Patients with Paget's Disease of Bone (PDB) more frequently require total hip arthroplasty (THA) and total knee arthroplasty (TKA). However, controversy remains regarding their outcome. This project aims to evaluate the current literature regarding outcomes following THA and TKA in PDB patients. MEDLINE, EMBASE and Cochrane databases were searched on February 15th, 2022. Inclusion criteria comprised studies evaluating outcomes following THA/TKA in PDB patients. Quality of included studies was assessed using the Newcastle-Ottawa Scale. 19 articles (published between 1976–2022) were included, comprising 58,695 patients (48,766 controls and 10,018 PDB patients), from 209 potentially relevant titles. No study was of high quality. PDB patient pooled mortality was 32.5% at mean 7.8(0.1-20) years following THA and 31.0% at mean 8.5(2-20) years following TKA. PDB patient revision rate was 4.4% at mean 7.2(0-20) years following THA and 2.2% at mean 7.4(2-20) years following TKA. Renal complications, respiratory complications, heterotopic ossification, and surgical site infection were the most common medical and surgical complications. The largest systematic review, to date, evaluating outcomes following THA and TKA in PDB patients. All functional outcome scores improved. PDB patient revision rate was comparable to UK National Joint Registry. However, there is a significant need for prospective matched case-control studies to robustly compare outcomes in PDB patients with unaffected counterparts.
The arcOGEN study identified the 9q33.1 locus as associated with hip osteoarthritis (OA) in females. TRIM32 lies within this locus and may have biological relevance to OA; it encodes a protein with E3 ubiquitin ligase activity. Sanger sequencing of TRIM32 in the youngest 500 female patients with hip OA from the arcOGEN study identified genetic polymorphisms in the proximal promoter, and 3'untranslated region of TRIM32 that are disproportionately represented in female patients with hip OA compared to the control population. Reduced expression of TRIM32 was identified in femoral head articular chondrocytes from patients with hip OA compared to control patients. Trim32 knockout resulted in increased aggrecanolysis in murine femoral head explants. Murine chondrocytes deficient in Trim32 exhibited increased expression of mature chondrocyte markers following anabolic cytokine stimulation, and increased expression of hypertrophic chondrocyte markers following catabolic cytokine stimulation. Trim32 knockout mice demonstrated increased cartilage degradation and tibial subchondral bone changes after surgically-induced knee joint instability. Increased cartilage degradation and medial knee subchondral bone changes were also identified in aged Trim32 knockout mice. These results further implicate TRIM32 in the genetic predisposition to OA, and indicate a role for TRIM32 in the joint degeneration evident in OA. These results support the further study of TRIM32 in the pathophysiology of OA and development of novel therapeutic strategies to manage OA.
Our aim is to investigate the role of TRIM32 in human and murine articular tissue. TRIM32 expression in human articular cartilage was examined by immunostaining. TRIM32 expression was compared in femoral head chondrocytes from patients with and without primary hip OA (n=6/group) and examined by Western blotting. Aggrecanolysis by femoral head explants from TRIM32 expression was demonstrated in human articular cartilage; TRIM32 expression by chondrocytes was reduced in patients with hip OA (p=0.03). Greater aggrecanolysis occurred in cartilage explants from T32KO mice after treatment with no stimulation (p=0.03), IL1α (p=0.02), and RA (p=0.001). Unstimulated T32KO chondrocytes expressed reduced These results indicate that altered TRIM32 expression in human articular tissue is associated with OA, and that
Paget's disease of bone (PDB) is the second most common metabolic bone disease. Osteoarthritis (OA) affects one-third of patients with PDB. The incidence of THR (total hip replacement) and TKR (total knee replacement) is 3.1- and 1.7-fold higher in PDB patients compared to non-affected age-matched controls. No large studies or joint registry reports exist describing the outcomes following THR or TKR in patients with PDB. The objectives of this study were to investigate the outcomes following THR and TKR in patients with PDB using national joint registry data. 144 THR and 43 TKR were identified using the Scottish Arthroplasty Project from 1996–2013. For THR, the most common early post-operative surgical complications were haematoma formation (1.4%), and surgical site infection (1.4%). The absolute incidence during follow-up of dislocation was 2.8%, and revision hip arthroplasty was performed in 2.8% of cases. Implant survival of the primary prosthesis was 96.3% (CI: 92.8 – 99.8) at 10-years, and patient survival was 50.0% (39.6 – 60.4) at 10-years. For TKR, the most common early post-operative surgical complication was surgical site infection (2.3%). The absolute incidence during follow-up of revision knee arthroplasty was 4.7%. On survival analysis, implant survival of the primary prosthesis was 94.5% (CI: 87.1 – 100) at 10-years, and patient survival was 38.3% (16.7 – 59.9) at 10-years. This is the largest reported series of outcomes following primary THR and TKR in patients with PDB. PDB patients are not at increased risk of surgical complications following primary THR or TKR compared to non-PDB patients.
