Bone Health and Osteoporosis Management of the Patient With Duchenne Muscular Dystrophy

Abstract

Duchenne muscular dystrophy is associated with an increased risk of bone fragility due to the adverse effects of prolonged glucocorticoid therapy and progressive muscle weakness on bone strength. Osteoporosis manifests clinically as low-trauma long-bone and vertebral fractures (VFs), with VFs frequent, particularly in those treated with glucocorticoid therapy. It is increasingly recognized that bone pain, medical complications of osteoporosis (such as fat embolism syndrome), and the potential for permanent, fracture-induced loss of ambulation can be mitigated with timely bone health surveillance and management. This includes periodic spine radiographs for VF detection because VFs can be asymptomatic in their early phases and thereby go undetected in the absence of monitoring. With this article, we provide a comprehensive review of the following 4 phases of bone health management: (1) bone health monitoring, which is used to identify early signs of compromised bone health; (2) osteoporosis stabilization, which is aimed to mitigate back pain and interrupt the fracture-refracture cycle through bone-targeted therapy; (3) bone health maintenance, which has the goal to preserve the clinical gains realized during the stabilization phase through ongoing bone-targeted therapy; and (4) osteoporosis therapy discontinuation, which places those who are eligible for discontinuation of osteoporosis treatment back on a health monitoring program. In the course of reviewing these 4 phases of management, we will discuss the criteria for diagnosing osteoporosis, along with detailed recommendations for osteoporosis intervention including specific drugs, dose, length of therapy, contraindications, and monitoring of treatment efficacy and safety.

FIGURE 1

Examples of VFs on a lateral thoracolumbar spine radiograph in a patient with DMD. This figure reveals the spine of a patient, age 10 years, with DMD who presented with back pain after 18 months of glucocorticoid therapy, in the absence of a previous history of routine spine health monitoring. Multiple VFs were identified on a lateral thoracolumbar spine radiograph, many in advanced stages of collapse. T10, thoracic vertebra 10; L5, lumbar vertebra 5.

FIGURE 2

Osteoporosis monitoring, diagnosis, and treatment algorithm for patients with DMD. DXA, dual-energy x-ray absorptiometry. *Signs of clinically significant bone fragility are low-trauma fractures of long bones or vertebra. †Clinical stability refers to the absence of nonvertebal fractures, stable healed VFs, absence of new VFs in previously normal vertebral bodies, absence of bone and back pain, and a BMD z score appropriate for height z score or >−2 SDs. (Reproduced with permission from Birnkrant DJ, Bushby K, Bann CM, et al; DMD Care Considerations Working Group. Diagnosis and management of Duchenne muscular dystrophy, part 2: respiratory, cardiac, bone health, and orthopaedic management. Lancet Neurol. 2018;17[4]:353.)

FIGURE 3

The evolution of spine morphology in a patient with DMD treated with glucocorticoid followed by IV bisphosphosphonate therapy for painful VFs. This figure is used to illustrate changes in vertebral morphology during glucocorticoid and IV bisphosphonate therapy. A, Early asymptomatic signs of T7 and T8 VFs on glucocorticoid therapy. B, Progressive vertebral collapse with an emergence of back pain triggering IV pamidronate therapy. C and D, Vertebral body reshaping on IV pamidronate therapy. Vertebral body reshaping is a growth-dependent process that is facilitated by bone strengthening therapy. The extent to which vertebral bodies can undergo reshaping on bisphosphonate therapy is determined by a number of clinical factors, including the degree of collapse, growth velocity, severity of ongoing risk factors for osteoporosis, and the magnitude of residual growth potential (before epiphyseal fusion). Patients with poor growth velocity have less potential for reshaping, as do patients who start therapy with more severe collapse and who are closer to attaining their final adult height. T7, Thoracic vertebra 7; T8, Thoracic vertebra 8.