Background The α-melanocyte-stimulating hormone (α-MSH), an endogenous neuropeptide derived from proopiomelanocortin (POMC), has been identified to suppress inflammation and prevent osteoblast damage. Objective The present study was aimed to investigate the role of serum α-MSH in non-traumatic osteonecrosis of the femoral head (ONFH). Methods Seventy-nine patients diagnosed with non-traumatic ONFH and 79 sex- and age-matched healthy controls were enrolled in the study. Serum α-MSH concentrations were examined with a double antibody radioimmunoassay. The radiographic progression of ONFH was assessed by X-ray plain film according to the FICAT grading system. The symptomatic severity was evaluated by visual analogue scale scores, Harris hip scores and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores. The serum concentrations of protective marker adiponectin and bone necrosis inflammation factor IL-33 concentrations were also examined. The receiver operating characteristic (ROC) analysis curve was performed to explore the diagnostic value of α-MSH, adiponectin and IL-33 for radiographic progression. Results Serum α-MSH concentrations were significantly lower in ONFH patients than in healthy controls. The case group included 29 non-traumatic ONFH patients with FICAT grade I/II, 27 with grade III and 23 with grade IV. ONFH patients with grade I/II had significantly higher α-MSH concentrations in serum compared with those with FICAT grades III and IV. ONFH patients with FICAT grade III showed significantly elevated concentrations of α-MSH in serum compared with those with FICAT grade IV. Serum α-MSH concentrations were negatively associated with radiographic progression by FICAT grading system, and symptomatic severity defined by visual analogue scale scores, Harris hip scores and WOMAC scores. In addition, serum α-MSH concentrations were positively related to the expression of adiponectin and negatively associated with IL-33. ROC analysis curve demonstrated that α-MSH exhibited the equal value for the diagnosis of ONFH radiographic progression compared with IL-33. Conclusions Serum α-MSH may act as a protective biomarker for non-traumatic ONFH. Systematic application of α-MSH serving as an adjunctive therapy for treating non-traumatic ONFH deserves further investigation.

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