Abstract Background Surgical treatment for lumbar spinal stenosis (LSS), carpal tunnel syndrome (CTS), total hip arthroplasty (THA), and total knee arthroplasty (TKA) have individually been proposed as early risk markers for amyloidosis. However, the association between multiple musculoskeletal procedures and amyloidosis risk remains unclear. Purpose To assess whether undergoing multiple musculoskeletal procedures is associated with an increased incidence of amyloidosis compared to a single procedure using a nationwide cohort". Methods This nationwide cohort study used Danish national health registries to identify patients aged 18 undergoing LSS, CTS, THA, or TKA between January 1, 1996, and December 31, 2020. The baseline was defined as discharge following the first procedure, and patients with prior amyloidosis were excluded. Individuals were categorized based on the number of musculoskeletal procedures: one, two, or more than two. Age was used as the underlying time scale, and time-dependent covariates updated at exposure group transition. Time-dependent Cox proportional hazards models estimated hazard ratios (HR) for amyloidosis, adjusting for atrial fibrillation, malignancy, diabetes, liver disease, chronic renal failure, stroke, and heart failure. Patients with only one procedure served as the reference. Results The cohort included 446,773 patients who underwent their first musculoskeletal procedure (41.8% men, median age 67.9 years (IQR 59.8-74.9)). Patients were categorized into three groups: 359,199 patients underwent a single procedure (Group 1), 77,533 underwent two procedures (Group 2), and 10,041 underwent more than two procedures (Group 3). The median follow-up time was 7.1 years (IQ 3.6-11.7) in Group 1, 5.2 years (IQR 2.5-8.9) in Group 2, and 4.2 (IQR 2.0-7.4) in Group 3. During follow-up, amyloidosis was diagnosed in 450 patients in Group 1, 215 patients in Group 2, and 45 in Group 3. The prevalence of heart failure was higher in Group 2 (5.0%) and Group 3 (6.7%) compared to Group 1 (3.1%, P0.0001). Similarly, atrial fibrillation was more prevalent at baseline in Group 2 (9.7%) and Group 3 (11.9%) compared to Group 1 (6.3%, P0.0001). In males, the risk of amyloidosis increased with the number of musculoskeletal procedures, with a hazard ratio (HR) of 5.17 (95% CI: 4.08–6.54) for those undergoing two procedures and 11.34 (95% CI: 7.64–16.82) for those undergoing more than two procedures. In females, the HR was 2.78 (95% CI: 1.88-4.13) for two procedures and 9.88 (95% CI: 5.64-17.32) for more than two procedures. Conclusion We found a dose-response relationship between number of musculoskeletal procedures and incident amyloidosis. Future studies on screening for amyloidosis should consider these results.
Noory et al. (Sat,) studied this question.