Growth hormone, testosterone can better protect against fractures
Osteoporosis drug zoledronic acid alone found less protective for bones in MD
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Growth hormone (GH) or testosterone can better protect against spinal fractures than a common osteoporosis medication alone in boys with Duchenne muscular dystrophy (DMD) or severe Becker muscular dystrophy (BMD), according to a long-term study.
Used to prevent or lessen osteoporosis, or weak and brittle bones, zoledronic acid (ZA) is a type of therapy known as biphosphonates and works to reduce the amount of calcium lost from bones.
“We, for the first time, provide supportive data that combination therapy with GH and/or T [testosterone] and ZA is more protective against than ZA alone,” researchers wrote.
The study, “Growth hormone and testosterone delay vertebral fractures in boys with muscular dystrophy on chronic glucocorticoids,” was published in Osteoporosis International.
DMD and BMD are dystrophinopathies, or conditions caused by reduced or no functionality of the muscle protein dystrophin. Both diseases are caused by mutations in the DMD gene, which has the instructions to make dystrophin. Mostly affecting boys, DMD and BMD differ in their severity, but can be collectively characterized as disorders causing muscle weakness.
Chronic glucocorticoid use linked to spinal fractures, delayed puberty
High-dose glucocorticoids, such as Emflaza (deflazacort) and prednisone, are immunosuppressants used to slow disease progression and prolong mobility.
However, their chronic use is associated with endocrine (hormone-related) complications, such as osteoporosis and delayed puberty. Vertebral compression fractures (VF, small breaks in the bones of the spine) occur in about three-quarters of people with Duchenne. Such complications have traditionally been treated with GH, testosterone, or ZA.
Following patients over time is needed to “help improve the quality of life of patients experiencing endocrine complications,” the researchers wrote.
In the study, a team led by researchers at Johns Hopkins University analyzed data from 27 boys with DMD or severe BMD (median age of 13.5 years) to describe the incidence of endocrine complications in patients with dystrophinopathies who were on chronic glucocorticoids. The researchers assessed the effects of GH, testosterone, and/or bisphosphonates on VF incidence in the boys.
All boys were being treated with glucocorticoids (starting treatment at a mean age of 4.5 years) and were followed for a median of 27.6 months, or about 2.3 years. Emflaza was given to 22 boys and the remaining five received prednisone.
Growth was found impaired in 23 of the 27 boys, with 12 of them receiving GH. Delayed puberty was detected in 17 of 21 boys, with 12 patients taking testosterone. The boys had the option to begin testosterone supplementation if they remained prepubertal at 14.
Osteoporosis was identified by a significant VF history independent of bone mineral density. At the start of the study (baseline), nine of 24 boys had at least one fracture, which increased to 21 (87.5%) by the most recent evaluation.
VFs were more commonly seen in the thoracic (T)11, T12, and lumbar (L)1 vertebrae.
Researchers use model to predict time to next spinal fracture
Finally, the researchers assessed whether they could predict the time until the next VF within the thoracic and lumbar region (T4-L4 vertebrae). For this, they used so-called accelerated failure time models, which allowed analysis of whether the different treatments affected the time to a fracture.
“Endocrine interventions were pursued based on discussion of potential benefits and risks of medications, with 52% of those with growth failure electing to try GH, 72% of those with delayed puberty taking testosterone, and 72% with osteoporosis utilizing ZA,” the scientists wrote.
Results showed treatment with GH or testosterone prolonged the time to the next VF when compared to ZA alone, but only GH was deemed statistical significant when analyzed apart from testosterone.
Adding GH or testosterone to ZA also prolonged the time to the next VF compared to ZA alone, with testosterone being a significant contributor.
Overall, these findings show that in DMD and BMD, “GH and testosterone each decreased VF risk in patients independent of or in combination with ZA,” the researchers concluded.
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