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The Journal of Bone and Joint Surgery 79:1721-5 (1997)
© 1997 The Journal of Bone and Joint Surgery, Inc.

Titanium Prosthetic Wear Debris in Remote Bone Marrow. A Report of Two Cases*

C. ANDERSON ENGH, JR., M.D.{dagger}, K. DAVID MOORE, M.D.{dagger}, ALEXANDRIA, TUYETHOA N. VINH, M.D.{ddagger}, WASHINGTON, D.C. and GERARD A. ENGH, M.D.{dagger}, ALEXANDRIA, VIRGINIA

Investigation performed at Anderson Orthopaedic Research Institute, Alexandria, and Armed Forces Institute of Pathology, Washington, D.C.


    Introduction
 Top
 Introduction
 Case Reports
 Discussion
 References
 
We report the cases of two patients who had a severely worn total joint implant. In each case, histological analysis of bone marrow from the iliac crest revealed macrophages that contained deep black, angular areas of pigmentation. Energy-dispersive x-ray analysis revealed the pigmentation to be titanium, aluminum, and vanadium.

We are not aware of any reports that have conclusively documented the presence of metallic wear debris in bone marrow that is remote from the site of a severely worn total joint implant. The findings of the present study demonstrate that techniques other than light microscopy are needed to identify and characterize wear debris at sites that are remote from a total joint implant. Our findings also support the hypothesis that wear particles can be systemically transported to and deposited at remote sites.


    Case Reports
 Top
 Introduction
 Case Reports
 Discussion
 References
 
CASE 1. A fifty-five-year-old woman who had degenerative joint disease was managed with a right total hip arthroplasty without cement in 1990. A titanium metal-backed acetabular component and a proximally porous-coated cobalt-chromium femoral component were used. Six months later, the patient reported clicking and subluxation of the right hip.

In February 1992, during the preoperative evaluation for a left total hip arthroplasty, the patient complained of migraine headaches. Laboratory studies revealed that the patient had borderline anemia.

The patient reported, in June 1995, that the right hip had dislocated and then had reduced spontaneously. She complained of intermittent fever and chills, gastrointestinal cramps, intermittent epistaxis, intermittent swelling of the lower extremities, and fatigue. The patient was mildly anemic (hemoglobin, 10.8 grams per deciliter [108 grams per liter]; normal range, 12.0 to 16.0 grams per deciliter [120 to 160 grams per liter]) and leukopenic (white blood-cell count, 3.6 x 103 per microliter [3.6 x 109 per liter]; normal range, 4.5 to 11.0 x 103 per microliter [4.5 to 11.0 x 109 per liter]). The Westergren sedimentation rate was 6.1 millimeters per hour. The serum titer for HLA-B27 was positive, but the serum titer for antinuclear antibody was negative.

Radiographs that were made in October 1995 revealed notable polyethylene wear and profound osteolysis of the proximal portion of the right femur. Aspiration of the hip joint revealed black synovial fluid. The possibility of titanium poisoning was considered. In December 1995, a workup by a hematologist confirmed persistent anemia and leukopenia with no obvious cause. The results of a biopsy of bone marrow from the right posterior iliac crest were unremarkable with the exception of unexplained black pigmentation in macrophages.

When the patient was referred to us, in January 1996, she had a four-year history of a squeaking sound emanating from the right hip. Physical examination revealed tenderness over the greater trochanter and a moderate antalgic gait. Radiographs showed stable fixation of the femoral component, extensive osteolysis of the proximal portion of the femur, and a pathological fracture of the greater trochanter secondary to the osteolysis. The acetabular component was stable, and severe wear of the polyethylene liner was evident. On the left side, the total hip components were well fixed and there was no visible wear of the polyethylene liner.

At the time of a reoperation, the patient was found to have catastrophic failure of the polyethylene liner as well as a massive amount of metallic debris and extensive osteolysis. The locking mechanism of the acetabular component had failed (Fig. 1), and the femoral component was easily disimpacted from the femur. Both components were revised without cement.



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Fig. 1. Case 1. Photograph of the worn titanium acetabular component.

 
Intraoperatively, specimens of periarticular tissue were taken from the region around the right hip and a biopsy specimen of bone marrow was obtained from the left iliac crest. The level of serum titanium, measured on the second postoperative day, was seventy-two micrograms per deciliter (normal range, zero to fifteen micrograms per deciliter13).

CASE 2. A seventy-five-year-old man who had degenerative joint disease had a right total knee replacement with cement in 1988. The procedure was performed at another institution. In 1989, he had a right bipolar hip replacement because of avascular necrosis. The patient did well until August 1995, when he was involved in an all-terrain-vehicle accident that resulted in trauma to the right knee. Subsequently, he had recurrent hemarthrosis. In September 1995, radiographs showed that the polyethylene surface of the patellar component had dissociated from its metal backing. However, operative treatment was delayed because the patient had minimum symptoms related to the knee, severe peripheral vascular disease, and a busy lifestyle.

In November 1995, the patient had an arthrotomy for removal of the failed patellar implant. At the time of the operation, he was noted to have extensive metallosis of the synovial tissue, extensive periarticular osteolysis, and severe wear in the trochlear groove of the titanium femoral component. Because of the unexpected complexity of the intraoperative findings, the patellar component was removed, the wound was closed, and the patient was referred to us.

At the time of presentation, the patient complained of severe pain and could walk only very short distances. He had no effusion in the joint. The passive range of motion was from full extension to 70 degrees of flexion, and there was a 40-degree extension lag. Radiographs showed severe osteolysis of the femur and tibia and evidence of metallic debris in the suprapatellar pouch.

A revision total knee arthroplasty was performed in June 1996. The failed metal-backed patellar component was found to have incompletely bisected the titanium femoral component (Fig. 2). Additional findings included massive femoral osteolysis, moderate tibial osteolysis, and extensive black metallic synovial staining. The knee was revised with use of a bulk allograft for the distal portion of the femur, particulate allograft for the proximal portion of the tibia, and long-stemmed revision components. A biopsy specimen of bone marrow was taken from the ipsilateral iliac crest for evaluation with light microscopy and energy-dispersive x-ray analysis. The level of serum titanium was determined on the first postoperative day, and it was found to be elevated to thirty micrograms per deciliter (normal range, zero to fifteen micrograms per deciliter13).



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Fig. 2. Case 2. Photograph of the titanium femoral component, which had been bisected as a result of wear with the metal-backed patellar implant.

 

Pathological Findings
CASE 1. Histological analysis of the periarticular tissue revealed numerous foreign-body giant cells containing polarizable particles of varying sizes and thicknesses. The synovial tissue was heavily infiltrated by macrophages that contained dark black, angular areas of pigmentation. The specimens of bone marrow from the right (Fig. 3) and left iliac crests were composed of normal cellular marrow, with the exception of the macrophages that contained dark black pigment with similar angular morphology. The areas of pigmentation were approximately one to two micrometers in size and were negative for iron on staining of specimens of bone marrow from the right and left iliac crests. No polyethylene wear particles were detected in the specimens of bone marrow.



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Fig. 3. Case 1. Photomicrograph of a sample of bone marrow from the right iliac crest. Arrowheads indicate deep black, angular areas of pigmentation. The areas of pigmentation are contained in macrophages within otherwise normal bone marrow (hematoxylin and eosin, x 1000).

 
A scanning electron microscopic study was performed with a digital scanning electron microscope (DSM 960A; Carl Zeiss, Thornwood, New York) that was equipped with a backscattered electron detector (GW Electronics, Norcross, Georgia) and an x-ray detector (Princeton Gamma Tech, Princeton, New Jersey). Backscattered electron micrographs used to select fields for the measurement and identification of elements with energy-dispersive x-ray analysis (EDAX, Mahwah, New Jersey).

The energy-dispersive x-ray analysis of the periprosthetic tissue revealed peaks for titanium, vanadium, and aluminum (Fig. 4). Analysis of the specimen of bone marrow from the right iliac crest revealed titanium and vanadium peaks, and analysis of the specimen of bone marrow from the left iliac crest revealed titanium and aluminum peaks.



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Fig. 4. Case 1. Backscattered electron micrograph of a specimen of periarticular tissue from the region of the right up hip (inset) and associated energy-dispersive x-ray analysis map demonstrating titanium, aluminum, and vanadium peaks.

 
CASE 2. Gross examination of the periarticular tissue revealed thickened, black synovial tissue. The biopsy of bone marrow from the right iliac crest, performed on the day of the revision total knee arthroplasty, revealed normal marrow cellularity and dark black pigment contained within macrophages. Energy-dispersive x-ray analysis of the specimen of bone marrow revealed a titanium peak. The deep black, angular particles of metal were more easily seen against the lighter pink background of the iron stain (Fig. 5) than against the darker background of the hematoxylin and eosin stain.



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Fig. 5 Case 2. Photomicrograph of a specimen of bone marrow from the iliac crest. Black angular particles are more easily seen against the lighter background of this stain (iron stain, x 750).

 


    Discussion
 Top
 Introduction
 Case Reports
 Discussion
 References
 
Metallic debris has been documented in periarticular soft tissue1,4,8,12, in periprosthetic bone1,8,11, and in regional lymph nodes2-5,7,12,14. Several authors have noted metallic particulate debris in the liver and spleen of patients who have had an arthroplasty5,12,15. The cases of our two patients clearly demonstrate that titanium particulate debris can be deposited in bone marrow at sites that are distant from a severely worn total joint implant.

Histological examination of the synovial tissue of both patients showed particles that had the characteristic morphology of metallic debris. The macrophages contained dark black, angular particles that stained negative for iron. These particles were seen in specimens of bone marrow and synovial tissue. The detection of such particles in the synovial tissue should alert the physician to the presence of metallic debris. Although polyethylene wear debris was present in the periarticular tissue of one of our patients (Case 1), it was not detected in the bone marrow of either patient.

The task of identifying possible particles of metal with use of light microscopy is straightforward. However, confirming that pigmented areas are metal, determining the type of metal, and establishing that these areas represent particulate debris from a total joint implant all present more difficulty. Although energy-dispersive x-ray analysis is an appropriate technique to confirm the presence of metal, the technique is difficult and time-consuming, particularly when used to evaluate biopsy specimens of bone marrow in which the particles are minute and few. Many backscattered electron micrographic fields and x-ray analyses of these areas on multiple sections are needed for the identification of the metallic elements that are contained within the bone marrow macrophages. In the case of our first patient (Case 1), similar peaks for titanium alloy were seen on energy-dispersive x-ray analysis of the periarticular tissue from the region of the hip as well as of the bone marrow from both iliac crests.

In both of our patients, the size of the particles was less than four micrometers. This finding was assessed easily on the specimens of bone marrow by comparing the size of the particles with that of the red blood cells, which are approximately two micrometers thick and approximately seven micrometers in diameter. The small size also was apparent because the particles were engulfed by single macrophages. We hypothesize that circulating monocytes engulf these particles at the site of a failed prosthesis and then return to systemic circulation. The monocytes would not normally be filtered by the lungs, liver, or spleen and thus could be found in the bone marrow. Another hypothesis is that the small particles actually enter the bloodstream of the patient and become systemically distributed. These particles are then engulfed by resident macrophages in the bone marrow.

The implications of metallic debris in the bone marrow are unknown. The first patient in the present report (Case 1) demonstrated fatigue, leukopenia, and anemia, all of which were attributed to titanium toxicity. We are not aware of any case of systemic titanium toxicity associated with titanium implants. In fact, occupational exposure to particles of titanium has not been found to cause clinical symptoms, with the exception of slight fibrosis of the lung reported after inhalation of titanium dioxide pigment6. Although we could not establish a diagnosis of titanium toxicity, the potential for systemic complications related to metallic wear debris warrants additional attention. Laboratory tests that were performed within two days postoperatively showed marked elevation of the level of serum titanium in both of our patients (the level was found to be seventy-two and thirty micrograms per deciliter in the first and second patients, respectively). Similarly elevated levels have been reported previously9,16, but the importance of elevated levels of titanium in the blood remains uncertain. Jacobs et al. found no association between the level of serum titanium and the deposition of titanium in the liver and spleen10. Both of our patients have been monitored yearly with regard to the level of serum titanium.

The use of energy-dispersive x-ray analysis was critical to the identification and characterization of the wear debris in both of our patients. Other authors have reported metallic pigmentation in patients managed with metal implants and have assumed that the pigmentation was wear debris5,12,15. In the present study, we identified, with energy-dispersive x-ray analysis, peaks that were consistent with titanium, aluminum, and vanadium. The combination of these elements in patients who had severely worn titanium-alloy implants is strong evidence that the metal in the bone marrow originated from the failed implants.

The material properties of titanium make that substance susceptible to abrasion. As a result, when a polyethylene bearing surface fails and titanium is allowed to articulate with a harder metal such as cobalt-chromium, the titanium quickly abrades. This abrasion results in a large volume of titanium particles. Additionally, the titanium surface quickly becomes congruent with the harder metal, potentially decreasing the severity of symptoms. The relative lack of symptoms in our two patients, both of whom had catastrophic failure of a component and massive metallic debris, points out the need for close clinical follow-up by an orthopaedic surgeon. Such follow-up should involve attention to wear of the component and prompt treatment when failure of the bearing surface is suspected.


    Footnotes
 
*One or more of the authors has received or will receive benefits for personal or professional use from a commercial party related directly or indirectly to the subject of this article. No funds were received in support of this study.

{dagger}Anderson Orthopaedic Research Institute, P.O. Box 7088, Alexandria, Virginia 22307.

{ddagger}Armed Forces Institute of Pathology, 14th and Alaska Avenue, N.W., Washington, D.C. 20306.


    References
 Top
 Introduction
 Case Reports
 Discussion
 References
 

  1. Agins, H. J.; Alcock, N. W.; Bansal, M.; Salvati, E. A.; Wilson, P. D., Jr.; Pellici, P. M.; and Bullough, P. G.: Metallic wear in failed titanium-alloy total hip replacements. A histological and quantitative analysis. J. Bone and Joint Surg., 70-A: 347-356, March 1988.[Abstract/Free Full Text]

  2. Albores-Saavedra, J.; Vuitch, F.; Delgado, R.; Wiley, E.; and Hagler, H.: Sinus histiocytosis of pelvic lymph nodes after hip replacement. A histiocytic proliferation induced by cobalt-chromium and titanium. Am. J. Surg. Pathol., 18: 83-90, 1994.[Medline]

  3. Benz, E. B.; Sherburne, B.; Hayek, J. E.; Falchuk, K. H.; Sledge, C. B.; and Spector, M.: Lymphadenopathy associated with total joint prostheses. A report of two cases and a review of the literature. J. Bone and Joint Surg., 78-A: 588-593, April 1996.[Free Full Text]

  4. Bos, I.; Johannisson, R.; Lohrs, U.; Lindner, B.; and Seydel, U.: Comparative investigations of regional lymph nodes and pseudocapsules after implantation of joint endoprostheses. Pathol. Res. and Pract., 186: 707-716, 1990.

  5. Case, C. P.; Langkamer, V. G.; James, C.; Palmer, M. R.; Kemp, A. J.; Heap, P. F.; and Solomon, L.: Widespread dissemination of metal debris from implants. J. Bone and Joint Surg., 76-B(5): 701-712, 1994.[Abstract/Free Full Text]

  6. Goyer, R. A.: Toxic effects of metals. In Casarett and Doull's Toxicology: The Basic Science of Poisons, edited by C. D. Klaassen. Ed. 5, pp. 691-736. New York, McGraw-Hill, 1996.

  7. Hicks, D. G.; Judkins, A. R.; Sickel, J. Z.; Rosier, R. N.; Puzas, J. E.; and O'Keefe, R. J.: Granular histiocytosis of pelvic lymph nodes following total hip arthroplasty. The presence of wear debris, cytokine production, and immunologically activated macrophages. J. Bone and Joint Surg., 78-A: 482-496, April 1996.[Abstract/Free Full Text]

  8. Huo, M. H.; Salvati, E. A.; Lieberman, J. R.; Betts, F.; and Bansal, M.: Metallic debris in femoral endosteolysis in failed cemented total hip arthroplasties. Clin. Orthop., 276: 157-168, 1992.

  9. Jacobs, J. J.; Skipor, A. K.; Black, J.; Urban, R. M.; and Galante, J. O.: Release and excretion of metal in patients who have a total hip-replacement component made of titanium-base alloy. J. Bone and Joint Surg., 73-A: 1475-1486, Dec. 1991.[Abstract/Free Full Text]

  10. Jacobs, J. J.; Skipor, A. K.; Urban, R. M.; Black, J.; Manion, L. M.; and Galante, J. O.: Transport of metal degradation products of titanium alloy total hip replacements to reticuloendothelial organs. An autopsy study. Trans. Soc. Biomater., 17: 318-325, 1994.

  11. Jones, D. A.; Lucas, H. K.; O'Driscoll, M.; Price, C. H. G.; and Wibberley, B.: Cobalt toxicity after McKee hip arthroplasty. J. Bone and Joint Surg., 57-B(3): 289-296, 1975.

  12. Langkamer, V. G.; Case, C. P.; Heap, P.; Taylor, A.; Collins, C.; Pearse, M.; and Solomon, L.: Systemic distribution of wear debris after hip replacement. A cause for concern?. J. Bone and Joint Surg., 74-B(6): 831-839, 1992.[Abstract/Free Full Text]

  13. National Science Services, Willow Grove, Pennsylvania.

  14. Onodera, K.; Ooya, K.; and Kawamura, H.: Titanium lymph node pigmentation in the reconstruction plate system of a mandibular bone defect. Oral Surg., Oral Med., Oral Pathol., 75: 495-497, 1993.[Medline]

  15. Peoc'h, M.; Moulin, C.; and Pasquier, B.: Systemic granulomatous reaction to a foreign body after hip replacement [letter]. New England J. Med., 335: 133-134, 1996.[Free Full Text]

  16. von Schroeder, H. P.; Smith, D. C.; Gross, A. E.; Pilliar, R. M.; Kandel, R. A.; Chernecky, R.; and Lugowski, S. J.: Titanemia from total knee arthroplasty. A case resulting from a failed patellar component. J. Arthroplasty, 11: 620-625, 1996.[Medline]


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