The pre-, and post-market evaluation and outcome of Uncemented Total knee replacements and their effect on patient safety

This thesis investigates the performance and durability of modern uncemented TKR, with a specific focus on the risk of aseptic loosening, a complication where the prosthesis detaches from the bone without infection. As more younger and active patients require TKR, uncemented fixation, which relies on bone ingrowth rather than cement, has gained interest due to its potential for durable long-term stability. This thesis is divided into two parts: the first part focuses on pre-market evaluations, and the second part addresses post-market surveillance. The pre-market studies aim to identify early warning signs of potential long-term failure, allowing high-risk implants to be recognized before widespread clinical use. The post-market evaluation assesses the real-world performance of uncemented TKR, examining functional outcomes, migration patterns, and revision risks. In the first part, Chapter 2 presents a laboratory study that assessed the osteogenic response of human osteoblasts and osteoclasts to different uncemented surface materials commonly used in uncemented TKR. Chapters 3 and 4 consisted of systematic reviews and meta-analyses of studies investigating TKR survival and studies utilizing radiostereometric analysis (RSA) to evaluate early implant migration. The results demonstrated that trabecular titanium surfaces stimulated higher osteoblast activity and lower osteoclast activation compared to hydroxyapatite-coated surfaces, suggesting a more favorable environment for bone ingrowth. The meta-analysis of RSA studies revealed that most implant migration occurs within the first six months post-surgery, with migration patterns differing mainly among uncemented TKRs depending on their surface modifications. Additionally, fixation-specific migration thresholds were established by correlating early migration data with long-term revision rates, offering a reliable tool to predict the risk of aseptic loosening up to 15 years for newly introduced implants during the pre-market evaluation phase. In the second part, Chapter 5, 6, 7, and 8 evaluated the short-term migration, and short- and long-term clinical and patient-reported outcomes and imaging diagnostics of bone scintigraphy with SPECT/CT of modern uncemented TKR. Chapter 5 showed that these implants provided rigid short-term fixation, strengthening the evidence that they can offer durable long-term fixation with a low risk of aseptic loosening. Chapter 6 demonstrated that a newly introduced uncemented design resulted in significant short-term improvements in function and low revision rates. Chapter 7 evaluated the diagnostic accuracy of bone scintigraphy with SPECT/CT in patients with uncemented TKR suspected of aseptic loosening, showing high specificity and supporting its use as an adjunct diagnostic tool, while recommending cautious interpretation of inconclusive scans. Chapter 8 confirmed that a semi-modern uncemented implant design provided durable fixation and sustained functional outcomes up to 15 years postoperatively, even in patients with a history of prior knee surgery. Chapters 9 and 10 examined the impact of surface modifications and constraint designs of uncemented TKR on the 10-year risk of aseptic loosening, using data from the Dutch Arthroplasty Register. These chapters revealed significant differences in risk related to these factors, showing that modern surface modifications carry a lower risk comparable to cemented implants, while cruciate ligament retaining designs have a lower risk of loosening than posterior cruciate ligament sacrificing designs. In summary, this thesis highlights the importance of combining pre-market and post-market evaluations to comprehensively assess uncemented total knee replacements. The findings provide new insights into the evaluation of uncemented TKR and contribute to the further development of guidelines for their safe and effective clinical application.