SCENIHR was requested to provide an opinion on the following: 1) To determine the short-, medium- and long-term local and systemic health effects caused by metal particles, metal ions, and metallo-organic compounds resulting from the implanted medical device and if possible to provide indications on limit values for the metals in any forms, 2) To advise on the predictive value of metal ions in body fluids, clinical strategies and other aspects needed to ensure the safety of implanted patients. Criteria that should inform the medical decision with respect to the implanted patient should be identified where possible, 3) To identify criteria regarding the safety and safe use of MoM implants used in arthroplasty, paying special attention to design and patient groups, and 4) Where relevant to identify needs for further research.

In response to the issue of short, medium and long term local and systemic health effects caused by metal particles, metal ions, metallo-organic compounds resulting from the implanted medical device, we summarise that Metal-on-Metal (MoM) hip arthroplasty leads to a release of metal products (e.g. particles and ions) which can in addition form metallo-organic compounds in the body. These products can be deposited in draining lymph nodes and internal organs and may result in local and systemic adverse health effects. However, it is not possible to determine whether these are due to metal particles, ions or metallo-organic compounds released from the implants.

Local responses consist of a broad clinical spectrum ranging from small asymptomatic tissue lesions to severe destruction of bone and soft tissues, which are designated as: metallosis, ALVAL (aseptic lymphocytic vasculitis associated lesion), pseudotumours and ARMD (adverse reactions to metal debris) and may occur short-, medium- and long-term post-operatively. Based on follow-up studies, a threshold value for clinical concern is expected to be within the range of 2 to 7 µg/L (exact levels have still to be determined within this range).

Animal and occupational toxicology studies for evaluating adverse effects of metals in patients with MoM hip arthroplasties are currently limited because the degradation products are not adequately characterised. Therefore, the observations in various animal studies cannot be extrapolated to the internal exposure by the release of metals from MoM implants. Specific concerns related to possible systemic exposure to cobalt and/or chromium after MoM-hip arthroplasty include systemic organ toxicity, carcinogenicity and teratogenicity, but the evidence is insufficient and further confirmation is needed. Additionally, transplacental passage of metal ions has been demonstrated in the absence of teratogenic effect. There is no distinction between short-, medium- and long-term systemic effects.

These adverse health effects apply to all types of these MoM hip arthroplasties including Total Hip Arthroplasty THA with either small (head diameter < 36 mm) or large-heads (head diameter > = 36 mm) and Resurfacing Hip Arthroplasty (HR, always large-head diameter). However, MoM arthroplasty with large diameters (resurfacing and especially large-head MoM THA) are associated with the highest incidence of local reactions. Remarkably, systemic health effects have not been associated with the type of implant or diameter. Local and systemic adverse effects may also occur with other types of metallic implants (e.g. plates, screws).

We conclude that critical values for systemic effects are not yet established for patients after MoM implantation because of the lack of data and therefore, it is not possible to provide indications on limit values for the metals in any forms.