What do we know about taper corrosion in total hip arthroplasty?

Mechanically assisted crevice corrosion (MACC) at metal/metal modular junctions in which at least one of the components is fabricated from cobalt-chromium alloy, has reemerged as a potential clinically significant complication in total hip arthroplasty. The clinical manifestation of MACC may include the development of an adverse local tissue reaction (ALTR), similar to what has been described in association with metal-on-metal bearing total hip and resurfacing arthroplasty. The clinical presentation of MACC-associated ALTRs may include pain and possibly late recurrent dislocations. Abnormal metal artifact reduction sequence magnetic resonance images and elevated serum metal levels (cobalt elevations out of proportion to chromium elevations) can be helpful in the diagnosis of these MACC-associated ALTRs.

Additive enhancement of implant fixation following combined treatment with rhTGF-beta2 and rhBMP-2 in a canine model.

BACKGROUND: Gaps at the interface between implant and bone increase the risk of diminished implant fixation and eventual loosening. The purpose of the present study was to determine if combined use of recombinant human transforming growth factor-beta 2 (rhTGF-beta2) and bone morphogenetic protein 2 (rhBMP-2) led to greater implant fixation strength in the presence of interface gaps than the use of either growth factor alone. METHODS: Twenty-eight skeletally mature adult male dogs received one porous-coated titanium implant in the proximal part of each humerus, for a total of fifty-six implantation sites. Spacers were used to establish an initial 3-mm gap between the implant and the host bone at all fifty-six sites. Forty-two implants were coated with hydroxyapatite-tricalcium phosphate and were used in three growth-factor-treatment groups in which the implants placed in the left humerus were loaded with 12 microg of rhTGF-beta2 (Group 1, seven animals), 25 microg of rhBMP-2 (Group 2, seven animals), or 12 microg of rhTGF-beta2 combined with 25 microg of rhBMP-2 (Group 3, seven animals). In these animals, the twenty-one implants that were placed in the right humerus were loaded with buffer only to serve as contralateral controls. In Group 4 (seven animals), the implants were not coated with hydroxyapatite-tricalcium phosphate, the gap in the left humerus was lightly packed with autogenous bone graft, and the gap in the right humerus was left empty to serve as a contralateral control. All animals were killed at twenty-eight days. The primary end points included three mechanical variables: fixation strength, interface stiffness, and energy to failure. Secondary end points included bone ingrowth and bone volume and trabecular architecture in the gap and in a region located 2 mm medial to the implantation site. RESULTS: The hydroxyapatite-tricalcium phosphate coating had no effect on implant fixation, bone ingrowth, or bone formation in the 3-mm gap. Individual growth factor treatments led to 2.3 to 3.2-fold increases in fixation strength and stiffness as compared with the values for the contralateral controls (p < 0.05). The combined growth factor treatment led to 5.7-fold increases in fixation strength and stiffness compared with the values for the contralateral controls (p < 0.01). Autogenous bone graft treatment was associated with 4.5 to 6.4-fold increases in implant fixation strength and stiffness as compared with the values for the contralateral controls (p < 0.01). Compared with the relevant contralateral controls, energy to failure was increased 3.5-fold in association with TGF-beta2 alone (p < 0.05), 4.5-fold in association with TGF-beta2 combined with BMP-2 (p < 0.01), and 2.5-fold in association with autogenous bone-grafting. As much as 63% of the variance in the mechanical end points was associated with variance in bone volume and architecture in the 3-mm gap and in the region of interest located 2 mm medial to the implantation site (p < 0.01). CONCLUSIONS: In this animal model, the combined use of TGF-beta2 and BMP-2 led to more secure mechanical fixation of the implant than did the use of either growth factor alone and demonstrated results that were similar to those associated with the use of autogenous bone graft.

A longitudinal study on an autoimmune murine model of ankylosing spondylitis.

BACKGROUND: Proteoglycan aggrecan (PG)-induced arthritis (PGIA) is the only systemic autoimmune murine model which affects the axial skeleton, but no studies have been performed characterising the progression of spine involvement. OBJECTIVES: To follow pathological events in experimental spondylitis, and underline its clinical, radiographic, and histological similarities to human ankylosing spondylitis (AS); and to determine whether the spondyloarthropathy is a shared phenomenon with PGIA, or an "independent" disease. METHODS: Arthritis/spondylitis susceptible BALB/c and resistant DBA/2 mice, and their F1 and F2 hybrids were immunised with cartilage PG, and radiographic and histological studies were performed before onset and weekly during the progression of spondylitis. RESULTS: About 70% of the PG immunised BALB/c mice develop spondyloarthropathy (proteoglycan-induced spondylitis (PGISp), and the progression of the disease is very similar to human AS. It begins with inflammation in the sacroiliac joints and with enthesitis, and then progresses upwards, affecting multiple intervertebral disks. In F2 hybrids of arthritis/spondylitis susceptible BALB/c and resistant DBA/2 mice the incidence of arthritis was 43.5%, whereas the incidence of spondylitis was >60%. Some arthritic F2 hybrid mice had no spondylitis, whereas others developed spondylitis in the absence of peripheral arthritis. CONCLUSIONS: The PGISp model provides a valuable tool for studying autoimmune reactions in spondylitis, and identifying genetic loci associated with spondyloarthropathy.

Locally delivered rhBMP-2 enhances bone ingrowth and gap healing in a canine model.

The purpose of the present study was to determine if recombinant human bone morphogenetic protein-2 (rhBMP-2) enhances bone ingrowth into porous-coated implants and gap healing around the implants. In the presence of a 3-mm gap between the implant and host bone, porous-coated implants were placed bilaterally for four weeks in the proximal humeri of skeletally mature, adult male dogs. In three treatment groups, the test implant was treated with HA/TCP and rhBMP-2 in buffer at a dose of 100 microg/implant (n=5), 400 microg/implant (n=6), or 800 microg/implant (n=5) and placed in the left humerus. In these same animals, an internal control implant was treated only with HA/TCP and buffer and placed in the right humerus. These groups were compared with a previously reported external control group of seven animals in which no growth factor was delivered [J. Orthop. Res. 19 (2001) 85]. The BMP treated implants in the two lower dose groups had significantly more bone ingrowth than the external controls with the greatest effect in the 100 g/implant group (a 3.5-fold increase over the external control, p=0.008). All three dose groups had significantly more bone formation in the 3-mm gap surrounding the BMP treated implants than the external controls with the greatest effect in the 800 microg group (2.9-fold increase, p<0.001). Thus, application of rhBMP-2 to a porous-coated implant stimulated local bone ingrowth and gap healing. The enhancement of bone formation within the implant (bone ingrowth) was inversely related to dose.

Aging does not lessen the effectiveness of TGFbeta2-enhanced bone regeneration.

Controversy exists over the potency of bone healing in the aged skeleton, and there is concern that enhancement of bone regeneration after use of bone-stimulating growth factors may not be effective in the aged. In this study, 30 skeletally mature beagles (1-2 or 10-12 years old) had titanium implants placed bilaterally in the proximal humerus for a period of 4 weeks in a model of intramembranous bone regeneration. A bony defect made at the time of surgery created a 3-mm gap between the implant surface and the host bone. Some of the implants were treated with recombinant human TGFbeta2 (rhTGFbeta2) at various does (0.32-35 microg per implant), and some served as paired controls. The dose response was similar in young and old animals. The most effective dose, 35 microg, led to a 3-fold increase in the volume fraction of new bone within the gap in both the young (p = 0.001) and old (p = 0.002) animals. At this dose, there was a 5-fold increase in osteoblast surface. While age did not significantly affect the quantity of new bone formed as assessed by backscatter scanning electron microscopy, the older animals had thinner regenerated trabeculae that tended to be spaced more closely than the younger animals. Coupled with the finding that the increase in osteoid was greater in the old animals compared with the young animals, these qualitative differences suggest that there may have been a slight delay in the rate or a defect of mineralization in the old animals.

Locally delivered rhTGF-beta2 enhances bone ingrowth and bone regeneration at local and remote sites of skeletal injury.

The purposes of the present study were to determine if recombinant human transforming growth factor-beta-2 (rhTGF-beta2) enhances bone ingrowth into porous-coated implants and bone regeneration in gaps between the implant and surrounding host bone. The implants were placed bilaterally for four weeks in the proximal humeri of skeletally mature, adult male dogs in the presence of a 3-mm gap. In three treatment groups of animals, the test implant was treated with hydroxyapatite/tricalcium phosphate (HA/TCP) and rhTGF-beta2 in buffer at a dose per implant of 1.2 microg (n = 6), 12 microg (n = 7), or 120 microg (n = 7) and placed in the left humerus. In these same animals, an internal control implant treated only with HA/TCP and buffer was placed in the right humerus. In a non-TGF-beta treated external control group of animals (n = 7), one implant was treated with HA/TCP while the contralateral implant was not treated with the ceramic. In vitro analyses showed that approximately 15%, of the applied dose was released within 120 h with most of the release occurring in the first 24 h. The TGF-beta treated implants had significantly more bone ingrowth than the controls with the greatest effect in the 12 microg/implant group (a 2.2-fold increase over the paired internal control (P = 0.004) and a 4-fold increase over the external control (P < 0.001)). The TGF-beta treated implants had significantly more bone formation in the gap than the controls with the greatest effect in the 12 and 120 microg groups (1.8-fold increases over the paired internal controls (P = 0.003 and P = 0.012, respectively) and 2.8-fold increases over the external controls (P < 0.001 and P = 0.001, respectively)). Compared to the external controls, the internal control implants tended to have more bone ingrowth (1.9-fold increase, P = 0.066) and had significantly more bone formation in the gap (1.7-fold increase. P = 0.008). Thus, application of rhTGF-beta2 to a porous-coated implant-stimulated local bone ingrowth and gap healing in a weakly dose-dependent manner and stimulated bone regeneration in the 3-mm gap surrounding the contralateral control implant, a site remote from the local treatment with the growth factor.

Focal osteolysis at the junctions of a modular stainless-steel femoral intramedullary nail.

BACKGROUND: During routine follow-up of patients treated with a three-piece stainless-steel modular femoral nail, osteolysis and periosteal reaction around the modular junctions of some of the nails were noted on radiographs. The purpose of this study was to evaluate the prevalence, etiology, and clinical relevance of these radiographic findings. METHODS: Forty-four femoral fractures or nonunions in forty-two patients were treated with a modular stainless-steel femoral intramedullary nail. Seventeen nails were excluded, leaving twenty-seven intramedullary nails in twenty-seven patients for this study. All patients had had a femoral diaphyseal fracture; nineteen had had an acute fracture and eight, a nonunion. These twenty-seven patients returned for radiographs, a physical examination, assessment of functional outcomes, assessment of thigh pain with a visual analog scale, determination of serum chromium levels, and nail removal if desired. A control group of sixteen patients treated with a one-piece stainless-steel femoral intramedullary nail was evaluated with use of the same outcome measures and was compared with the group treated with the modular femoral nail with regard to prevalence of thigh pain and serum chromium levels. Twelve modular femoral nails were removed according to the study protocol. The modular nail junctions were analyzed for corrosion products, and histopathologic analysis of tissue specimens from the femoral canal was performed. RESULTS: The twenty-seven patients were seen at a mean of twenty-one months after fracture fixation; twenty-six of the twenty-seven fractures healed. Twenty-three femora had at least one of three types of abnormalities-osteolysis, periosteal reaction, or cortical thickening--localized to one or both modular junctions. Eighteen patients had severe reactions, defined as osteolysis of > or =2 mm, cortical thickening of > or =5 mm, and/or a periosteal reaction (group 1). Nine patients had mild or no reactions (group 2). Serum chromium levels in group 1 (mean, 1.27 ng/ mL; range, 0.34 to 3.12 ng/mL) were twice as high as those in group 2 (mean, 0.53 ng/mL; range, 0.12 to 1.26 ng/mL). However, this difference did not reach significance with the numbers available. The differences in serum chromium levels between group 1 and the control group with a one-piece nail (mean, 0.26 ng/mL; range, 0.015 to 1.25 ng/mL) (p<0.01) and a control group without an implant (mean, 0.05 ng/mL; range, 0.015 to 0.25 ng/ mL) (p<0.01) were significant. The level of thigh pain recorded on the visual analog scale was also significantly different between group 1 and the control group with a one-piece implant (p = 0.03). Retrieved modular nails had signs of fretting corrosion as well as stainless-steel corrosion products adherent to the junction where the osteolysis occurred. Histologic and spectrographic analysis revealed two types of corrosion products that were consistent with stainless-steel within the peri-implant tissue and were associated with a foreign-body granulomatous response. CONCLUSIONS: The presence of corrosion products at the taper junctions suggests that particulate debris was a major factor in the etiology of the radiographic findings of osteolysis, periosteal reaction, and cortical thickening. Serum chromium levels were substantially elevated in the patients with a modular femoral nail, and such levels may serve as a marker of fretting corrosion of these devices.

Animal models relevant to cementless joint replacement.

This review focuses on animal models used to study certain aspects of 'cementless' joint replacement. Implants used in this application are designed to become attached to the host skeleton through either bone ingrowth into porous surfaces or bone apposition (ongrowth) onto other types of surfaces. Biological fixation of cementless joint replacement implants relies on intramembranous bone regeneration. We describe a framework for understanding research design in light of the type of research questions now being asked. In particular, species choice, implant design and placement, and experimental endpoints are described in some detail. We provide a summary of recent studies specifically focused on implant fixation, demonstrating that most work is still at the morphological and biomechanical levels with little understanding at the molecular level. We also provide a more comprehensive listing of studies using hip and knee replacement models, demonstrating that most work is focused on the interface, and responses of the immediately adjacent trabecular bone and the more distant cortical bone. We conclude by encouraging investigators to design their experiments so that there is enough power to answer a limited number of questions as opposed to providing limited data on a broader number of issues.

Serum titanium level for diagnosis of a failed, metal-backed patellar component.

A case is presented in which an elevated serum titanium level was used to make the diagnosis of a failed metal-backed patellar component. The preoperative serum titanium level was 536.8 ppb, which was 98 times higher than the patient's previous level (taken 1 year earlier, when he was asymptomatic) and 2 orders of magnitude higher than the expected level with a well-functioning implant of this type. Revision surgery confirmed that the polyethylene portion of the patellar component had worn through, leaving the titanium portion of the patellar implant to articulate with the femoral component. Wear-through was not evident on preoperative radiographs or clinical examination. As knowledge about the expected ranges for serum metal ion levels after total joint arthroplasty continues to increase, the diagnostic utility of serum metal ion testing in the evaluation of joint arthroplasty function will continue to improve.

Dissemination of wear particles to the liver, spleen, and abdominal lymph nodes of patients with hip or knee replacement.

BACKGROUND: The importance of particles generated by wear and corrosion of joint replacement prostheses has been understood primarily in the context of the local effects of particle-induced periprosthetic osteolysis and aseptic loosening. We studied dissemination of wear particles in patients with total hip and knee replacement to determine the prevalence of and the histopathological response to prosthetic wear debris in the liver, spleen, and abdominal para-aortic lymph nodes. METHODS: Postmortem specimens from twenty-nine patients and biopsy specimens from two living patients with a failed replacement were analyzed. Specimens of tissue obtained from the cadavera of fifteen patients who had not had a joint replacement served as controls. The concentration of particles and the associated tissue response were characterized with the use of light microscopy of stained histological sections. Metallic particles were identified by electron microprobe analysis. Polyethylene particles were studied with the use of oil-red-O stain and polarized light microscopy. The composition of polyethylene particles was confirmed in selected cases by Fourier transform infrared spectroscopy and hot-stage thermal analysis. Twenty-one of the patients studied post mortem had had a primary total joint replacement. Eleven of them had had a hip prosthesis for a mean of sixty-nine months (range, forty-three to 171 months), and ten had had a knee replacement for a mean of eighty-four months (range, thirty-one to 179 months). The other eight patients studied post mortem had had a hip replacement in which one or more components had loosened and had been revised. The mean time between the initial arthroplasty and the time of death was 174 months (range, forty-seven to 292 months), and the mean time between the last revision procedure and the time of death was seventy-one months (range, one to 130 months). RESULTS: Metallic wear particles in the liver or spleen were more prevalent in patients who had had a failed hip arthroplasty (seven of eight) than in patients who had had a primary hip (two of eleven) or knee replacement (two of ten). The principal source of wear particles in the majority of these patients involved secondary nonbearing surfaces rather than wear between the two primary bearing surfaces as intended. In one living patient, dissemination of titanium alloy particles from a hip prosthesis with mechanical failure was associated with a visceral granulomatous reaction and hepatosplenomegaly, which required operative and medical treatment. Metallic wear particles were detected in the paraaortic lymph nodes in 68 percent (nineteen) of the twenty-eight patients with an implant from whom lymph nodes were available for study. In 38 percent (eleven) of all twenty-nine patients with an implant who were studied post mortem, metallic particles had been further disseminated to the liver or spleen, where they were usually found within small aggregates of macrophages occurring as infiltrates without apparent pathological importance. Polyethylene particles elicited a similar response. They were identified in the paraaortic lymph nodes of 68 percent (nineteen) of the twenty-eight patients and the liver or spleen of 14 percent (four) of the twenty-nine patients. The majority of the disseminated wear particles were less than one micrometer in size. Currently available methods lack the sensitivity and specificity necessary to detect very low concentrations of submicrometer polyethylene particles and probably underestimated the prevalence of polyethylene wear debris in the liver and spleen. CONCLUSIONS: In this study, systemic distribution of metallic and polyethylene wear particles was a common finding, both in patients with a previously failed implant and in those with a primary total joint prosthesis. The prevalence of particles in the liver or spleen was greater after reconstructions with mechanical failure. (ABSTRACT TRUNCATED)

Postmortem retrieval of total joint replacement components.

Improved understanding of the clinical outcomes of orthopedic implants requires the study of implants at the end of their service life. Previous studies focused on the retrieval of so-called failed implants during surgical revision. Interest is now moving to the study of successful implants, which are those still in place at the patient's death. A procedure was developed for recruitment of implant patients and their families and for safe and effective device and tissue retrieval after death. More than 50 retrievals were performed to support various research efforts.

Functional adaptation and ingrowth of bone vary as a function of hip implant stiffness.

The purpose of the present study was to test the hypothesis that cortical bone loss, trabecular bone density and the amount of bone ingrowth vary as a function of stem stiffness in a canine cementless hip replacement model. The study was motivated by the problem of cortical bone atrophy in the proximal femur following cementless total hip replacement. Two stem stiffnesses were used and both designs were identical in external geometry and porous coating placement. The high stiffness stem caused approximately 26% cortical bone stress-shielding and the low stiffness stem caused approximately 7.5% stress-shielding, as assessed by beam theory. Each group included nine adult, male canines who received unilateral arthroplasties for a period of six months. The animals with the low stiffness stems tended to lose less proximal cortical bone than the animals with high stiffness stems (4% +/- 9 as opposed to 11% +/- 14), but the difference was not statistically significant (p = 0.251). However, the patterns of bone ingrowth into the implant and change in medullary bone density adjacent to the implant were fundamentally different as a function of stem stiffness (p < 0.01). Most importantly, while the high stiffness group had peaks in these variables at the distal end of the stem, the low stiffness group had peak values proximally. These different patterns of functional adaptation are consistent with the idea that reduced stem stiffness enhances proximal load transfer.

Maintenance of proximal cortical bone with use of a less stiff femoral component in hemiarthroplasty of the hip without cement. An investigation in a canine model at six months and two years.

A canine model of hemiarthroplasty of the hip was used to determine if the use of a less stiff femoral stem can reduce the amount of bone loss induced by stress-shielding. Two types of stem were used: the stiffer stems were made of a titanium alloy, and the less stiff stems were composed of a cobalt-chromium-alloy core with an outer polymer layer. The stems were identical in shape, and both types were circumferentially coated along their entire length (except for the distal five millimeters) with commercially pure titanium fiber metal. Ten dogs with each type of stem were followed for six months, and twelve dogs with each type of stem were followed for two years. Loss of cortical bone from the proximal part of the femur was associated with both types of stem, but typically 50 per cent less bone was lost with the less stiff implants. Most of the cortical loss occurred at the subperiosteal surface. The amount of medullary bone adjacent to the proximal and distal aspects of both types of stem increased; the less stiff stems were associated with a greater increase in the proximal region, and the stiffer stems were associated with a greater increase in the distal region. Similarly, there were peaks in the amount of bone growth into the proximal and distal portions of both types of stem, with a greater peak in proximal bone growth into the less stiff stems and a greater peak in distal bone growth into the stiffer stems.

Human monocyte/macrophage response to cobalt-chromium corrosion products and titanium particles in patients with total joint replacements.

The responses of human peripheral blood monocytes of 10 normal volunteers and 14 patients with total hip replacements to particles of commercially pure titanium and chromium orthophosphate (a corrosion product from cobalt-chromium alloy implants) were studied. In addition, these phagocytosable particles were added to cultured mononuclear cells isolated from the interfacial membrane of 14 patients with failed implants. Peripheral blood monocytes from patients who had had a total hip replacement produced significantly higher levels of interleukin-1 (both interleukin-1 alpha and interleukin-1 beta) and prostaglandin E2 following particulate stimulation than those from normal volunteers. Supernatants from both titanium and chromium orthophosphate-stimulated peripheral blood monocytes from the volunteers and patients with total hip replacement induced bone resorption (assayed in organ cultures of newborn mouse calvariae) and the proliferation of human fibroblasts. The levels of bone resorption were significantly higher (p < 0.05) in patients with implants than in normal volunteers. There were no significant differences in the responses of cells between patients with focal osteolysis and those without osteolysis. Interfacial membrane mononuclear cells also produced high levels of interleukin-1 alpha, interleukin-1 beta, and prostaglandin E2 and expressed bone resorptive activities following stimulation with either titanium or chromium orthophosphate. More importantly, interfacial membrane mononuclear cells "spontaneously" produced high levels of prostaglandin E2 that were comparable with the response of peripheral blood monocytes stimulated with particulate wear debris. The clinical relevance of this study is 2-fold. First, mononuclear cells from patients with total hip replacement were some-how "sensitized" to metal particles in comparison with mononuclear cells from individuals without an implant. Second, the chromium orthophosphate corrosion product was a potent macrophage/monocyte activator and may contribute to macrophage-mediated osteolysis and aseptic loosening.

The bone-implant interface of femoral stems with non-circumferential porous coating.

UNLABELLED: A histological study was performed of the bone-implant interface of fifteen titanium-alloy femoral stems with porous coating limited to three proximal areas that did not cover the full circumference of the device. The specimens were obtained at autopsy from ten cadavera at a mean of forty-six months (range, one to eighty-nine months) after the implant had been inserted without acrylic cement. The volume fraction of bone within the porous spaces (the percentage of the porous space that was filled with bone) and the extent of bone ingrowth (the percentage of the porous-coated surface covered with in-grown bone that was more than one-half fiber-diameter deep, as measured from the outer surface of the porous coating), were determined with histomorphometric methods. Eleven of the fifteen stems had bone within the porous coating that was in continuity with the surrounding medullary bone. The mean volume fraction of bone ingrowth in these specimens was 26.9 per cent (range, 12.2 to 61.0 per cent), and the mean extent of bone ingrowth was 64.3 per cent (range, 28.6 to 95.2 per cent). Both of these parameters increased with time. In the other four stems, the bone lacked continuity with the surrounding trabecular bed. Two of these stems had a limited amount of bone within the porous coating, and two stems (from one patient) had no bone ingrowth. Periprosthetic membranes surrounded by a shell of trabecular bone covered the uncoated surfaces of the stems. The membranes of implants that had been in situ for eight months or more demonstrated polyethylene wear debris, and other particles generated at the level of the joint, within histiocytes throughout the length of the femoral stem. CLINICAL RELEVANCE: The findings in this study are relevant to the utilization and mechanisms of failure of femoral stems inserted without cement. Bone ingrowth and the resulting stability of the implant can be achieved with porous-coated stems. However, the extent of the surface that is porous-coated must be sufficient to prevent trabecular fracture as a secondary mechanism of loosening. Interruptions in the circumferential extent of the porous surface are associated with the formation of periprosthetic membranes, which provide a pathway for migration of particulate wear and corrosion products to the distal part of the stem. A circumferential coating may retard the access of particles and thus decrease the possibility of diaphyseal osteolysis.

Local and distant products from modularity.

In this study, the local and distant distribution of solid and soluble products of corrosion from the head and neck junction of modular femoral total hip prosthetic components were characterized. Particulate corrosion products from retrieved implants and surrounding tissues were analyzed. Serum transport and urinary excretion of metal was measured in correlation with the degree of corrosion at the head and neck junction. Particles of metal oxides, metal chlorides, and chromium phosphate corrosion products were identified on implants of 10 designs from 6 manufacturers. The most abundant solid corrosion product on the implant and within the periprosthetic tissues (size range, < 1-200 micrometers) was an amorphous chromium orthophosphate hydrate-rich material. Serum cobalt and urine chromium concentrations were elevated significantly in patients with implants that had moderate to severe corrosion in comparison with those with no to mild corrosion. Solid corrosion products from modular femoral stems may accelerate articular wear via a 3-body mechanism. Phagocytosable particles of these corrosion products may stimulate macrophage-mediated periprosthetic bone loss. Systemic dissemination of metallic corrosion products raises the issue of systemic toxicity; however, no overt evidence of metal toxicity was observed in this study.

Enhancement of bone ingrowth by transforming growth factor-beta.

Enhancement of bone ingrowth with transforming growth factor-beta was evaluated in a canine model. Ten dogs had bilateral implantation of a titanium-fiber-metal-coated rod in the proximal part of the humerus. A three-millimeter gap between the outer surface of the porous coating and the surrounding cancellous bone was created to impair bone ingrowth. All of the implants were plasma-flame-sprayed with hydroxyapatite and tricalcium phosphate. In each animal, one implant was also treated with recombinant transforming growth factor-beta 1 while the other implant, which was not so treated, served as a paired control. Two doses of transforming growth factor-beta 1 were used: 335 micrograms in five animals and 120 micrograms in the other five. At four weeks, the amount of bone ingrowth in the implants that had been treated with 120 micrograms of transforming growth factor-beta 1 was threefold higher than that in the paired controls (p = 0.009), but with the numbers available there was no significant increase in bone ingrowth with the higher dose. The amount of new-bone formation in the three-millimeter gaps adjacent to the treated implants was twice that in the gaps of the paired controls, regardless of the dose. The differences between the treated and control implants with regard to the architecture of the new bone in the gap indicate that the mechanism of action of transforming growth factor-beta 1 may include both proliferation of osteoprogenitor cells and production of matrix by committed osteoblasts. Compared with the findings in a previous study in which this canine model was used, the data from the present investigation indicate that enhancement of bone ingrowth in implants that have been treated with a combination of a hydroxyapatite-tricalcium phosphate coating and transforming growth factor-beta 1 may exceed that obtainable with grafting of the gap with autogenous cancellous bone.