Efficacy and safety of stem cell therapy for the early-stage osteonecrosis of femoral head: a systematic review and meta-analysis of randomized controlled trials

Abstract

Background Osteonecrosis of femoral head (ONFH) is a seriously degenerative disease with no effective therapies to slow its progression. Several studies have reported short-term efficacy of stem cells on early-stage ONFH. However, its long-term effect was still unclear especially on progression events. This study was performed to evaluate the long-term efficacy and safety of stem cells and analyze its optimal age group and cell number. Methods Our review was registered on PROSPERO (http://www.crd.york.ac.uk/PROSPERO), registration number CRD42020136094. Following PRISMA guideline, we searched 8 electronic databases on January 5, 2020, and rigorous random controlled trials (RCTs) utilizing stem cell therapy on early-stage ONFH were included. Quality and bias were analyzed. Pooled analysis was performed to assess difference between various outcomes. Results A total of 13 RCTs (619 patients with 855 hips) were included. The application of stem cells significantly delayed collapse of femoral head(I2, 70%; RR, 0.54; 95% CI, 0.33 to 0.89; P < .00001) and total hip replacement (THR) (I2, 68%; RR, 0.55; 95% CI, 0.34 to 0.90; P = .02) in the long term. It effectively decreased the events of collapse of femoral head (≥ 60 months) (I2, 0%; RR, 0.37; 95% CI, 0.28 to 0.49; P < .00001) and THR (> 36 months) (I2, 0%; RR, 0.32; 95% CI, 0.23 to 0.44; P < .00001). There existed a beneficial effect for patients under 40 (Collapse of femoral head: I2, 56%; RR, 0.41; 95% CI, 0.23 to 0.76; P = .004) (THR: I2, 0%; RR, 0.31; 95% CI, 0.23 to 0.42; P < .00001). In addition, quantity of stem cells at 108 magnitude had better effects on disease progression events (I2, 0%; RR, 0.34; 95%CI, 0.16 to 0.74; P = .007). Besides, there were no significant differences on adverse events between the stem cell group and control group (I2, 0%; RR, 0.82; 95% CI, 0.39 to 1.73; P = .60). Conclusion Our findings build solid evidence that stem cell therapy could be expected to have a long-term effect on preventing early-stage ONFH patients from progression events, such as collapse of femoral head and total hip replacement. Furthermore, patients under 40 may be an ideal age group and the optimal cell number could be at 108 magnitude for this therapy. Further studies including strict RCTs are required to evaluate a clear effect of stem cells on ideal patient profile and the procedures of implantation.

Knowledge structure and emerging trends on osteonecrosis of the femoral head: a bibliometric and visualized study

“…Based on current trends, Mont et al [ 23 ] reported that the total number of individuals affected by ONFH is estimated to reach 20 million by next 10 years worldwide. Besides, the increase in annual publications is inseparable from the advances in basic research and clinical trials in recent years [ 24 , 25 ].…”

Osteonecrosis of the Femoral Head Safely Healed with Autologous, Expanded, Bone Marrow-Derived Mesenchymal Stromal Cells in a Multicentric Trial with Minimum 5 Years Follow-Up

“…Remarkable aspects in the study include the clinical use of a high dose of expanded autologous MSC (140-million cells total dose), higher than other reported trials. Interestingly, a cell dose of 1 × 10 8 (100 million cells) has been defined in a meta-analysis as a threshold for better effects on disease progression [ 32 ]. This dose safely obtained the clinical and radiological healing of femoral head in our study, both in males and females, despite the limited number of cases in such an early trial.…”

Cell therapy for osteonecrosis of femoral head and joint preservation

“…A meta-analysis of ONFH, in 13 RCTs 619patients (855 hips) published, 49 show clear evidence in support of stem cell therapy to slow down the femoral head collapse and total hip replacement. Ideal age is found to be less than 40 years and optimal cell count of 108 for this treatment.…”