Bone‑origin repair in diabetic foot ulcers: Mechanisms of callus formation and endocrine effects in healing (Review)
Abstract
Diabetic foot ulcers (DFUs) represent a severe complication of diabetes mellitus, affecting ~1/3 of diabetic patients during their lifetime and imposing substantial clinical and economic burdens globally. While conventional understanding attributes DFU pathogenesis primarily to peripheral neuropathy, vascular insufficiency and infection, emerging evidence reveals that bone involvement plays a previously underappreciated but important role in wound chronicity. The present review introduces the concept of 'bone‑origin repair', a therapeutic framework that leverages the skeleton's intrinsic regenerative and endocrine capacity to support soft‑tissue healing in bone‑adjacent DFUs. Diabetes profoundly impairs bone health through cortical thinning, bone marrow stromal cell exhaustion and disrupted callus biology, creating a permissive environment for ulceration and delayed healing. Beyond structural compromise, bone functions as a multifunctional endocrine organ secreting bioactive molecules (osteokines) including osteocalcin (OCN), sclerostin, fibroblast growth factor‑23 and receptor activator of nuclear factor‑κB ligand/osteoprotegerin that regulate systemic metabolism, angiogenesis and immune function. In diabetic patients, dysregulated osteokine secretion, characterized by reduced OCN and elevated sclerostin, establishes a catabolic milieu that impairs wound healing capacity. Controlled bone injury triggers substantial osteokine release, with platelet‑derived growth factor‑BB…
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