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.

TRIM32 is a candidate gene at the 9q33.1 genetic susceptibility locus for hip osteoarthritis (OA). Increased cartilage degradation typical of OA has previously been demonstrated in Trim32 knockout mice.

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 knockout (T32KO) and wild-type (WT) mice was compared following stimulation with IL1α or retinoic acid (RA) and was assessed by DMMB assay (n=4/group). Expression of chondrocyte phenotype markers was measured by qPCR and compared between articular chondrocytes from WT and T32KO mice following catabolic (IL1α/TNFα) or anabolic (Oncostatin-M (OSM)/IGF1) stimulation.

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 Col2a1 (p=8.53×10⁻⁵), and Sox9 (p=2.35×10⁻⁶). Upon IL1α treatment, T32KO chondrocytes expressed increased Col10a1 (p=0.0003). Upon anabolic stimulation, T32KO chondrocytes expressed increased Col2a1 (OSM: p=0.001; IGF: p=0.001), and reduced Sox9 (OSM: p=0.0002; IGF: p=0.0006).

These results indicate that altered TRIM32 expression in human articular tissue is associated with OA, and that Trim32 knockout results in increased cartilage degradation in murine femoral head explants. Predisposition to cartilage degeneration with reduced Trim32 expression may involve increased chondrocyte hypertrophy upon catabolic cytokine stimulation and dysregulation of Col2a1 and Sox9 expression upon anabolic stimulation.