Obesity and Bone Fractures in Children with PWS Tied to High Blood Levels of Protein, Study Says

Children with Prader-Willi syndrome (PWS) have high levels of a protein called LIGHT/TNFSF14, which may contribute to obesity and low bone mineral density (BMD), a study suggests.

The research, “High levels of LIGHT/TNFSF14 in Prader-Willi syndrome,” was presented at the European Society of Pediatric Endocrinology 2019 meeting in Vienna (Session 2, pg 84) and published in the journal Hormone Research in Paediatrics.

Low bone mineral density (BMD) affects almost half of all teenagers and adults with PWS, putting them at a higher risk of bone fractures. However, the reason why low BMD exists in such a large proportion of these patients remains to be understood.

LIGHT/TNFSF14 is a protein implicated in the activation of lymphoid cells and proliferation of immune T-cells.

As studies also indicate that LIGHT/TNFSF14 is involved in bone remodeling and obesity, researchers in Italy assessed blood serum levels of this protein in 19 children with PWS (average age, about 11). And the team tested whether these levels correlate with parameters of obesity and bone quality.

Bone status, lean mass, and fat mass were assessed by Dual-energy X-ray absorptiometry (DXA) scan, a common technique to determine bone density and body composition.

Results revealed that PWS patients have significantly higher blood levels of LIGHT/TNFSF14 levels compared to controls (426.73 pg/ml vs. 162.26 pg/ml).

Higher protein levels significantly correlated with greater amounts of parathyroid hormone (PTH), a higher proportion of trunk fat, as well as with more total fat and left/right arm fat.

PTH increases the release of calcium from bones. When its levels are too high, the amount of calcium in bones drops low, increasing the risk for fracture.

In turn, higher LIGHT/TNFSF14 levels were linked with a lower concentration of IGF-1 (a critical mediator of bone growth and bone health), proportion of lean mass, femoral z-score, and lumbar z-score.

A Z-score compares the bone density of children with PWS to that of healthy children of the same age and sex. As such, these results link high LIGHT/TNFSF14 levels with lower BMD in the femur (thigh) and lower spine (lumbar region).

These results suggest that LIGHT/TNFSF14 levels are associated with those of parameters that contribute to both obesity and low BMD.

“We demonstrated high serum levels of LIGHT/ TNFSF14 in PWS children that correlated with both fat and bone mass,” the researchers wrote.

This protein, the team added, “could contribute to obesity and bone disease affecting PWS patients, therefore representing a good pharmacological target.”