Managing osteoporosis and bone health in Duchenne muscular dystrophy occurs in a high-risk environment for fractures due to disease-related loss of muscle and movement, adverse effects of glucocorticoid therapy, and endocrine considerations including delayed puberty.
The effects of established and newly approved therapies for Duchenne can be an additional source of complexity.
"Bone health is important to patients and families living with Duchenne muscular dystrophy since fractures can have serious consequences including early loss of ambulation and back pain," said researcher Leanne Ward, MD, of the University of Ottawa in Canada.
"The key to optimization of bone health is early, anticipatory intervention with bone protection therapy prior to first fractures," Ward told MedPage Today.
Shift to Primary Prevention
Over time, expert consensus has shifted from secondary to primary fracture prevention.
In a 2025 workshop report published in the Journal of Neuromuscular Disorders, Ward and colleagues reviewed the evolution of bone health management in Duchenne, noting that around 2010, spine x-rays were recommended to detect vertebral fractures in patients with back pain or kyphoscoliosis. Intravenous (IV) bisphosphonate therapy was started if vertebral fractures were present.
However, a key study showed that vertebral fractures -- an important sign of bone fragility in many glucocorticoid-treated conditions -- were frequently asymptomatic. Other research suggested that multiple long bone fractures were not required to diagnose osteoporosis in high-risk settings like Duchenne.
In 2018, updated recommendations published in Lancet Neurology emphasized routine surveillance to detect fractures early and starting bone protection therapy after a single low-trauma vertebral or long bone fracture.
By 2025, growing concerns about waiting for the first fracture before starting IV bisphosphonate therapy led to proposals for primary prevention, even though a larger number of patients would be treated under this scheme compared with a fracture-triggered approach.
A more tailored strategy could use risk factors to identify very high-risk children pre-fracture and seek to minimize the negative effects of anti-inflammatory or gene-directed Duchenne therapy on bone health and preserve ambulation.
Such an approach might generate a score that included data like bone mineral density declines, increased loss of muscle function, weight gain, higher glucocorticoid exposure scores, or signs of systemic glucocorticoid exposure on physical examination, Ward noted. A time-to-stand score of greater than 5 seconds could be a threshold to begin primary osteoporosis therapy, given its association with a 96% higher risk of losing ambulation compared with children with scores of 3.6 to 5 seconds, she added.
A 2023 study of boys and young males with Duchenne identified that prevalent vertebral or non-vertebral fracture predicted incident fracture. Prevalent fractures were seen after 4.1 years of glucocorticoid exposure in 24% of patients, highlighting the need for primary osteoporosis prevention.
Treatment
Despite advances in muscle-targeted therapy for Duchenne, long-term, high-dose glucocorticoids remain the backbone of treatment for the foreseeable future, Ward and co-authors noted. Prednisone and deflazacort (Emflaza) are standard of care, and among other benefits, have been shown to delay loss of ambulation.
A meta-analysis showed evidence of improved muscle strength and function for glucocorticoids over placebo at 6 months of daily treatment in Duchenne, as well as benefit on time to rise from the floor, timed walks, climbing, weight lifting, leg function, and forced vital capacity.
The association between fractures and glucocorticoid exposure was emphasized in a study that showed fracture risk was highest with daily oral deflazacort, then with daily oral prednisone, followed by intermittent dosing.
Other serious bone-related consequences and complications of long-term glucocorticoid therapy combined with the progressive myopathy of Duchenne include fat embolism syndrome after a fracture or sub-clinical bone injury and unrecognized or untreated glucocorticoid-induced adrenal suppression, both of which can be fatal.
Duchenne patients also are at increased risk for premature loss of ambulation following osteoporotic fractures or excess weight gain, a deleterious cycle with the potential for multiple adverse events. Periodic screening for vitamin D deficiency is important, as is treatment of excess weight exacerbated by steroid treatment and loss of physical function, Ward and co-authors noted.
Related indices of bone health and function include bone mineral density; decreases have been associated with increased vertebral fractures and worse mobility. Bone mineral density has also been shown to decline with loss of ambulation in Duchenne.
An alternative to using standard glucocorticoids is the synthetic dissociative steroid vamorolone (Agamree), which was developed to have fewer adverse effects. Vamorolone was approved to treat Duchenne in 2023 and a long-term registry study is ongoing. As with glucocorticoids, patients on vamorolone are at risk of adrenal suppression.
Bisphosphonates are routine in Duchenne care, but questions of oral versus IV use revolve around 1% or less bioavailability with oral agents versus the adverse events associated with IV dosing. A systematic review in Neurology found evidence that bisphosphonate use increased the lumbar spine bone mineral density in glucocorticoid-treated Duchenne patients.
Boys with Duchenne muscular dystrophy also experience profound pubertal and growth delay. A small study of testosterone-induced puberty in Duchenne suggested that testosterone could be co-administered with bisphosphonates to increase bone density and stabilize vertebral fracture.
"Individuals with Duchenne muscular dystrophy should involve an endocrinologist in their care, one that will partner with the individual and their family to optimize endocrine and bone health care starting at a young age," Ward suggested.
Disclosures
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