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Osseous integration of bovine hydroxyapatite ceramic in metaphyseal bone defects of the distal radius
Osseous Integration of Bovine Hydroxyapatite Ceramic in Metaphyseal Bone Defects of the Distal Radius Klaus-Dieter Werber, MD, Robert B. Brauer, MD, Wolfgang Weiß, MD, Karen Becker, MD, Mu¨nchen, Germany Hydroxyapatite ceramic made of bovine spongiosa was used as structural support material in a prospective study to correct bone defects experienced after reduction in distal radius fractures. The study took place over a 3-year period (1992–1999) and comprised 14 patients. Osseous integration was analyzed via biopsies and magnetic resonance imaging. Long-term follow-up monitoring involving magnetic resonance imaging in 13 of the 14 patients showed fibrovascular growth within incorporated hydroxyapatite material. Osseous integration was demonstrated in magnetic resonance images by gadolinium uptake and by the presence of osteoid layers and endothelialized vessels. Hydroxyapatite ceramic offers a biologically acceptable alternative to autologous bone when augmenting distal radius fracture fixation. (J Hand Surg 2000;25A:833– 841. Copyright © 2000 by the American Society for Surgery of the Hand.) Key words: Hydroxyapatite ceramic, osseous integration, distal radius fracture, bone defects.
Impaction of the articular surface is not uncommon in cases of high-energy fractures to the distal radius. In some cases reduction with elevation of the articular surface reveals a metaphyseal bone defect requiring structural support to prevent malunion or articular incongruency.1–3 In young individuals it is particularly important to avoid malposition of the radiocarpal joint surface, which leads not only to pain but also to premature arthrosis. Structural supFrom the Departments of Surgery, Radiology, and Pathology, Klinikum rechts der Isar, Technische Universita¨t Mu¨nchen, Mu¨nchen, Germany. Received for publication October 5, 1998; accepted in revised form April 10, 2000. No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article. Reprint requests: Klaus-Dieter Werber, MD, Department of General Surgery, Klinikum rechts der Isar, Technische Universita¨t Mu¨nchen, Handsurgery, Ismaningerstraße 22, 81675 Mu¨nchen, Germany. Copyright © 2000 by the American Society for Surgery of the Hand 0363-5023/00/25A05-0017$3.00/0 doi: 10.1053/jhsu.2000.16354
port has been traditionally provided by autologous bone chips.3,4 Procurement of cancellous bone requires a second surgical incision associated with additional morbidity.5– 8 There is sufficient experience in the use of coralline hydroxyapatite (HA) for animal studies investigating new bone formation,9 –11 osseous integration,12and biocompatibility.13 Coralline HA has been used in thousands of cases since the 1980s in experimental surgery,14 in orthognatic surgery,15–17 in reconstruction of the middle ear,18 in the filling of bone cysts,19,20and as structural support in orthopedic surgery.14,21–24 An alternative is to substitute bone with bovine HA ceramic, a material derived from natural biological substances modified through physicochemical treatment. Interporous anorganic HA ceramic possesses an interconnecting pore structure as well as biomechanical properties that closely resemble human bone.19 This material, produced from bovine spongiosa and heated to 1,200°C, is void of protein content. The basic and highly attractive profile of this The Journal of Hand Surgery 833
834 Werber et al / Hydroxyapatite Ceramic in Metaphyseal Bone Defects
material is due to its lack of local or systemic toxicity and inflammatory body response and its apparent ability to become directly bonded to bone.25 The pore size of HA of bovine origin ranges from 0.1 to 1.5 mm19 and its compressive strength ranges between 700 to 7,000 N/cm2. Its tensile strength is 250 N/cm2.25 In comparison, the pore size of autologous spongiosa ranges between 0.2 and 0.6 mm and its compressive strength ranges between 4,100 and 6,200 N/cm2. The tensile strength of autologous spongiosa is 350 N/cm2, depending on the method and preparation of the probe.25 There is, however, a lack of data pertaining to the clinical application of ceramic HA in hand surgery.24 In an effort to avoid an additional surgical procedure HA ceramic blocks were used as structural support for the correction of metaphyseal bone defects resulting from reduction following distal radius fracture. In a prospective clinical trial osteosynthesis was performed using an internal fixation with a plate or external fixator. Integration of the HA was monitored and documented over a 15- to 19-month period via postoperative magnetic resonance imaging (MRI) as well as histologic biopsy. Th purpose of this study was to investigate the osseous integration of bovine HA as a bone substitute in the distal radius metaphysis.
Materials and Methods Fourteen patients (9 women and 5 men) ranging in age from 21 to 80 years (average age, 46 years) were admitted for treatment of distal radius fracture.
Twelve of the patients had experienced injury on the right side. Structural support with HA was indicated by articular depression, dorsal bone defect due to reduction, and metaphyseal bone defect. Using the Association of the Study of Internal Fixation (ASIF) classification scheme, 5 patients sustained type A fractures, 1 patient type B fracture, and the remaining 8 patients type C1 (n ⫽ 3) and C2 (n ⫽ 5) fractures (Table 1). The patients were included in the prospective study after providing informed consent.
Hydroxyapatite Ceramic Block Hydroxyapatite ceramic blocks (12.5 ⫻ 12.5 ⫻ 10 mm) derived from bovine spongiosa were obtained from Merck Biomaterials (Endobon; Darmstadt, Germany). The HA ceramic blocks have interconnecting pores ranging in size between 0.1 and 1.5 mm with an average of 451 m. Pressure stability is from 250 up to 1,600 N/cm2 (similar to that of heat-inactivated allogenic human spongiosa). Endobon is made of up to 95% pentacalciummonohydroxyorthophosphate. Biocompatibility was approved according to the Europe Standard 30993 for medical products. Food and Drug Administration approval for Endobon was issued in April 1998 for dental and oral surgery; FDA approval for other indications is in process.
Surgical Procedure Before correction of the bone defect, closed reduction of the distal radius fracture was performed under
Table 1. Patient Characteristics Injured Side
Type of Fracture
ASIF Classification
F F F M
Right Right Right Left
Colles’ Smith Smith Smith
C 1.2 C 2.2 A 3.3 C 2.2
F F M M F M F F F M
Right Right Right Right Right Right Right Left Right Right
Colles’ Colles’ Colles’ Colles’ Colles’ Colles’ Colles’ Colles’ Colles’ Colles’
C 2.2 A 3.2 C 2.1 B 2.3 A 3.2 C 1.2 C 1.2 C 2.2 A 3.2 A 3.2
Patient No.
Age (yr)
Gender
1 2 3 4
54 70 56 21
5 6 7 8 9 10 11 12 13 14
27 38 34 80 32 59 24 57 27 65
CTS, carpal tunnel syndrome.
Cause of Trauma Fall Fall Traffic accident Motorcycle accident Fall Fall Ice skating Staircase fall Fall Syncope Free climbing Skiing Snowboarding Fall
Osteosynthesis
Complication
ASIF plate External fixator ASIF plate ASIF plate
— — CTS CTS
External fixator ASIF plate External fixator External fixator External fixator ASIF plate External fixator ASIF plate ASIF plate ASIF plate
— — — — — — — — — —
Figure 1. (A) Dorsal in situ view at the distal part of the radius after placement of an HA ceramic block into the metaphyseal part of the radius before fixation of the ASIF plate. (B) Placement of the plate from dorsal before fixation.
836 Werber et al / Hydroxyapatite Ceramic in Metaphyseal Bone Defects
Magnetic Resonance Imaging Evaluation Long-term follow-up evaluation of the incorporated HA ceramic was investigated in 13 of the 14 study patients using MRI in T1- and T2-weighted sequences before and after intravenous injection of gadolinium (DTPA Magnevist; Schering, Berlin, Germany) 12 to 15 months after surgery, when osteosynthesis was removed. Scans were obtained using fixed hand or forearm splints to avoid motion artifacts. Corresponding scans were deducted from one another in a form of subtraction MRI for better differentiation between bone marrow signal and contrast enhancement. Magnetic resonance imaging was performed in 8 cases in a 1.0T Magnetom Expert (Siemens, Erlangen, Germany) and in 6 cases in a low-field 0.2T dedicated system (Artoscan; Fa. Esaote, Genoa, Italy). Time of acquisition was 8 minutes 40 seconds in the 1.0T Magnetom Expert and 12
Figure 2. Plain radiograph of the distal fracture of the radius in a 27-year-old woman with structural support by an HA block and osteosynthesis with 5-pin external fixation. Two weeks following surgery, the HA is hyperdense.
local anesthesia in all the patients (Fig. 1). Osteosynthesis was performed using an ASIF plate in 8 cases and an external fixator in the remaining 6 (Fig. 2). Following elevation and fixation of the articular surface, the HA ceramic block was shaped and formed with a rongeur to fit the defect. No further fixation of the block was necessary. Representative biopsy specimens of the HA block were obtained at the time of removal of the plates 12 to 15 months after the procedure in 4 cases. The remaining 10 patients denied consent for biopsies.
Histologic Evaluation Biopsy specimens obtained at the time of plate removal (12–15 months after the procedure) were fixed in 10% formalin, embedded in paraffin, sectioned, and stained with hematoxylin-eosin and Elastica van Giesson.
Figure 3. Plain radiograph of the HA block used as structural support after fracture of the distal part of the radius in a 38-year-old woman. The ASIF plate was removed 15 months after surgery. The HA block remained as hyperdense as it was at the time of surgery. Osseous integration therefore cannot be sufficiently evaluated by plain radiographs.
The Journal of Hand Surgery / Vol. 25A No. 5 September 2000 837
Figure 4. (A) In 13 of 14 cases the native T1-weighted sequence demonstrated bone marrow and fat equivalent structures within the HA block. After intravenous administration of gadolinium, the signal was enhanced in 13 of 14 cases. (B) Due to the fact that gadolinium is transported via vessels, contrast enhancement in T1-weighted sequences corresponds with a significant fibrovascular ingrowth within the HA block. (Figure continues)
minutes 20 seconds in the low-field 0.2T system. Data derived from the MRI scans regarding gadolinium uptake in the HA block were defined as fibrovascular incorporation or biologic incorporation.
tion by an experienced pathologist. This quantification is not absolutely precise and offers only estimated values.
Results
Integration of Hydroxyapatite Plain radiographs were not suitable for evaluation of osseous integration of HA (Fig. 3). Osseous integration was defined when fibrovascular ingrowth and osteoid layers and vessels with endothelium were detected in the biopsy specimens. Osteoid formation in histologic biopsy specimens quantified by evaluation of 10 different high-power fields in each sec-
Osseous Integration Osseous integration could not be sufficiently evaluated by plain radiographs in that the HA block was already hyperdense at the time of surgery (Fig. 3). Osseous union was defied when there was no radiographic evidence of cyst formation or osteolysis in the final follow-up radiographs within the area of the
838 Werber et al / Hydroxyapatite Ceramic in Metaphyseal Bone Defects
demonstrated by the deduction MRI technique (Fig. 4). These results indicated that fibrovascular or biologic incorporation had occurred with the implanted HA blocks in these cases.
Biocompatibility and Tolerance Osteosynthesis was performed using a plate in 8 cases (Fig. 2) and an external fixator in the remaining 6 (Fig. 3). Following elevation and fixation of the articular surface, the HA ceramic block was easily shaped and formed with a rongeur to fit the defect. No further fixation of the HA block was necessary. In the follow-up evaluations, which were up to 18 months in duration, there was no clinical evidence of intolerance of the HA ceramic. None of the 14 patients showed signs of infection, local erythema, nonunion, or any other complication related to the structural support of the HA block. Only 1 patient was concerned about having a foreign body implanted permanently. All the other patients accepted the implanted HA well because it avoided a second incision.
Histology
Figure 4. (Continued) (C) The patient’s hand and forearm were fixed in a splint during MRI acquisition to avoid artifacts due to motion. Corresponding scans of the T1weighted sequences before and after application of gadolinium were subtracted from each other. The resulting subtraction images exhibited homologous contrast enhancement as an indication of neovascularization.
HA ceramic as well as when the HA ceramic was coated by new cortical bone. In the long-term follow-up protocol, incorporation was investigated by MRI at 12 to 15 months after surgery when the plate was removed. Magnetic resonance imaging was nondiagnostic in only 1 case in which a broken screw caused extensive artifacts. Signal enhancement in MRI occurred in 13 of the 14 cases following gadolinium injection. Eighty percent to 90% of the HA block was uniformly enhanced after gadolinium injection. This could be especially
The specimens obtained from the 4 patients who consented to biopsy uniformly demonstrated apositional growth, endothelialized vessels, and intraluminal erythrocytes. Some collagen structures along with fat cells were also adherent within the HA ceramic block (Fig. 5). Approximately 70% of the surface of the ceramic was coated with thin osteoid layers 12 to 15 months after implantation of the HA block.
Discussion Autogenous bone grafts are harvested via a second surgical incision with an additional risk of donor site morbidity.5– 8,26,27 Several investigators have reported using HA ceramic successfully in experimental animal models whereby HA exhibited excellent biocompatibility, mechanical stability, and osseous integration to the bone defect.11,12,28 Graft elements of the HA cannot be resorbed or replaced by new bone formation. The advantage HA ceramic blocks has over cancellous bone is that a second surgical incision for procurement of cancellous bone can be avoided. Another advantage is the absence of transmitted infectious disease, such as the human immunodeficiency virus and hepatitis) due to the ultraheating process. The disadvantages include the requirement of a solid osteosynthesis and the fragil-
The Journal of Hand Surgery / Vol. 25A No. 5 September 2000 839
Figure 5. Representative biopsy specimens obtained from the HA block at the time of removal of the ASIF plate (15 months after surgery). Within the HA ceramic, appositional growth of osteoid layers (O) and vessels with endothelium and intraluminal erythrocytes (V) were prominent at this time. Some collagen structures and fat cells within the HA ceramic block were adherent. (A) Patient 10. (Hematoxylin-eosin stain; magnification ⫻250.) (B) Patient 13. (Elastica van Giesson stain; magnification ⫻350.)
840 Werber et al / Hydroxyapatite Ceramic in Metaphyseal Bone Defects
ity to mechanical stress. Torsional force can actually break the HA block. Promising results are reported in the literature pertaining to middle ear reconstruction,18 the treatment of periodontal bone defects,15–17 the filling of small bone cysts,19,20 and reconstruction of defects in foot and ankle surgery.29 –31 One report explained the advantages of porous HA bone graft from coralline origin as substitutes in distal radius fracture, but assessment of osseous bone integration following surgery was only documented through plain radiographs.24 Porous HA should not be used as structural support in the presence of osteomyelitis or malignant bone disease, although there is no evident in the literature regarding contraindications for the application of HA from bovine origin. External fixators were removed 8 to 10 weeks after HA implantation. This was 2 weeks longer than suggested in most series without bone graft. This expected delay in healing time may be accounted for by the smaller surface of the vascularized bone. There were no other experiences available in the literature to base comparison or result. Because the HA ceramic is always hyperdense in plain radiographs only the bone healing in the margins around the HA ceramic block could be evaluated. This explains why time to healing and osseous integration could not be adequately measured or compared with osseous integration of autogenous bone graft. Magnetic resonance imaging sequences provided information surrounding the osseous integration of HA into the bone but could only be performed following removal of all magnetic materials. Hydroxyapatite ceramic is low on protons and appears as low signal-like-bone on MRIs. While gadolinium is transported by the vascular system, the increase in contrast in T1-weighted sequences within the HA block corresponds to a noteworthy fibrovascular ingrowth in all but 1 patient. This was also observed by other investigators.32–34 The results of the MRI sequences were consistent with the results of the 4 representative biopsy specimens at the time of removal of the plate. It would have been preferable to perform a biopsy in all the treated patients in this study, but biopsy specimens were obtained from only those patients receiving an osteosynthesis with a plate at the time of plate removal. Hydroxyapatite ceramic offers only passive structural support in well-vascularized locations and acts as a matrix for vessels, osteoblasts, and connective tissue. Osseous integration was also documented by histologic biopsy specimens showing osteoid layers
as well as vessels within the interconnective pore system in 4 cases 15 months after surgery. This information is consistent with reports involving histologic biopsy specimens taken from HA ceramic in human subjects.17,19 Hydroxyapatite ceramic provides an optional alternative in the correction of metaphysical bone defects following distal radial fracture. It was demonstrated that the bone not only healed around the graft material, but also incorporated the HA by fibrovascular ingrowth. Although not directly compared with autogenous bone grafts, bovine HA provides a biologically acceptable alternative that was well tolerated and incorporated into the host bone without adverse clinical effects. The authors thank Dr Clayton Peimer for carefully reading the manuscript.
References 1. Leung KS, Shen WY, Leung PC, Kinninmonth AWG, Chang JCW, Chan GPY. Ligamentotaxis and bone grafting for comminuted fractures of the distal radius. J Bone Joint Surg 1989;71B:838 – 842. 2. Leung KS, Shen WY, Tsang HK, Chiu KH, Leung PC, Hung LK. An effective treatment of comminuted fractures of the distal radius. J Hand Surg 1990;15A:11–17. 3. McBirnie J, Court-Brown CM, McQueen MM. Early open reduction and bone grafting for unstable fractures of the distal radius. J Bone Joint Surg 1995;77B:571–575. 4. Leung KS, So WS, Chiu VDF, Leung PC. Ligamentotaxis for comminuted distal radial fractures modified by primary cancellous grafting and functional bracing: long-term results. 0rthop Trauma 1991;5:265–271. 5. Laurie SWS, Kaban LB, Mulliken JB, Murray JE. Donorsite morbidity after harvesting rib and iliac bone. Plast Reconstr Surg 1984;73:933–938. 6. Banwart JC, Asher MA, Hassanein RS. Iliac crest bone graft harvest donor site morbidity: a statistical evaluation. Spine 1995;20:1055–1060. 7. Arrington ED, Smith WJ, Chambers HG, Bucknell AL, Davino NA. Complications of iliac crest bone graft harvesting. Clin Orthop 1996;329:300 –309. 8. Goulet JA, Senunas LE, DeSilva GL, Greenfield MLVH. Autogenous iliac crest bone graft: complications and functional assessment. Clin Orthop 1997;339:76 – 81. 9. Holmes R, Mooney V, Bucholz R, Tencer A. A coralline hydroxyapatite bone graft substitute. Preliminary report. Clin Orthop 1984;188:252–262. 10. Mandelkow HK, Hallfeldt KKJ, Kessler SB, Gayk M, Siebeck M, Schweiberer L. Knochenneubildung nach Implantation verschiedener Hydroxylapatitkeramiken: Tierexperimentelle Studie am Bohrlochmodell der Schaftstibia. Unfallchirurg 1990;93:376 –379. 11. Klinge B, Alberius P, Isaksson S, Jo¨nsson J. Osseus response to implanted natural bone mineral and synthetic
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hydroxylapatite ceramic in the repair of experimental skull bone defects. J Oral Maxillofac Surg 1992;50:241–249. Isaksson B. Aspects of bone healing and bone substitute incorporation: an experimental study in rabbit skull bone defects. Swed Dent J Suppl 1992;84:1– 46. Gumaer KI, Sherer AD, Slighter RG, Rothstein SB, Drobeck HP. Tissue response in dogs to dense hydroxylapatite implantation in the femur. J Oral Maxillofac Surg 1986; 44:618 – 627. Holmes RE, Bucholz RW, Mooney V. Porous hydroxyapatite as a bone-graft substitute in metaphyseal defects. A histometric study. J Bone Joint Surg 1986;68A:904 –911. Galgut PN, Waite IM, Brookshaw JD, Kingston CP. A 4-year controlled clinical study into the use of a ceramic hydroxylapatite implant material for the treatment of periodontal bone defects. J Clin Periodontol 1992;19:570 –577. Rosen HM. Porous, block hydroxyapatite as an interpositional bone graft substitute in orthognathic surgery. Plast Reconstr Surg 1989;83:985–990. Oguchi H, Ishikawa K, Mizoue K, Seto K, Eguchi G. Long-term histological evaluation of hyroxyapatite ceramics in humans. Biomaterials 1995;16:33–38. Grote JJ. Reconstruction of the middle ear with hydroxylapatite implants: long-term results. Ann Otol Rhinol Laryngol Suppl 1990;144:12–16. Liebendo¨rfer A, Tro¨ster S. Hydroxylapatitkeramik im klinischen Einsatz: Histologische Befunde von 23 Patienten. Unfallchirurgie 1997;23:60 – 68. Schaller P, Geldmacher J, Freiberger N, Flu¨gel M. Die Auffu¨tterung kleiner Knochenho¨hlen mit Knochenkeramik (Hydroxylapatit). Handchir Mikrochir Plast Chir 1993;25: 184 –190. Buchholz RW, Carlton A, Holmes R. Interporous hydroxyapatite as a bone graft substitute in tibial plateau fractures. Clin Orthop 1988;240:53– 62. Sartoris DJ, Gershuni DH, Akeson WH, Holmes RE, Resnick D. Coralline hydroxyapatite bone graft substitutes: preliminary report of radiographic evaluation. Radiology 1986;159:133–137.
23. Sartoris DJ, Holmes RE, Resnick D. Coralline hydroxyapatite bone graft substitutes: radiographic evaluation. J Foot Surg 1992;31:301–313. 24. Wolfe SW, Pike L, Slade JF III, Katz LD. Augmentation of distal radius fracture fixation with coralline hydroxyapatite bone graft substitute. J Hand Surg 1999;24A: 816 – 827. 25. Jarcho M. Calcium phosphate ceramics as hard tissue prosthetics. Clin Orthop 1981;157:259 –278. 26. Canady JW, Zeitler DP, Thompson SA, Nicholas CD. Suitability of the iliac crest as a site for harvest of autogenous bone grafts. Cleft Palate Craniofac J 1993;30:579 – 581. 27. Younger EM, Chapman MW. Morbidity at bone graft donor sites. J Orthop Trauma 1989;3:192–195. 28. Cook SD, Reynolds MC, Whitecloud TS, et al. Evaluation of hydroxyapatite graft materials in canine cervical spine fusions. Spine 1985;11:305–309. 29. Nesheiwat F, Brown WM, Healey KM. Post-traumatic first metatarsal reconstruction using coralline hydroxyapatite. J Am Podiatr Med Assoc 1998;88:130 –134. 30. Rahimi F, Maurer BT, Enzweiler MG. Coralline hydroxyapatite: a bone graft alternative in foot and ankle surgery. J Foot Ankle Surg 1997;36:192–203. 31. Elsinger EC, Leal L. Coralline hydroxyapatite bone graft substitutes. J Foot Ankle Surg 1996;35:396 –399. 32. De Potter P, Shields CL, Shields JA, Flanders AE, Rao VM. Role of magnetic resonance imaging in the evaluation of the hydroxyapatite orbital implant. Ophthalmology 1992;99:824 – 830. 33. Hamilton HE, Christianson MD, Williams JP, Thomas RA. Evaluation of vascularization of coralline hydroxyapatite ocular implants by magnetic resonance imaging. Clin Imaging 1992;16:243–246. 34. Spirnak JP, Nieves N, Hollsten DA, White WC, Betz TA. Gadolinium-enhanced magnetic resonance imaging assessment of hydroxyapatite orbital implants. Am J Ophthalmol 1995;119:431– 440.
Impaction of the articular surface is not uncommon in cases of high-energy fractures to the distal radius. In some cases reduction with elevation of the articular surface reveals a metaphyseal bone defect requiring structural support to prevent malunion or articular incongruency.1–3 In young individuals it is particularly important to avoid malposition of the radiocarpal joint surface, which leads not only to pain but also to premature arthrosis. Structural supFrom the Departments of Surgery, Radiology, and Pathology, Klinikum rechts der Isar, Technische Universita¨t Mu¨nchen, Mu¨nchen, Germany. Received for publication October 5, 1998; accepted in revised form April 10, 2000. No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article. Reprint requests: Klaus-Dieter Werber, MD, Department of General Surgery, Klinikum rechts der Isar, Technische Universita¨t Mu¨nchen, Handsurgery, Ismaningerstraße 22, 81675 Mu¨nchen, Germany. Copyright © 2000 by the American Society for Surgery of the Hand 0363-5023/00/25A05-0017$3.00/0 doi: 10.1053/jhsu.2000.16354
port has been traditionally provided by autologous bone chips.3,4 Procurement of cancellous bone requires a second surgical incision associated with additional morbidity.5– 8 There is sufficient experience in the use of coralline hydroxyapatite (HA) for animal studies investigating new bone formation,9 –11 osseous integration,12and biocompatibility.13 Coralline HA has been used in thousands of cases since the 1980s in experimental surgery,14 in orthognatic surgery,15–17 in reconstruction of the middle ear,18 in the filling of bone cysts,19,20and as structural support in orthopedic surgery.14,21–24 An alternative is to substitute bone with bovine HA ceramic, a material derived from natural biological substances modified through physicochemical treatment. Interporous anorganic HA ceramic possesses an interconnecting pore structure as well as biomechanical properties that closely resemble human bone.19 This material, produced from bovine spongiosa and heated to 1,200°C, is void of protein content. The basic and highly attractive profile of this The Journal of Hand Surgery 833
834 Werber et al / Hydroxyapatite Ceramic in Metaphyseal Bone Defects
material is due to its lack of local or systemic toxicity and inflammatory body response and its apparent ability to become directly bonded to bone.25 The pore size of HA of bovine origin ranges from 0.1 to 1.5 mm19 and its compressive strength ranges between 700 to 7,000 N/cm2. Its tensile strength is 250 N/cm2.25 In comparison, the pore size of autologous spongiosa ranges between 0.2 and 0.6 mm and its compressive strength ranges between 4,100 and 6,200 N/cm2. The tensile strength of autologous spongiosa is 350 N/cm2, depending on the method and preparation of the probe.25 There is, however, a lack of data pertaining to the clinical application of ceramic HA in hand surgery.24 In an effort to avoid an additional surgical procedure HA ceramic blocks were used as structural support for the correction of metaphyseal bone defects resulting from reduction following distal radius fracture. In a prospective clinical trial osteosynthesis was performed using an internal fixation with a plate or external fixator. Integration of the HA was monitored and documented over a 15- to 19-month period via postoperative magnetic resonance imaging (MRI) as well as histologic biopsy. Th purpose of this study was to investigate the osseous integration of bovine HA as a bone substitute in the distal radius metaphysis.
Materials and Methods Fourteen patients (9 women and 5 men) ranging in age from 21 to 80 years (average age, 46 years) were admitted for treatment of distal radius fracture.
Twelve of the patients had experienced injury on the right side. Structural support with HA was indicated by articular depression, dorsal bone defect due to reduction, and metaphyseal bone defect. Using the Association of the Study of Internal Fixation (ASIF) classification scheme, 5 patients sustained type A fractures, 1 patient type B fracture, and the remaining 8 patients type C1 (n ⫽ 3) and C2 (n ⫽ 5) fractures (Table 1). The patients were included in the prospective study after providing informed consent.
Hydroxyapatite Ceramic Block Hydroxyapatite ceramic blocks (12.5 ⫻ 12.5 ⫻ 10 mm) derived from bovine spongiosa were obtained from Merck Biomaterials (Endobon; Darmstadt, Germany). The HA ceramic blocks have interconnecting pores ranging in size between 0.1 and 1.5 mm with an average of 451 m. Pressure stability is from 250 up to 1,600 N/cm2 (similar to that of heat-inactivated allogenic human spongiosa). Endobon is made of up to 95% pentacalciummonohydroxyorthophosphate. Biocompatibility was approved according to the Europe Standard 30993 for medical products. Food and Drug Administration approval for Endobon was issued in April 1998 for dental and oral surgery; FDA approval for other indications is in process.
Surgical Procedure Before correction of the bone defect, closed reduction of the distal radius fracture was performed under
Table 1. Patient Characteristics Injured Side
Type of Fracture
ASIF Classification
F F F M
Right Right Right Left
Colles’ Smith Smith Smith
C 1.2 C 2.2 A 3.3 C 2.2
F F M M F M F F F M
Right Right Right Right Right Right Right Left Right Right
Colles’ Colles’ Colles’ Colles’ Colles’ Colles’ Colles’ Colles’ Colles’ Colles’
C 2.2 A 3.2 C 2.1 B 2.3 A 3.2 C 1.2 C 1.2 C 2.2 A 3.2 A 3.2
Patient No.
Age (yr)
Gender
1 2 3 4
54 70 56 21
5 6 7 8 9 10 11 12 13 14
27 38 34 80 32 59 24 57 27 65
CTS, carpal tunnel syndrome.
Cause of Trauma Fall Fall Traffic accident Motorcycle accident Fall Fall Ice skating Staircase fall Fall Syncope Free climbing Skiing Snowboarding Fall
Osteosynthesis
Complication
ASIF plate External fixator ASIF plate ASIF plate
— — CTS CTS
External fixator ASIF plate External fixator External fixator External fixator ASIF plate External fixator ASIF plate ASIF plate ASIF plate
— — — — — — — — — —
Figure 1. (A) Dorsal in situ view at the distal part of the radius after placement of an HA ceramic block into the metaphyseal part of the radius before fixation of the ASIF plate. (B) Placement of the plate from dorsal before fixation.
836 Werber et al / Hydroxyapatite Ceramic in Metaphyseal Bone Defects
Magnetic Resonance Imaging Evaluation Long-term follow-up evaluation of the incorporated HA ceramic was investigated in 13 of the 14 study patients using MRI in T1- and T2-weighted sequences before and after intravenous injection of gadolinium (DTPA Magnevist; Schering, Berlin, Germany) 12 to 15 months after surgery, when osteosynthesis was removed. Scans were obtained using fixed hand or forearm splints to avoid motion artifacts. Corresponding scans were deducted from one another in a form of subtraction MRI for better differentiation between bone marrow signal and contrast enhancement. Magnetic resonance imaging was performed in 8 cases in a 1.0T Magnetom Expert (Siemens, Erlangen, Germany) and in 6 cases in a low-field 0.2T dedicated system (Artoscan; Fa. Esaote, Genoa, Italy). Time of acquisition was 8 minutes 40 seconds in the 1.0T Magnetom Expert and 12
Figure 2. Plain radiograph of the distal fracture of the radius in a 27-year-old woman with structural support by an HA block and osteosynthesis with 5-pin external fixation. Two weeks following surgery, the HA is hyperdense.
local anesthesia in all the patients (Fig. 1). Osteosynthesis was performed using an ASIF plate in 8 cases and an external fixator in the remaining 6 (Fig. 2). Following elevation and fixation of the articular surface, the HA ceramic block was shaped and formed with a rongeur to fit the defect. No further fixation of the block was necessary. Representative biopsy specimens of the HA block were obtained at the time of removal of the plates 12 to 15 months after the procedure in 4 cases. The remaining 10 patients denied consent for biopsies.
Histologic Evaluation Biopsy specimens obtained at the time of plate removal (12–15 months after the procedure) were fixed in 10% formalin, embedded in paraffin, sectioned, and stained with hematoxylin-eosin and Elastica van Giesson.
Figure 3. Plain radiograph of the HA block used as structural support after fracture of the distal part of the radius in a 38-year-old woman. The ASIF plate was removed 15 months after surgery. The HA block remained as hyperdense as it was at the time of surgery. Osseous integration therefore cannot be sufficiently evaluated by plain radiographs.
The Journal of Hand Surgery / Vol. 25A No. 5 September 2000 837
Figure 4. (A) In 13 of 14 cases the native T1-weighted sequence demonstrated bone marrow and fat equivalent structures within the HA block. After intravenous administration of gadolinium, the signal was enhanced in 13 of 14 cases. (B) Due to the fact that gadolinium is transported via vessels, contrast enhancement in T1-weighted sequences corresponds with a significant fibrovascular ingrowth within the HA block. (Figure continues)
minutes 20 seconds in the low-field 0.2T system. Data derived from the MRI scans regarding gadolinium uptake in the HA block were defined as fibrovascular incorporation or biologic incorporation.
tion by an experienced pathologist. This quantification is not absolutely precise and offers only estimated values.
Results
Integration of Hydroxyapatite Plain radiographs were not suitable for evaluation of osseous integration of HA (Fig. 3). Osseous integration was defined when fibrovascular ingrowth and osteoid layers and vessels with endothelium were detected in the biopsy specimens. Osteoid formation in histologic biopsy specimens quantified by evaluation of 10 different high-power fields in each sec-
Osseous Integration Osseous integration could not be sufficiently evaluated by plain radiographs in that the HA block was already hyperdense at the time of surgery (Fig. 3). Osseous union was defied when there was no radiographic evidence of cyst formation or osteolysis in the final follow-up radiographs within the area of the
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demonstrated by the deduction MRI technique (Fig. 4). These results indicated that fibrovascular or biologic incorporation had occurred with the implanted HA blocks in these cases.
Biocompatibility and Tolerance Osteosynthesis was performed using a plate in 8 cases (Fig. 2) and an external fixator in the remaining 6 (Fig. 3). Following elevation and fixation of the articular surface, the HA ceramic block was easily shaped and formed with a rongeur to fit the defect. No further fixation of the HA block was necessary. In the follow-up evaluations, which were up to 18 months in duration, there was no clinical evidence of intolerance of the HA ceramic. None of the 14 patients showed signs of infection, local erythema, nonunion, or any other complication related to the structural support of the HA block. Only 1 patient was concerned about having a foreign body implanted permanently. All the other patients accepted the implanted HA well because it avoided a second incision.
Histology
Figure 4. (Continued) (C) The patient’s hand and forearm were fixed in a splint during MRI acquisition to avoid artifacts due to motion. Corresponding scans of the T1weighted sequences before and after application of gadolinium were subtracted from each other. The resulting subtraction images exhibited homologous contrast enhancement as an indication of neovascularization.
HA ceramic as well as when the HA ceramic was coated by new cortical bone. In the long-term follow-up protocol, incorporation was investigated by MRI at 12 to 15 months after surgery when the plate was removed. Magnetic resonance imaging was nondiagnostic in only 1 case in which a broken screw caused extensive artifacts. Signal enhancement in MRI occurred in 13 of the 14 cases following gadolinium injection. Eighty percent to 90% of the HA block was uniformly enhanced after gadolinium injection. This could be especially
The specimens obtained from the 4 patients who consented to biopsy uniformly demonstrated apositional growth, endothelialized vessels, and intraluminal erythrocytes. Some collagen structures along with fat cells were also adherent within the HA ceramic block (Fig. 5). Approximately 70% of the surface of the ceramic was coated with thin osteoid layers 12 to 15 months after implantation of the HA block.
Discussion Autogenous bone grafts are harvested via a second surgical incision with an additional risk of donor site morbidity.5– 8,26,27 Several investigators have reported using HA ceramic successfully in experimental animal models whereby HA exhibited excellent biocompatibility, mechanical stability, and osseous integration to the bone defect.11,12,28 Graft elements of the HA cannot be resorbed or replaced by new bone formation. The advantage HA ceramic blocks has over cancellous bone is that a second surgical incision for procurement of cancellous bone can be avoided. Another advantage is the absence of transmitted infectious disease, such as the human immunodeficiency virus and hepatitis) due to the ultraheating process. The disadvantages include the requirement of a solid osteosynthesis and the fragil-
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Figure 5. Representative biopsy specimens obtained from the HA block at the time of removal of the ASIF plate (15 months after surgery). Within the HA ceramic, appositional growth of osteoid layers (O) and vessels with endothelium and intraluminal erythrocytes (V) were prominent at this time. Some collagen structures and fat cells within the HA ceramic block were adherent. (A) Patient 10. (Hematoxylin-eosin stain; magnification ⫻250.) (B) Patient 13. (Elastica van Giesson stain; magnification ⫻350.)
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ity to mechanical stress. Torsional force can actually break the HA block. Promising results are reported in the literature pertaining to middle ear reconstruction,18 the treatment of periodontal bone defects,15–17 the filling of small bone cysts,19,20 and reconstruction of defects in foot and ankle surgery.29 –31 One report explained the advantages of porous HA bone graft from coralline origin as substitutes in distal radius fracture, but assessment of osseous bone integration following surgery was only documented through plain radiographs.24 Porous HA should not be used as structural support in the presence of osteomyelitis or malignant bone disease, although there is no evident in the literature regarding contraindications for the application of HA from bovine origin. External fixators were removed 8 to 10 weeks after HA implantation. This was 2 weeks longer than suggested in most series without bone graft. This expected delay in healing time may be accounted for by the smaller surface of the vascularized bone. There were no other experiences available in the literature to base comparison or result. Because the HA ceramic is always hyperdense in plain radiographs only the bone healing in the margins around the HA ceramic block could be evaluated. This explains why time to healing and osseous integration could not be adequately measured or compared with osseous integration of autogenous bone graft. Magnetic resonance imaging sequences provided information surrounding the osseous integration of HA into the bone but could only be performed following removal of all magnetic materials. Hydroxyapatite ceramic is low on protons and appears as low signal-like-bone on MRIs. While gadolinium is transported by the vascular system, the increase in contrast in T1-weighted sequences within the HA block corresponds to a noteworthy fibrovascular ingrowth in all but 1 patient. This was also observed by other investigators.32–34 The results of the MRI sequences were consistent with the results of the 4 representative biopsy specimens at the time of removal of the plate. It would have been preferable to perform a biopsy in all the treated patients in this study, but biopsy specimens were obtained from only those patients receiving an osteosynthesis with a plate at the time of plate removal. Hydroxyapatite ceramic offers only passive structural support in well-vascularized locations and acts as a matrix for vessels, osteoblasts, and connective tissue. Osseous integration was also documented by histologic biopsy specimens showing osteoid layers
as well as vessels within the interconnective pore system in 4 cases 15 months after surgery. This information is consistent with reports involving histologic biopsy specimens taken from HA ceramic in human subjects.17,19 Hydroxyapatite ceramic provides an optional alternative in the correction of metaphysical bone defects following distal radial fracture. It was demonstrated that the bone not only healed around the graft material, but also incorporated the HA by fibrovascular ingrowth. Although not directly compared with autogenous bone grafts, bovine HA provides a biologically acceptable alternative that was well tolerated and incorporated into the host bone without adverse clinical effects. The authors thank Dr Clayton Peimer for carefully reading the manuscript.
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