DMTs may reduce risk of children’s bone fractures in SMA: Study
But drug therapy failed to normalize bone density in certain patients
Disease-modifying therapies (DMTs) may help lower the risk of children’s bone fractures among young patients with spinal muscular atrophy (SMA), a study by U.S. researchers suggests.
“Drug therapy led to a decrease in fracture occurrence,” the scientists wrote, noting that “patients on treatment had fewer fractures compared [with] pretreatment.”
However, the use of DMTs did not normalize bone density among patients with low bone mineral density (BMD) before treatment, the data showed.
According to the team, these findings highlight the need for “adequate outpatient follow-up to determine bone health,” which the researchers called “essential.”
The study, “Bone Mineral Density Changes in Patients on Drug Therapy for Spinal Muscular Atrophy” was published in the journal Neuromuscular Disorders.
Investigating the effects of Spinraza, Zolgensma and Evrysdi on bone health
SMA is chiefly caused by mutations in the SMN1 gene, which lead to muscle weakness and wasting. Individuals with SMA are also at higher risk for bone health issues, such as low BMD and fractures, which can affect any bone in the body.
The DMTs approved in the last decade for SMA — namely Spinraza (nusinersen), Zolgensma (onasemnogene abeparvovec-xioi), and Evrysdi (risdiplam) — have all been shown to help infants achieve motor milestones previously unheard of with this disease. The trio of treatments also have been demonstrated to improve or maintain motor, breathing, and swallowing skills in older patients.
However, studies on their impact on bone health are still lacking, according to the team of researchers, from the University of Cincinnati College of Medicine and the Cincinnati Children’s Hospital Medical Center, both in Ohio.
To learn more, the team analyzed data from 27 children with SMA, who had type 1, type 2 , or type 3, and were followed at their center at some point during the period from 2008 to 2023. The patients comprised 12 boys and 15 girls. All had their BMD evaluated using dual energy X-ray absorptiometry scans, known as DXA testing. In this exam, an X-ray beam with two different energy peaks is used to assess bone.
A total of 13 children underwent scans before and after starting DMTs. The other 14, who tended to be younger, had their first DXA only after starting treatment; some were diagnosed via newborn screening, the study noted.
Children’s bone fractures found to be reduced with drug therapies
Among participants with scans conducted only after starting treatment, normal BMD in a part of the femur, or thigh bone, was seen in two patients, while normal BMD was found in the lumbar spine in half of the children. In six children, normal BMD was seen in the whole body (except the head). In that group, SMA type 1 patients were more likely to have low BMD than those with type 2 and 3 at a younger age.
In comparison, among children with scans done before and after starting therapy, one youngster showed normal BMD in the femur before treatment. Normal BMD in the lumbar spine, or the lower back, was seen in two children, and in the whole body (except the head) in four.
These children underwent new DXA scans after 15 months, or 1.4 years, on average. In three patients — two with SMA type 1 and one with type 2 — BMD improved at any site after the start of treatment. While the lowest BMD scores were found in SMA type 1 children both before and after starting a DMT, these participants showed the greatest average increases. However, DMTs did not normalize BMD in children with low bone mineral density before treatment.
The researchers then compared two patients identified through newborn screening with three others who were diagnosed based on symptoms. All received Zolgensma at an average age of 11 months.
The results showed that children diagnosed early through newborn screening or before birth were more likely to have normal BMD in the lumbar spine compared with those diagnosed after symptoms appeared. Those who could walk also had better bone density scores. One child with a history of fractures showed a significant improvement in lumbar spine bone density two years after the initial DXA scan.
Before treatment, more than half of the patients (52%) experienced at least one fracture, mostly in long bones. After treatment, this dropped to 14%. The children were monitored for an average of 4.5 years before, and four years after, receiving treatment.
SMA drug therapy may decrease fractures in patients with low BMD [bone mineral density]. … More studies are needed to see [the] effect [of DMTs] over the lifespan.
In addition, six children, including five with type 1, were diagnosed with disuse osteoporosis — a condition, characterized by low bone density and multiple children’s bone fractures by age 10. Due to severe bone loss and recurring fractures, all six began bisphosphonate therapy: three before and three after starting a DMT. Bisphosphonates are a group of medications designed to slow bone loss.
Overall, these findings suggest that “SMA drug therapy may decrease fractures in patients with low BMD,” the scientists wrote. However, the team noted that “more studies are needed to see [the] effect [of DMTs] over the lifespan.”
Among the study’s limitations, the researchers noted that “the sample size was also too small to recognize differences between the three drugs.”
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