Haiwei Tang ^* Tingxian Ling ^* Enze Zhao Mingke You Xi Chen ^* Gang Chen ^* Kai Zhou ^* Zongke Zhou ^*

• Department of Orthopedics, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China

The debate continues on whether combining CD with regenerative therapy provides a more effective treatment for early femoral head necrosis than CD alone. This meta-analysis endeavored to assess its efficacy.We searched PubMed, Web of Science, and Cochrane Library through July 2024 for RCTs and cohort studies evaluating the impact of CD with regenerative therapy versus CD alone in early-stage ONFH.Bias was evaluated using the Cochrane ROB 2.0 for RCTs and the NOS for cohort studies. The primary outcome was disease progression, measured by the incidence of staging advancement and THA conversion. Clinical outcomes, including VAS, HHS, WOMAC, and Lequesne index, were secondary measures. Subgroup analyses were performed for variables such as age,BMI,follow-up period,and dosage in the BMAC group, with results depicted in forest plots.Results:A total of seven RCTs and eight cohort trials involving 954 hips. CD, when combined with agents, exhibited considerably enhanced efficacy over CD alone (RR=0.55, p < 0.001) and 0.59, p = 0.001). However, a significant difference was exclusive to the CD combined with BMAC group in terms of stage progression outcomes(stage progression, RR = 0.47, p = 0.004); THA conversions, RR = 0.41, p < 0.001).Secondary outcomes showed improved results when CD was combined with other regenerative agents, such as BMSCs and BMPs, etc. In the reported data, the regenerative group 2 demonstrated significantly higher rates of subjective improvement in pain and functional outcomes compared to those in the CD group (71.74% (66/92) vs 56.38% (53/94)). Subgroup analysis revealed superior outcomes in the low-dose BMAC group and patients aged under 40 years old in stage progression rate and THA conversion rate.Conclusion: CD, when combined with regenerative therapy, can diminish hip pain and enhance functionality, but its ability to slow disease progression remains uncertain. BMAC presents a more substantiated efficacy evidence than other agents, with low-doses of BMAC in patients under 40 years potentially slowing ONFH progression. Nonetheless, the high heterogeneity and relatively short follow-up time of these studies make it difficult to draw accurate conclusions, which necessitates verification through future trials comparing CD versus CD combined with regenerative therapy, with a focus on extended follow-up periods.