Gait and Bone Health in SMA

Dual X-Ray Absorptiometry (DXA)

Bone mineral density (BMD), a measure of the mineral content in bones is assessed using dual x-ray absorptiometry (DXA). DXA can be used to identify individuals with low bone mass (LBM). DXA uses low-power x-ray and is a safe and reliable measure validated to diagnose osteoporosis. DXA provides a t-score and z-score so that based on age, low bone mass can be appropriately determined. DXA also provides a subtotal BMD score as well as scores specific to certain body regions, both of which will be utilized in the first aim.

Blood collection

Blood will be collected to assess for routine markers related to bone mineral density. Blood will be tested for levels of calcium, vitamin D, bone alkaline phosphatase (BALP), and C-terminal telopeptide of type I collagen (CTx). The amount of blood collected will be within hospital rules for children. The total amount of blood will be approximately 2 mL or 1/2 a teaspoon. BALP is a bone formation marker while CTx is a bone resorption marker. Calcium and vitamin D are known to be positively associated with BMD.

Fracture history

Details regarding lifetime fracture history will be collected via questioning at the in-clinic visit and during remote follow up visits, every three months for one year. The participant will be asked to describe each incident separately, including the age at fracture, mechanism of injury (how it happened, its nature, and force), any preceding events like falls or dizziness, and associated symptoms. Fractures will be characterized by location, type and treatment (surgical or conservative).

Fall history

Details regarding falls, that occurred within the past year, will be collected using a structured questionnaire at the in-clinic visit and during the one-year follow-up. Falls will be described by mechanism, environment and outcome.

Ten Meter Walk Run (10MWR)

The 10MWR is an objective evaluation of function that measures the speed at which an individual can complete 10 meters. Gait speed is a commonly used indicator in NMD, and this test can be done by either walking or running. The 10MWR has been demonstrated to be safe to administer in individuals with SMA.

Timed Up and Go Test (TUG)

The TUG test, a method to assess balance and mobility, measures the time it takes an individual to stand up from a chair, walk 3 meters, turn around, and sit down in the same chair. In SMA, TUG scores are associated with total leg and knee flexor strength, gross motor function, the 10-meter walk/run, and 6MWT. TUG test is a sensitive and reliable measure of functional impairment in inherited neuromuscular disorders.

30 Second Sit to Stand (30-STS)

The 30-STS test is used to evaluate basic muscle power and function. The participant is to complete as many sit-to-stands as possible, with or without using their hands for support, in 30 seconds.

SMA EFFORT

The SMA EFFORT is a perceived physical fatigability patient-reported outcome measure (PROM) that provides a percent (PPF%) total score to each participant based on their participation over the past 30 days. PPF% total scores are calculated as the sum of activity item ratings divided by the number of items rated multiplied by five (highest rating on Likert scale), with higher scores indicating greater perceived physical fatigability (PPF).Participants are instructed to not endorse any item that has not been performed in the past 30 days, ensuring a PPF% total score that is unique to their current level of function. In addition to the PPF% total score (across all activities performed), PPF% subscale scores corresponding to the specific activities across 4 different domains of function are similarly derived (Exercise/Recreation, Mobility, Postural Control, and Activities of Daily Living (ADLs).