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

Abstract

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.

Role of Calcium and Low-Fat Dairy Foods in Weight-Loss Outcomes Revisited: Results from the Randomized Trial of Effects on Bone and Body Composition in Overweight/Obese Postmenopausal Women

“…Waning et al showed in the metastatic mouse models that the bone breakdown results in higher muscle weakness due to elevated secretion of transforming growth factor (TGF)-beta from the bone surface, suppressing Ca ++ induced muscle force production and strength [86]. The review [88] in burn patients with burn-induced muscle cachexia, who also suffer from bone loss, reported that early administration of bisphosphonates spares not just the bone, but the muscle as well. It is not quite known what the actual mechanism is, but the author suggests that the suppression of bone-resorptive agents’ secretion by bisphosphonates might exert the sparing effect on muscle mass and strength, similarly to that by calcium.…”

Undercarboxylated osteocalcin and ibandronate combination ameliorates hindlimb immobilization‐induced muscle wasting

“…This discrepancy between studies might be attributed to differences in mouse/cell models and bisphosphonate type as well as treatment doses and durations. Furthermore, the bisphosphonate‐mediated preservation of bone mass has been suggested to render healthy bone–muscle interaction, thus preserving muscle mass via the production of osteokines with anabolic functions, such as prostaglandin E2 (Klein, 2018). In addition, the antiresorptive activity of bisphosphonates inhibits the release of negative regulators of skeletal muscle from bone, such as members of the transforming growth factor‐β (TGF‐β) family, thereby reducing protein catabolism in muscle induced by these factors (Klein, 2018; Waning et al., 2015).…”

Plasmin drives burn-induced systemic inflammatory response syndrome

“…Burn-induced SIRS has been shown to affect other tissues, and the consequences of severe burn-provoked inflammation on tissue health have been extensively demonstrated by the phenomenon of burn-induced osteoporosis and muscle wasting (49)(50)(51). Although we used a remote muscle injury to investigate how the systemic response to burn affects inflammatory signaling in distant tissues, tissue inflammation is often observed in a multitude of other organs following burn injuries, resulting in MODS (8,52).…”