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Current Concepts Review - Total Hip Arthroplasty with Hydroxyapatite-Coated Prostheses*

WILLIAM L. JAFFE, M.D. and DAVID F. SCOTT, M.D., NEW YORK, N.Y.

Investigation performed at the Department of Orthopaedic Surgery, Hospital for Joint Diseases, New York City.

	Introduction

Top Introduction Basic-Science and Preclinical... Clinical Experience with... Overview References

 

	Basic-Science and Preclinical Studies

Top Introduction Basic-Science and Preclinical... Clinical Experience with... Overview References

 

History of the Use of Hydroxyapatite in Orthopaedics
The term apatite was first applied to minerals by Werner⁴⁵, in 1788. It now denotes a family of crystals with the formula M₁₀(RO₄)₆X₂, where M is usually calcium, R is usually phosphorus, and X is hydroxide or a halogen such as fluorine. The relationship to bone mineral was first suggested by Proust and Klaproth⁴⁵, also in 1788. Only after the development and use of x-ray diffraction did Dejong confirm, in 1926, that the inorganic phase of bone was an apatite⁴⁹. Bone mineral was found to be quite complex and included various types of hydrated calcium phosphates, the most common being calcium hydroxyapatite (Ca₁₀[PO₄]₆[OH]₂).

To the best of our knowledge, the earliest use of calcium-phosphate materials in humans was as a powder of varying crystalline composition to improve bone-healing. Albee and Morrison, in 1920, reported accelerated formation of callus³, but others later observed no major advantage with use of the hydroxyapatite powder^80,147. As a bulk implant, calcium-phosphate materials were first used for dental applications¹³³, as reported in 1971. More recent reports in the dental literature have attested to the success of bulk calcium-phosphate materials composed of pure hydroxyapatite and used as a bone-graft substitute^{12,35,57,68,135,137}. Patients who had hydroxyapatite grafts were followed for a maximum of seven years⁵⁷ and were evaluated clinically^12,35,57,137, radiographically^12,35,57, and with computer-assisted densitometry⁶⁸. In two studies^135,137, biopsy specimens were obtained for histological analysis. In addition to impressive evidence of osseointegration, no adverse effects of hydroxyapatite were noted. The dental experience with hydroxyapatite-coated metal implants showed a substantial advantage with use of these implants compared with use of uncoated implants of the same design and having the same metallurgical characteristics^77,78,122. With respect to the use of hydroxyapatite coatings for total joint implants, the earliest reports of hydroxyapatite-coated femoral stems in humans, to our knowledge, were by Furlong and Osborn⁶⁷, who began clinical trials in 1985, and by Geesink⁷⁰, who reported on a series begun in 1986.

Basic Science
The calcium-phosphate family of biomaterials includes numerous compounds that might have applicability to the manufacture of orthopaedic implants. However, only two such compounds—tricalcium phosphate and hydroxyapatite—have been exposed to extensive in vitro and in vivo testing. These two compounds are easily differentiated from each other by their calcium-to-phosphate ratio. The ratio for tricalcium phosphate (Ca₃[PO₄]₂) is 1.5, while that for hydroxyapatite (Ca₁₀[PO₄]₆[OH]₂) is 1.67. The American Society for Testing and Materials has developed standards for these two compounds so that their purity can be determined and controlled^4,5. Tricalcium phosphate can exist in several states with an identical chemical composition but a different crystallographic structure, depending on the method with which it was manufactured and sintered. These different states are known as isomorphs (for example, -tricalcium phosphate and ß-tricalcium phosphate), and they may differ with respect to their solubility and biological stability^54,55. The most popular method of manufacturing these compounds is chemical precipitation, in which a phosphate-containing solution is added to a calcium-ion-containing solution under controlled conditions². The resulting compound, amorphous calcium phosphate, is then sintered to a dense polycrystalline form by firing. Organic bone mineral is an unacceptable raw material for this process because of the highly variable composition of its mineral phases and the difficulty of extracting pure compounds from bone³⁶.

The method with which the calcium-phosphate compound is manufactured and the temperature to which it is exposed affect its transformation to and from hydroxyapatite, its crystalline structure, its porosity, and its solubility. At 700 to 1125 degrees Celsius, in a calcium-deficient environment, ß-tricalcium phosphate is produced; at temperatures of greater than 1450 degrees Celsius, -tricalcium phosphate is formed. At physiological pH, amorphous calcium phosphate is more soluble than -tricalcium phosphate, which is more soluble than ß-tricalcium phosphate, which is more soluble than hydroxyapatite^54,55. Because solubility at physiological pH is a major factor responsible for bioresorption, hydroxyapatite appears to have a definite advantage, compared with tricalcium phosphate, as a biological implant material. In acidic environments, all calcium phosphates, including hydroxyapatite, are highly soluble and unstable. In an acid medium tricalcium phosphate dissolved 12.3 times faster than hydroxyapatite, and in a basic medium it dissolved 22.3 times faster⁹⁵. The most common precursor to hydroxyapatite, during both in vivo bone formation and in vitro manufacturing, is amorphous tricalcium phosphate, which is highly soluble and unstable at physiological pH. Hydroxyapatite, as found in organic bone matrix, exists over a compositional range that can be characterized by its calcium-to-phosphate ratio. It can vary from stoichiometric hydroxyapatite (Ca₁₀[PO₄]₆[OH]₂), with a calcium-to-phosphate ratio of 1.67, to calcium-deficient hydroxyapatite (Ca_[10-X][HPO₄]_X[OH]_[2-X]), with a calcium-to-phosphate ratio as low as 1.5. Biological apatites are known to be calcium-deficient, bone apatites contain carbonate, and dental apatites contain substantial amounts of fluoride¹⁰. Commercially available calcium-phosphate materials can be classified as biphasic calcium phosphate (mixed ß-tricalcium phosphate and hydroxyapatite phases), ß-tricalcium phosphate, hydroxyapatite, non-sintered calcium-phosphate powders, coralline hydroxyapatite, and bone-derived materials¹¹⁶.

Biological fixation is defined, for the purpose of this paper, as the process by which prosthetic components become firmly bonded to host bone by ongrowth of ingrowth without the use of bone cement. Because the goal of the use of hydroxyapatite is to obtain prompt biological fixation to bone, it is of interest to consider the mechanism by which such fixation occurs. It has been suggested that the apatite must first partially dissolve, thereby increasing the concentration of calcium and phosphate in the microenvironment. Carbonate apatite microcrystals then form and associate with the organic matrix of bone, causing biological growth of bone tissue¹¹⁷. There appears to be a conflict between the ability to manufacture a stable, slowly resorbing material and the ability to achieve rapid union with host bone. Additional stabilization of a calcium-phosphate apatite by increasing its crystallinity results in a decrease in the release of calcium and phosphate from its surface, as in vivo studies have clearly demonstrated that the higher the percentage of crystallinity of a coating the lower the rate of degradation¹⁷³. The source of free calcium and phosphorus that is present even at the interface of highly crystalline, stable hydroxyapatite coatings appears to be the amorphous calcium-phosphate phase, which is found in all hydroxyapatite coatings¹⁷³. It is likely that some critical amount of degradation is essential to obtain rapid biological fixation, but premature dissolution of a coating or loss of mechanical bonding to a metal substrate must be avoided. Currently, highly crystalline, pure, stable hydroxyapatite appears to contain adequate amorphous calcium phosphate to allow early biological fixation to be achieved without the use of less crystalline hydroxyapatite or more soluble tricalcium phosphate.

Other Bioactive Coatings
Bioactive coatings are substances that are added to the surface of an implant to promote and to enhance biological fixation. Bioactive coatings other than hydroxyapatite have been tested in vivo with varying degrees of success. Fluorapatite was found to be biocompatible and to bond readily to bone in several animal studies^43,88,138. It was also more thermostable than hydroxyapatite, and it did not demonstrate the chemical dissociation noted with hydroxyapatite during the use of high-temperature plasma-spraying techniques¹²¹. When tested in vivo, it had superior long-term degradation characteristics and the same excellent push-out strength as hydroxyapatite⁵⁰.

Whitlockite is a calcium-phosphate mineral in the phase of ß-tricalcium phosphate. Initial investigations into the effects of adding magnesium to ß-whitlockite to form magnesium whitlockite suggested reduced rates of biodegradation compared with those of hydroxyapatite¹⁰⁹. More recent in vivo tests did not confirm these findings and demonstrated inferior push-out strength compared with that of hydroxyapatite⁵⁰.

Bioglass coatings composed of sodium carbonate, calcium carbonate, phosphorus pentoxide, and silica have been shown to bond to host bone by forming a surface layer of calcium phosphate with a hydroxyapatite structure¹³⁹. However, the coatings themselves are prone to failure in vivo⁷⁹, and the silica-containing calcium-phosphate glasses may be toxic because of the presence of dissolved silica ions¹³⁶.

Bioactive polymer coatings—chemically known as poly(ethylene oxide), poly(tetramethylene terephtalate) segmented copolymer—have demonstrated bone-bonding properties by cell-mediated osteogenesis that are comparable with those of hydroxyapatite and tricalcium-phosphate ceramic coatings. Ceramics are defined as calcium-phosphate materials with a composition and structure that are similar to the inorganic components of bone⁸⁷. Stress-analysis studies have suggested that this flexible polymer coating may have mechanical advantages compared with more brittle ceramic coatings such as hydroxyapatite⁴⁸. Additional in vivo testing will be required before the clinical role of these coatings can be determined.

Metal Substrate
The mechanical properties of calcium-phosphate-ceramic materials—specifically, their poor tensile strength and resistance to impact as well as their brittle nature—make them unacceptable as load-bearing implants⁹⁵. The application of ceramic to a metal substrate combines the strength of metal with the biocompatibility of ceramic^76,105. While it is possible to coat most metals with hydroxyapatite, the most experience and success with hydroxyapatite-coated implants used for arthroplasty has been with titanium, its alloy Ti-6Al-4V, and cobalt-chromium alloy. Compared with cobalt-chromium, titanium demonstrated a 33 per cent increase in bonding strength to a hydroxyapatite coating in vitro. It was suggested that this increase was due to a chemical bond between titanium and hydroxyapatite in addition to the expected mechanical bond^62,76,115.

The difference in the modulus of elasticity of the metals (210 gigapascals for cobalt-chromium alloy as compared with 110 gigapascals for titanium) results in less potential proximal stress-shielding and bone resorption with the more flexible titanium femoral stem¹⁸³. However, increased motion at the coating-bone interface with use of the more flexible stem might neutralize this advantage, as micromotion at the interface was shown to inhibit biointegration in a dog model¹⁶⁴. It must be emphasized that both of these metals are considerably stiffer than cortical bone (modulus of elasticity, twenty gigapascals¹⁸³) and that the proximal cross-sectional area of most modern femoral implants is generous, resulting in an inelastic prosthesis. When all of these factors are weighed, titanium alloy currently appears to be the metal substrate of choice.

The surface of the metal substrate can be textured to one of three forms: smooth (microstructured), macrostructured, or porous. A smooth surface, grit-blasted to a roughness of four to ten micrometers, is a typical microstructured finish used in preparation for application of a plasma-sprayed coating. This prepared metal surface appears histologically similar to the natural undulations of the hydroxyapatite-coated surface³⁰. Several investigators have demonstrated successful biological fixation to bone with this microstructured and coated surface, with failure ultimately occurring at the coating-substrate interface when the implant is subjected to high shear and tensile forces^28,170. Geesink et al., in a study of dogs that involved push-out testing of twenty-seven transcortical plugs, rarely observed failure at this interface; failure was more commonly noted to occur within the hydroxyapatite coating or at the hydroxyapatite-bone interface⁷⁶.

Macrostructuring of the surface increases the resistance of the coating to pure shear forces and could result in improved long-term fixation between the implant and the bone if biodegradation of the coating occurs^20,104. Macrostructuring can take the form of grooves, threads, or deposited metal coating. Improved fixation with grooved-surface implants was demonstrated in vivo at early time-periods^167,170 as well as one year after implantation, suggesting a comprehensive interface. This resulted in the sharing of mechanical loads between the areas in which bone had grown onto the hydroxyapatite coating and the areas in which it had grown into the metal grooves¹⁴⁴. A titanium-alloy (Ti-6Al-4V) substrate can be coated with commercially pure titanium with use of an arc-deposition process to form a macrostructured surface. This surface is then given a preparatory grit-blasting followed by a plasma-sprayed hydroxyapatite coating. Although the grit-blasting and the hydroxyapatite coating result in a 38 per cent decrease in the roughness of the surface compared with that of the arc-deposited surface⁸⁵, the arc-deposited hydroxyapatite-coated surface demonstrated remarkably superior biological fixation compared with that for the uncoated arc-deposited surface in several animal models^85,143 (Fig. 1).

View larger version (132K): [in this window] [in a new window]   Fig. 1. Backscatter electron-imaging photomicrograph, made six weeks postoperatively, showing the interfaces around a fifty-micrometer air-plasma-sprayed hydroxyapatite coating on a grit-blasted titanium implant retrieved from a dog. M = metal substrate, H = hydroxyapatite coating, and B = host bone (x 200). (Courtesy of J. Ricci.)

Application of Hydroxyapatite Coating
Several methods are available for the application of a hydroxyapatite coating to a metal substrate, and the chemical, mechanical, and biological properties of the coating depend on the method that is used^99,110,111. The techniques that commonly are used include dip-coating, electrophoretic deposition, immersion-coating, hot isostatic pressing, solution deposition, sputter-coating, and flame-spraying. Only the latter three methods are currently applicable to orthopaedic implants.

The disadvantage of the dip-coating and immersion-coating methods is that they require high temperatures for the post-sintering of the hydroxyapatite layer, which can degrade the strength of the metal and compromise the purity of the hydroxyapatite^120,185. Electrophoresis results in impurities, non-uniform thickness, and poor biological fixation to the metal substrate¹⁸⁵. Isostatic pressing is a cumbersome two-stage technique with which it is difficult to seal borders on implants with complex shapes. In addition, isostatic pressing requires high temperatures during the second stage, which could denature the hydroxyapatite¹⁸⁵.

A solution-deposition process in which hydroxyapatite is precipitated at a low temperature results in a pure, highly crystalline, firmly adherent coating that is twenty micrometers thick⁵⁶. As it is not a line-of-sight process (the coating is applied only perpendicular to the surface as it is in flame-spraying), porous and beaded surfaces can be coated evenly. Porous-coated cobalt-chromium bone plugs that were coated with this method demonstrated successful biological fixation in a dog model¹. Porous-coated femoral and acetabular components with a hydroxyapatite coating applied with use of solution deposition are currently marketed in Europe but have not been approved for use in the United States. As the process is apparently limited to coatings with a thickness of twenty micrometers⁵⁶, it seems to represent an augmentation of biological fixation rather than a primary mode of fixation.

Sputter-coating is a process in which molecules of a material are ejected from a target by the bombardment of high-energy ions and are deposited on a substrate that has been placed in a vacuum chamber. Most sputter-coating techniques are too slow and have an inadequate rate of deposition, but an enhanced method (RF magnetron sputtering) in which a magnetically increased radiofrequency is used has been described^34,94. However, an analysis of the chemical nature of the hydroxyapatite coating applied with this method revealed a calcium-to-phosphate ratio that was consistently higher than that of standard synthetic hydroxyapatite¹⁷⁴.

Flame-spraying techniques involve the acceleration of hydroxyapatite feedstock powder to a high velocity and temperature, resulting in a dense, tightly adherent coating with a maximum thickness of 100 micrometers that can be applied in less than two minutes. The coating can be applied to implants with complex shapes; areas that are not to be coated can be easily masked. Three techniques—air plasma-spraying, vacuum plasma-spraying, and the high-velocity oxygen-fuel method—have been described and tested¹⁸². With plasma-spraying, an arc is created between an anode and a cathode, resulting in a temperature of as high as 30,000 degrees kelvin (29,727 degrees Celsius), which causes gas dissociation. The hydroxyapatite powder with a carrier gas such as argon is passed into the arc, which melts the surface of the hydroxyapatite particles and accelerates them onto the metal substrate (Fig. 2). The metal is heated to less than 300 degrees Celsius, which does not degrade its mechanical properties. With the high-velocity oxygen-fuel technique, the particles are heated to substantially lower temperatures but are applied at higher velocities than with the arc-deposition process. Comparison of the three techniques has demonstrated that the coatings decrease in density in the following sequence: air plasma-spraying, vacuum plasma-spraying, and the high-velocity oxygen-fuel method⁴⁸. While a coating applied with the high-velocity oxygen-fuel method is more stable chemically because of the lower temperature of application, the strength of the coating-substrate bond may be less than optimum⁸¹. Although enhanced bonding strength and improved purity of the hydroxyapatite have been claimed for vacuum plasma-spraying as compared with air plasma-spraying, no clinical advantage has yet been demonstrated, and the coating-related factors associated with clinical success, such as density, porosity, crystallinity, and chemistry, are still not entirely understood.

View larger version (156K): [in this window] [in a new window]   Fig. 2. Secondary electron-imaging photomicrograph showing the surface of an air-plasma-sprayed hydroxyapatite coating on a grit-blasted titanium substrate (x 200). (Courtesy of J. Ricci.)

Hydroxyapatite is neither osteogenic (capable of stimulating the formation of bone) nor osteoinductive (capable of supporting the mitogenesis of undifferentiated perivascular mesenchymal cells, leading to the formation of osteoprogenitor cells with the capacity to form new bone¹⁷²). Hydroxyapatite is osteoconductive (capable of supporting the ingrowth of sprouting capillaries, perivascular tissues, and osteoprogenitor cells from the recipient host bed into the three-dimensional structure of an implant or graft¹⁷²) in a manner similar to that of allograft bone. It acts as a trellis for the deposition and ingrowth of new bone¹⁴⁸. A dense coating with high crystallinity to decrease the rate of bioresorption does not appear to compromise the osteoconductive property of the hydroxyapatite¹⁰⁸. Plasma-sprayed hydroxyapatite coatings contain sufficient microporosity, macroporosity, and amorphous hydroxyapatite to ensure maintenance of biological activity¹⁸⁷. Starting with a pure feedstock of hydroxyapatite and employing a plasma-spraying process that does not denature the hydroxyapatite to less stable calcium phosphates or introduce contaminants allow a reliable, inexpensive, bioactive coating to be applied to a prepared metal substrate of an orthopaedic implant.

	Clinical Experience with Hydroxyapatite-Coated Components for Total Hip Arthroplasty

Top Introduction Basic-Science and Preclinical... Clinical Experience with... Overview References

 

The European Experience with Hydroxyapatite-Coated Femoral Components
Geesink^70-72 as well as Geesink and Hoefnagels⁷⁴ performed hip replacements with use of a metaphysis-filling titanium femoral stem that had a fifty-micrometer-thick air-plasma-sprayed coating of hydroxyapatite on the proximal one-third of its surface. Initially, a threaded acetabular cup was chosen, but a hemispherical acetabular component was subsequently used. The rate of survival of the prosthesis at six years for the first 118 patients was 100 per cent for the 118 hydroxyapatite-coated stems and 99 per cent for the 100 hydroxyapatite-threaded cups, and there was a very low prevalence of pain in the thigh⁷⁴.

Kärrholm et al. prospectively studied the results for sixty hips that had been randomly assigned to receive the same type of femoral component (a straight-stem titanium-alloy design with a collar) that was to be fixed with cement, a hydroxyapatite coating, or a porous coating¹⁰¹. The hydroxyapatite was applied to the proximal one-third of the surface and was 200 micrometers thick. At two years, the clinical results did not differ among the groups with respect to the Harris hip scores or the pain scores, but the hydroxyapatite-coated components demonstrated less subsidence and rotation.

Søballe et al. performed a prospective study in which twenty-seven patients were randomly assigned to receive a femoral component of the same design with either an arc-deposited titanium coating or an air-plasma-sprayed hydroxyapatite coating on the proximal one-fourth of the stem¹⁶⁶. Roentgen stereophotogrammetric analysis performed at twelve months revealed less migration of the hydroxyapatite-coated components, and the Harris hip scores and the pain scores were better for the group that had received a hydroxyapatite-coated implant.

Kroon and Freeman performed a controlled study of sixty-nine identical press-fit titanium stems with and without an eighty to 120-micrometer-thick proximal air-plasma-sprayed hydroxyapatite coating¹¹⁴. They reported a tenfold increase in subsidence of the uncoated stems at one year as measured with x-ray digitization. Epinette reported no failures and excellent scores for pain and function in a study of thirty-one hydroxyapatite-coated stems and threaded acetabular components after five years of follow-up⁶¹. Other European investigators who have reported good results with hydroxyapatite-coated total hip components have included Furlong⁶⁶, who followed a large series of patients for a maximum of eight years, and Livesley et al.¹¹⁹, who prospectively compared the results of the use of press-fit and hydroxyapatite-coated titanium bipolar prostheses for the treatment of displaced fractures of the femoral neck. Reports of a large Italian series documented excellent short-term clinical results^150,171. Several other reports in the French and German literature have attested to the safety and efficacy of hydroxyapatite-coated total hip components, although details of the thickness, extent, and purity of the coatings were limited^{64,82,112,128,131,177,178,180}. The experience with hydroxyapatite-coated implants in revision hip arthroplasty is limited, but the results of one series⁷³ of fifty patients who were followed for a minimum of four years are encouraging.

The North American Experience with Hydroxyapatite-Coated Femoral Components
In the largest North American clinical trial of which we are aware, 436 hip arthroplasties were performed between January 1988 and November 1990^{21,40,42,93,127}. This prospective, multicenter study was approved by the Food and Drug Administration under an Investigational Device Exemption. The femoral component was a grit-blasted, straight, collarless, titanium implant that had normalization steps on the anterior and posterior proximal surfaces as well as a fifty-micrometer-thick air-plasma-sprayed hydroxyapatite coating on the proximal one-third of the surface. The acetabular components were either porous-coated or hydroxyapatite-coated implants and were of three different designs. The investigators reported very encouraging results at two, three, and five years^{21,40,42,93,127}. At the five-year evaluation, the rate of mechanical loosening of the femoral component, representing stems that been revised because of aseptic loosening (two) and those that were radiographically unstable (zero), was 0.46 per cent²¹. No progressive subsidence was reported, and endosteal osteolysis was noted in only one patient (0.8 per cent). These excellent results also applied to the youngest patients in the series: at five years, eighty-eight patients, who had an average age of thirty-eight years, had had no mechanical failures of the femoral component²².

Vaughn et al., in a non-randomized study, reported the results obtained with use of a straight, collarless, metaphysis-fitting titanium stem that was coated on the proximal one-third of its surface with either arc-deposited titanium (fifty implants) or a fifty to seventy-five-micrometer-thick air-plasma-sprayed hydroxyapatite coating (fifty-three implants)^175,176. Both types of stems were associated with excellent short-term clinical results, but the implants that had an arc-deposited titanium coating were associated with a higher rate of radiolucent lines, including a 10 per cent prevalence in the proximal, coated region.

Rothman et al. reported the two-year results for a matched-pair series of fifty-two patients who had received a collarless, porous-coated titanium femoral stem with or without a proximal hydroxyapatite coating¹⁵¹. The clinical and radiographic results did not differ between the two groups.

A number of authors^{51,52,65,125,126} reported on two series of air-plasma-sprayed hydroxyapatite-coated components. In the first series, a retrospective matched-pair study of eighty-four hips that had a metaphysis-fitting titanium-alloy femoral component with proximal porous patches, one-half of the stems had a supplemental hydroxyapatite coating^125,126. At a minimum of three years, there was no difference between the matched groups with respect to the fixation of the femoral stem, but greater hypertrophy of cancellous bone was noted proximally in association with the stems coated with hydroxyapatite. The second series involved a press-fit version of the same type of stem with and without a hydroxyapatite coating on the grooved, grit-blasted proximal surface^52,65,125. This prospective, randomized, multicenter trial revealed substantial differences between the two groups at a minimum of two and a half years. The Harris hip scores and the relief of pain were better for the hydroxyapatite-coated stems, and the prevalence of radiolucent lines in the coated region was approximately 1 per cent for that group compared with approximately 25 per cent for the press-fit stems.

Clinical Experience with Hydroxyapatite-Coated Acetabular Components
Most clinical trials of hydroxyapatite-coated implants have focused on the performance of the femoral component rather than that of the acetabular component. In one study, fully porous-coated hemispherical acetabular components supplemented with a hydroxyapatite coating demonstrated improved fixation radiographically at a minimum of three years as compared with partially porous-coated components without a hydroxyapatite coating¹²⁶. In the multicenter study of D'Antonio et al., three hydroxyapatite-coated acetabular cups in a series of 320 components had migrated measurably at two years but none had been revised for aseptic loosening⁴⁰. That study was unique because it included titanium acetabular components of three different designs: a microstructured, fully coated, dual-radius hemispherical component designed to optimize the peripheral rim fit; a fully coated threaded cup; and a non-hydroxyapatite-coated porous-coated cup. At the five-year follow-up examination, the 165 non-threaded hemispherical hydroxyapatite-coated cups had a combined rate of radiographic and clinical failure of 19 per cent^22,38. This finding is in direct contrast to both the results for the 103 non-hydroxyapatite-coated porous-coated cups (a combined rate of failure of 6 per cent) and those for the hydroxyapatite-coated threaded cups from the same manufacturer in the two European trials (a combined rate of failure of 3 per cent of 118 and 0 per cent of 107, respectively). Additionally, Geesink and Hoefnagels reported a six-year survival rate of 99 per cent for 100 hydroxyapatite-coated threaded acetabular components⁷⁴. It is paradoxical that these components yielded excellent results compared with those for hemispherical cups, as non-hydroxyapatite-coated threaded cups have been associated with poor results in other series^63,160,184. Geesink and Hoefnagels found that fixation with screws, holes in the cup, the locking mechanism of the polyethylene, and the method of sterilization of the polyethylene did not contribute to the increased rate of failure of the microstructured cups⁷⁴. Factors that were found to be associated with loosening were the use of a thirty-two-millimeter femoral head, female gender, and an age of forty-five years or less. The most important factor was believed to be the lack of any macrostructuring (as with threads, beads, or arc-deposited titanium) that would have allowed for a mechanical interlock⁷⁴.

Moilanen et al., in a retrospective study, reported the two to three-year results for press-fit cobalt-chromium acetabular components with a central peg and two superolateral flanges, with or without a hydroxyapatite coating that was eighty to 120 micrometers thick¹³². There were no differences in the clinical results, but the hydroxyapatite-coated components were associated with fewer radiolucent lines and less rotational and proximal migration.

Adaptive Host-Bone Remodeling in Association with Hydroxyapatite-Coated Femoral Components
Proximally hydroxyapatite-coated femoral stems were associated with a characteristic radiographic remodeling pattern in multiple trials^{22,39-42,65,72,74,101,114,166,175,176}. The common findings were a high prevalence of radiolucent lines surrounding the distal, uncoated portion of the stem and a low prevalence of radiolucent lines adjacent to the proximal, coated portion of the stem^{39,41,65,72,74,101,114,166,175,176}; cancellous condensation at the distal extent of the coating^{39,41,72,74,126}; and fusiform cortical hypertrophy beginning at the transition between the coated and uncoated regions and extending distally^{39-42,72,74,101} (Fig. 3). In the largest study of radiographic remodeling of the femur after implantation of a hydroxyapatite-coated femoral stem of which we are aware, 68 per cent of 224 stems had radiolucent lines surrounding the distal, uncoated portion of the stem and 2 per cent had radiolucent lines around the proximal, coated region as seen on both anteroposterior and lateral radiographs⁴¹. These findings of new-bone formation and extensive proximal fixation were consistent and progressive throughout the seven-year follow-up period (Figs. 4-A, 4-B, 4-C through 4-D).

View larger version (142K): [in this window] [in a new window]   Fig. 3 Left: Anteroposterior radiograph made eight years after a total hip arthroplasty performed with use of a hydroxyapatite-coated femoral component. There is relative osteopenia (top arrow), bone condensation and hypertrophy (middle arrow), and radiolucency around the uncoated portion of the stem (bottom arrow). Right: Photograph showing the prosthesis (Osteonics, Allendale, New Jersey).

View larger version (107K): [in this window] [in a new window]   Figs. 4-A through 4-D: Anteroposterior and lateral radiographs showing progressive femoral remodeling around a stem with a proximal hydroxyapatite coating. Fig. 4-A: Six months postoperatively.

View larger version (101K): [in this window] [in a new window]   Fig. 4-B One year postoperatively.

View larger version (93K): [in this window] [in a new window]   Fig. 4-C Three years postoperatively.

View larger version (101K): [in this window] [in a new window]   Fig. 4-D Seven years postoperatively.

In a cross-sectional, retrospective study of eighty-eight patients who were followed for seven years after implantation of a hydroxyapatite-coated femoral stem, dual-energy x-ray absorptiometry revealed a 25 per cent decrease in bone-mineral density proximally between six weeks and six months postoperatively¹⁵⁶. Between six months and two years, bone-mineral density increased proximally, with an average loss of 15 per cent, and it increased distally, returning to values equal to or greater than those before the operation. There was no bone loss between two and seven years. In another study, proximal bone loss in a matched group of eighty-seven patients was found to be greater, two to five years postoperatively, in patients who had a porous-coated, diaphysis-filling, cobalt-chromium stem than in those who had a proximally fitting hydroxyapatite-coated titanium stem¹⁵⁷. The average bone loss in the two proximal zones of Gruen et al. was 29 per cent for the porous-coated implants and 14 per cent for the hydroxyapatite-coated implants.

Analysis of hydroxyapatite-coated femoral components with use of dual-energy x-ray absorptiometry has revealed results that are favorable compared with those of studies, performed with use of the same modality, of stems inserted with cement and evaluated retrospectively^123,145, of porous-coated stems retrieved at autopsy^59,124,169, and of porous-coated stems evaluated retrospectively^{90,106,107,145}. A paired, bilateral, dual-energy x-ray absorptiometry comparison of hydroxyapatite-coated and porous-coated stems of the same design revealed greater proximal bone loss in association with the porous-coated components¹⁵⁵.

Titanium stems with a proximal hydroxyapatite coating have been associated with minimum, non-progressive proximal loss of bone and with strong evidence of proximal biological fixation in densitometric and radiographic studies^{39-42,65,72,74,101,114,130,155-157,166,175,176,181}. Non-hydroxyapatite-coated titanium stems also have been associated with minimum short-term decreases in bone-mineral density, although radiographic signs of biological fixation have been lacking. Radiographic and dual-energy x-ray absorptiometry analyses have shown that porous-coated cobalt-chromium stems and stems inserted with cement caused greater resorption of femoral bone than hydroxyapatite-coated stems and that biological fixation did not occur as consistently in association with porous-coated stems.

Analysis of Retrieved Hydroxyapatite-Coated Implants
Most retrieved hydroxyapatite-coated components have been femoral stems. There are two types of retrieval studies of hydroxyapatite-coated components, revision and autopsy, and they have demonstrated different results. Studies of implants retrieved at the time of a revision hip arthroplasty have revealed findings of concern, including dissolution and delamination of the coating. Examination of a patient who initially had a well fixed hydroxyapatite-coated titanium femoral component but who had severe pain in the thigh at two years did not reveal histological evidence of the original hydroxyapatite coating, but the prosthesis-host interface was covered predominantly with trabecular bone¹⁹. Bloebaum et al. reported on a series of fourteen different implants retrieved for a variety of reasons, including osteolysis, excessive wear of the polyethylene, infection, pain in the hip, trauma, loosening, and death^13,16. The implants had been in situ for an average of twenty-eight months and were of six different designs. In addition to titanium and polyethylene debris, hydroxyapatite particulate material was discovered in the periprosthetic tissues and was found to be embedded in the surfaces of the polyethylene liner. In some areas, a ten to twenty-micrometer gap was evident between the hydroxyapatite and the metal substrate, suggesting delamination of the hydroxyapatite coating. Those authors noted that it was not possible to determine which of the three types of particles—titanium, polyethylene, or hydroxyapatite—had caused the osteolysis; however, they cited references suggesting that hydroxyapatite particulate material could cause an inflammatory tissue response and osteolysis^13,16.

In order to assess indirectly the potential problem of hydroxyapatite particulate debris and resultant third-body wear, Bauer et al. used laser interference microscopy to measure the roughness of the surface of the modular cobalt-chromium femoral heads of fifteen clinically retrieved hydroxyapatite-coated components and to compare it with that of the heads of fifteen retrieved porous-coated components that had been inserted without cement and also with that of the heads of fifteen components that had been inserted with cement⁹. They found increased median surface roughness as compared with the initial specifications of the manufacturer in all groups; however, the heads from the hydroxyapatite-coated components had less roughness and fewer deep scratches than those from either the porous-coated components or the components that had been inserted with cement. This suggests that the problem of third-body wear is not greater with hydroxyapatite-coated implants than with porous-coated implants or with implants inserted with cement.

There also has been a number of investigations of hydroxyapatite-coated implants retrieved at autopsy. Bloebaum et al. examined retrieved bilateral femoral components with identical porous-coated titanium stems, except that the stem retrieved from the right hip had a seventy to 100-micrometer proximal air-plasma-sprayed hydroxyapatite coating¹⁴. Backscattered electron analysis showed 50 per cent more bone in the implants with a hydroxyapatite coating. In another autopsy-retrieval study, Bloebaum et al. performed an analysis of hydroxyapatite-coated femoral and ace-tabular components retrieved three weeks after implantation¹⁵. Light microscopy showed the presence of osteoid on 20 per cent and 40 per cent of the femoral and acetabular regions, respectively. Bauer et al. performed a histological analysis of five autopsy-retrieved hydroxyapatite-coated femoral stems that had been in situ for an average of twelve months⁷. A uniform coating of hydroxyapatite was identified on each stem, with extensive direct apposition of bone. There was no evidence of delamination of the coating, formation of a fibrous membrane, inflammation, or necrosis.

Five other reports concerning autopsy-retrieved components revealed early deposition of woven bone directly on the hydroxyapatite surface, with extensive formation of bone and without intervening fibrous tissue^{44,67,83,84,163}. Resorption of the hydroxyapatite coating was identified in one implant, with host bone in direct contact with the metal.

The disparity between the findings from the two types of retrieval studies of hydroxyapatite-coated femoral components makes interpretation of the results difficult. The studies of components retrieved during revision revealed delamination of the coating as well as hydroxyapatite particulate debris, but the studies of components retrieved at autopsy did not corroborate these findings. It is possible that the stems that were retrieved at the time of revision had failed because of a direct complication associated with the hydroxyapatite coating, but it is equally possible that there was another primary cause of failure, such as infection (which reduces pH and therefore adversely affects the hydroxyapatite coating), malposition, or excessive wear of the polyethylene. Thus, the damage to the hydroxyapatite coating could have been secondary, and it could have been complicated by artefactual damage during removal of the component. We believe that additional retrieval studies are needed before clear conclusions can be made regarding the failure of the hydroxyapatite coating and its severity.

Hydroxyapatite-coated acetabular components have been specifically examined in only a few retrieval studies. In one such study, apposition of bone was found to be most prominent in areas of load transmission around the periphery, and focal loss of hydroxyapatite without a histiocytic tissue response was observed in areas of low load transmission⁸. Another study of components that were revised early because of malposition revealed a thin membrane of connective tissue between the hydroxyapatite and the bone, without evidence of biological fixation¹⁵². A third study demonstrated the presence of osteoid on 40 per cent of a retrieved component¹¹⁵.

It is revealing to compare the results of these reports concerning retrieved hydroxyapatite-coated prostheses with those of reports concerning retrieved porous-coated components. Several studies have demonstrated minimum bone ingrowth in association with porous-coated femoral and acetabular components^{17,26,27,29,60,86,96,100}.

Optimum Design of Hydroxyapatite-Coated Components for Total Hip Arthroplasty
The initial biological fixation of the femoral component depends on the stability of the implant, and long-term fixation depends on preservation of bone and minimization of particulate and ionic debris. We believe that, in order to achieve these goals, hydroxyapatite-coated femoral stems designed for primary hip arthroplasty should be fabricated from titanium^{25,90,145,157,179}, have excellent metaphyseal fit and fill, and have a coating that is limited to the proximal portion of the stem^58,92. We also believe that these stems should be collarless^24,118,129 because an easily seated collar prevents fit and fill and a collar that is difficult to seat promotes fracture of the calcar. A macrostructured or porous substrate, or a threaded design, should be used for the acetabular component. The hydroxyapatite coating should be of the highest crystallinity and purity. The process of application should be closely monitored with strict quality-control measures, and the thickness of the coating should be between fifty and seventy-five micrometers^46,47,75. Currently, air or vacuum plasma-spraying is the preferred method of application.

Indications for the Use of Hydroxyapatite-Coated Components for Total Hip Arthroplasty
The indications for the use of any type of femoral component without cement are unclear, and there are no specific indications for the use of hydroxyapatite-coated as opposed to porous-coated components. Historically, femoral components inserted with cement have demonstrated poor longevity in younger patients^53,103 but have performed well in older patients who place a lower demand on the implant^{69,102,103,154}. However, there have been recent reports of better performance of so-called second and third-generation femoral components inserted with cement in young, active patients^6,168. The indications for insertion of acetabular components with cement are better defined, and fixation without cement is preferred except in patients more than seventy years old^6,168.

We believe that insertion of the femoral component with cement is still the best choice for patients who place a low or moderate demand on the implant. Stems that rely on biological fixation should be reserved for healthy, physically active patients less than sixty years old who have non-inflammatory osteoarthrosis, good bone quality, and a femoral geometry that is amenable to proximal fixation. It is unclear what role hydroxyapatite-coated components should have in revision procedures, but Geesink reported encouraging results⁷³.

Future Directions in the Development of Hydroxyapatite-Coated Components for Total Hip Arthroplasty
Several recent developments may lead to improved performance of hydroxyapatite-coated hip components. So-called sandwich coatings, consisting of a composite of a deep layer of hydroxyapatite and a surface layer of rapidly dissolving biphasic calcium phosphates, and alternative types of ceramics, such as fluorapatite or bioactive polymer coatings, may improve initial osseointegration and long-term stability. Other methods of application of the coating, such as sputter-coating, which allow a uniform coating on an implant with a complex shape, and low-temperature precipitation processes, which permit the incorporation of bioactive substances into the hydroxyapatite coating, also hold promise. Osteoinductive agents^{89,140,146,153} such as bone morphogenetic protein might accelerate biological fixation. Antibiotics adsorbed to the hydroxyapatite coating^113,158,186 could be released into the immediate periprosthetic area as prophylaxis against infection in patients having a primary hip arthroplasty or as therapeutic agents in patients having a revision hip arthroplasty because of infection. These improvements may be applicable primarily to the acetabular component, as the rate of mechanical failure of the femoral component has remained extremely low.

Biomechanically optimum stem designs (for example, isoelastic polymer stems^{25,92,98,141,142,159} or more radical designs such as short-stemmed components^97,134) may be developed. Hydroxyapatite coatings may make such designs more successful. Finite element modeling has suggested that application of hydroxyapatite in specific patterns (for example, stripes)⁹¹ could minimize proximal stress-shielding while maintaining biological fixation.

	Overview

Top Introduction Basic-Science and Preclinical... Clinical Experience with... Overview References

 
Except for hydroxyapatite-coated microtextured hemispherical acetabular shells, hydroxyapatite-coated components have proved to be equal to, and in most instances better than, non-hydroxyapatite-coated components with regard to the achievement of prompt biological fixation. Proximal hydroxyapatite coating enhances the early fixation of the femoral component, which has a positive effect on femoral remodeling and bone density. Radiographs of the femur have provided evidence of successful biological fixation of the proximal hydroxyapatite-coated zones, with stress transfer to the femur at the junction of the coated and uncoated regions of the stem.

Hydroxyapatite-coated components permit a less intimate fit of the prosthesis than do other components designed to be inserted without cement because biological fixation may occur with larger gaps in the bone-prosthesis interface. There is no firm evidence of loosening caused by failure or delamination of the coating, although the long-term stability of hydroxyapatite coatings is unknown. If one accepts the premise that all bioactive ceramic coatings will eventually resorb or be replaced by host bone, hydroxyapatite appears to do so at a rate that does not result in a fibrous layer at the bone-prosthesis interface. The encouraging experimental evidence as well as the intermediate-term clinical results, coupled with the questionable long-term results associated with stems inserted with cement and with porous-coated stems in young patients who place a high functional demand on the implant, support the continued clinical use of hydroxyapatite-coated components in total hip arthroplasty for this population of patients.

	Footnotes

 
*Although none of the authors have received or will receive benefits for personal or professional use from a commercial party related directly or indirectly to the subject of this article, benefits have been or will be received but are directed solely to a research fund, foundation, educational institution, or other non-profit organization with which one or more of the authors are associated. No funds were received in support of this study.

1095 Park Avenue, New York, N.Y. 10128.

Hospital for Joint Diseases Orthopaedic Institute, New York University Medical Center, 301 East 17th Street, New York, N.Y. 10003.

	References

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