Muscle and bone in muscular dystrophy: Why not?

Anna Rufo, Fabrizio De Benedetti, Anna Teti

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Reduction in mechanical strength, due to paralysis, disuse or prolonged bed rest, isassociated with bone loss and contributes to age-related osteopenia. The extreme case ofspaceflight shows a bone loss caused by mechanical unloading at an average rate of1.5%/month for the hip. By contrast, various models of overloading by physical exercisehave been shown to preserve or increase skeletal mass, emphasizing the closerelationship between muscle function and bone. Muscular dystrophies are characterizedby myofiber necrosis, reduced muscular strength, inflammation, osteoporosis andincreased risk of fractures. Duchenne Muscular Dystrophy (DMD) is an X-linked,progressive muscle-wasting disease affecting male children, caused by mutations in thedystrophin gene, that leads to membrane fragility, myofiber necrosis and replacement ofskeletal muscle by fibrous and fatty connective tissue. This means that critical stimulifrom muscular work are reduced during the period of childhood and adolescence in DMDpatients and explains why they are affected by a marked reduction of bone mass,fracturing at a rate of 18 to 44%. Especially spine and lower limbs are affected in DMDchildren and in the MDX mouse, the best animal model of DMD, which also mimics thebone defects of the disease. Recently, a reduction of bone mass and an increase of boneturnover has been observed in DMD patients with early disease and moderate muscleimpairment. This skeletal response was hypothesized to be due not only to mechanicalunloading but also to additional unrecognized factors. In this context, in DMD patientswe found an imbalance of systemic and local cytokines, including IL-6, IL-11, InhibinßA and TGF ß2, which are known to affect bone cells. In particular, IL-6 is elevated inthe circulation of DMD patients and MDX mice and could play an important role in inducing bone loss, stimulating osteoclast bone resorption and inhibiting osteoblast boneformation. Currently, no therapy is able to cure this disease but glucocorticoids arecommonly used to relieve the effects of muscle inflammation. These drugs stabilizemuscle strength and function in DMD patients but their long-term use induces severe sideeffects, including excessive weight gain, retarded growth and bone loss. In the light of theabove, the identified role of IL-6 could open new therapeutic perspectives based on anti-IL-6 treatment, which is already being tested in clinical practice for juvenile arthritis.This intervention could be hypothesized to be more specific and with fewer side effectsthan glucocorticoid therapy.

Original languageEnglish
Title of host publicationMuscular Dystrophy: Causes and Management
PublisherNova Science Publishers, Inc.
Pages427-437
Number of pages11
ISBN (Print)9781626184602
Publication statusPublished - 2013

ASJC Scopus subject areas

  • Medicine(all)
  • Neuroscience(all)

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