Therapeutic Peptides in Orthopaedics: Applications, Challenges, and Future Directions

Rahman OF, Lee SJ, Seeds WA · JAAOS Global Research and Reviews

States that the orthopaedic peptide literature is dominated by animal models, small prospective cohorts and case series with very limited randomised trials, and that clinical use should be framed as exploratory and hypothesis-generating rather than standard of care. Groups GHK-Cu with the wound-healing peptides acting through angiogenesis, integrin-mediated matrix remodelling and fibroblast activation. Reports BPC-157 administered at 200 to 1000 mcg a day across regimens with no consensus on a therapeutic threshold, names pentadecapeptide arginate as a stabilised form, and reads the intra-articular knee case series as 17 patients with reduced symptoms in more than 90% at a minimum of six months. Groups ipamorelin, CJC-1295, tesamorelin and sermorelin as growth-hormone secretagogues acting through GH, IGF-1 and PI3K/Akt/mTOR, says that large-scale orthopaedic trials of them are lacking and that animal studies and indirect clinical evidence provide the biologic rationale, and describes AOD-9604 as a growth-hormone fragment that promotes fat metabolism without markedly altering IGF-1, citing a rabbit osteoarthritis model in which intra-articular AOD-9604 with hyaluronic acid improved cartilage morphology and a six-trial human safety meta-analysis showing no effect on serum IGF-1. Describes epithalon as a synthetic tetrapeptide derived from epithalamin, associated with melatonin regulation, circadian normalisation and telomerase activation, and says in its own words that it does not directly target musculoskeletal tissue, proposing only an indirect recovery benefit through sleep and hormonal regulation. Sets out sourcing hazards for compounded peptides (purity, potency, sterility, endotoxin contamination from direct-to-consumer suppliers) and a minimum reporting standard for future studies.

Population

Narrative review of therapeutic peptides in orthopaedic practice, grouped as wound-healing peptides (BPC-157, TB-500, GHK-Cu), growth-hormone secretagogues and AOD-9604, sleep and recovery peptides (epithalon, delta sleep-inducing peptide, pinealon) and neuroactive peptides

Intervention

n/a

Comparator

n/a

Limitations

Narrative review with no search protocol and no risk-of-bias appraisal; mechanistic framing is drawn from the dermal and pulmonary literature rather than from orthopaedic data. Its two epithalon citations are institute papers and neither is a joint study. Its 17-patient reading of the BPC-157 knee case series differs from other secondary readings of the same paper. The authors declare nothing of value received; one author is affiliated with a private peptide-medicine clinic (Redox Medical Group).