Night-shift work and risk of incident musculoskeletal disorders: a prospective cohort study with proteomic mediation analysis in the UK Biobank

ntroduction Night-shift work disrupts circadian rhythms and may contribute to musculoskeletal disorders (MSDs). However, large-scale prospective evidence on this association and potential biological pathways remains limited.

Methods We conducted a prospective cohort study of 179 924 employed UK Biobank participants free of MSDs at baseline and followed for a median of 13.1 years. Night-shift exposure was classified as rare, some and usual/permanent. Cox proportional hazards models were used to estimate HRs for incident MSDs. Proteomic analyses were performed to identify circulating proteins associated with night-shift work and MSD outcomes and to evaluate their potential mediating roles.

Results Compared with day workers, all night-shift categories were associated with higher MSD risk: rare (HR 1.12, 95% CI 1.09 to 1.16), some (HR 1.13, 95% CI 1.08 to 1.17) and usual/permanent (HR 1.15, 95% CI 1.10 to 1.20). Associations were particularly evident for osteoarthritis (HR 1.23, 95% CI 1.15 to 1.32), spinal disorders (HR 1.20, 95% CI 1.05 to 1.37) and mechanical and pain disorders of the spine (HR 1.30, 95% CI 1.19 to 1.42), with stronger associations among individuals with ≥10 years of exposure. Elevated risks were most pronounced in healthcare, manufacturing, tourism and cleaning sectors. Proteomic analyses identified 78 candidate mediator proteins shared across key outcomes, including apolipoprotein F, angiotensin-converting enzyme 2 and proline-rich acidic protein 1.

Conclusion Night-shift work was associated with increased risk of multiple MSDs, and proteomic analyses suggested potential molecular pathways linking night-shift exposure to MSD risk. These findings support the importance of circadian-friendly scheduling and targeted occupational interventions to reduce MSD burden.