LOW BONE MASS IS COMMON AND ASSOCIATED WITH DELAYED ESTROGEN REPLACEMENT THERAPY IN ADULT BRAZILIAN WOMEN WITH TURNER SYNDROME

Available online 15 October 2025, 101635

Author links open overlay panel, , , , , , , , ABSTRACTIntroduction

Turner syndrome is a rare chromosomal abnormality in females who typically present with short stature, hypogonadism and increased risk of osteoporosis. Areal bone densitometry (aBMD) usually underestimates bone mass in people with short stature and the bone mineral apparent density (BMAD) can be used as an adjustment for height. The study aimed to assess the frequency of low bone mass and associated factors in Brazilian women with TS at a referral center.

Methodology

Cross-sectional dual-energy X-ray absorptiometry scans at the lumbar spine and femur were performed to assess bone mass. The association of aBMD, BMAD, age, height, history of fractures, karyotype, use of somatropin (rhGH) and estrogen replacement therapy (ERT) with low bone mass was tested and p-value < 0.05 was considered statistically significant.

Results

Forty-six patients with a mean age of 32 years and height (SDS) 145 cm (-2.89) were evaluated. Five (11%) had a history of fracture. Thirty-five (83%) patients had delayed puberty (> 13 years), 4 (9%) had spontaneous menarche, 19 (41%) were treated with rhGH. Lumbar aBMD was positively correlated to height (p = 0.010). Low bone mass was more frequently detected with aBMD (49% lumbar spine and 48% femoral neck) than with BMAD (31% lumbar spine and 13% femoral neck) and was associated with estrogen status (p=0,002). All patients with delayed puberty and without ERT at the time of the study had low bone mass at the lumbar spine. In contrast, all patients with spontaneous menarche had normal bone mass at both sites. No significant correlation between treatment with rhGH or karyotype with low bone mass was observed.

Conclusions

Low bone mass is a common finding in a cohort of Brazilian women with TS and is associated with delayed puberal induction or start of ERT. Our results highlight the importance of early diagnosis and prompt initiation of ERT to optimise bone mass acquisition.

Section snippetsINTRODUCTION

Turner Syndrome (TS) is a rare disorder caused by partial or complete loss of one X-chromosome that affects up to 1/2,500 live birth females. Short stature and ovarian insufficiency are the most common TS features. The clinical presentation is variable and with no definitive phenotype-genotype association. In many countries, TS is often diagnosed late, with an average age of 15 years. Delay in diagnosis hinders the early detection of TS comorbidities and timely implementation of age-relevant

MATERIALS AND METHODS

A cross-sectional study assessed lumbar and femoral aBMD and BMAD in adult women with TS. Participants were recruited during routine medical visits to a TS outpatient clinic at a university hospital in Fortaleza, Brazil. Inclusion criteria included: TS diagnosis confirmed by karyotype; age over 20 years; no comorbidities or medical therapies that affect bone mass (e.g., use of corticosteroids, hyperthyroidism, celiac disease, inflammatory bowel disease, or hyperparathyroidism); and ability to

RESULTS

Of the 50 patients recruited between September 2020 and June 2023, four were excluded for various reasons: two for psychiatric disorders or intellectual disability, one for coeliac disease, and one for active hyperthyroidism. Clinical, biochemical and radiological data of 46 patients with TS are presented in Table 1.

The mean age at first visit to the specialty referral center was 19 ± 11 years. The mean age at time of karyotype was 22.1 ± 13 years, at which the diagnosis of TS was established.

DISCUSSION

The present study evaluated aBMD and BMAD, as well as the factors associated with low bone mass in Brazilian adult women with TS. The mean age at the first clinical visit and at karyotype confirmation were 19 years and 22 years, respectively, reflecting a late referral to specialized care and diagnosis. Early diagnosis remains a global challenge and a priority in current guidelines1. Phenotypic variability and clinical heterogeneity may contribute to diagnostic difficulties. Timely

CONCLUSIONS

Low bone mass is a common finding in a cohort of Brazilian women with TS from a referral center and is associated with delayed pubertal induction. BMAD analysis is more suitable than aBMD for assessing bone mass in individuals with TS as it does not vary with height and avoids over-diagnosis of low bone mass in individuals who are less than 150 cm tall. Our results highlight the importance of the early diagnosis and prompt pubertal induction to optimise bone mass acquisition in this population.

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