Patients with metal containing joint replacement have increased Metal Concentrations in CSF: JAMA

Researchers have found in a new study that patients with metal-containing joint replacements had significantly higher concentrations of cobalt in their cerebrospinal fluid (CSF) compared to those without arthroplasties. However, the study did not determine whether these increased metal levels led to adverse clinical effects. The study was published in JAMA Network Open by Anastasia R. and colleagues.

The NeuroWear trial was a hospital-based, single-site cross-sectional study between November 2019 and April 2018. Laboratory and investigation staff were blinded to group assignments. Patients undergoing elective surgery under spinal anesthesia or lumbar puncture at a university medical center were eligible for enrollment. There were 204 patients analyzed, of whom 103 had at least one large joint replacement and 101 age- and sex-matched arthroplasty-naive controls. Data analysis was conducted from May 2023 to February 2024.

Concentrations of arthroplasty-related metals, such as aluminum, cobalt, chromium, molybdenum, nickel, niobium, tantalum, titanium, vanadium, and zirconium, were measured in CSF, whole blood, and serum. The main aim was to compare metal concentrations between patients with and without joint implants.

Key Findings

• Cobalt Concentrations in CSF: Patients with implants had a significantly greater median concentration of cobalt in CSF (0.03 µg/L; range, 0.01-0.64) compared with controls (0.02 µg/L; range, 0.01-0.19).

• Blood Metal Concentrations: Whole blood concentrations of cobalt (0.27 vs. 0.16 µg/L), chromium (0.47 vs. 0.42 µg/L), titanium (8.05 vs. 7.15 µg/L), niobium (0.02 vs. 0.01 µg/L), and zirconium (0.05 vs. 0.03 µg/L) were all significantly greater in patients with implants than in controls.

• CSF Metal Accumulation: Increased CSF concentrations of titanium (0.75 vs. 0.57 µg/L), niobium (0.02 vs. 0.01 µg/L), and zirconium (0.05 vs. 0.04 µg/L) were found in implant patients, especially if these metals were increased in serum.

• Cobalt-Specific Transport Mechanisms: A high correlation between cobalt concentrations in CSF and both serum (r=0.72) and whole blood (r=0.82) indicated cobalt-specific transport across neural barriers.

• Cobalt-Chromium-Molybdenum Implants: Patients with these implant materials had significantly elevated median chromium levels in CSF (0.31 vs. 0.23 µg/L) than controls.

The NeuroWear study showed that metals used in arthroplasty, such as cobalt, chromium, titanium, niobium, and zirconium, are able to accumulate in CSF and even pass through neural barriers. The clinical implications of this finding are not certain, but further investigation is required to determine whether metal accumulation in CSF causes neurotoxicity, especially in at-risk patient groups.

Reference:

Rakow A, Kowski A, Treskatsch S, et al. Metal Concentrations in Blood and Cerebrospinal Fluid of Patients With Arthroplasty Implants. JAMA Netw Open. 2025;8(3):e252281. doi:10.1001/jamanetworkopen.2025.2281