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In four studies, this thesis investigates periprosthetic bone metabolism and the clinical utility of advanced imaging in total joint arthroplasty, with the overall aim of evaluating the biological and densitometric effects of pharmacological bone modulation following total hip arthroplasty (THA) and assessing the diagnostic performance of positron emission tomography/computed tomography (PET/CT) in evaluating painful hip and knee arthroplasties.

Study I examined systemic immunological and bone-related biomarkers after denosumab treatment following THA, finding that denosumab was linked to significant upregulation of receptor activator of nuclear factor κB ligand (RANKL) and reduced expression of tumour necrosis factor receptor superfamily member 9 (TNFRSF9), suggesting compensatory osteoclastogenesis stimulation potentially driving the ‘rebound phenomenon’ observed after treatment discontinuation.

Study II evaluated the long-term impact of denosumab on periprosthetic bone mineral density (pBMD) following THA. At the five-year postoperative follow-up, no significant differences in femoral or acetabular pBMD were observed between the denosumab and placebo groups. These findings suggest that early densitometric benefits of short-term antiresorptive therapy are transient and do not confer sustained protection against periprosthetic bone loss in this population.

Study III assessed the diagnostic accuracy of fluorine-18 sodium fluoride (18F-fluoride) PET/CT for detecting aseptic loosening in painful hip and knee arthroplasties. The technique demonstrated high accuracy and reproducibility, particularly for THA, but its performance was reduced for certain components in total knee arthroplasty.

Study IV compared 18F-fluorodeoxyglucose (18F-FDG) and 18F-fluoride PET/CT for diagnosing periprosthetic joint infection (PJI) using EBJIS criteria as the reference standard. 18F-FDG PET/CT demonstrated superior diagnostic accuracy, especially for THA stems and tibial components in knee arthroplasties, whereas 18F-fluoride PET/CT showed limited discriminatory capacity. Quantitative SUVmax measurements were reproducible across most implant components, supporting their potential role in standardised diagnostic assessment.

In conclusion, short-term denosumab treatment failed to confer sustained preservation of periprosthetic bone after THA. It may induce biological responses—specifically, RANKL upregulation—that contribute to rapid bone loss after treatment discontinuation. PET/CT offers valuable diagnostic support in painful arthroplasties, with 18F-fluoride PET/CT most effective for assessing mechanical loosening and 18F-FDG PET/CT demonstrating superior accuracy for detecting PJI.