Abstract | | | Background : Autogenous bone is regarded as the best bone graft material. Various grafting materials have been advocated to fill bony defects. Our purpose was to study the utility of amorphous hydroxyapatite as an autogenous bone graft substitute in cancellous and cortical bone. Methods : A prospective study was undertaken over a period of five years. Patients included were those which would otherwise require bone grafting in cancellous and cortical bone fractures (15 in each group). Hydroxyapatite (HA) ceramic blocks of standard size (5mm x10m) were either used alone or mixed with autogenous cancellous graft in metaphyseal locations, along with bone marrow (derived from reaming or drilling) in intertrochanteric regions and mixed with cancellous graft in cortical areas. The results were assessed on standard radiographs. Biopsy of hydroxyapatite regenerated bone was taken at implant removal. Results: In cancellous areas as graft incorporation ensues over months the intrinsic structure of the hydroxyapatite blocks blurred with blunting of the sharp edges (on radiographs). Biopsy confirmed bone in-growth. In cortical areas the blocks did not show evidence of bone in-growth. Conclusion: Hydroxyapatite alone or when mixed with cancellous bone marrow is an effective adjuvant for autogenous bone grafts, especially in cancellous areas of bone. Mixing it with host marrow provides osteoinductive stimulus. It is biocompatible, osteoconductive but not osteogenic. Keywords: Hydroxyapatite; Bone substitutes. How to cite this article: Agarwala S, Bhagwat A. Hydroxyapatite as a bone graft substitute: Use in cortical and cancellous bone. Indian J Orthop 2005;39:254-6 | Introduction | | |
Autogenous bone is regarded as the gold standard for bone graft materials as it provides the three elements necessary to generate and maintain bone: scaffolding for osteoconduction, growth factors for osteoinduction, and progenitor cells for osteogenesis [1] . Various alternate grafting materials have been advocated to fill bone defects or stimulate bone healing. These are generally grouped as naturally occurring or artificially bone substitutes. Hydroxyapatite is such a bone substitute, cheap and easily available. Autologous bone requires a secondary surgical harvest site, with its inherent morbidity [2],[3] . Freeze-dried bone undergoes significant resorption and remodeling, takes longer to heal, and has a higher infection rate [4] . Our purpose was to study the utility of amorphous hydroxyapatite as an autogenous bone graft substitute in cancellous and cortical bone and find these differences in behavior in vivo.
Material and Methods | | |
A prospective study was undertaken over a period of five years. Patients included were those which would otherwise require bone grafting in cancellous and cortical bone fractures. Fifteen patients in each group were selected. In every case hydroxyapatite ceramic blocks (Surgiwear, Gbone, Shahjahanpur, India) of standard size(5mm x10m) were either used alone or mixed with autogenous cancellous graft, or with bone marrow (derived from reaming or drilling) from the intertrochanteric regions and mixed with cancellous graft in cortical areas. Hydroxyapatite ceramic was used in the form of rectangular brickquettes with well defined margins which are clearly seen radiologically. Standard surgical techniques were employed for internal fixation of these fractures. Routine post operative surgical protocol was followed. A regular post operative follow up was done clinically and radiologically at 1, 3, 6, 12 and 18mths and 2 years.
The following factors were looked for:
- Healing of fracture site.
- Exoskeletal architecture of amorphous hydroxyapatite blocks which included margin definition.
- Radiolucent line around blocks and
- Number of surfaces in contact with the surrounding bone (which correlated with osteointegration).
We had an opportunity to remove the implants used for internal fixation in 11 patients, six in metaphyseal area and five in cortical bone. Biopsy from the bone regenerated hydroxyapatite ceramic area was taken in every case and sent for histopathological examination in normal saline.
Results | | |
Cancellous bone
A comparison of immediate post operative radiographs with films taken at the last follow up showed that the intrinsic structure of the graft used in cancellous area was gradually lost in association with poor marginal definition beginning from approximately six months from implantation. At 1 years there was blurring of the sharp margins of the hydroxyapatite blocks, no radiolucent line was seen surrounding the blocks (i.e. no sequestration), and all the surfaces seen were in contact with cancellous bone which was related with osteointegration. There was no alteration of fracture construct and fracture site had healed. Biopsies of sample showed bone ingrowth which appeared histologicaly similar and was present in all areas of the hydroxyapatite block sections. Within the biopsy sample the bone appeared trabecular and usually was in direct apposition to the trabeculae of hydroxyapatite ceramic. No evidence of chronic inflammation or fibrous encapsulation was seen [Figure - 1].
Cortical bone
Post operative radiographs showed no loss of structure. Pieces of hydroxyapatite continued to remain free within the soft tissue with no incorporation into the bone. Though some blurring of sharp edges of the brickquetts was seen it was not as significant as seen in the cancellous area. No bone ingrowth was seen on biopsy. At the end of two years hydroxyapatite blocks were still distinguishable though there was no additional increase in the rate of infection.
Discussion | | |
Ideal bone graft substitute should be cheap, easily available, easily fabricated, strong enough and should possess osteogenic, osteoinductive and osteoconductive properties [3] .
Bone graft substitutes can be broadly divided into [3],[5],[6],[7] :
- Substitutes which provide a scaffold for osteoconduction: osteoconductive agents.
- Substitutes which induce differentiation of stem cells: osteoinductive agents.
- Substitutes which provide stem cells (osteogenic): bone marrow aspirate.
- Various combinations of above agents.
Hydroxyapatite is a apatite of calcium phosphate, Ca10(PO4)6 (OH)2, a ceramic naturally found in vertebrate tooth and bone. The compound has a Ca/P mole ratio of 1.67, and is formed by precipitation of calcium nitrate and ammonium dihydrogen phosphate. Each pore is 100-140Um with constant interporous distance. Hydroxyapatite alone has been found to be insufficient for formation of bone in numerous studies[2],[4] . Hydroxyapatite has only osteoconductive properties[2],[4] . Mixing it with autologous bone marrow or graft would provide an osteoinductive stimulus [1],[2] .
Since the ceramic is brittle and has less tensile strength than bone we had decided to use standard internal fixation for all the fractures[1],[4].
All fractures in cancellous areas healed and had signs of union at approximately three months. The hydroxyapatite blocks had blurred outline at 2 years but there was no lucent line surrounding them suggesting incorporation into the surrounding bone. It has been shown that hydroxyapatite is essentially non-degradable, with resorption rates of only 5% to 15% per year [1] . In cortical areas, in our series, hydroxyapatite blocks showed no incorporation or bone growth inside them. At implant removal the hydroxyapatite blocks did not show any incorporation or bone growth on histopathology.
Biopsies of hydroxyapatite regenerated bone in cancellous area in 6 cases at implant removal 2 years after surgery showed bone ingrowth in all the sections and specimens.
With autogenous bone grafts, the normal healing process includes the initial revascularization and resorption of osteons [3] .The interstitial bone remains and serves as a stromal frame work for the formation of new bone. The residual bony matrix contains pores large enough to permit tissue ingrowth. Because of its special porous nature, hydroxyapatite ceramic is osteoconductive and allows intimate bone growth. The pore size of hydroxyapatite is not only similar to normal osteon bone size (190U) but also conforms to research that confirms a minimum pore size of 100U, preferably 150 to 200U for bone ingrowth [1],[3],[4] .
The ceramic materials are sufficiently adaptable to lend themselves to the management of the defect pattern encountered in the individual patient. The blocks can be readily inserted into a metaphyseal defect. Contouring can be achieved with a rongeur or scalpe [8] . As compared to other bone graft substitutes synthetic hydroxyapatite ceramic is the cheapest.
Hydroxyapatite is an effective adjuvant for autogenous bone grafts for use in fractures when good primary mechanical stability and contact with host bone are present, especially in cancellous areas of bone and not in cortical bone. It supplements cancellous grafts when required in large amounts. It is osteoconductive but not osteogenic. Mixing it with host marrow provides osteoinductive stimulus. For fracture healing it has to have support from ideal internal fixation techniques. It is biocompatible, avoids graft site morbidity and is cost effective.
Acknowledgement : To Dr Ramesh Deshpande, Dept of Histopathology for help with biopsy material. References | | | 1. | Vaccaro AR. The role of the osteoconductive scaffold in synthetic bone graft. Orthopedics. 2002 supplement. | 2. | Johnson KD, Frierson KE, Keller TS, Cook C, Scheinberg R, Zerwekh J, Meyers L, Sciadini MF. Porous ceramics as bone graft substitutes in long bone defects: a biomechanical, histological, and radiographic analysis. J Orthop Res. 1996; 14:351-69. | 3. | Parikh SN. Bone graft substitutes: past, present, future. J Postgrad Med. 2002;48:142-8. | 4. | Wolford LM, Frietas RZ. Porous block hydroxyapatite as a bone graft substitute in the correction of jaw and craniofacial deformities. BUMC proceedings. 1999;12:243-246. | 5. | Gouin F, Delecrin J, Passuti N, Touchais S, Poirier P, Bainvel JV. Filling of bone defects using biphasic macroporous calcium phosphate ceramic. Aprops of 23 cases. Rev chir Orthop reparatrice appar mot.1995; 81; 59-65. | 6. | Bucholz RW, Carlton A, Holmes R. Interporous hydroxyapatite as a bone graft substitute in tibial plateau fractures. Clin Orthop.1989; 240:5362. | 7. | Holmes RE, Bucholz RW, Mooney V. Porous hydroxyapatite as a bone- graft substitute in metaphyseal defects. A histometric study. J Bone Joint Surg (Am). 1986; 68: 904-911. | 8. | Doursounian L, Cazeau C, Rene-Claude T. Use of tricalcium phosphate ceramics in tibial plateau fracture repair. Departnent of Surgery, Hotel-Dieu University hospital, Place du Parvis Notre-Dame,F-75004 Paris, France. | Correspondence Address: Abhijit Bhagwat Department of Orthopaedics, PD Hinduja Hospital & Research Center, Mumbai India
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