Introduction: Ox in a dose of 0.03-0.05 mg/kg per day in addition to GH treatment significantly increases adult height in TS more than GH alone. To date, the long term effects of Ox in childhood on bone mineral density (BMD) in adulthood are unknown.
Methods: This is a follow-up study of a previous randomized controlled trial, performed in the Netherlands. In the original trial, 133 girls were treated with GH. Placebo (Pl), Ox 0.03, or Ox 0.06 was added to GH when the age of 8 years was reached. Estrogens started from 12 years of age following a standard pubertal induction scheme. GH and Ox were stopped after adult height was reached. 66 women participated in the double-blind follow-up study (Pl, n=21; Ox 0.03, n=27; Ox 0.06, n=18). Mean age, 24.0 years; mean time since stopping GH, 8.7 years; and mean time of Ox/Pl use, 4.9 years. BMD of the lumbar spine, femoral neck and total body were assessed using dual-energy X-ray absorptiometry (DXA) scans (QDR 4500 densitometer, Hologic). Mean Z-scores were calculated and compared between Ox dose groups using ANOVA. In addition, mean Z-scores were compared to reference values of healthy women using t-tests.
Results: In the Pl group BMD Z-score of the lumbar spine (-0.82), femoral neck (-0.74) and total body (-0.63) were significantly lower (P< 0.005) compared to healthy women. In the Ox 0.03 group only the BMD Z-score of the lumbar spine and in the Ox 0.06 the BMD of the femoral neck were significantly lower than healthy individuals. BMD Z-score of the lumbar spine was significantly higher in girls treated with Ox (Ox 0.03:-0.32; Ox 0.06:-0.08) compared to girls treated with Pl (-0.82, P=.014), without significant difference between dose treatment groups. Although there was a trend towards a higher BMD Z-score of the femoral neck (Pl:-0.74; Ox 0.03: -0.22; Ox 0.06: -0.49) and total body (Pl:-0.63; Ox 0.03:-0.21; Ox 0.06:-0.24) in the Ox groups compared to Pl, no significant differences were found.
Conclusions: DXA Hologic scans in adult TS treated with GH in childhood show a lower BMD, not adjusted for height, than healthy individuals of the same age. The addition of Ox to GH in childhood results in a significantly higher lumbar spine BMD than GH alone, with a similar trend for the femoral neck and total body. No significant differences were found between Ox 0.03 and Ox 0.06.
19 - 21 Sep 2019
European Society for Paediatric Endocrinology