ERT may improve bone health in late-onset Pompe: Small study

Bone density in femur, lumbar region increased significantly with treatment

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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Starting people with late-onset Pompe disease on enzyme replacement therapy (ERT) at any age can benefit their bone health, including reducing the risk of weak, brittle bones, or osteoporosis, a small study suggests.

The study, “Effects of enzyme replacement therapy on bone density in late onset Pompe disease,” was published in Molecular Genetics and Metabolism by researchers in the U.S.

Pompe disease occurs due to a deficiency of alpha-glucosidase (GAA). The enzyme breaks down glycogen, a large sugar, into smaller sugar molecules for use as an energy source. Without enough GAA, glycogen builds up to toxic levels in cells.

Glycogen accumulates in many types of tissue, but primarily in muscles, damaging them and impairing their ability to function properly. People with Pompe typically have muscle weakness, poor muscle tone, and trouble breathing.

In Pompe disease, little physical activity, immobility, and reduced weight bearing lead to decreased bone density, or a reduced amount of bone mineral. This makes bones more prone to breaking.

There are no guidelines on how to monitor and manage bone problems such as osteoporosis and osteopenia (a stage before osteoporosis where there is milder bone loss), however.

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ERT’s effects on late-onset Pompe disease

ERT for Pompe disease provides the missing enzyme to the body. Its benefits to muscles are well documented, but not much is known about its potential effects on bones, leading researchers to study 15 (13 men, 2 women) people diagnosed with late-onset Pompe, a form of the disease that begins to manifest after age 1 and may not become apparent until later in childhood or adulthood.

The patients’ ages ranged from 25-76 and all were being given a 20 mg infusion of Sanofi‘s Lumyzime (alglucosidase alfa) per kg of body weight once every two weeks. They were on ERT for different lengths of time, however.

To measure bone density around the hips and spine, the researchers used a type of scan called dual-energy x-ray absorptiometry (DEXA). Based on it, 10 patients had osteopenia, two had osteoporosis, and three had normal bone density. The women, both older than 55, had bone fractures.

“Some patients with osteopenia or osteoporosis started vitamin D and calcium after the results of their first DEXA scan,” the researchers wrote, noting the supplements have shown a “negligible effect” on bone density.

For a one-year increase in age, there was a significant increase in the Z-score in the femur (thigh bone) and the lumbar region (lower back). The Z-score shows how a person’s bone density compares to what’s expected for someone of the same age, sex, and ethnicity. This means as the patients got older, their bone density in the femur and lumbar region increased significantly over what was expected for their group.

The T-score and bone density also increased as the patients got older, but not significantly. The T-score compares a person’s bone density to that of a healthy young adult.

When the researchers looked at data from all DEXA scans taken after ERT started, they found a significant increase in the Z-score in the lumbar region for each one-year increase in age.

“Our results indicate that ERT treatment can reduce the risk of osteoporosis over the study span of 12 years and can reduce the natural aging process in Pompe disease,” the researchers wrote.

Women had significantly lower T-score and bone density in the lumbar region than men, so they may be at higher risk for osteoporosis. That only two women participated was noted as a study limitation.

While the benefits to bone health appear to be “related to the duration of treatment with ERT, independent of the age,” the findings show better guidelines and treatment for managing osteopenia/osteoporosis in Pompe disease are needed, the researchers said.

The study was supported by the Lysosomal Storage Diseases registry from Sanofi-Genzyme.