- Email: [email protected]
Metal–metal hip replacement: Indications for intervention
SE
M I N A R S I N
A
R T H R O P L A S T Y
] (2016) ]]]–]]]
Available online at www.sciencedirect.com
www.elsevier.com/locate/semanthroplasty
Metal–metal hip replacement: Indications for intervention Franco Russo, MD, and Jay R. Lieberman, MDn Department of Orthopaedic Surgery, Keck School of Medicine of USC, 1520 San Pablo St Suite 2000, Los Angeles, CA, 90033
article info
abstra ct
Keywords:
Metal-on-metal bearing surfaces were frequently used because of their potential for
metal-on-metal
increased stability and lower wear rates. However, data reported by multiple nation-wide
adverse local tissue reaction
registries over the past 5 years, has demonstrated an increase in failure rates compared to
bearing surface
metal-on-polyethylene bearings. In addition, adverse local tissue reactions associated with
revision total hip arthroplasty
pseudotumors and destruction of the soft tissue around the joint have led to revision of these implants. Currently, there is no definitive algorithm to manage these patients and no single test should be used to determine treatment. This review discusses an evidencebased approach in managing this patient population. & 2016 Elsevier Inc. All rights reserved.
1.
Introduction
Metal-on-metal implants (MoM) were initially described by Wiles over 70 years ago, and were popularized in the 1960s with the advent of the McKee–Farrar prosthesis [1]. The development of polyethylene lead to a decreased interest in metal-on-metal bearings. However, in the 1990s, with concerns regarding polyethylene wear limiting the longevity of total hip arthroplasty, there was a renewed interest in metal-on-metal bearings. The use of metal-on-metal bearings gained traction because of two favorable attributes; potentially advantageous wear properties, and larger femoral heads that afford increased stability [2]. It has been estimated that since 1996, greater than one million metal-on-metal implants have been implanted worldwide, with over 38,000 implanted in the United States alone during the year 2006 [3]. However, increased revision rates of up to three fold in comparison to conventional metal-on-polyethylene as reported by several nation-wide registries, prompted the rapid decline in the use of metal-on-metal bearings [4,5]. These failure rates have since been attributed to the release of metal ions in the periprosthetic joint space, leading to n
Corresponding author. E-mail address: [email protected] (J.R. Lieberman).
http://dx.doi.org/10.1053/j.sart.2016.06.024 1045-4527/& 2016 Elsevier Inc. All rights reserved.
sterile effusions, osteolysis, pseudotumor formation, and in some cases, destruction of the surrounding soft tissues [3]. This disease process is now more commonly referred to as adverse local tissue reaction or ALTR [3]. Routine surveillance and clinical evaluation of patients with a history of a metal-on-metal prosthesis remains paramount in diagnosing and treating these lesions. Apart from history and physical exam, other modalities such as advanced imaging and laboratory evaluation can help to guide management. Despite several studies documenting risk factors such as femoral head size, cup position, and cutoff values for serum ion levels, no definitive algorithm has been universally adopted to guide treatment. Given the potential catastrophic complications associated with ALTR, it is incumbent upon the treating surgeon to maintain a high level of suspicion when caring for this patient population.
2.
ALTR
In the early 2000s, Willert et al. [6] described an immunologic reaction to the release of metal particles from associated
2
SE
M I N A R S I N
AR
T H R O P L A S T Y
corrosive wear between the femoral head and acetabular liner; a delayed type hypersensitivity reaction termed aseptic lymphocyte dominant vasculitis associated lesion (ALVAL). An ALTR can present in a number of different ways. Patients may develop a perivascular lymphocytic infiltration (ALVAL), a pseudotumor, or osteolysis. Individuals that develop an ALTR may have all or any of these three tissue responses. Histologic evaluation of the periprosthetic tissues in patients with ALVAL, demonstrate perivascular and intramural lymphocytic infiltration of the postcapillary venules, distinctive of a cell mediated delayed type IV hypersensitivity reaction [6]. This response is characterized by antigen activation of Helper T Cells (CD4þ). Activation of these cells triggers release of a number of cytokines including interferon-gamma (IFN-gamma), tumor-necrosis factor-alpha (TNF-alpha) as well interleukins 1 and 2, which, in combination with antigen presenting cells, provide chemotaxis for macrophage and further T cell recruitment. Macrophage activation triggers further T cell mobilization, effectively creating a positive-feedback loop, which could be associated with pseudotumor formation and even extensive damage to the muscles surrounding the joint. A pseudotumor is defined as a sterile solid and/or fluid inflammatory mass that can develop in the soft tissues surrounding a metal-on-metal prosthesis [7,8]. These lesions have been associated with numerous complications, such as pain, swelling, thromboembolic events, infection, and soft tissue destruction resulting in revision surgery [9,10]. In addition, patients with an ALTR may also develop osteolytic lesions in response to metal debris. The majority of case reports and prospective studies have focused on symptomatic patients [11,12]. However, a recent study discovered pseudotumor formation in 6.5% of asymptomatic patients with a well functioning prosthesis during routine followup [13]. This raises the question of which patients warrant further evaluation of these lesions, and how to risk stratify them.
3.
History and physical
Initial evaluation of patients with metal-on-metal total hip arthroplasty begins with a thorough history and physical examination. More broadly, these patients can be classified as symptomatic or asymptomatic. Below, we discuss the evaluation of the patient with a painful metal-on-metal prosthesis.
3.1.
] (2016) ]]]–]]]
History
The differential diagnosis for a painful total hip arthroplasty is quite extensive; however, it can be subdivided into intrinsic and extrinsic etiologies as listed in the Table. Common causes of intrinsic issues include infection, mechanical loosening, implant failure, periprosthetic fracture, and osteolysis [14,15]. Diagnoses extrinsic to the joint include lumbar spine pathology, malignancy, trochanteric bursitis, iliopsoas tendonitis, vascular claudication, complex regional pain syndrome, metabolic disease (stress fracture), or referred pain [16,17]. A thorough history and physical exam serves as the cornerstone in the evaluation of a painful total hip arthroplasty. A detailed history provides valuable information that can considerably narrow the differential diagnosis. When did the pain begin? The chronology of symptoms, date of onset, and pain characteristics all provide insight to the root cause. Was there ever a pain-free interval following surgery? Has there ever been drainage from the wound? Pain persisting from the date of surgery, especially in the setting of delayed wound healing, suggests the possibility that the pain is secondary to infection [18]. Patients with metal-on-metal issues usually do not develop pain until several years following component implantation. History of skin changes or familial history of metal hypersentivity? It is unclear if metal hypersensitivity contributes to osteolysis and prosthesis failure, or if the patient develops the hypersensitivity following an immune response to the wear debris [19]. The treating surgeon should document a history of metal hypersensitivity and its possible sequelae, including neurologic changes, renal function impairment, thyroid dysfunction, presence of urticaria, or reactive dermatitis [20].
3.2.
Physical examination
The physical exam should be focused on inspection of previous incision(s), the joint, surrounding soft tissues, gait, range of motion, neurovascular status, and examination of adjacent joints and spine to rule out sources of referred pain [18]. The surgical scar should be scrutinized for evidence of infection and the skin should be examined for evidence of reactive urticaria or dermatitis. Palpation should be performed to illicit tenderness characteristic of trochanteritic bursitis, or generalized soft tissue swelling. Iliopsoas tenderness also needs to be ruled out. Range of motion should be assessed and a thorough evaluation of the patient’s
Table – The Differential Diagnosis of the Painful Total Hip Arthroplasty Intrinsic Causes
Extrinsic Causes
Infection
Lumbar spine pathology Malignancy Peripheral vascular disease Complex regional pain syndrome Hernia, femoral or inguinal Referred pain Metabolic disease (stress fracture)
Aseptic loosening Osteolysis Periprosthetic fracture Implant malrotation/malpositioning Inflammatory bursitis/tendonitis (trochanteric/iliopsoas)
SE
M I N A R S I N
AR
T H R O P L A S T Y
neurovascular status could alert the clinician to radiculopathy or vascular insufficiency that can manifest as hip pain.
4.
Clinical work-up
4.1.
Radiographic evaluation
If available, radiographs from the time of the index procedure through the most recent follow-up should be evaluated. In addition to documenting the type of prosthesis used, irregularities and lucencies around the implant should be noted. Attention should be paid particularly to the position of the acetabular component and the size of the femoral head used, as both have been associated with higher revision rates and elevated serum metal ions, respectively [4,5] (Image 1). The Australian registry reported a correlation of femoral head size in excess of 32 mm with an increased rate of revision in the setting of a metal-on-metal prosthesis [6]. Additionally, increased abduction of the acetabular component, in excess of 501, can potentially increase edge loading and thereby generate metal debris [21,22]. Computed tomography (CT) can be useful in identifying osteolysis and component malposition. CT scan can further characterize soft tissue lesions as solid or cystic in close proximity to the implant [7,11].
4.2.
Advanced imaging—MARS MRI
Metal artifact reduction sequence, or MARS MRI, has been shown to reproducibly quantify adverse local tissue reaction in the setting of a metal-on-metal total hip arthroplasty [23]. MARS imaging is most effective in determining the extent of pseudotumor burden, and most importantly, it can reveal abductor muscle involvement. Several studies have documented a similar rate of adverse local tissue reaction in both symptomatic and asymptomatic patients [23,24].
4.3.
3
Ultrasound
Ultrasound has been utilized as a screening tool to detect the presence of a periprosthetic soft tissue mass in the setting of a metal-on-metal hip replacement. It can serve as a beneficial cost-effective alternative to MRI in those patients with implantable defibrillators, metallic implants, or claustrophobia. However, this modality is operator dependent and given limited transmission, it may not adequately evaluate deeper lesions or completely assess those patient’s with a larger body habitus [25].
4.4.
Laboratory evaluation
ESR and CRP values should be obtained to rule out an infectious process, however, these values have been found to be elevated in the setting of patients with ALTR without underlying infection [26]. Aspiration of synovial fluid should be a documented step in the algorithm to differentiate ALTR from infection. Aspirate in the setting of psuedotumor has been classically described as grayish and hazy, with a dishwater consistency, in contrast to turbid purulence in the setting of infection. Each specimen should be sent for manual cell count as opposed to an automated cell count, given that debris in the suspension from the aspirate could falsely elevate automated counts [27]. In addition, cell differential, culture, and crystal analysis should be obtained. Blood and serum cobalt (Co) and chromium (Cr) concentrations have been demonstrated to correlate with wear rates in metal-on-metal implants. A cobalt (Co) or chromium (Cr) level of greater than 5 mg/l, which has a sensitivity and specificity of 52% and 89%, respectively, has generally been accepted as an indication for advanced imaging [27,28]. A 2012 medical safety alert issued by The Medicines and Healthcare Products Regulatory Agency (MHRA) from the United Kingdom, did not recommend asymptomatic patients with MoM implants undergo routine blood metal ion screening [29]. However, a recent study by Gulraj et al. [30] investigated whether blood metal ions could identify which patients, that had previously been treated with one of two specific metalon-metal implants, were at risk of developing an ALTR. They found that patients with implant-specific serum cobalt cutoff values less than 2.15 mg/l for the Birmingham Hip Resurfacing (BHR; Smith and Nephew) and 3.57 mg/l for the Corail– Pinnacle (Depuy Synthes) total hip replacement systems, were at low risk for developing an ALTR [30]. This data suggests that cobalt (Co) and chromium (Cr) serum threshold levels need to be assessed for each individual metal-on-metal implant. At the present time, for most metal-on-metal implants, serum metal ion values alone are not an absolute indication for surgery.
5. Image 1 – A 67-year-old female status post metal-on-metal total hip arthroplasty, with an excessively abducted acetabular component and greater trochanteric fracture presenting with recurrent dislocation.
] (2016) ]]]–]]]
Skin patch testing
Skin patch testing is the most common tool to assess metal hypersensitivity. However, it only provides exposure for a limited amount of time (24–48 h) whereas the implant exposure is constant in the periprosthetic environment.
4
SE
M I N A R S I N
AR
T H R O P L A S T Y
Additionally, the patch test exposes the allergen to a different subset of antigen presenting cells (dendritic cells, Langerhans cells) than those found in periprosthetic tissues (synoviocytes) [19]. In a study of 54 patients administered patch testing prior to and following total hip replacement, Rooker et al. reported, of six patients with a positive pre-operative test, five lost their hypersensitivity at the time of postoperative testing [31]. In the setting of a symptomatic metal-on-metal hip replacement, few studies have documented a higher rate of failure in patients with a metal hypersensitivity on skin patch testing as compared to those without a positive test [19,32]. The causal relationship between metal hypersensitivity and metal-on-metal implant failure remains unclear, and skin patch testing is not a routine part of the work-up of these patients.
6.
When to consider revision surgery
6.1.
Risk stratification
No universally accepted algorithm exists to determine when an operation is necessary. It is important to risk stratify these patients, to better understand who requires close follow-up and/or early intervention. In a consensus statement released from the American Association of Hip and Knee Surgeons and the American Academy of Orthopaedic Surgeons, Kwon et al. presented an algorithm for patients with dual modular taper stems. Risk should be assigned based on a number of different factors including the patient’s activity level, symptomatology, implant characteristics, serum metal ion level, and soft tissue findings on advanced imaging [27]. Patients with a painful total hip and evidence of soft tissue destruction on MARS MRI (i.e., abductor muscle involvement) will most likely require immediate surgical intervention. However, the presence of a pseudotumor without soft tissue destruction does not require urgent surgical intervention. Further study is required to determine the optimal metal ion thresholds for specific metal-on-metal implants to identify patients at increased risk for developing an ALTR (Fig. 1).
6.2.
Low-risk patients
Low-risk patients are asymptomatic and maintain a lowdemand lifestyle. On radiographic imaging, their acetabular component will exhibit excellent orientation, their femoral head is o36 mm, and there will be no evidence of osteolysis or subsidence [27]. Additionally, lab values will demonstrate serum metal ion levels o3 ppb with no evidence of infection. The FDA recommends these patients can be followed up every 1 to 2 years, and do not require metal ion or advanced imaging surveillance. However, this decision should be made on a patient-to-patient basis and ultimately is at the discretion of the treating surgeon [33].
6.3.
Moderate risk patients
These patients are generally community ambulators, report mild localized symptoms, and may or may not present with a
] (2016) ]]]–]]]
limp. Components may or may not exhibit acceptable orientation and the femoral head may be 36 mm or greater. Radiographic analysis should demonstrate no evidence of osteolysis or subsidence [27]. Serum metal ion levels may be normal to elevated, ranging from 3 to 10 ppb (this value may be implant specific). In the setting of progressive symptoms and rising ion levels, MARS MRI should be the next step in evaluation and may demonstrate abnormal soft tissue reaction with small fluid or cystic lesions, without muscle destruction [27]. The FDA recommends routine follow-up every 6–12 months in symptomatic patients; however, currently there is a lack of evidence to demonstrate a correlation between metal ion level and ALTR [20,34]. We recommend close follow-up for these patients, with a low threshold to consider revision surgery in the setting of progressive symptoms and/or deficits on exam.
6.4.
High-risk patients
The high-risk patient is typically an active individual that presents with severe symptoms that may include abductor insufficiency. Radiographic imaging will demonstrate components in suboptimal position, and/or femoral head size 436 mm. Metal ion levels will be 45 ppb (this value may be implant specific), ESR and or CRP may be elevated, and synovial fluid analysis may support evidence of underlying infection [27]. Advanced imaging may demonstrate significant soft tissue destruction, osteolysis, component subsidence, or periprosthetic fracture [27]. MARS imaging demonstrating extensive pseudotumor burden with abductor muscle involvement, is an absolute indication for surgical intervention.
7.
Revision arthroplasty
The decision to move forward with revision surgery is not always simple, because revision does not always lead to an excellent outcome. In a review of 37 failed MoM prosthesis, of the 10 patients revised secondary to presumed ALTR, all patients reported never fully recovering following the index procedure [35]. Surgeons must recognize at-risk patients, including female patients and those with increased abduction of the acetabular component [36]. During revision surgery, intraoperative specimens should be obtained and associated findings should be documented. Periprosthetic tissues should be sent for culture, frozen section, and permanent sections for pathology review and histologic analysis. If the components are well fixed and in an acceptable position, it is generally accepted that these patients can be converted to a metal on polyethelyne or ceramic on polyethelene liner. The surgeon should document to what degree the abductors have been compromised, and consider a dual mobility component or even a constrained liner in the setting of abductor insufficiency (Images 2,3).
SE
M I N A R S I N
AR
T H R O P L A S T Y
5
] (2016) ]]]–]]]
Image 2 – The same 67-year-old female with identification of a pseudotumor at the time of operative exploration of the hip joint.
8.
Summary
The painful MoM total hip arthroplasty with a large femoral head is at increased risk for failure. Risk stratification of these patients is paramount, and requires a systematic evaluation using a variety of different tests such as serum metal ion levels and advanced imaging to determine the appropriate treatment. Over-reliance on any one diagnostic tool should be avoided. Additional research is required to better understand the natural history of metal-onmetal bearing failure and to validate the current investigative instruments used in diagnosing adverse reaction to metal debris.
Image 3 – The same 67-year-old female following revision total hip arthroplasty.
Hisotry of Metal on Metal Total Hip Arthroplasty
Symptomatic
Asymptomatic
<50 deg Abduction/ Femoral head < 36 mm
Low Risk stratiicationroutine follow up
Cup Position >50 deg Abduction and/or Femoral Head> 36mm
Cup <50 deg Abduction / Femoral head <36mm
>50 deg Abduction or femoral head> 36 mm
Serum Metal <5ppb#
Serum Metal >5ppb#
Routine follow up and/or MARS MRI*
MARS MRI*
Metal Ions <5ppb#
No evidence of soft tissue destruction
Soft Tissue Destruction evident
Close Follow up
Recommend Revision Surgery
Metal Ions >5ppb#
Will likely require revision surgery
No evidence of soft tissue destruction on MARS MRI*
Soft Tissue destruction on MARS MRI*
No evidence of soft tissue destruction on MARS MRI*
Soft Tissue destruction evident on MARS MRI*
Weigh risks and beneits with patient
Recommend Revision Surgery
Weigh risks and beneits with patient
Recommend revision surgery
Figure 1 – Metal-on-metal hip replacement: indications for intervention [27]. * ¼ metal artifact reduction sequence MRI; # ¼ parts per billion.
6
SE
M I N A R S I N
AR
T H R O P L A S T Y
r e f e r e n c e s [20] [1] McKee GK, Watson-Farrar J. Replacement of arthritic hips by the McKee–Farrar prosthesis. The Journal of Bone and Joint Surgery. British Volume 1966;48:245–59. [2] Smith TM, Berend KR, Lombardi AV Jr, et al. Metal-on metal total hip arthroplasty with large heads may prevent early dislocation. Clinical Orthopaedics and Related Research 2005;441:137–42. [3] Lombardi AV Jr, Barrack RL, Berend KR, et al. The Hip Society: algorithmic approach to diagnosis and management of metal-on-metal arthroplasty. The Journal of Bone and Joint Surgery. British volume 2012;94:14–8. [4] Australian Orthopaedic Association National Joint Replacement Registry: Annual Report 2010. Adelaide, SA, Australia: Australian Orthopaedic Association; 2010. [5] National Joint Registry for England and Wales: Seventh Annual Report. Hemel Hempstead, Hertfordshire, UK: National Joint Registry Centre; 2010. [6] Willert HG, Buchhorn GH, Fayyazi A, et al. Metal-on-metal bearings and hypersensitivity in patients with artificial hip joints: a clinical and histomorphological study. The Journal of Bone and Joint Surgery. American Volume 2005;87:28–36. [7] Pandit H, Glyn-Jones S, McLardy-Smith P, et al. Pseudotumors associated with metal-on-metal hip resurfacings. The Journal of Bone and Joint Surgery. British Volume 2008;90: 847–51. [8] Van Der Weegen W, Sjibesma T, Hoekstra H, et al. Treatment of pseudotumors after metal-on-metal hip resurfacing based on magnetic resonance imaging, metal ion levels and symptoms. The Journal of Arthroplasty 2014;29:416–21. [9] Memon AR, Galbraith JG, Harty JA, et al. Inflammatory pseudotumor causing deep vein thrombosis after metal-onmetal hip resurfacing arthroplasty. The Journal of Arthroplasty 2013;28:197–209. [10] Watters TS, Eward WC, Hallows RK, et al. Pseudotumor with superimposed periprosthetic infection following metal-onmetal total hip arthroplasty: a case report. The Journal of Bone and Joint Surgery. American Volume 2010;92:1666. [11] Hart AJ, Sabah S, Henckel J, et al. The painful metal-on-metal hip resurfacing. The Journal of Bone and Joint Surgery. British Volume 2009;91:738–44. [12] Langton DJ, Joyce TJ, Jameson SS, et al. Adverse reaction to metal debris following hip resurfacing: the influence of component type, orientation and volumetric wear. The Journal of Bone and Joint Surgery. British Volume 2011; 93:164–71. [13] Kwon YM, Ostlere SJ, McLardy-Smith P, et al. “Asymptomatic” pseudotumors after metal-on-metal hip resurfacing arthroplasty: prevalence and metal ion study. The Journal of Arthroplasty 2011;31:260–3. [14] Bozic KJ, Rubash HE. The painful total hip replacement. Clinical Orthopaedics and Related Research 2004;420:18–25. [15] Smith P, Rorabeck C. Clinical evaluation of the symptomatic total hip arthroplasty. In: Steinberg M, Garino J, et al., eds. Revision total hip arthroplasty. Philadelphia, PA: Lippincott Williams & Wilkins; 1999. 109–20. [16] Bohl W, Steffee A. Lumbar spinal stenosis: a cause of continued pain and disability in patients after total hip arthoplasty. Spine 1974;4:168–73. [17] Gaunt M, Tan S, Dias J. Strangulated obturator hernia masquerading as pain from a total hip replacement. The Journal of Bone and Joint Surgery. British Volume 1992;74:782–3. [18] Springer B. The diagnosis of periprosthetic joint infection. The Journal of Arthroplasty 2015;6:908–11. [19] Park YS, Moon YW, Lim SJ, et al. Early osteolysis following second-generation metal-on-metal hip replacement. The
[21]
[22]
[23]
[24]
[25]
[26]
[27]
[28]
[29] [30]
[31]
[32] [33]
[34]
[35]
[36]
] (2016) ]]]–]]]
Journal of Bone and Joint Surgery. American Volume 2005;87:1515–21. U.S. Food and Drug Administration: metal-on-metal hip implants. http://www.fda.gov/ MedicalDevices/ Productsand MedicalProcedures/ ImplantsandProsthetics/ MetalonMetal HipImplants/default.htm [accessed Feb 13, 2016]. Campbell P, Beaulé PE, et al. The John Charnley Award: a study of implant failure in metal-on-metal surface arthroplasties. Clinical Orthopaedics and Related Research 2006; 453:35–46. Hart AJ, Ilo K, Underwood R, et al. The relationship between the angle of version and rate of wear of retrieved metal-on metal resurfacings: a prospective, CT based study. The Journal of Bone and Joint Surgery. British Volume 2011;93: 315–20. Nawabi D, Hayter C, Su E, et al. Magnetic resonance imaging findings in symptomatic versus asymptomatic subjects following metal-on-metal hip resurfacing arthroplasty. The Journal of Bone and Joint Surgery. American Volume 2013;95:895–902. Mistry A, Cahir J, Donell ST, et al. MRI of asymptomatic patients with metal-on-metal and polyethylene-on-metal total hip arthroplasties. Clinical Radiology 2011;66:540–5. Hayter C, Potter H, Su E. Imaging of metal-on-metal hip resurfacing. The Orthopedic clinics of North America 2011; q42:195–205. Langton DJ, Sidaginamale RP, Joyce TJ, et al. The clinical implications of elevated blood metal ion concentrations in asymptomatic patients with MoM hip resurfacings: a cohort study. BMJ Open 2013;3(3). Kwon YM, Lombardi AV, Jacobs JJ, et al. Risk stratification algorithm for management of patients with metal-on-metal hip arthroplasty: consensus statement of the American Association of Hip and Knee Surgeons, the American Academy of Orthopaedic Surgeons, and the Hip Society. The Journal of Bone and Joint Surgery. American Volume 2014; 29:2060–4. Hart AJ, Sabah SA, Bandi AS, et al. Sensitivity and specificity of blood cobalt and chromium metal ions for predicting failure of metal-on-metal hip replacement. The Journal of Bone and Joint Surgery. British Volume 2011;93:1308–13. Medical Device Alert Ref: MDA/2012/008. Gulraj MS, Berryman F, Brash L, et al. The effectiveness of blood metal ions in identifying patients with unilateral Birmingham hip resurfacing an corail-pinnacle metal-on metal-hip implants at risk of adverse reactions to metal debris. The Journal of Bone and Joint Surgery. American Volume 2016;98:617–26. Rooker GD, Wilkinson JD. Metal sensitivity in patients undergoing hip replacement. A prospective study. The Journal of Bone and Joint Surgery. British Volume 1980;62:502–5. Antony FC, Holden CA. Metal allergy resurfaces in failed hip endoprostheses. Contact Dermatitis 2003;48:49–50. Bolognesi M, Ledford C. Metal-on-metal total hip arthroplasty: patient evaluation and treatment. The Journal of the American Academy of Orthopaedic Surgeons 2015; q23:724–31. Bayley N, Khan H, Grosso P, et al. What are the predictors and prevalence of pseudotumor and elevated metal ions after large-diameter metal-on-metal THA? Clinical Orthopaedics and Related Research 2015;473:477–84. Browne JA, Bechtold CD, Berry DJ, et al. Failed metal-onmetal hip arthroplasties: a spectrum of clinical presentations and operative findings. Clinical Orthopaedics and Related Research 2010;468:2313–20. Laitteier MJ, Berend KR, Lombardi AV Jr, et al. Gender is a significant factor for failure of metal-on-metal total hip arthroplasty. The Journal of Arthroplasty 2011;26:19–23.
M I N A R S I N
A
R T H R O P L A S T Y
] (2016) ]]]–]]]
Available online at www.sciencedirect.com
www.elsevier.com/locate/semanthroplasty
Metal–metal hip replacement: Indications for intervention Franco Russo, MD, and Jay R. Lieberman, MDn Department of Orthopaedic Surgery, Keck School of Medicine of USC, 1520 San Pablo St Suite 2000, Los Angeles, CA, 90033
article info
abstra ct
Keywords:
Metal-on-metal bearing surfaces were frequently used because of their potential for
metal-on-metal
increased stability and lower wear rates. However, data reported by multiple nation-wide
adverse local tissue reaction
registries over the past 5 years, has demonstrated an increase in failure rates compared to
bearing surface
metal-on-polyethylene bearings. In addition, adverse local tissue reactions associated with
revision total hip arthroplasty
pseudotumors and destruction of the soft tissue around the joint have led to revision of these implants. Currently, there is no definitive algorithm to manage these patients and no single test should be used to determine treatment. This review discusses an evidencebased approach in managing this patient population. & 2016 Elsevier Inc. All rights reserved.
1.
Introduction
Metal-on-metal implants (MoM) were initially described by Wiles over 70 years ago, and were popularized in the 1960s with the advent of the McKee–Farrar prosthesis [1]. The development of polyethylene lead to a decreased interest in metal-on-metal bearings. However, in the 1990s, with concerns regarding polyethylene wear limiting the longevity of total hip arthroplasty, there was a renewed interest in metal-on-metal bearings. The use of metal-on-metal bearings gained traction because of two favorable attributes; potentially advantageous wear properties, and larger femoral heads that afford increased stability [2]. It has been estimated that since 1996, greater than one million metal-on-metal implants have been implanted worldwide, with over 38,000 implanted in the United States alone during the year 2006 [3]. However, increased revision rates of up to three fold in comparison to conventional metal-on-polyethylene as reported by several nation-wide registries, prompted the rapid decline in the use of metal-on-metal bearings [4,5]. These failure rates have since been attributed to the release of metal ions in the periprosthetic joint space, leading to n
Corresponding author. E-mail address: [email protected] (J.R. Lieberman).
http://dx.doi.org/10.1053/j.sart.2016.06.024 1045-4527/& 2016 Elsevier Inc. All rights reserved.
sterile effusions, osteolysis, pseudotumor formation, and in some cases, destruction of the surrounding soft tissues [3]. This disease process is now more commonly referred to as adverse local tissue reaction or ALTR [3]. Routine surveillance and clinical evaluation of patients with a history of a metal-on-metal prosthesis remains paramount in diagnosing and treating these lesions. Apart from history and physical exam, other modalities such as advanced imaging and laboratory evaluation can help to guide management. Despite several studies documenting risk factors such as femoral head size, cup position, and cutoff values for serum ion levels, no definitive algorithm has been universally adopted to guide treatment. Given the potential catastrophic complications associated with ALTR, it is incumbent upon the treating surgeon to maintain a high level of suspicion when caring for this patient population.
2.
ALTR
In the early 2000s, Willert et al. [6] described an immunologic reaction to the release of metal particles from associated
2
SE
M I N A R S I N
AR
T H R O P L A S T Y
corrosive wear between the femoral head and acetabular liner; a delayed type hypersensitivity reaction termed aseptic lymphocyte dominant vasculitis associated lesion (ALVAL). An ALTR can present in a number of different ways. Patients may develop a perivascular lymphocytic infiltration (ALVAL), a pseudotumor, or osteolysis. Individuals that develop an ALTR may have all or any of these three tissue responses. Histologic evaluation of the periprosthetic tissues in patients with ALVAL, demonstrate perivascular and intramural lymphocytic infiltration of the postcapillary venules, distinctive of a cell mediated delayed type IV hypersensitivity reaction [6]. This response is characterized by antigen activation of Helper T Cells (CD4þ). Activation of these cells triggers release of a number of cytokines including interferon-gamma (IFN-gamma), tumor-necrosis factor-alpha (TNF-alpha) as well interleukins 1 and 2, which, in combination with antigen presenting cells, provide chemotaxis for macrophage and further T cell recruitment. Macrophage activation triggers further T cell mobilization, effectively creating a positive-feedback loop, which could be associated with pseudotumor formation and even extensive damage to the muscles surrounding the joint. A pseudotumor is defined as a sterile solid and/or fluid inflammatory mass that can develop in the soft tissues surrounding a metal-on-metal prosthesis [7,8]. These lesions have been associated with numerous complications, such as pain, swelling, thromboembolic events, infection, and soft tissue destruction resulting in revision surgery [9,10]. In addition, patients with an ALTR may also develop osteolytic lesions in response to metal debris. The majority of case reports and prospective studies have focused on symptomatic patients [11,12]. However, a recent study discovered pseudotumor formation in 6.5% of asymptomatic patients with a well functioning prosthesis during routine followup [13]. This raises the question of which patients warrant further evaluation of these lesions, and how to risk stratify them.
3.
History and physical
Initial evaluation of patients with metal-on-metal total hip arthroplasty begins with a thorough history and physical examination. More broadly, these patients can be classified as symptomatic or asymptomatic. Below, we discuss the evaluation of the patient with a painful metal-on-metal prosthesis.
3.1.
] (2016) ]]]–]]]
History
The differential diagnosis for a painful total hip arthroplasty is quite extensive; however, it can be subdivided into intrinsic and extrinsic etiologies as listed in the Table. Common causes of intrinsic issues include infection, mechanical loosening, implant failure, periprosthetic fracture, and osteolysis [14,15]. Diagnoses extrinsic to the joint include lumbar spine pathology, malignancy, trochanteric bursitis, iliopsoas tendonitis, vascular claudication, complex regional pain syndrome, metabolic disease (stress fracture), or referred pain [16,17]. A thorough history and physical exam serves as the cornerstone in the evaluation of a painful total hip arthroplasty. A detailed history provides valuable information that can considerably narrow the differential diagnosis. When did the pain begin? The chronology of symptoms, date of onset, and pain characteristics all provide insight to the root cause. Was there ever a pain-free interval following surgery? Has there ever been drainage from the wound? Pain persisting from the date of surgery, especially in the setting of delayed wound healing, suggests the possibility that the pain is secondary to infection [18]. Patients with metal-on-metal issues usually do not develop pain until several years following component implantation. History of skin changes or familial history of metal hypersentivity? It is unclear if metal hypersensitivity contributes to osteolysis and prosthesis failure, or if the patient develops the hypersensitivity following an immune response to the wear debris [19]. The treating surgeon should document a history of metal hypersensitivity and its possible sequelae, including neurologic changes, renal function impairment, thyroid dysfunction, presence of urticaria, or reactive dermatitis [20].
3.2.
Physical examination
The physical exam should be focused on inspection of previous incision(s), the joint, surrounding soft tissues, gait, range of motion, neurovascular status, and examination of adjacent joints and spine to rule out sources of referred pain [18]. The surgical scar should be scrutinized for evidence of infection and the skin should be examined for evidence of reactive urticaria or dermatitis. Palpation should be performed to illicit tenderness characteristic of trochanteritic bursitis, or generalized soft tissue swelling. Iliopsoas tenderness also needs to be ruled out. Range of motion should be assessed and a thorough evaluation of the patient’s
Table – The Differential Diagnosis of the Painful Total Hip Arthroplasty Intrinsic Causes
Extrinsic Causes
Infection
Lumbar spine pathology Malignancy Peripheral vascular disease Complex regional pain syndrome Hernia, femoral or inguinal Referred pain Metabolic disease (stress fracture)
Aseptic loosening Osteolysis Periprosthetic fracture Implant malrotation/malpositioning Inflammatory bursitis/tendonitis (trochanteric/iliopsoas)
SE
M I N A R S I N
AR
T H R O P L A S T Y
neurovascular status could alert the clinician to radiculopathy or vascular insufficiency that can manifest as hip pain.
4.
Clinical work-up
4.1.
Radiographic evaluation
If available, radiographs from the time of the index procedure through the most recent follow-up should be evaluated. In addition to documenting the type of prosthesis used, irregularities and lucencies around the implant should be noted. Attention should be paid particularly to the position of the acetabular component and the size of the femoral head used, as both have been associated with higher revision rates and elevated serum metal ions, respectively [4,5] (Image 1). The Australian registry reported a correlation of femoral head size in excess of 32 mm with an increased rate of revision in the setting of a metal-on-metal prosthesis [6]. Additionally, increased abduction of the acetabular component, in excess of 501, can potentially increase edge loading and thereby generate metal debris [21,22]. Computed tomography (CT) can be useful in identifying osteolysis and component malposition. CT scan can further characterize soft tissue lesions as solid or cystic in close proximity to the implant [7,11].
4.2.
Advanced imaging—MARS MRI
Metal artifact reduction sequence, or MARS MRI, has been shown to reproducibly quantify adverse local tissue reaction in the setting of a metal-on-metal total hip arthroplasty [23]. MARS imaging is most effective in determining the extent of pseudotumor burden, and most importantly, it can reveal abductor muscle involvement. Several studies have documented a similar rate of adverse local tissue reaction in both symptomatic and asymptomatic patients [23,24].
4.3.
3
Ultrasound
Ultrasound has been utilized as a screening tool to detect the presence of a periprosthetic soft tissue mass in the setting of a metal-on-metal hip replacement. It can serve as a beneficial cost-effective alternative to MRI in those patients with implantable defibrillators, metallic implants, or claustrophobia. However, this modality is operator dependent and given limited transmission, it may not adequately evaluate deeper lesions or completely assess those patient’s with a larger body habitus [25].
4.4.
Laboratory evaluation
ESR and CRP values should be obtained to rule out an infectious process, however, these values have been found to be elevated in the setting of patients with ALTR without underlying infection [26]. Aspiration of synovial fluid should be a documented step in the algorithm to differentiate ALTR from infection. Aspirate in the setting of psuedotumor has been classically described as grayish and hazy, with a dishwater consistency, in contrast to turbid purulence in the setting of infection. Each specimen should be sent for manual cell count as opposed to an automated cell count, given that debris in the suspension from the aspirate could falsely elevate automated counts [27]. In addition, cell differential, culture, and crystal analysis should be obtained. Blood and serum cobalt (Co) and chromium (Cr) concentrations have been demonstrated to correlate with wear rates in metal-on-metal implants. A cobalt (Co) or chromium (Cr) level of greater than 5 mg/l, which has a sensitivity and specificity of 52% and 89%, respectively, has generally been accepted as an indication for advanced imaging [27,28]. A 2012 medical safety alert issued by The Medicines and Healthcare Products Regulatory Agency (MHRA) from the United Kingdom, did not recommend asymptomatic patients with MoM implants undergo routine blood metal ion screening [29]. However, a recent study by Gulraj et al. [30] investigated whether blood metal ions could identify which patients, that had previously been treated with one of two specific metalon-metal implants, were at risk of developing an ALTR. They found that patients with implant-specific serum cobalt cutoff values less than 2.15 mg/l for the Birmingham Hip Resurfacing (BHR; Smith and Nephew) and 3.57 mg/l for the Corail– Pinnacle (Depuy Synthes) total hip replacement systems, were at low risk for developing an ALTR [30]. This data suggests that cobalt (Co) and chromium (Cr) serum threshold levels need to be assessed for each individual metal-on-metal implant. At the present time, for most metal-on-metal implants, serum metal ion values alone are not an absolute indication for surgery.
5. Image 1 – A 67-year-old female status post metal-on-metal total hip arthroplasty, with an excessively abducted acetabular component and greater trochanteric fracture presenting with recurrent dislocation.
] (2016) ]]]–]]]
Skin patch testing
Skin patch testing is the most common tool to assess metal hypersensitivity. However, it only provides exposure for a limited amount of time (24–48 h) whereas the implant exposure is constant in the periprosthetic environment.
4
SE
M I N A R S I N
AR
T H R O P L A S T Y
Additionally, the patch test exposes the allergen to a different subset of antigen presenting cells (dendritic cells, Langerhans cells) than those found in periprosthetic tissues (synoviocytes) [19]. In a study of 54 patients administered patch testing prior to and following total hip replacement, Rooker et al. reported, of six patients with a positive pre-operative test, five lost their hypersensitivity at the time of postoperative testing [31]. In the setting of a symptomatic metal-on-metal hip replacement, few studies have documented a higher rate of failure in patients with a metal hypersensitivity on skin patch testing as compared to those without a positive test [19,32]. The causal relationship between metal hypersensitivity and metal-on-metal implant failure remains unclear, and skin patch testing is not a routine part of the work-up of these patients.
6.
When to consider revision surgery
6.1.
Risk stratification
No universally accepted algorithm exists to determine when an operation is necessary. It is important to risk stratify these patients, to better understand who requires close follow-up and/or early intervention. In a consensus statement released from the American Association of Hip and Knee Surgeons and the American Academy of Orthopaedic Surgeons, Kwon et al. presented an algorithm for patients with dual modular taper stems. Risk should be assigned based on a number of different factors including the patient’s activity level, symptomatology, implant characteristics, serum metal ion level, and soft tissue findings on advanced imaging [27]. Patients with a painful total hip and evidence of soft tissue destruction on MARS MRI (i.e., abductor muscle involvement) will most likely require immediate surgical intervention. However, the presence of a pseudotumor without soft tissue destruction does not require urgent surgical intervention. Further study is required to determine the optimal metal ion thresholds for specific metal-on-metal implants to identify patients at increased risk for developing an ALTR (Fig. 1).
6.2.
Low-risk patients
Low-risk patients are asymptomatic and maintain a lowdemand lifestyle. On radiographic imaging, their acetabular component will exhibit excellent orientation, their femoral head is o36 mm, and there will be no evidence of osteolysis or subsidence [27]. Additionally, lab values will demonstrate serum metal ion levels o3 ppb with no evidence of infection. The FDA recommends these patients can be followed up every 1 to 2 years, and do not require metal ion or advanced imaging surveillance. However, this decision should be made on a patient-to-patient basis and ultimately is at the discretion of the treating surgeon [33].
6.3.
Moderate risk patients
These patients are generally community ambulators, report mild localized symptoms, and may or may not present with a
] (2016) ]]]–]]]
limp. Components may or may not exhibit acceptable orientation and the femoral head may be 36 mm or greater. Radiographic analysis should demonstrate no evidence of osteolysis or subsidence [27]. Serum metal ion levels may be normal to elevated, ranging from 3 to 10 ppb (this value may be implant specific). In the setting of progressive symptoms and rising ion levels, MARS MRI should be the next step in evaluation and may demonstrate abnormal soft tissue reaction with small fluid or cystic lesions, without muscle destruction [27]. The FDA recommends routine follow-up every 6–12 months in symptomatic patients; however, currently there is a lack of evidence to demonstrate a correlation between metal ion level and ALTR [20,34]. We recommend close follow-up for these patients, with a low threshold to consider revision surgery in the setting of progressive symptoms and/or deficits on exam.
6.4.
High-risk patients
The high-risk patient is typically an active individual that presents with severe symptoms that may include abductor insufficiency. Radiographic imaging will demonstrate components in suboptimal position, and/or femoral head size 436 mm. Metal ion levels will be 45 ppb (this value may be implant specific), ESR and or CRP may be elevated, and synovial fluid analysis may support evidence of underlying infection [27]. Advanced imaging may demonstrate significant soft tissue destruction, osteolysis, component subsidence, or periprosthetic fracture [27]. MARS imaging demonstrating extensive pseudotumor burden with abductor muscle involvement, is an absolute indication for surgical intervention.
7.
Revision arthroplasty
The decision to move forward with revision surgery is not always simple, because revision does not always lead to an excellent outcome. In a review of 37 failed MoM prosthesis, of the 10 patients revised secondary to presumed ALTR, all patients reported never fully recovering following the index procedure [35]. Surgeons must recognize at-risk patients, including female patients and those with increased abduction of the acetabular component [36]. During revision surgery, intraoperative specimens should be obtained and associated findings should be documented. Periprosthetic tissues should be sent for culture, frozen section, and permanent sections for pathology review and histologic analysis. If the components are well fixed and in an acceptable position, it is generally accepted that these patients can be converted to a metal on polyethelyne or ceramic on polyethelene liner. The surgeon should document to what degree the abductors have been compromised, and consider a dual mobility component or even a constrained liner in the setting of abductor insufficiency (Images 2,3).
SE
M I N A R S I N
AR
T H R O P L A S T Y
5
] (2016) ]]]–]]]
Image 2 – The same 67-year-old female with identification of a pseudotumor at the time of operative exploration of the hip joint.
8.
Summary
The painful MoM total hip arthroplasty with a large femoral head is at increased risk for failure. Risk stratification of these patients is paramount, and requires a systematic evaluation using a variety of different tests such as serum metal ion levels and advanced imaging to determine the appropriate treatment. Over-reliance on any one diagnostic tool should be avoided. Additional research is required to better understand the natural history of metal-onmetal bearing failure and to validate the current investigative instruments used in diagnosing adverse reaction to metal debris.
Image 3 – The same 67-year-old female following revision total hip arthroplasty.
Hisotry of Metal on Metal Total Hip Arthroplasty
Symptomatic
Asymptomatic
<50 deg Abduction/ Femoral head < 36 mm
Low Risk stratiicationroutine follow up
Cup Position >50 deg Abduction and/or Femoral Head> 36mm
Cup <50 deg Abduction / Femoral head <36mm
>50 deg Abduction or femoral head> 36 mm
Serum Metal <5ppb#
Serum Metal >5ppb#
Routine follow up and/or MARS MRI*
MARS MRI*
Metal Ions <5ppb#
No evidence of soft tissue destruction
Soft Tissue Destruction evident
Close Follow up
Recommend Revision Surgery
Metal Ions >5ppb#
Will likely require revision surgery
No evidence of soft tissue destruction on MARS MRI*
Soft Tissue destruction on MARS MRI*
No evidence of soft tissue destruction on MARS MRI*
Soft Tissue destruction evident on MARS MRI*
Weigh risks and beneits with patient
Recommend Revision Surgery
Weigh risks and beneits with patient
Recommend revision surgery
Figure 1 – Metal-on-metal hip replacement: indications for intervention [27]. * ¼ metal artifact reduction sequence MRI; # ¼ parts per billion.
6
SE
M I N A R S I N
AR
T H R O P L A S T Y
r e f e r e n c e s [20] [1] McKee GK, Watson-Farrar J. Replacement of arthritic hips by the McKee–Farrar prosthesis. The Journal of Bone and Joint Surgery. British Volume 1966;48:245–59. [2] Smith TM, Berend KR, Lombardi AV Jr, et al. Metal-on metal total hip arthroplasty with large heads may prevent early dislocation. Clinical Orthopaedics and Related Research 2005;441:137–42. [3] Lombardi AV Jr, Barrack RL, Berend KR, et al. The Hip Society: algorithmic approach to diagnosis and management of metal-on-metal arthroplasty. The Journal of Bone and Joint Surgery. British volume 2012;94:14–8. [4] Australian Orthopaedic Association National Joint Replacement Registry: Annual Report 2010. Adelaide, SA, Australia: Australian Orthopaedic Association; 2010. [5] National Joint Registry for England and Wales: Seventh Annual Report. Hemel Hempstead, Hertfordshire, UK: National Joint Registry Centre; 2010. [6] Willert HG, Buchhorn GH, Fayyazi A, et al. Metal-on-metal bearings and hypersensitivity in patients with artificial hip joints: a clinical and histomorphological study. The Journal of Bone and Joint Surgery. American Volume 2005;87:28–36. [7] Pandit H, Glyn-Jones S, McLardy-Smith P, et al. Pseudotumors associated with metal-on-metal hip resurfacings. The Journal of Bone and Joint Surgery. British Volume 2008;90: 847–51. [8] Van Der Weegen W, Sjibesma T, Hoekstra H, et al. Treatment of pseudotumors after metal-on-metal hip resurfacing based on magnetic resonance imaging, metal ion levels and symptoms. The Journal of Arthroplasty 2014;29:416–21. [9] Memon AR, Galbraith JG, Harty JA, et al. Inflammatory pseudotumor causing deep vein thrombosis after metal-onmetal hip resurfacing arthroplasty. The Journal of Arthroplasty 2013;28:197–209. [10] Watters TS, Eward WC, Hallows RK, et al. Pseudotumor with superimposed periprosthetic infection following metal-onmetal total hip arthroplasty: a case report. The Journal of Bone and Joint Surgery. American Volume 2010;92:1666. [11] Hart AJ, Sabah S, Henckel J, et al. The painful metal-on-metal hip resurfacing. The Journal of Bone and Joint Surgery. British Volume 2009;91:738–44. [12] Langton DJ, Joyce TJ, Jameson SS, et al. Adverse reaction to metal debris following hip resurfacing: the influence of component type, orientation and volumetric wear. The Journal of Bone and Joint Surgery. British Volume 2011; 93:164–71. [13] Kwon YM, Ostlere SJ, McLardy-Smith P, et al. “Asymptomatic” pseudotumors after metal-on-metal hip resurfacing arthroplasty: prevalence and metal ion study. The Journal of Arthroplasty 2011;31:260–3. [14] Bozic KJ, Rubash HE. The painful total hip replacement. Clinical Orthopaedics and Related Research 2004;420:18–25. [15] Smith P, Rorabeck C. Clinical evaluation of the symptomatic total hip arthroplasty. In: Steinberg M, Garino J, et al., eds. Revision total hip arthroplasty. Philadelphia, PA: Lippincott Williams & Wilkins; 1999. 109–20. [16] Bohl W, Steffee A. Lumbar spinal stenosis: a cause of continued pain and disability in patients after total hip arthoplasty. Spine 1974;4:168–73. [17] Gaunt M, Tan S, Dias J. Strangulated obturator hernia masquerading as pain from a total hip replacement. The Journal of Bone and Joint Surgery. British Volume 1992;74:782–3. [18] Springer B. The diagnosis of periprosthetic joint infection. The Journal of Arthroplasty 2015;6:908–11. [19] Park YS, Moon YW, Lim SJ, et al. Early osteolysis following second-generation metal-on-metal hip replacement. The
[21]
[22]
[23]
[24]
[25]
[26]
[27]
[28]
[29] [30]
[31]
[32] [33]
[34]
[35]
[36]
] (2016) ]]]–]]]
Journal of Bone and Joint Surgery. American Volume 2005;87:1515–21. U.S. Food and Drug Administration: metal-on-metal hip implants. http://www.fda.gov/ MedicalDevices/ Productsand MedicalProcedures/ ImplantsandProsthetics/ MetalonMetal HipImplants/default.htm [accessed Feb 13, 2016]. Campbell P, Beaulé PE, et al. The John Charnley Award: a study of implant failure in metal-on-metal surface arthroplasties. Clinical Orthopaedics and Related Research 2006; 453:35–46. Hart AJ, Ilo K, Underwood R, et al. The relationship between the angle of version and rate of wear of retrieved metal-on metal resurfacings: a prospective, CT based study. The Journal of Bone and Joint Surgery. British Volume 2011;93: 315–20. Nawabi D, Hayter C, Su E, et al. Magnetic resonance imaging findings in symptomatic versus asymptomatic subjects following metal-on-metal hip resurfacing arthroplasty. The Journal of Bone and Joint Surgery. American Volume 2013;95:895–902. Mistry A, Cahir J, Donell ST, et al. MRI of asymptomatic patients with metal-on-metal and polyethylene-on-metal total hip arthroplasties. Clinical Radiology 2011;66:540–5. Hayter C, Potter H, Su E. Imaging of metal-on-metal hip resurfacing. The Orthopedic clinics of North America 2011; q42:195–205. Langton DJ, Sidaginamale RP, Joyce TJ, et al. The clinical implications of elevated blood metal ion concentrations in asymptomatic patients with MoM hip resurfacings: a cohort study. BMJ Open 2013;3(3). Kwon YM, Lombardi AV, Jacobs JJ, et al. Risk stratification algorithm for management of patients with metal-on-metal hip arthroplasty: consensus statement of the American Association of Hip and Knee Surgeons, the American Academy of Orthopaedic Surgeons, and the Hip Society. The Journal of Bone and Joint Surgery. American Volume 2014; 29:2060–4. Hart AJ, Sabah SA, Bandi AS, et al. Sensitivity and specificity of blood cobalt and chromium metal ions for predicting failure of metal-on-metal hip replacement. The Journal of Bone and Joint Surgery. British Volume 2011;93:1308–13. Medical Device Alert Ref: MDA/2012/008. Gulraj MS, Berryman F, Brash L, et al. The effectiveness of blood metal ions in identifying patients with unilateral Birmingham hip resurfacing an corail-pinnacle metal-on metal-hip implants at risk of adverse reactions to metal debris. The Journal of Bone and Joint Surgery. American Volume 2016;98:617–26. Rooker GD, Wilkinson JD. Metal sensitivity in patients undergoing hip replacement. A prospective study. The Journal of Bone and Joint Surgery. British Volume 1980;62:502–5. Antony FC, Holden CA. Metal allergy resurfaces in failed hip endoprostheses. Contact Dermatitis 2003;48:49–50. Bolognesi M, Ledford C. Metal-on-metal total hip arthroplasty: patient evaluation and treatment. The Journal of the American Academy of Orthopaedic Surgeons 2015; q23:724–31. Bayley N, Khan H, Grosso P, et al. What are the predictors and prevalence of pseudotumor and elevated metal ions after large-diameter metal-on-metal THA? Clinical Orthopaedics and Related Research 2015;473:477–84. Browne JA, Bechtold CD, Berry DJ, et al. Failed metal-onmetal hip arthroplasties: a spectrum of clinical presentations and operative findings. Clinical Orthopaedics and Related Research 2010;468:2313–20. Laitteier MJ, Berend KR, Lombardi AV Jr, et al. Gender is a significant factor for failure of metal-on-metal total hip arthroplasty. The Journal of Arthroplasty 2011;26:19–23.