Musculoskeletal pathology as an early warning sign of systemic amyloidosis: a systematic review of amyloid deposition and orthopedic surgery

Abstract

Background: Transthyretin and immunoglobulin light-chain amyloidoses cause amyloid deposition throughout various organ systems. Recent evidence suggests that soft tissue amyloid deposits may lead to orthopedic conditions before cardiac manifestations occur. Pharmacologic treatments reduce further amyloid deposits in these patients. Thus, early diagnosis improves long term survival. Questions/purposes: The primary purpose of this systematic review was to characterize the association between amyloid deposition and musculoskeletal pathology in patients with common orthopedic conditions. A secondary purpose was to determine the relationship between amyloid positive biopsy in musculoskeletal tissue and the eventual diagnosis of systemic amyloidosis. Methods: We performed a systematic review using PRISMA guidelines. Inclusion criteria were level I-IV evidence articles that analyzed light-chain or transthyretin amyloid deposits in common orthopedic surgeries. Study methodological quality, risk of bias, and recommendation strength were assessed using MINORS, ROBINS-I, and SORT. Results: This systematic review included 24 studies for final analysis (3606 subjects). Amyloid deposition was reported in five musculoskeletal pathologies, including carpal tunnel syndrome (transverse carpal ligament and flexor tenosynovium), hip and knee osteoarthritis (synovium and articular cartilage), lumbar spinal stenosis (ligamentum flavum), and rotator cuff tears (tendon). A majority of studies reported a mean age greater than 70 for patients with TTR or AL positive amyloid. Conclusions: This systematic review has shown the presence of amyloid deposition detected at the time of common orthopedic surgeries, especially in patients ≥70 years old. Subtyping of the amyloid has been shown to enable diagnosis of systemic light-chain or transthyretin amyloidosis prior to cardiac manifestations. Level of evidence: Level IV.