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As a result of an aging population, musculoskeletal disease is a growing source of health and economic burden in the United States. In 2019, musculoskeletal conditions affected approximately 127.4 million people (more than a third of the U.S. population); they were the top driver of health-care spending in 2016, with an estimated direct annual cost of $380.9 billion. While musculoskeletal conditions represent a substantial and growing burden in terms of prevalence, disability, and health-care costs, National Institutes of Health (NIH) research funding has remained disproportionately allocated to other disease conditions. Therefore, our purpose was to provide an assessment of the current burden of musculoskeletal disease in terms of prevalence, disability, and health-care costs, and compare the changing burden of disease to trends in NIH funding.

Transthyretin cardiac amyloidosis (ATTR-CA) is a restrictive cardiomyopathy that has been associated with multiple orthopedic pathologies years before it manifests in the heart. There have been no studies on the prevalence of a wide range of shoulder pathologies in patients with cardiac amyloidosis (CA). Due to the preferential deposition of transthyretin in the soft tissues and joints, we predicted a greater prevalence of shoulder pathologies and other orthopedic manifestations in patients with ATTR-CA. This single-center, retrospective, case-control study, analyzed 1,310 patients with CA, 830 with ATTR-CA, and 480 with light-chain CA (AL-CA) from a dedicated CA REDcap database. Odds ratios comparing patients with CA to the age-matched published estimate of over 300 million patients in the general population were determined for shoulder, hip, and knee arthroplasty. Years between a patient's first shoulder pathology (i.e., shoulder arthroplasty) and the year of their diagnosis with CA were determined using data from patients with a known date of surgery. Overall, patients with ATTR-CA compared with patients with AL-CA presented more frequently with shoulder pathologies (p0.001) and at least 1 orthopedic manifestation (p0.001). The odds of patients with ATTR-CA and AL-CA aged 60 years or older who underwent shoulder arthroplasty was 6.05 times greater (95% confidence interval 4.26 to 8.60) and 1.63 times greater (95% confidence interval 0.67 to 3.94), respectively, compared with age-matched controls. Shoulder pathologies and concomitant orthopedic pathologies are common in patients with ATTR-CA and may help identify patients with CA earlier in their disease progression for earlier intervention and treatment.