Bone mineral density is low in girls, young women with Rett: Study
Reduced BMD tied to small size, impaired mobility, use of valproic acid
Bone mineral density, an indicator of bone strength, is significantly lower in girls and young women with Rett syndrome compared with healthy girls and women of the same age, a study shows.
Reduced bone mineral density was tied to small body size, impaired mobility, and the use of the anti-seizure medication valproic acid.
Four patients, all of whom used wheelchairs and had been treated with valproic acid, saw their bone mineral density improve over time after being treated with the osteoporosis medication zoledronate.
“Our findings are important in light of the increasing life expectancy of individuals with [Rett] and the consequent need to prioritize bone health in this population,” wrote the scientists, who said data also supported “the effectiveness and safety of zoledronate for treating osteoporosis in patients with [Rett].” The study, “Bone health and bisphosphonate treatment in females with Rett syndrome in a national center,” was published in Pediatric Research.
Rett syndrome is a neurodevelopmental disorder that mainly affects females and is marked by difficulties in cognitive, emotional, sensory, and motor skills, that typically start in early childhood.
Its most common non-neurological features are those that affect the joints, bones, and muscles, and include scoliosis, hip displacement, low bone mass, or osteoporosis, and bone fragility. The factors that affect bone health with Rett include poor nutrition, specifically low calcium and vitamin D intake, joint contractures, limited mobility, and certain anti-seizure medications.
Risk factors of poor bone health evaluated
Scientists at Tel Aviv University in Israel retrospectively examined the bones of 40 girls and young women with Rett syndrome, ages 5-21, to identify risk factors for poor bone health. They measured bone mineral density (BMD) in the lower spine using dual-energy X-ray absorptiometry (DXA) scans. A trabecular bone score (TBS) obtained from the images provided indirect information about bone microarchitecture.
Of the 27 Rett patients with epilepsy (68%), 24 were treated with the anti-seizure medication valproic acid. About 1 in 5 (18%) had at least one fracture, 27 (68%) had scoliosis, and five (13%) had hip displacement. The median Gross Motor Function Classification System (GMFCS) score was 4 (range, 1 to 5), indicating the patients’ walking abilities were severely limited.
The mean BMD of the Rett patients was significantly lower than what’s expected in a healthy population, as indicated by a Z-score of -2.1. Z-scores measure the BMD relative to the population average for a person’s age and sex, so a negative Z-score indicates a lower than normal BMD, with larger negative values reflecting worsening BMD.
More than half the patients (62.5%) had BMD Z-scores lower than -2, about 1 in 3 (30%) had scores between -2 and 0, and three patients (7.5%) had Z-scores above 0, meaning higher than average BMD. Conversely, the mean TBS Z-score wasn’t significantly different from the score expected in a healthy population.
Link between bone density and TBS
Lower BMD significantly correlated with reduced body weight, shorter height, and a lower body mass index (BMI), a measure of body fat content based on height. Lower TBS scores, indicating degraded bone microarchitecture, significantly correlated with lower height, weight, and BMD. Worse GMFCS scores for walking ability also correlated with lower BMD.
“The association between BMD and trabecular bone score (TBS) in the context of [Rett] is a novel finding,” the researchers wrote.
No relationships were found between DXA data and blood levels of calcium, phosphorus, vitamin D, or alkaline phosphatase, a bone health marker.
The patients treated with valproic acid had significantly lower BMD Z-scores than those who weren’t (-2.6 vs. -1.5). While the BMD was lower in those with scoliosis than in those without, the difference didn’t reach statistical significance, meaning it may have occurred by chance.
Half the patients received vitamin D supplementation; 1 in 6 (15%) received calcium supplements, and about 1 in 4 (23%) received zoledronate. Before treatment, those who received zoledronate had lower BMD and TBS scores, and a higher frequency of fractures than those who didn’t (56% vs. 6%).
Of the four patients who had repeat DXA scans before and after starting zoledronate — all used wheelchairs and were taking valproic acid — the mean BMD Z-score improved from the pre-treatment scan to the follow-up scan (-2.2 vs. -1.4).
“Females with [Rett] exhibited low BMD, together with a high incidence of low energy fractures,” the scientists wrote. “We observed significant correlations of BMD with [body] measurements, ambulation status, valproic acid treatment, and TBS. Further longitudinal prospective studies are necessary to assess the long-term impact of [zoledronate] therapy on bone health in this population.”
About the Author
