Clinical Heterogeneity in Response to Exercise-Based Musculoskeletal Rehabilitation: A Critical Narrative Review and...

Exercise produces a modest average benefit in musculoskeletal rehabilitation that varies by condition, comparator, and outcome, but this average conceals considerable clinical heterogeneity in baseline presentation, magnitude and direction of change, trajectory, and which outcomes improve. Evidence on this variation is dispersed across pain science, exercise physiology, psychology, and rehabilitation research, and is often translated prematurely into treatment-matching recommendations before the underlying evidence has been shown to modify treatment effect rather than simply predict outcome.

To clarify the meaning and measurement of heterogeneous clinical response to exercise-based musculoskeletal rehabilitation, synthesise patient-related, intervention-related, and contextual determinants of response variation, distinguish prognostic factors from true treatment-effect modifiers, and propose a staged framework for evaluating apparent non-response.

Critical narrative review; no protocol was registered. PubMed, Scopus, and Web of Science Core Collection were searched from inception through 30 June 2026. Of 2675 unique records identified after deduplication, 229 were considered in full text and 60 were included, comprising direct and indirect evidence together with conceptual or methodological sources. Screening and selection were undertaken by a single author, disclosed as a limitation.

Four overlapping forms of clinical heterogeneity are distinguished. Apparent non-response is frequently attributable to measurement artefact, incomplete treatment exposure, or a mismatch between the intervention and the patient's principal limitation rather than a fixed inability to benefit. Across seven candidate domains of determinants, most evidence is associative, prognostic, mechanistic, or indirect rather than confirmatory of validated treatment-by-characteristic interactions. A five-stage clinical response framework is proposed, linking baseline characterization, treatment-target specification, documented exposure, trajectory evaluation, and adaptation.

Clinical heterogeneity in exercise-based musculoskeletal rehabilitation is multidimensional and explained mainly by prognostic, mechanistic, or contextual factors rather than confirmed treatment-effect modifiers. The proposed staged framework offers a testable, evidence-informed approach to evaluating apparent non-response, pending prospective validation.