Hunger Hormone Ghrelin May Predict Early Onset of Scoliosis in PWS Children

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by Steve Bryson, PhD |

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hunger hormone ghrelin/ biomarker for early onset scoliosis

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The hunger hormone ghrelin, when measured in infancy, may be a biomarker for predicting the early onset of scoliosis — a sideways curvature of the spine that looks like the letter C or S — in children with Prader-Willi syndrome (PWS), a study suggested.

Beginning in early infancy, children with high ghrelin levels should be followed for scoliosis, the researchers recommended.

“If our findings are confirmed, ghrelin levels during the first year of life … could predict the development and progression of the spinal deformity,” the investigators wrote.

The study, “Is ghrelin a biomarker of early-onset scoliosis in children with Prader–Willi syndrome?” was published in the Orphanet Journal of Rare Diseases.

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A genetic disease, PWS is caused by defects in genes that control body growth, metabolism, cognitive skills, social behavior, and appetite. As children, PWS patients grow slowly and have weak muscles. Throughout their lives, people with the disorder experience an insatiable appetite, known as hyperphagia, which can lead to obesity.

In PWS, high levels of the hormone ghrelin, which is secreted by cells in the digestive tract to stimulate food intake, have been linked to the development of obesity. Referred to as the “hunger hormone,” ghrelin has two forms: acylated ghrelin or AG, and unacylated ghrelin, known as UAG, which functionally blocks AG.

Studies suggest ghrelin also plays a role in bone metabolism and growth, especially with long bones, such as those of the arms and legs.

Scoliosis is a spinal deformity characterized by a sideways curvature of the backbone. In patients with PWS, the overall prevalence of scoliosis is about 40% and increases with age, from 23% in children to upward of 75% in adults.

Based on these observations, researchers in France wondered whether high ghrelin levels in patients with PWS were associated with, and could predict, a vulnerability to early onset scoliosis (EOS), which occurs before the age of 10.

“To our knowledge, no study has explored this hypothesis,” the researchers wrote.

The team collected data from the French Reference Center for PWS (FRC-PWS), which included medical information from 20 hospitals that follow PWS children. All selected participants were being treated with growth hormone at the time of the study.

The first part of the study compared ghrelin levels in 60 PWS children, with and without scoliosis. A total of 30 children, ages 2 to about 5 years, had scoliosis, with their hormone levels measured at the time of the condition’s diagnosis. The other group of 30 age- and weight-matched children, without scoliosis, also had ghrelin measured prior to their selection into the study.

AG and UAG were measured from blood samples, and the total ghrelin (AG plus UAG), as well as the ratio of AG to UAG (AG/UAG), were calculated.

The analysis revealed the AG/UAG ratio was significantly lower in PWS children with scoliosis than those without the condition, “suggesting that ghrelin may be a biomarker of scoliosis in PWS,” the team wrote.

In contrast, no significant differences were found in total median ghrelin, AG, or UAG levels. The median AG was lower in those with scoliosis, but the difference was not statistically significant.

Elevated total ghrelin and UAG levels were positively correlated with a larger Cobb angle — a measurement of the degree of spinal curvature, with a higher angle meaning more curvature — “suggesting that higher [total ghrelin] and UAG are linked to scoliosis severity,” the team added.

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The second part of the study aimed to determine whether ghrelin concentrations in the first year of life — before growth hormone treatment — could predict later scoliosis development by the age of 4.

The researchers compared a total of eight PWS infants with scoliosis with 29 PWS age- and weight-matched infants without scoliosis, all with ghrelin measurements taken in the first year of life. Growth hormone was started in both groups between a median of 10 to 11 months of age.

At scoliosis diagnosis, the children were a median age of 1.8 years and had a median Cobb angle of 23.5 degrees. For a diagnosis of scoliosis, the Cobb angle needs to be 10 degrees or higher. At a median age of 2.1 years, all of the scoliosis patients underwent bracing, in which pressure is applied to the spine to prevent the curvature from progressing.

There was no difference in clinical characteristics at the time of ghrelin measurement between the two groups, except significantly lower levels of IGF-1, a critical mediator of bone growth and bone health, were seen in infants who later developed scoliosis.

Although median UAG and AG/UAG did not significantly differ between the two groups, the median levels of total ghrelin were almost twofold higher in infants that were eventually diagnosed with scoliosis (926.5 vs. 574.0 picograms/mL), as were AG levels (430.0 vs. 233.7 picograms/ml). However, these differences did not reach statistical significance, “perhaps due to lack of power,” meaning the small number of participants, the researchers noted.

“Our results suggest that ghrelin may play a role in the [development] of scoliosis in patients with PWS,” the team concluded. “Currently, at the FRC-PWS, we are implementing a prospective follow-up of a larger sample of patients with PWS undergoing ghrelin measurement who will be evaluated for scoliosis in a standardized manner to demonstrate if ghrelin could be used as a biomarker for EOS.”

“If ghrelin is an important factor of vulnerability of EOS, new therapeutic approaches with drugs targeting the ghrelin system may be an interesting opportunity for treating or preventing scoliosis,” they added.