Midkine is a Potential Novel Biomarker for Acro-osteolysis in Systemic Sclerosis

Background: Digital acro-osteolysis can result from ischemia and is a complication of systemic sclerosis (SSc). Midkine (MK) is an angiogenic growth factor that plays a key role in bone remodeling. The objective of this study was to examine serum MK level as a biomarker of acro-osteolysis in SSc. Methods: The study population consisted of patients who consented to undergo ethics approval at two institutions and had Raynaud's phenomenon (RP), abnormal capillaroscopy, and hand radiographs. Age- and sex-matched healthy controls without hypertension, Raynaud phenomenon, or digital lesions were included. Serum MK concentration was measured using an enzyme-linked immunosorbent assay. An analysis of variance test assessed the differences in MK concentrations among SSc patients with acro-osteolysis, SSc patients without acro-osteolysis, and age-and sex-matched healthy controls. Results: A total of 54 SSc registry patients and 20 age-sex matched healthy controls were included in the cross-sectional analysis of MK levels. Except for digital ulcers, there were no sociodemographic or clinical features that were statistically significantly associated with the presence of acro-osteolysis. There were significantly higher MK levels between SSc without acro-osteolysis than in acro-osteolysis (p=0.0001), as well as in SSc without acro-osteolysis and in healthy controls (p=0.01). There were no significant differences between SSc patients with acro-osteolysis and healthy controls (p=0.31). Conclusions: Our study suggests that MK may maintain an intact digital tip in SSc patients. A reduction in serum MK level is associated with progressive digital vasculopathy,defined by the presence of acro-osteolysis. Author Contributions: TMF, VG, GA, AJD, SW, RZ contributed to the design and implementation of the research analysis of the results and to the writing of the manuscript. TMF conceived the original and supervised the project.