Growth Hormone Cartilage Regenerative Potential for Knee Osteoarthritis: a Systematic Review of Preclinical Animal Studies

Purpose: Currently, no osteoarthritis (OA) nonsurgical therapeutic modality targets its degenerative pathogenesis. Growth hormone (GH) promotes growth effects on bone and cartilage. Therefore, this study aimed to review the best evidence in preclinical studies regarding the potential of intra-articular GH injection in knee osteoarthritis. Methods: We searched Pubmed, ScienceDirect, and EBSCO databases using keywords and Medical Subject Headings (MeSH) terms ([(osteoarthritis OR knee osteoarthritis OR degenerative arthritis)] AND ([growth hormone OR pituitary growth hormone OR recombinant growth hormone OR somatotropin)]) for English-language study. We conducted a systematic review using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. Results: A total of four animal randomized controlled studies were identified, involving 155 samples. The knee OA was induced using collagenase injection in 83 samples (54%) and anterior cruciate ligament transection with partial medial meniscectomy in 72 samples (46%). Three studies reported significantly better Mankin microscopic scores in the GH group than in the control group (p < 0.05). All studies reported significantly better macroscopic improvement measured by Yoshimi score and better clinical outcomes assessed by faster lameness period and returned to normal weight-bearing. No systemic side effects were reported. Conclusion: Growth hormone triggers early neovascularization, which is crucial in producing stem cells for cartilage regeneration and stimulates chondrocytes to synthesize type II collagen. Combination with hyaluronic acid (HA), with its large particle size, increases the GH effect duration in joints. Intra-articular GH injection has shown promising results in cartilage regeneration and repair in knee osteoarthritis, as stated in available preclinical studies, without systemic adverse effects. Lay Summary and Future Works: Early neovascularization, which is essential for the production of stem cells for cartilage repair, is stimulated by growth hormone. Combining HA with its big particle size increases the duration of the action and decreases the systemic absorption of GH in joints. Therefore, according to published preclinical animal research, intra-articular growth hormone injection and hyaluronic acid have demonstrated encouraging outcomes in cartilage regeneration and repair in knee osteoarthritis. With the promising growth hormone potential in preclinical investigations, we advocate a randomized, controlled clinical trial to evaluate the efficacy of intra-articular growth hormone injection in knee osteoarthritis.