The Effect of the Rate of Increase of Estrogen Replacement Therapy on Bone Mineral Density Accrual in Young Patients with Turner Syndrome.

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 that ERT start at 12 years, increasing slowly, simulating pubertal progression. Many studies show that ERT increases BMD in adolescents with TS, but uncertainty remains as to how the rate of increase in ERT affects BMD.

METHODS

Institutional review board approval was obtained from our institution for this retrospective chart review from 1991 to 2020. Charts were requested for the database using ICD 9-10 codes for TS and patients undergoing dual-energy X-ray absorptiometry. Biometric data and 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 dual-energy X-ray absorptiometry techniques. Analyses were done with SAS software (version 9.4, Cary, NC).

RESULTS

Twenty-eight patients met the inclusion criteria. The mean age at TS diagnosis was 6.9 years; 8 patients had monosomy X, 16 had mosaic karyotypes, and 4 had unknown karyotypes. The average age for starting hormone replacement therapy was 14.1 years. Thirteen patients had spontaneous pubertal onset before starting hormone replacement therapy. tbBMD increased significantly with age (P = .03). However, change in BMD by age did not vary between patients who reached final adult doses of ERT within 0-2.5 years compared with patients who took 2.5-5.5 years (P = .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 with 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.

CONCLUSION

BMD in adolescents with TS increases with age. Neither absolute tbBMD values nor tbBMD z-scores increased faster when ERT doses were maximized within 2.5 years. This study identified a cohort of children under 12 years with TS who had not had any ERT or BMD measurements, a potential population for future larger prospective studies.