Low Bone Mineral Density Risk Increases with Age in SMA

Low bone mineral density (BMD) appears to be common among children with spinal muscular atrophy (SMA), especially if those children are aged 6 years and older, according to a new study.

The findings come from a single-center analysis of 66 patients with SMA who underwent quantitative computed tomography (QCT) to measure BMD. The study was published in BMC Pediatrics.¹

Children with SMA are commonly affected by low bone mineral density | image credit: PT - stock.adobe.com

Corresponding author Haibo Qu, MD, of Sichuan University, in China, explained along with colleagues that skeletal system abnormalities are a major factor in limiting the quality of life of children with the inherited motor-neuron disorder.

“Consequently, there has been a growing emphasis on assessing bone health status as an essential component of SMA management in recent years,” they wrote.

The investigators said current guidelines suggest whole spine X-ray to detect scoliosis and dual-energy X-ray absorptiometry (DXA) scans to monitor BMD. Yet, they said 2-dimensional DXA imaging is imprecise, and can overestimate BMD in patients with spinal rotation or scoliosis.

Instead, the authors propose using QCT. They said the 3-dimensional imaging strategy can more accurately reflect the actual BMD content in smaller individuals, such as children with SMA.

“Previous studies have confirmed the application value of QCT in evaluating BMD in pediatric patients, but no cases have been reported in SMA,” they wrote.

The investigators identified 66 patients with SMA who were treated at Sichuan University’s West China Second University Hospital between July 2017 and July 2023 and had complete medical records. None of the patients in the study had received disease-modifying treatment.

The patients ranged in age from 2.4 years to 9.7 years, and 14 had type 1 SMA, 37 had type 2 SMA, and 15 had type 3 SMA.

Qu and colleagues said 19 patients (28.8%) were diagnosed with low lumbar spine BMD (defined as Z-scores ≤ −2) upon QCT imaging. The mean Z score was −1.5 ± 1.0, they said.

The investigators also sought to understand what factors, if any, were associated with low BMD. One factor, in particular, stood out.

“Our findings suggest that age might be a useful indicator for assessing the risk of low BMD of the lumbar spine in patients with SMA" they said (β=-0.153, P = .001).

Specifically, they found that children ages 6.3 years and older were more likely to have low BMD (sensitivity 68.4%; specificity 68.1%).

“It is not unexpected that age is the factor associated with low BMD, as SMA children may not be able to increase bone mass through exercise and physical activity compared to healthy children, leading to a progressive bone mass deficient state,” they wrote.

A similar study that used DXA to assess BMD in 12 patients with SMA found that only the oldest patients, aged 19 and 20, had low BMD, while younger patients were still in the normal range.² Most of the patients (n = 8) in that study had the milder type 3 SMA, and 6 of the patients in the trial were still ambulant. The 2 patients with low BMD, however, were not ambulant. Like this new study, the earlier study suggested that age was a bigger factor in BMD status than disease severity or ambulatory status.

Qu and colleagues also analyzed SMA phenotype, serum phosphorus, alkaline phosphatase, and 25-Hydroxyvitamin D levels, but none of those factors was independently predictive of BMD status.

The investigators noted that their study had a small sample size, and they said they did not have access to other information that might affect BMD, such as patients’ dietary histories and intake of calcium and vitamin D. Even though their study suggested older patients are at a higher risk of low BMD, they said younger patients with SMA should still be considered at risk of low BMD.

“Regular BMD monitoring is necessary for all types of SMA children, especially those aged ≥ 6.3 years,” they concluded, “so that early diagnosis and appropriate intervention can be planned to prevent the [complications] related to low BMD.”

References

1. Liu C, Yang D, Luo L, et al. Low bone mineral density and its influencing factors in spinal muscular atrophy without disease-modifying treatment: a single-centre cross-sectional study. BMC Pediatr. 2024;24(1):651. doi:10.1186/s12887-024-05120-3
2. Kinali M, Banks LM, Mercuri E, Manzur AY, Muntoni F. Bone mineral density in a paediatric spinal muscular atrophy population. Neuropediatrics. 2004;35(6):325-328. doi:10.1055/s-2004-830366