The Role of Bone Secreted Factors in Burn-Induced Muscle Cachexia

Burn injury results in resorptive bone loss, failure to make new bone, and muscle protein breakdown resulting in cachexia. The purpose of this review is to examine the relationship between bone loss and muscle atrophy in burn injury with a view to understanding the process at work and how it may apply to other conditions that have similar features.

We present data suggesting that the use of bisphosphonates in the first 10 days following the burn prevents not only the resorptive bone loss but also the muscle wasting. While an extra-osseous effect of bisphosphonates remains possible, existing evidence points to a paracrine effect of bone on maintenance of muscle mass and strength. Proposed paracrine factors produced by bone include prostaglandin E2 and components of the Wnt signaling pathway. TGFβ may be a bone paracrine factor that causes oxidative damage to muscle. In the light of the pattern of evidence, burn patients suffer acute resorptive bone loss and muscle wasting. This is likely due to the effects of inflammatory cytokines and endogenous glucocorticoid production in exacerbating oxidative stress. Early use of bisphosphonates can maintain bone mass leading to a paracrine effect of bone in the maintenance of muscle mass, although one cannot completely discount a direct effect of bisphosphonate on muscle. Because investigators report this relationship in a variety of conditions in addition to burns, physicians should seriously consider the early use of bisphosphonates to maintain bone and muscle mass in a variety of neuromuscular and skeletal diseases.