AT ENDO 2016

BOSTON (FRONTLINE MEDICAL NEWS) – The longer that estrogen therapy is delayed in girls with Turner syndrome, the lower their bone density will be in subsequent years, based on results of a retrospective, cross-sectional study from Monash University, in Melbourne, Australia.

For every year after age 11 that Turner patients went without estrogen – generally due to delayed initiation, but sometimes noncompliance – there was a significant reduction in bone mineral density in both the lumbar spine (Beta -0.582, P less than 0.001) and femoral neck (Beta -0.383, P = 0.008).

Estrogen deficiency and subsequent suboptimal bone mass accrual are known to contribute to the increased risk of osteoporosis in women with Turner syndrome, and about a doubling of the risk of fragility fractures, mostly of the forearm. About a third of the 76 women in the study had at least one fracture, explained investigator Dr. Amanda Vincent, head of the Midlife Health and Menopause Program at Monash.

“Avoiding estrogen deficiency is important to optimize bone health in Turner syndrome.” It “depends on early diagnosis, age-appropriate pubertal induction, and optimization of compliance,” Dr. Vincent said at the Endocrine Society annual meeting.

The median age of Turner syndrome diagnosis was 11 years, but estrogen treatments didn’t begin until a median age of 15. The women in the study were a median of about 30 years old, which means that they were adolescents at the time when estrogen treatment was often delayed in the mistaken belief that growth hormone therapy would be more effective before puberty was induced.

It’s now known that estrogen replacement works synergistically with, and even potentiates, the effects of growth hormone. Current guidelines recommend pubertal induction by age 13 (J Clin Endocrinol Metab. 2007 Jan;92(1):10-25).

The women had at least one dual-energy x-ray absorptiometry scan at Monash since 1998. Z-scores below – 2, indicating low bone density, were found in the lumbar spines of about a quarter the subjects, and in the femoral necks of about 8%. Primary amenorrhea and premature menopause, followed by vitamin D deficiency, were the most common risk factors for low bone mass. Almost 40% of the women reported non-continuous use of estrogen. About half had undergone growth hormone therapy.

At a median height of 149 cm, the subjects were about 15 cm shorter than age-matched, healthy controls, and also had a slightly higher median body mass index of 25.6 kg/m2. Lumbar spine bone area, bone mineral content, areal bone mineral density, and bone mineral apparent density were significantly lower in Turner syndrome patients. In the femoral neck, areal bone mineral density was significantly lower.

There was no relationship between bone markers and growth hormone use or Turner syndrome karyotype; the predominant karyotype was 45XO, but the study also included mosaic karyotypes.

The investigators had no disclosures.

aotto@frontlinemedcom.com

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