types of chromosome. After receiving ERT, AP fundal diameter was significantly longer in classic TS women (P = .034) compared with those with variant type.
Long-term ERT increased uterine length (before: 4.4 cm; after: 7.2 cm) and AP fundal diameter (before: 0.9 cm; after: 2.4 cm), and improved BMD in TS women with POI. After ERT, in TS women with POI, uterine length, BMD at lumbar 2-4 and femoral neck were similar to those of TS women with IOF. Therefore, TS women with POI can catch up to those with IOF by receiving ERT.
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Primary ovarian insufficiency (POI) is a rare but important cause of ovarian hormone deficiency and infertility in women. In addition to causing infertility, POI is associated with multiple health risks, including bothersome menopausal symptoms, decreased bone density and increased risk of fractures, early progression of cardiovascular disease, psychologic impact that may include depression, anxiety, and decreased perceived psychosocial support, potential early decline in cognition, and dry eye syndrome. Appropriate hormone replacement therapy (HRT) to replace premenopausal levels of ovarian sex steroids is paramount to increasing quality of life for women with POI and ameliorating associated health risks. In this review, we discuss POI and complications associated with this disorder, as well as safe and effective HRT options. To decrease morbidity associated with POI, we recommend using HRT formulations that most closely mimic normal ovarian hormone production and continuing HRT until the normal age of natural menopause, ∼50 years. We address special populations of women with POI, including women with Turner syndrome, women with increased risk of breast or ovarian cancer, women approaching the age of natural menopause, and breastfeeding women.
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Clinical studyBone mineral density and fractures in Turner syndrome

Abstract

Purpose

Methods

Results

Conclusion

Section snippets

Subjects

Results

Discussion

Growth Horm IGF Res

Fertil Steril

J Clin Epidemiol

Fertil Steril

A useful radiologic sign for the diagnosis of Turner's syndrome

Pediatrics

Turner syndrome and osteoporosismechanisms and prognosis

Pediatrics

Pseudoautosomal deletions encompassing a novel homeobox gene cause growth failure in idiopathic short-stature and Turner syndrome

Nat Genet

The Leri-Weill and Turner syndrome homeobox gene SHOX encodes a cell-type specific transcriptional activator

Hum Mol Genet

The short-stature homeobox gene SHOX is involved in skeletal abnormalities in Turner syndrome

Hum Mol Genet

Phenotypes associated with SHOX deficiency

J Clin Endocrinol Metab

Skeletal size and bone mineral content in Turner's syndromerelation to karyotype, estrogen treatment, physical fitness, and bone turnover

Calcif Tissue Int

Osteoporosis in Turner's syndrome and other forms of primary amenorrhoea

Clin Endocrinol (Oxf)

Bone mineral density in middle-aged women with Turner's syndrome

Eur J Endocrinol

Osteoporosis and fractures in Turner syndrome-importance of growth promoting and oestrogen therapy

Clin Endocrinol (Oxf)

Clinical study
Bone mineral density and fractures in Turner syndrome