2026 Theses Doctoral

Factors Associated with Bone Health in Ambulatory Children and Adults with Spinal Muscular Atrophy

Kanner, Cara H.

Individuals with spinal muscular atrophy (SMA) are at risk for poor bone health and low bone mass (LBM) because of decreased muscle strength and limited physical activity. In healthy individuals, several predictors of bone health have been identified, including lean muscle mass and weight-bearing activity. Individuals with LBM are known to have increased fracture risk. Fractures can negatively impact quality of life for people with SMA (pwSMA) by altering mobility status and independence.

The purpose of this study was to (a) identify low bone mass in ambulatory pwSMA, (b) evaluate the association of body composition and BMD in ambulatory pwSMA, (c) explore the association of bone health with muscle quality, muscle volume, strength, and function and (d) identify factors that influence bone health in ambulatory pwSMA.

This dissertation is a retrospective data analysis of data previously collected as part of an ongoing, observational, cross-sectional study (Columbia University Irving Medical Center Institutional Review Board [IRB] #AAAT5811 and Teachers College IRB #25-434). Magnetic resonance imaging (MRI) was used to study bone health, measured by cortical bone area (CBA) and bone marrow adipose tissue (BMAT) as well as muscle volume and quality of the bilateral lower extremities. Additionally, strength and function were assessed and their association with bone health was examined. The focus of this study was to better understand factors that are associated with and influence bone health in ambulatory pwSMA who are treated with disease-modifying therapy.

Muscle volume was moderately associated with both CBA (r = .614, p = .001) and BMAT (rs = .511, p = .009). Worse muscle quality as measured by greater inter-/intra-muscular adipose tissue was also moderately associated with increased CBA (r = .521, p = .008), although the association was weaker, implicating that lean muscle is more beneficial for building larger, stronger bone. CBA was moderately associated with ankle dorsiflexion (r = .504, p = .010) and ankle plantarflexion (r = .455, p = .025) but not significantly associated with knee flexion or extension strength (p > .05), which may be due to the increased strength distally in SMA. In individuals who reported a history of fracture(s) (n = 9), there was significantly higher BMAT (p = .037).

Children and adults with SMA have poorer bone health than their healthy peers. CBA and BMAT are two variables that can be used to assess bone health and demonstrate associations with measures of muscle volume, quality, and strength. This dissertation addressed a gap in the literature by studying bone health in ambulatory pwSMA on disease-modifying therapy. Additionally, it is the first study to evaluate MRI-measured CBA and BMAT in pwSMA. While these results provided a baseline understanding and implied that these variables are relevant in pwSMA, further work is needed to better understand how BMAT is related to other known variables of bone health such as BMD and how these measures change over time.

Overall, this work will help contribute to improvement in the assessment and identification of bone health in pwSMA and eventually lead to more targeted interventions and treatment to improve care for individuals with poor bone health.