[Application of osteoclast-inhibitory strategy based on RANKL/OPG signaling pathway in hip-preserving treatment of osteonecrosis of the femoral head].

Abstract

Objective: To explore application effect of osteoclast inhibition based on nuclear factor-κB receptor activator ligand(RANKL)/osteoprotegerin(OPG) signaling pathway in hip preservation treatment of femoral the head necrosis (ONFH), and to compare therapeutic efficacy differences between osteoclast inhibition combined with core decompression and simple core decompression.

Methods: Sixty-four patients with Association Research Circulation Osseous(ARCO) stageⅠ-Ⅱ ONFH who underwent unilateral core decompression treatment from January 2021 to June 2024 were selected, and were divided into experimental group and control group based on intervention method and propensity score matching method. There were 32 patients in experimental group, including 21 males and 11 females;aged from 26 to 61 years old with an average of (48.9±6.8) years old;body mass index(BMI) ranged from 18.5 to 30.7 kg·m^-2 with an average of (23.0±4.1) kg·m^-2;10 patients were hormone-related and 22 patients were alcohol-related;3 patients were stageⅠand 29 patients were stageⅡaccording to ARCO grading;core decompression combined with osteoclast inhibition were performed. There were 32 patients in control group, including 21 males and 11 females;aged from 27 to 61 years old with an average of (49.2±6.4) years old;BMI ranged from 18.2 to 30.5 kg·m^-2 with an average of (22.5±4.3) kg·m^-2;10 patients were hormonal origin and 22 patients were alcoholic origin;3 patients were stageⅠand 29 patients were stageⅡaccording to ARCO grading;core decompression treatment was performed. At 12 months after operation, visual analogue scale (VAS), Harris hip score, classification of bone marrow edema (edema, E0-E3), and fibrosis stage (fibrosis, F0-F2) , the levels of serum RANKL and OPG, as well as RANKL/OPG ratio between two groups were compared;and the incidence of adverse reactions between two groups were compared.

Results: Both of groups were followed up, and follow-up period for experimental group for 12 to 14 months with an average of (12.9±0.9) months, and for control group for 12 to 14 months with an average of (12.7±0.7) months, there was no statistically significant difference between two groups (P<0.05). At 12 months after operation, serum RANKL level and RANKL/OPG ratio in experimental group were(570.8±125.6) pg·mL^-1 and(1.83±0.51) respectively, which were lower than those in control group [(681.5±82.1) pg·mL^-1 and (2.21±0.49)], and the differences were statistically significant (P<0.05). The scores for bone marrow edema and fibrosis in experimental group were both lower than those before operation, and were even lower than those in control group (P<0.05). VAS and Harris scores of experimental group were (2.13±0.82) and (85.8±9.80), which were better than those of control group (2.83±1.13) and (79.2±9.10), and the differences were statistically significant (P<0.05);Harris pain and function scores of experimental group were(38.2±4.8) and(40.5±5.5), which were higher than those of control group (35.0±4.6) and (37.5±5.2), and the differences were also statistically significant (P<0.05). There was no statistically significant difference in incidence of adverse reactions between two groups (P>0.05).

Conclusion: The osteoclast inhibition strategy based on RANKL/OPG signaling pathway could enhance therapeutic effect of core decompression. Denosumab could inhibit activation of osteoclasts, alleviate vicious cycle of bone marrow edema, inflammatory response and oxidative stress, and combined with core decompression surgery could effectively relieve pain, improve hip joint function, and has good safety. This provides a new and effective treatment option for ONFH.