Background: Joint replacement implants are usually manufactured from cobalt-chromium or titanium alloys. After the device is implanted, wear and corrosion generate metal particles and ions, which are released into local tissue and blood. The metal debris can cause a range of adverse local and systemic effects in patients. Research problem: In the case of cobalt and chromium, a blood level exceeding 7 µg L-1 indicates potential for local toxicity, and a failing implant. It has been repeatedly suggested in the literature that measurement of titanium could also be used to assess implant function. Despite an increasing interest in this biomarker, and growing use of titanium in orthopaedics, it is unclear what blood concentrations should raise concerns. This is partly due to the technical challenges involved in the measurement of titanium in biological samples. Aim: This Review summarises blood/serum titanium levels associated with well-functioning and malfunctioning prostheses, so that the prospects of using titanium measurements to gain insights into implant performance can be evaluated. Conclusion: Due to inter-laboratory analytical differences, reliable conclusions regarding "normal" and "abnormal" titanium levels in patients with orthopaedic implants are difficult to draw. Diagnosis of symptomatic patients should be based on radiographic evidence combined with blood/serum metal levels.

Carcinogenic forms of chromium might arise in vital organs of total joint arthroplasty patients. Further studies are warranted with patients with metal-on-metal implants, which tend to have an increased release of cobalt and chromium compared to metal-on-polyethylene hips.

Background: Hip implants are usually manufactured from cobalt-chromium and titanium alloys. As the implants wear and corrode, metal debris is released into the surrounding tissue and blood, providing a potential biomarker for their function. Whilst there are laboratory reference levels for blood cobalt and chromium in patients with well and poorly functioning hip implants, there are no such guidelines for titanium. This is despite the increasing use of titanium implants worldwide. Patients and methods: We recruited a consecutive series of 95 patients (mean age 71 years, mean time after surgery 8.5 years) with one hip implant type, inserted by the same surgeon. We assessed clinical and radiological outcome, and measured blood and plasma titanium using high resolution inductively-coupled plasma mass spectrometry. Results: The upper normal reference limit for blood and plasma titanium was 2.20 and 2.56 g L-1 , respectively, and did not differ significantly between males and females. Conclusion: We are the first to propose a laboratory reference level for blood and plasma titanium in patients with well-functioning titanium hip implants. This is an essential starting point for further studies to explore the clinical usefulness of blood titanium as a biomarker of orthopaedic implant performance, and comes at a time of considerable controversy regarding the use of certain titanium alloys in hip arthroplasty.