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However, its clinical indications and application restrictions remain unclear. This study aims to determine the clinical, histological, and radiological outcomes of a combination treatment using mechanical support and a targeted intra\u2010arterial infusion of PBSCs for painful ONFH with a cap\u2010shaped separation (CSS) cartilage defect. Compared with the standard pain management (control group), this combination treatment did not improve the Harris Hip Score (HHS) at 36 months. Micro\u2010CT and histologic analyses showed severe focal destruction in all CSS\u2010ONFH femoral heads in both the combination and control groups. Femoral heads showed a higher percentage of bone lesions in the combination treatment group than in the control group. There was no significant difference in osteoclast number in the subchondral bone areas between the two groups. A high level of expression of inflammatory cytokines, including tumor necrosis factor\u2010\u03b1 and interleukin\u20101\u03b2, was detected in blood vessels around the subchondral bone in both groups. The RANKL\/OPG (receptor activator of the nuclear factor\u2010kB ligand\/osteoprotegerin) ratio was also similar between the control and combination treatment groups. Our results indicate that this combination treatment is not an effective method for the treatment of patients with painful CSS\u2010ONFH. Moreover, this combination treatment did not inhibit inflammatory osteoclastogenesis in patients with more advanced disease. \u00a9 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. 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