What’s New in Musculoskeletal Basic Science 2025

New findings in musculoskeletal basic science are presented in the new JBJS Specialty Update What’s New in Musculoskeletal Basic Science. Here, we highlight 5 compelling recent studies, as selected by the author team.

Utilizing “Omics” to Enhance Diagnosis and Research

Spatial transcriptomics-based mechanomics, an approach described in a proof-of-principle study, focuses on finding links between mechanical strain magnitude within a fracture site and local changes in gene expression¹. “This spatial molecular mapping,” write Specialty Update authors Drs. Bahney et al., “has the potential to explain why some fractures heal poorly, despite adequate mechanical stability.”

Using patient-derived samples and a knockout mouse model, researchers investigating the mechanisms of fibrous nonunion in patients with congenital pseudarthrosis of the tibia found that NF1-deficient Schwann cells contributed to pseudarthrosis. MEK-SHP2 pathway inhibition was suggested as a potential therapeutic strategy for preventing fibrous nonunion in this population².

Multiomics techniques were used to study the role of leptin in osteoarthritis pain and severity. The investigators demonstrated that cartilage damage and pain were independently regulated by leptin and adipsin derived from adipose tissue outside the joint³. As Drs. Bahney et al. explain, “This new mechanistic link creates novel druggable molecular targets that could prevent or treat obesity-related osteoarthritis by addressing a root systemic cause of the disease.”

Biomarkers in Musculoskeletal Disease and Injury

A recent study evaluated the diagnostic efficacy of the degradation product of collagen X marker (CXM) as a biomarker of endochondral bone turnover in fracture assessment. The CXM values of patients with early fracture-healing peaked at 6 weeks and were higher than the 6-week values of patients with normal healing. The median time to peak CXM was 25.5 days after the fracture, which is considerably earlier than the point at which radiographic signs of healing typically appear⁴.

Next-Generation Gene Therapy

Intravenous administration of macrophage-inspired lipid nanoparticles in a post-traumatic osteoarthritic mouse model demonstrated that these nanoparticles, or “orthosomes,” accumulate in sites of articular cartilage trauma. This finding suggests that orthosomes have potential as a regenerative RNA therapeutic for tissue-specific targeting following an injury⁵.

What’s New in Musculoskeletal Basic Science is freely available at JBJS.org.

What’s New by Subspecialty

Each month, JBJS publishes a review of the most pertinent studies from the orthopaedic literature in a select subspecialty. To read the reports, visit the What’s New by Subspecialty collection at JBJS.org.

Recent OrthoBuzz posts include: What’s New in Musculoskeletal Tumor Surgery, What’s New in Musculoskeletal Infection, and What’s New in Orthopaedic Rehabilitation.

References

1. Mathavan N, Singh A, Marques FC, Günther D, Kuhn GA, Wehrle E, Müller R. Spatial transcriptomics in bone mechanomics: exploring the mechanoregulation of fracture healing in the era of spatial omics. Sci Adv. 2025 Jan 3;11(1):eadp8496.
2. Perrin S, Protic S, Bretegnier V, Laurendeau I, de Lageneste OD, Panara N, Ruckebusch O, Luka M, Masson C, Maillard T, Coulpier F, Pannier S, Wicart P, Hadj-Rabia S, Radomska KJ, Zarhrate M, Ménager M, VidaudD, Topilko P, Parfait B, Colnot C. MEK-SHP2 inhibition prevents tibial pseudarthrosis caused by NF1loss in Schwann cells and skeletal stem/progenitor cells. Sci Transl Med. 2024 Jun 26;16(753):eadj1597.
3. Collins KH, Lenz KL, Welhaven HD, Ely E, Springer LE, Paradi S, Tang R, Braxton L, Akk A, Yan H, Zhang B, Wu X, Atkinson JP, Oestreich AK, June RK, Pham CTN, Guilak F. Adipose-derived leptin and complement factor D mediate osteoarthritis severity and pain. Sci Adv. 2025 Apr25;11(17):eadt5915.
4. Working ZM, Czachor ME, Nelson AL, O’Hara KM, Lancaster K, HellwinkelJE, Whitney K, Marchand LS, Bzovskys S, DeKeyser GJ, Friess DM, Miclau T, Horton WA, Sprague SA, O’Hara NN, Johnstone B, PierpointLA, Slobogean GP, Bahney CS; Vita-Shock Investigators. Efficacy of biomarkers in the endochondral phase of fracture repair and healing in long bones: a clinical observational study. PLoS Med. 2025 Aug29;22(8):e1004640.
5. Mancino C, Pasto A, De Rosa E, Dolcetti L, Rasponi M, McCulloch P, Taraballi F. Immunomodulatory biomimetic nanoparticles target articular cartilage trauma after systemic administration.  2023 May 28;9(6):e16640.