STRUCTURED ABSTRACT
BACKGROUND
Turner syndrome (TS) is caused by partial/complete X-chromosome monosomy with variable
phenotypes, characterized by hypogonadism and short stature. To achieve pubertal changes,
up to 50-79% of patients with TS require estrogen replacement therapy (ERT) and 80%
have low bone mineral density (BMD). Studies show that pubertal delays are associated
with decreased BMD. Currently, guidelines suggest ERT start at 12 years, increasing
slowly, simulating pubertal progression. Many studies show that ERT increases BMD
in TS adolescents, but uncertainty remains as to how the rate of increase in ERT affects
BMD.
METHODS
IRB approval was obtained from our institution for this retrospective chart review
from 1991-2020. Charts were requested for the database using ICD 9-10 codes for TS
and patients undergoing dual-energy X-ray absorptiometry (DEXA). Biometric data, medical
and treatment histories were extracted from charts. Multilevel random effects models
were constructed to assess the time dependent associations between ERT and bone density
parameters. The primary independent variable of interest was the rate at which patients
went from initiating ERT to reaching final doses. The primary dependent variables
measured were total body BMD (tbBMD) and corresponding z-scores, calculated using
DEXA techniques. Analyses were done with SAS software (version 9.4, Cary, NC).
RESULTS
28 patients met inclusion criteria. Mean age of TS diagnosis was 6.9 years; 8 patients
had monosomy X, 16 had mosaic karyotypes, 4 had unknown karyotypes. The average age
for starting HRT was 14.1 years. 13 patients had spontaneous pubertal onset before
starting HRT. tbBMD increased significantly with age (p = 0.03). However, change in
BMD by age does not vary between patients who reached final adult doses of ERT within
0-2.5 years, compared to patients who took 2.5-5.5 years (p=0.7). Patients who took
2.5-5.5 years to reach final adult doses of ERT had a more negative trend in z-scores
(-2.144) in comparison to patients who took 0-2.5 years (-1.776), although this difference
did not reach statistical significance (p=.15). Future larger studies are needed to
better understand the relationship between duration of ERT use and tbBMD.
CONCLUSIONS
BMD in TS adolescents increases with age. Neither absolute tbBMD values nor tbBMD
z-scores increased faster when ERT doses were maximized within 2.5 years. This study
has identified a cohort of children under 12 years with TS who have not had any ERT
or BMD measurements - a potential population for future larger prospective studies.
KEYWORDS
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Martinez-Millana A, Hulst JM, Boon M, Witters P, Fernandez-Llatas C, Asseiceira I, Calvo-Lerma J, Basagoiti I, Traver V, De Boeck K, Ribes-Koninckx C. Optimisation of children z-score calculation based on new statistical techniques.
Article info
Publication history
Accepted:
March 10,
2023
Received in revised form:
February 5,
2023
Received:
August 4,
2022
Publication stage
In Press Journal Pre-ProofIdentification
Copyright
© 2023 Published by Elsevier Inc. on behalf of North American Society for Pediatric and Adolescent Gynecology.
