Hip resurfacing versus metal-on-metal total hip arthroplasty: are metal ion levels different?
Abstract: A systematic review and meta-analysis of trials comparing hip resurfacing to metal-on-metal total hip arthroplasty was conducted to determine if there is a difference in serum metal ion levels in patients receiving these implants. EMBASE[R] and MEDLINE[R] databases were searched from inception to December 2010 for all trials involving the use of these devices. Eligibility for inclusion in the review were studies with 1. comparative trials that were both retrospective and prospective; 2. inclusion of a treatment arm receiving hip resurfacing; 3. inclusion of a treatment arm receiving metal-on-metal total hip arthroplasty; and 4. analysis of chromium and cobalt ions, or either, in patient serum or whole blood at a minimum of 1 year after implantation. The literature search identified 87 potential studies, of which 10 met the inclusion criteria. Pooled mean differences were calculated for serum cobalt and chromium ion levels. Mean differences for serum cobalt and chromium metal ions were not significantly different between hip resurfacing and metal-on-metal total hip arthroplasty patients, although there was a tendency for lower serum cobalt ion levels in patients receiving hip resurfacing. Larger prospective randomized trials are required to better substantiate a difference in metal ion levels occurring between these implants.
Article Type: Clinical report
Subject: Orthopedic implants (Usage)
Orthopedic implants (Research)
Metal ions (Usage)
Metal ions (Research)
Authors: Kuzyk, Paul R.T.
Sellan, Michael
Olsen, Michael
Schemitsch, Emil H.
Pub Date: 01/01/2011
Publication: Name: Bulletin of the NYU Hospital for Joint Diseases Publisher: J. Michael Ryan Publishing Co. Audience: Academic Format: Magazine/Journal Subject: Health Copyright: COPYRIGHT 2011 J. Michael Ryan Publishing Co. ISSN: 1936-9719
Issue: Date: Jan, 2011 Source Volume: 69 Source Issue: 1
Topic: Event Code: 310 Science & research
Accession Number: 289216155
Full Text: Metal-on-metal bearings are considered alternative bearing surfaces for young, active patients who require total hip arthroplasty (THA). (1) Wear particles from these bearings are taken up by the circulation and result in higher than normal levels of metal ions in the serum, blood, and urine. (2,3) Although serum metal ion levels in ranges produced by metal-on-metal implants have never been linked to serious systemic disease, it is generally believed that these levels should be minimized. Some studies suggest that metal-on-metal THA produces higher levels of serum metal ions compared to hip resurfacing, as corrosion and fretting at the head-neck taper may be an additional source of ions. (4,5) The purpose of this systematic review and meta-analysis is to summarize the findings of studies that compare metal ion production from hip resurfacing implants to that of metal-on-metal THA implants.

Materials and Methods Systematic Review

Comparative trials reported in any language were identified through a systematic search of MEDLINE[R] and EMBASE[R] databases from inception to December 2010. Keyword search strategy used (hip resurfacing) and [(metal ion) or (cobalt) or (chromium)]. Bibliographies of all retrieved studies also were reviewed for relevant articles. The online indices from the following journals were specifically searched from 1990 to December 2010 for relevant articles: Journal of Bone and Joint Surgery (American and British volumes), Journal of Arthroplasty, and Clinical Orthopaedics and Related Research.

Each article was reviewed, and its eligibility for inclusion evaluated based on the following criteria: 1. comparative trials, both retrospective and prospective; 2. treatment arm that included hip resurfacing; 3. treatment arm that included metal-on-metal THA; and 4. analysis of chromium or cobalt ions, or both, in patient serum or whole blood, at a minimum of 1 year after implantation.

Pertinent information was extracted from each article and used to construct a database of the following: manufacturer and type of implant; number of hips and patients; gender; age; body mass index (BMI) or weight, or both; rate of follow-up; time to last follow-up; and whole blood and serum metal ion levels.

Meta-Analysis

Mean differences were calculated for the continuous variables of chromium whole blood and serum levels, as well as cobalt whole blood and serum levels. Variance around the mean difference was estimated using the standard deviation. When standard deviations were not reported, they were calculated using one of two methods: 1. when a p-value was available, the standard error was calculated and used to determine the standard deviation; and 2. when only quartiles were reported, these were used to derive the standard deviation. If the median was reported without the mean, the median was taken to approximate the mean. Data was estimated from figures when data was not reported within the text of the article. All calculations were conducted according to methods described in the Cochrane Handbook. (6)

Tests of significance for treatment effects were two-tailed and a p-value of less than 0.05 was considered significant. RevMan 5.0 (The Nordic Cochrane Centre, The Cochrane Collaboration, 2008, Copenhagen) meta-analysis software was used to perform the statistical analysis on all outcome measures pooled from the included studies.

Heterogeneity between studies was quantified using the [I.sup.2] statistic. An [I.sup.2] value of 0% represents no heterogeneity, and values of 25%, 50%, and 75% or more represent low, moderate, and high heterogeneity, respectively. (7)

Results

The literature search strategy identified 87 potential studies; following their review, 55 were eliminated as irrelevant topics. The abstracts of the remaining 32 studies were reviewed (Fig. 1); 10 publications met the eligibility criteria and were reviewed in full. (4,5,8-15) Two publications dealt with the identical study population, and one publication reported on two different study populations. This left nine articles reporting on 10 studies, which included a total of 1,002 hip resurfacings and 473 metal-on-metal THAs. Two studies were prospective randomized clinical trials (level I evidence) and the other eight studies were non-randomized comparative studies (level III evidence).

Seven studies compared hip resurfacing to 28 mm metal-on-metal THA, and three studies compared hip resurfacing to large head metal-on-metal THA (Table 1). Types of hip resurfacing arthroplasties included the Birmingham Hip Resurfacing (BHR; Smith & Nephew, Memphis, Tennessee) in six studies, Articular Surface Replacement (ASR[TM]; DePuy Orthopaedics, Warsaw, Indiana) in two studies, Durom[R] (Zimmer Inc., Warsaw, Indiana) in three studies, and Cormet 2000 (Corin Surgical, Cirencester, England, United Kingdom) in one study. Types of metal-on-metal THAs included Metasul[R] (Zimmer Inc., Warsaw, Indiana) 28 mm head in six studies and large head in two studies, Ultima[R] (DePuy Orthopaedics, Warsaw, Indiana) 28 mm head in one study, and ASR[TM] (DePuy Orthopaedics, Warsaw, Indiana) large head in one study.

[FIGURE 1 OMITTED]

Hip Resurfacing Versus 28 mm Metal-on-Metal Total Hip Arthroplasty

Five of the seven studies comparing metal ion levels in hip resurfacing to 28 mm metal-on-metal THAs reported median values and compared groups using nonparametric statistics (Table 1). This suggests that the data reported in these five studies was skewed. Only one level III study found that hip resurfacing produced significantly greater serum chromium and more cobalt ions than metal-on-metal THA. The other five level III studies and one level I study found no significant differences between treatment groups.

A meta-analysis was performed on the seven studies, including 224 hip resurfacings and 188 metal-on-metal THAs. There was very high heterogeneity when pooling the seven studies ([I.sup.2] = 84%). Removing the study by Witzleb and colleagues, (13) which displayed the largest calculated standard deviation and range among the seven studies for the hip resurfacing group, reduced heterogeneity to [I.sup.2] = 74%. Futhermore, removing the study by Clarke and coworkers (14) that included two types of implants in its resurfacing groups (BHR and Cormet 2000), reduced heterogeneity to [I.sup.2] = 21%. Pooling the data from the remaining five studies that compared BHR to Metasul[R] implants yielded a mean difference of chromium ion levels between hip resurfacing and THA groups of only 0.07 [micro]g/L (95% C.I. of -0.20 to 0.34), which was not a significant difference (p = 0.60) (Table 2).

Pooling data from these five studies for cobalt ion levels yielded an almost significant mean difference (p = 0.05) between hip resurfacing and metal-on-metal THA of -0.28 [micro]g/L (95% C.I. of -0.56 to 0.00) (Table 3). Heterogeneity among the five studies was not significant with [I.sup.2] = 0%. Thus, cobalt ion levels tended to be lower in the hip resurfacing group than in the 28 mm metal-on-metal THA group, while chromium levels were not different between groups.

Hip Resurfacing Versus Large Head Metal-on-Metal Total Hip Arthroplasty

Three studies compared hip resurfacing to large-diameter head metal-on-metal THA (Table 1), and all found higher cobalt ion levels in patients receiving metal-on-metal THA compared to hip resurfacing. The study by Langton and associates (11) did not statistically compare metal ion levels in hip resurfacing and metal-on-metal total arthroplasty groups. Rather, the purpose of that study was to demonstrate high rates of early failure of the ASR[TM] metal-on-metal bearing when used for resurfacing or THA. The ASR[TM] bearing since has been withdrawn from clinical use.

A randomized controlled study (level I) by Garbuz and colleagues (4) found significantly higher levels of both chromium and cobalt ion levels in metal-on-metal THA patients. A retrospective comparative study (level III) by Vendittoli and coworkers (5) found significantly higher levels of cobalt ions in patients with metal-on-metal THA, but no significant difference in chromium ions. Both of these studies compared Durom[R] implants to Metasul[R] large head implants.

Discussion

Our systematic review and meta-analysis suggest that serum cobalt ion levels tend to be higher in patients who have received metal-on-metal THA than in patients who have received hip resurfacings. This appears to be true when hip resurfacing is compared to either 28 mm femoral heads or large femoral head implants. Interestingly, there does not appear to be a significant difference in serum chromium ion levels between hip resurfacing and metal-on-metal THA.

These findings raise several questions. Why are cobalt ion levels higher in patients receiving metal-on-metal THA procedures? The prevailing theory is that fretting and crevice corrosion occurs between the femoral neck and the head of metal-on-metal THA implants, while this source of metal ion production is not present in hip resurfacing implants. (4,5) Corrosion and resulting metal ion production is enhanced by the contact of two dissimilar metals. In THA, the femoral head is commonly made from a Co-Cr alloy, while the femoral stem is made from a titanium alloy. (16,17) Jacobs and associates (18) found that fretting and crevice corrosion at the head-neck coupling produced serum metal ion levels in patients with metal-on-polyethylene THAs that were significantly higher than in control subjects without implants. Patients receiving 28 mm metal-on-metal bearings have a third source of metal ions and that is the fretting and corrosion that occur between the acetabular shell and the metal liner. Again, these components are made from dissimilar metals, as the acetabular shell is made from titanium alloy and the liner is made from Co-Cr alloy.

Why are serum cobalt ion levels higher in metal-on-metal THA as compared to hip resurfacing, while serum chromium ion levels are not different? Langton and colleagues (11) measured metal ion levels in the joint fluid and blood of 17 patients with metal-on-metal bearings, who required revision surgery for early failure. They found that chromium ions predominated in the joint fluid (with chromium ion concentrations four-times higher than cobalt ion concentrations), while cobalt ions predominated in the blood (with cobalt ion concentrations two- to three-times higher than chromium ion concentrations). This led them to conclude that chromium remains sequestered around the joint space, while cobalt is more easily released into the circulation. Another possible explanation is that there is more than twice the amount of cobalt than there is chromium in Co-Cr alloys (typical ratio of Co: Cr is 2.4:1). Therefore, a difference in cobalt ion levels may be more easily detected than a difference in chromium ion levels.

There are several limitations to our systematic review and meta-analysis. A number of variables have been shown to affect serum metal ion levels in patients with metal-on-metal articulations. Implant design, high acetabular inclination angle, and female gender all have been correlated with higher serum metal ion levels. (11,19-23) All 10 studies we identified had similar inclination angles for their acetabular components (means ranged from 40[degrees] to 48.8[degrees]). However, all studies included patients with inclination angles greater than 50[degrees], and angles greater than 50[degrees] have been associated with increased metal ion production. (21,22) Only two studies were randomized controlled trials (level I), and the other eight were nonrandomized comparative studies (level III). The use of nonrandomized studies in a meta-analysis may introduce confounders that result in shifting the result of the intervention effect (systematic bias) or excessive heterogeneity between studies, or both. (6) Of note is that six of the 10 studies reported median values instead of mean values and used nonparametric statistics for comparisons, indicating that data in these studies was skewed. The use of skewed data further increases heterogeneity between pooled studies. (6) Also, two different methods to determine metal ion concentrations (atomic absorption spectrometry and inductively coupled plasma mass spectrophotometry) were used in the studies included in the meta-analysis, and one study reported whole blood instead of serum metal ion levels. Metal ion levels were measured at 1 or 2 years in nine of the 10 studies (only one study measured levels at 5 years). It is assumed that serum metal ion levels reach steady state at approximately 6 months after implantation.

However, it is possible that metal ion levels may change at long-term follow-up.

Conclusions

Although there are only two level 1 clinical studies, there is fair evidence that hip resurfacing tends to produce a lesser degree of serum cobalt ions than metal-on-metal THA procedures. The difference noted in most studies is small and may not represent a clinically significant difference. Further study involving large prospective randomized controlled trials, longer follow-up, and accurate reporting of early failure and revision surgery, or either, is required to better substantiate a difference in metal ion production between the two types of implants.

Disclosure Statement

None of the authors have a financial or proprietary interest in the subject matter or materials discussed, including, but not limited to, employment, consultancies, stock ownership, honoraria, and paid expert testimony.

References

(1.) Jacobs JJ, Urban RM, Hallab NJ, et al. Metal-on-metal bearing surfaces. J Am Acad Orthop Surg. 2009 Feb; 17(2): 69-76.

(2.) Back DL, Young DA, Shimmin AJ. How do serum cobalt and chromium levels change after metal-on-metal hip resurfacing? Clin Orthop Relat Res. 2005 Sep; 438: 177-81.

(3.) Daniel J, Ziaee H, Pradhan C, et al. Blood and urine metal ion levels in young and active patients after Birmingham hip resurfacing arthroplasty: four-year results of a prospective longitudinal study. J Bone Joint Surg Br. 2007 Feb; 89(2): 169-73.

(4.) Garbuz DS, Tanzer M, Greidanus NV, et al. The John Charnley Award: metal-on-metal hip resurfacing versus large-diameter head metal-on-metal total hip arthroplasty: a randomized clinical trial. Clin Orthop Relat Res. 2010 Feb; 468(2): 318-25.

(5.) Vendittoli PA, Amzica T, Roy AG, et al. Metal ion release with large-diameter metal-on-metal hip arthroplasty. J Arthroplasty. 2010 Mar 3; Epub ahead of print.

(6.) Higgins JPT, Green S. Cochrane handbook for systematic reviews of interventions version 5.0.2 [updated September 2009]. The Cochrane Collaboration, 2009. Available at: www.cochrane-handbook.org. Accessed December 2010.

(7.) Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002; 21: 1539-58.

(8.) Moroni A, Savarino L, Cadossi M, et al. Does ion release differ between hip resurfacing and metal-on-metal THA? Clin Orthop Relat Res. 2008 Mar; 466(3): 700-7.

(9.) Moroni A, Savarino L, Hoque M, et al. Do ion levels in hip resurfacing differ from metal-on-metal THA at midterm? Clin Orthop Relat Res. 2010 Jun 11; Epub ahead of print.

(10.) Antoniou J, Zukor DJ, Mwale F, et al. Metal ion levels in the blood of patients after hip resurfacing: a comparison between twenty-eight and thirty-six-millimeter-head metal-on-metal prostheses. J Bone Joint Surg Am. 2008 Aug; 90(Suppl 3): 142-8.

(11.) Langton DJ, Jameson SS, Joyce TJ, et al. Early failure of metal-on-metal bearings in hip resurfacing and large-diameter total hip replacement: a consequence of excess wear. J Bone Joint Surg Br. 2010 Jan; 92(1): 38-46.

(12.) Daniel J, Ziaee H, Salama A, et al. The effect of the diameter of metal-on-metal bearings on systemic exposure to cobalt and chromium. J Bone Joint Surg Br. 2006 Apr; 88(4): 443-8.

(13.) Witzleb WC, Ziegler J, Krummenauer F, et al. Exposure to chromium, cobalt and molybdenum from metal-on-metal total hip replacement and hip resurfacing arthroplasty. Acta Orthop. 2006 Oct; 77(5): 697-705.

(14.) Clarke MT, Lee PT, Arora A, Villar RN. Levels of metal ions after small- and large-diameter metal-on-metal hip arthroplasty. J Bone Joint Surg Br. 2003 Aug; 85(6): 913-7.

(15.) Vendittoli PA, Roy A, Mottard S, et al. Metal ion release from bearing wear and corrosion with 28 mm and large-diameter metal-on-metal bearing articulations: a follow-up study. J Bone Joint Surg Br. 2010 Jan; 92(1): 12-9.

(16.) Collier JP, Surprenant VA, Jensen RE, et al. Corrosion between the components of modular femoral hip prostheses. J Bone Joint Surg Br. 1992 Jul; 74(4): 511-7.

(17.) Goldberg JR, Gilbert JL, Jacobs JJ, et al. A multicenter retrieval study of the taper interfaces of modular hip prostheses. Clin Orthop Relat Res. 2002 Aug; (401): 149-61.

(18.) Jacobs JJ, Skipor AK, Patterson LM, et al. Metal release in patients who have had a primary total hip arthroplasty. A prospective, controlled, longitudinal study. J Bone Joint Surg Am. 1998 Oct; 80(10): 1447-58.

(19.) Kwon YM, Glyn-Jones S, Simpson DJ, et al. Analysis of wear of retrieved metal-on-metal hip resurfacing implants revised due to pseudotumours. J Bone Joint Surg Br. 2010 Mar; 92(3): 356-61.

(20.) De Smet K, De Haan R, Calistri A, et al. Metal ion measurement as a diagnostic tool to identify problems with metal-on-metal hip resurfacing. J Bone Joint Surg Am. 2008 Nov; 90(Suppl 4): 202-8.

(21.) De Haan R, Pattyn C, Gill HS, et al. Correlation between inclination of the acetabular component and metal ion levels in metal-on-metal hip resurfacing replacement. J Bone Joint Surg Br. 2008 Oct; 90(10): 1291-7.

(22.) Hart AJ, Buddhdev P, Winship P, et al. Cup inclination angle of greater than 50 degrees increases whole blood concentrations of cobalt and chromium ions after metal-on-metal hip resurfacing. Hip Int. 2008 Jul-Sep; 18(3): 212-9.

(23.) Langton DJ, Jameson SS, Joyce TJ, et al. The effect of component size and orientation on the concentrations of metal ions after resurfacing arthroplasty of the hip. J Bone Joint Surg Br. 2008 Sep; 90(9): 1143-51.

Paul R.T. Kuzyk, M.A.Sc., M.D., F.R.C.S.(C), Michael Sellan, M.Sc., Michael Olsen, Ph.D., and Emil H. Schemitsch, M.D., F.R.C.S.(C) are from the Division of Orthopaedic Surgery, Department of Surgery, University of Toronto, Toronto, Ontario, Canada.

Correspondence: Dr. Emil Schemitsch, Suite 800, St. Michael's Hospital, 55 Queen Street East, Toronto, Ontario M5C 1R6, Canada; schemitsche@smh.ca.
Table 1 Summary of Articles Comparing Metal Ion Levels in Hip
Resurfacing Patients to Metal-on-Metal Total Hip Arthroplasty
Patients

                                      Sample and
                                      Method of
Study                 Study Design    Analysis      Statistics

Moroni et al (9),     Level III, RC   Serum, AAS    NP
2010
Vendittoli et         Level I,        Serum,        S
al (15), 2010         RCT             ICP-MS
Antoniou et           Level III, RC   Serum,        NP
al (10), 2008                         ICP-MS
Daniel et al (12),    Level III, RC   Blood,        S
2006                                  ICP-MS
Witzleb et al (13),   Level III, RC   Serum, AAS    NP
2006
Clarke et al (14),    Level III, RC   Serum,        NP
2003                                  ICP-MS
Garbuz et al (4),     Level I,        Serum,        NP
2010                  RCT             ICP-MS
Vendittoli et         Level III, RC   Serum,        S
al (5), 2010                          ICP-MS
Langton et al (11),   Level III, RC   Serum,        Statistical
2010                                  ICP-MS        comparison
                                                    not
                                                    performed

                      Implant   Sample   Sex     Age
Study                 Type      Size     (% F)   (Range)

Moroni et al (9),     BHR       20       45      53
2010                                             (30-65)
                      Metasul   35       45.7    60
                      (28 mm)                    (41-79)
                      BHR       15       46.7    49
                                                 (26-75)
                      Metasul   25       56      48
                      (28 mm)                    (30-64)
Vendittoli et         Durom     64       34.4    49.3
al (15), 2010                                    (25-64)
                      Metasul   53       37.7    51.0
                      (28 mm)                    (30-65)
Antoniou et           ASR       70       22.9    55
al (10), 2008                                    (33-73)
                      Metasul   28       60.7    61
                      (28 mm)                    (32-74)
Daniel et al (12),    BHR       26       NR      52.9
2006                                             (28.7-67.1)
                      Metasul   20       NR      63.3
                      (28 mm)                    (55-74.7)
Witzleb et al (13),   BHR       23       60      51
2006                                             (46-58)
                      Metasul   34       30      54
                      (28 mm)                    (45-62)
Clarke et al (14),    BHR and   22       NR      53
2003                  Cormet                     (39-68)
                      2000
                      Ultima    22       NR      60.9
                      (28 mm)                    (39-77) *
Garbuz et al (4),     Durom     13       10.4    51.5
2010
                      Metasul   13       10.7    52
                      (Large
                      Head)
Vendittoli et         Durom     53       NR      NR
al (5), 2010
                      Metasul   29       48      50
                      (Large                     (31-62)
                      Head)
Langton et al (11),   BHR       155      43      51
2010                                             (32-67)
                      ASR       418      44      56
                                                 (28-77)
                      ASR       87       61      67
                      THA                        (25-85)
                      (Large
                      Head)

                      Cup Angle                    Time of
                      ([degrees])    BMI           Sample
Study                 (Range)        (Range)       (Years)

Moroni et al (9),     46             28            5
2010                  (30-60)        (22-37)
                      42             25            5
                      (28-58)        (22-30)
                      40             29            2
                      (28-61)        (24-40)
                      42             25            2
                      (31-58)        (22-30)
Vendittoli et         46.6           27.1          2
al (15), 2010         (31.2-61.0)    (17.6-44.9)
                      45.1           29.2          2
                      (34.5-55.7)    (21.3-48.1)
Antoniou et           NR             NR            1
al (10), 2008         NR             NR            1
Daniel et al (12),    NR             NR            1
2006                  NR             NR            1
Witzleb et al (13),   46             27            2
2006                  (42-50)        (24-30)
                      44             28            2
                      (39-48)        (25-31)
Clarke et al (14),    NR             NR            0.6-4.7
2003                  NR             NR            0.8-3.6
Garbuz et al (4),     45.8           28.3          2
2010                  44.2           28.2          2
Vendittoli et         NR             NR            1
al (5), 2010          NR             27            1
                                     (20-36)
Langton et al (11),   48.3           NR            1
2010                  (32-70)
                      48.5           NR            1
                      (31-70)
                      48.8           NR            1
                      (36-76)

                      Cr Level            Co Level
                      ([micro]g/L)        ([micro]g/L)
Study                 (Range)             (Range)

Moroni et al (9),     2.26                1.13
2010                  (0.49-10.47)        (0.30-5.60)
                      1.96                1.44
                      (0.06-8.00)         (0.08-7.31)
                      2.18                1.17
                      (0.69-7.24)         (0.08-8.96)
                      1.76                1.35
                      (0.22-6.6)          (0.34-5.32)
Vendittoli et         1.58                0.67
al (15), 2010         (0.4-3.7)           (0.2-2.89)
                      1.62                0.94
                      (0.8-5.7)           (0.24-4.89)
Antoniou et           0.5 ([dagger])      2.4 ([dagger])
al (10), 2008         (0.1-3.8)           (1.0-11.8)
                      0.6 ([dagger])      2.6 ([dagger])
                      (0.1-5.4)           (1.0-6.9)
Daniel et al (12),    2.4                 1.3
2006                  1.7                 1.7

Witzleb et al (13),   5.12 ([dagger]) *   4.28 ([dagger]) *
2006                  (2.5-25)            (0-21)
                      1.22 ([dagger])     1.70 ([dagger])
                      (0.05-6)            (0-9)
Clarke et al (14),    2.76 ([dagger])     2.24 ([dagger])
2003                  (1.3-8.58)          (0.82-8.48)
                      0.99 ([dagger])     1.30 ([dagger])
                      (0.1-3.0)           (0.88-5.12)
Garbuz et al (4),     0.84 ([dagger])     0.54 ([dagger])
2010                  (0.7-1.1)           (0.4-0.7)
                      2.88 ([dagger]) *   5.48 ([dagger]) *
                      (1.1-4.0)           (3.5-7.2)
Vendittoli et         1.61                0.67
al (5), 2010                            (0.2-2.1)
                      1.34                2.21*
                      (0.6-3)             (0.2-5.7)
Langton et al (11),   4.42                1.96
2010                  (1.8-77)            (0.7-190)
                      4.46                2.82
                      (0.6-115)           (0.4-228)
                      3.84                4.27
                      (1.6-33)            (1.0-29)

Mean and range are reported unless otherwise specified;
([dagger]) median reported; RC, Retrospective Comparative;
RCT, Randomized controlled trial; NR, Value not reported;
* Significantly greater metal ion level; AAS, Atomic
Absorption Spectrometry; ICP-MS, Inductively coupled plasma
mass spectrophotometry; NP, Non-parametric statistics used
for comparison; S, Student's t test used for comparison.

Table 2 Meta-Analysis Forest Plot on Trials Comparing Serum and
Whole Blood Chromium Metal Ions in Patients with Hip Resurfacing
to Patients with Metal-on-Metal Total Hip Arthroplasty

                           Hip Resurfacing     Metal-on-Metal THA
                                               (28 mm)

Study or Subgroup        Mean    SD    Total   Mean    SD    Total

Daniel et al. 2006       2.4    1.18    26     1.7    1.18    20
Antoniou et al. 2008     0.5    0.67    70     0.6    0.74    28
Moroni et al. 2010       2.26   2.15    20     1.96   2.11    35
Moroni et al 2010 b      2.18   1.92    15     1.76   1.7     25
Vendittoli et al. 2010   1.58   0.7     48     1.62   0.7     24
Total (95% CI)                          179                   132

                                    Mean Difference
                                  IV, Random, 95% CI

Study or Subgroup        Weight

Daniel et al. 2006       13.0%     0.70 [0.01, 1.39]
Antoniou et al. 2008     40.5%    -0.10 [-0.42, 0.22]
Moroni et al. 2010        4.9%     0.30 [-087, 1.47]
Moroni et al 2010 b       4.9%    0.42 [-0.76, 1.60]
Vendittoli et al. 2010   36.7%    -0.04 [-0.38, 0.30]
Total (95% CI)           100.0%   0.07 [-0.38, 0.30]

Heterogeneity: [Tau.sup.2] = 0.02; [Chi.sup.2] = 5.08; df = 4 (p =
0.28); [I.sup.2] = 21%; Test for overall effect: Z = 0.52 (p = 0.60).

Table 3 Meta-Analysis Forest Plot on Trials Comparing Serum and
Whole Blood Cobalt Metal Ions in Patients with Hip Resurfacing
to Patients with Metal-on-Metal Total Hip Arthroplasty

                           Hip Resurfacing     Metal-on-Metal THA
                                                    (28 mm)

Study or Subgroup        Mean    SD    Total   Mean    SD    Total

Daniel et al. 2006       1.3    1.23    26     1.7    1.23    20
Antoniou et al. 2008     2.4    1.48    70     2.6    1.41    28
Moroni et al, 2010       1.13   1.19    20     1.44   1.61    35
Vendittoli et al. 2010   0.67   0.85    48     0.94   0.85    24
Moroni et al 2010 b      1.17   2.28    15     1.35   1.28    25
Total (95%) CI                          179                   132

                                    Mean Difference
                                  IV, Random, 95% CI

Study or Subgroup        Weight

Daniel et al. 2006       15.3%    -0.40 [-1.12, 0.32]
Antoniou et al. 2008     20.1%    -0.20 [-0.83, 0.43]
Moroni et al, 2010       14.2%    -0.31 [-1.06, 0.44]
Vendittoli et al. 2010   45.5%    -0.27 [-0.69, 0.15]
Moroni et al 2010 b       5.0%    -0.18 [-1.44, 1.08]
Total (95%) CI           100.0%

Heterogeneity: [Tau.sup.2] = 0.00; [Chi.sup.2] = 0.20; df = 4 (p =
1.00); [I.sup.2] = 0%; Test for overall effect: Z = 1.93 (p = 0.05).
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