Precision Medicine Approaches to Orthopedics and Sports Medicine: From Molecular Profiling to Individualized Care

Musculoskeletal disorders — encompassing conditions of bone, cartilage, tendon, ligament, and skeletal muscle — are among the leading contributors to disability worldwide, yet they remain highly heterogeneous in their molecular pathophysiology, clinical presentation, and therapeutic response. This heterogeneity has long constrained the effectiveness of one-size-fits-all treatment paradigms in orthopedics and sports medicine. The emergence of precision medicine offers a transformative opportunity: by integrating individual-level molecular, genomic, and digital data, clinical decision-making can move toward truly personalized strategies that predict disease trajectory, guide treatment selection, and optimize patient outcomes.

Progress in multi-omics technologies — including genomics, transcriptomics, proteomics, and metabolomics — has begun to reveal the molecular subtypes underlying osteoarthritis, tendinopathy, stress fracture susceptibility, and musculoskeletal degeneration. Concurrently, advances in quantitative imaging, liquid biopsy, circulating biomarkers, and wearable sensor technologies are providing new windows into real-time, patient-specific musculoskeletal biology. Artificial intelligence and machine learning models are enabling the integration of these diverse data streams into predictive tools that can stratify patients, forecast surgical outcomes, and personalize rehabilitation. Yet, the translation of these molecular insights into routine clinical practice in orthopedics and sports medicine remains nascent. Significant gaps persist between biomarker discovery and validated clinical application, between patient subtyping frameworks and guideline-concordant treatment, and between proof-of-concept studies and real-world precision care.

This Research Topic invites contributions that advance precision medicine in orthopedics and sports medicine, with an emphasis on patient-level molecular characterization, biomarker-guided clinical decision-making, and individualized therapeutic strategies. We welcome articles addressing, but not limited to, the following themes:
o Molecular subtyping and patient stratification in musculoskeletal diseases: genomic, epigenomic, transcriptomic, and proteomic profiling of osteoarthritis, tendinopathy, bone stress injuries, and related conditions to define biologically meaningful patient subgroups
o Biomarker discovery and clinical validation: circulating biomarkers (serum, synovial fluid, or plasma), imaging-based biomarkers (radiomics, quantitative MRI), and wearable-derived digital biomarkers for precision diagnosis, disease monitoring, and prognosis in orthopedic and sports medicine populations
o Pharmacogenomics and individualized therapeutic selection: genetic and molecular determinants of response to biologics, analgesics, orthobiologics (PRP, MSC-based therapies), or surgical interventions in musculoskeletal conditions
o AI and machine learning for individualized outcome prediction: patient-specific models integrating clinical, molecular, imaging, and sensor data to predict surgical outcomes, injury risk, rehabilitation trajectories, and return-to-sport timelines
o Application of new surgical and minimally invasive techniques, including computer-navigated or AI-assisted procedures: precision-guided surgical approaches that incorporate patient-specific anatomical, biomechanical, or molecular data to optimize intraoperative decision-making, implant selection, and postoperative outcomes in orthopedics and sports medicine
o Multi-omics and systems medicine approaches applied to the pathogenesis of musculoskeletal disorders, with a focus on clinically actionable targets and patient-stratification implications
o Development and evaluation of biomaterials and tissue-engineered constructs for orthopedic applications: patient-informed design of scaffolds, hydrogels, and composite constructs that leverage individual biological profiling to enhance tissue integration, regeneration, and functional recovery across bone, cartilage, tendon, and muscle repair
o Patient-specific and precision regenerative strategies: individualized cell-based therapies, gene therapy applications, or personalized biomaterial platforms designed based on the patient’s molecular or cellular profile
o Precision clinical trials and biomarker-stratified study designs in orthopedics and sports medicine: adaptive trial designs, enrichment strategies, and patient-reported outcome integration in molecularly defined cohorts

Article types and fees

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Case Report
• Clinical Trial
• Data Report
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• ... View all formats

Articles that are accepted for publication by our external editors following rigorous peer review incur a publishing fee charged to Authors, institutions, or funders.

Article types

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Case Report
• Clinical Trial
• Data Report
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Review
• Study Protocol
• Systematic Review
• Technology and Code

Keywords: Precision orthopedics, Musculoskeletal multi-omics, Biomarker-guided patient stratification, Inflammatory phenotyping and precision rehabilitation, AI-assisted clinical decision-making

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.