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| Year : 2014 | Volume
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| Issue : 5 | Page : 594-601 |
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| Comparative evaluation of bovine derived hydroxyapatite and synthetic hydroxyapatite graft in bone regeneration of human maxillary cystic defects: A clinico-radiological study |
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Vivekanand S Kattimani, Srinivas P Chakravarthi, K Naga Neelima Devi, Meka S Sridhar, L Krishna Prasad
Department of Oral and Maxillofacial Surgery, SIBAR Institute of Dental Sciences, Guntur, Andhra Pradesh, India
Click here for correspondence address and email
| Date of Submission | 06-Jan-2014 |
| Date of Decision | 28-Mar-2014 |
| Date of Acceptance | 06-Jun-2014 |
| Date of Web Publication | 16-Dec-2014 |
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 Abstract | | |
Introduction: Bone grafts are frequently used in the treatment of bone defects. Bone harvesting can cause postoperative complications and sometimes does not provide a sufficient quantity of bone. Therefore, synthetic biomaterials have been investigated as an alternative to autogenous bone grafts.
Aim and Objectives: The aim of this study was to evaluate and compare bovine derived hydroxyapatite (BHA) and synthetic hydroxyapatite (SHA) graft material as bone graft substitute in maxillary cystic bony defects. Patients were analyzed by computerized densitometric study and digital radiography.
Materials and Methods: In this study, 12 patients in each group were included randomly after clinical and radiological evaluation. The integration of hydroxyapatite was assessed with mean bone density, surgical site margin, and radiological bone formation characteristics, of the successful graft cases using computer densitometry and radio-visiograph. Statistical analysis was carried out using Mann-Whitney U-test, Wilcoxon matched pairs test and paired t-test.
Results: By the end of 24 th week, the grafted defects radiologically and statistically showed similar volumes of bone formation. However, the significant changes observed in the formation of bone and merging of material and surgical site margin at 1 st week to 1 st month. The results were significant and correlating with all the parameters showing the necessity of the grafting for early bone formation. However, the bone formation pattern is different in both BHA and SHA group at 3 rd month interval with significant P value.
Conclusion: Both BHA and SHA graft materials are biocompatible for filling bone defects, showing less resorption and enhanced bone formation with similar efficacy. Our study showed maximum bone healing within 12 weeks of grafting of defects. The BHA is economical; however, price difference between the two is very nominal. Keywords: bone graft, bone regeneration, bovine derived hydroxyapatite, densitometry, dental radio-visiography, observer strategy for bone healing, synthetic hydroxyapatite
How to cite this article:
Kattimani VS, Chakravarthi SP, Neelima Devi K N, Sridhar MS, Prasad L K. Comparative evaluation of bovine derived hydroxyapatite and synthetic hydroxyapatite graft in bone regeneration of human maxillary cystic defects: A clinico-radiological study. Indian J Dent Res 2014;25:594-601 |
How to cite this URL:
Kattimani VS, Chakravarthi SP, Neelima Devi K N, Sridhar MS, Prasad L K. Comparative evaluation of bovine derived hydroxyapatite and synthetic hydroxyapatite graft in bone regeneration of human maxillary cystic defects: A clinico-radiological study. Indian J Dent Res [serial online] 2014 [cited 2023 Mar 30];25:594-601. Available from: https://www.ijdr.in/text.asp?2014/25/5/594/147100 |
Bone grafts are frequently used in the treatment of bone defects. [1],[2] Bone harvesting can cause postoperative complications and sometimes does not provide a sufficient quantity of bone. [2] Therefore, synthetic biomaterials have been investigated as an alternative to autogenous bone grafts.
Synthetic and bovine derived hydroxyapatite (BHA) grafts are commonly used in oral, maxillofacial, and orthopedic surgery for various indications, such as the filling of bone cavities, augmentation for dental implants, and reconstruction of the bone lost during tumor removal or trauma. [1],[2],[3] In particular, these form a quick bond with bone through a hydroxyapatite (HA) layer. [4] Fortunately, this bioactive HA layer can be formed on the bioactive graft surface even in acellular simulated body fluid with ion concentrations nearly equal to those of human blood plasma. Formation of the HA layer has been reported to be fastest for graft materials with the highest level of bioactivity. [4],[5],[6] A recent study by El-Ghannam et al. indicated that the greater bioactive effect of the HA ceramic was the result of the ability of the Hydroxycarbonate apatite layer to concentrate active fibronectin on its surface. [7]
In this study, bone regeneration and graft material resorption were compared in bony defects filled with BHA and synthetic hydroxyapatite (SHA). In addition, the effect of grafting on bone regeneration in human cystic bone defects was evaluated using computer densitometry and direct digital radiographic image technique.
| Materials and methods | |  |
Hydroxyapatite is apatite calcium phosphate (Ca 10 (PO 4 ) 6 (OH) 2 ). HA is being used in many disciplines of surgery. [2],[3],[4],[5] HA can be obtained for clinical use in block form or granules, in porous or dense form. Both BHA and SHA are commercially available in the market. These does not cause any foreign body reaction since it is an inorganic substance/ceramic. Hard tissue grows into the graft since it is porous and mingles with natural tissues. [2],[3],[4],[5],[6],[7],[8],[9]
Bovine derived hydroxyapatite
Derived from natural sources that is, bovine origin, it refills the gap in bone and aids in augmentation of bony structures.
Synthetic hydroxyapatite
The synthetic granules are obtained from synthetic calcium HA in low crystalline form. It is a mixture of HA, tri-calcium phosphate and other forms of calcium such as calcium carbonate and calcium phosphate. This polycrystalline structure is responsible for the strength of the substance.
Clinical study
The study was conducted in the Department of Oral and Maxillofacial Surgery in our institute. A total of 24 patients aged between l5 and 45 years [Table 1] and [Table 2] with periapical cyst/residual cyst of anterior maxilla, which required cystectomy were enrolled to reconstruct jaw bone defects after cystectomy and/or apicoectomy. The cyst sizes were ranged from 2 to 6 cm in diameter. Patients were divided randomly into two groups with 12 in each group. In Group-1, patients the cystic defects were filled with BHA, whereas in Group-2 patients filled with SHA. All the patients were followed for 1 st week, 1 st month, 3 rd month and 6 th month intervals postoperatively. | Table 1: Distribution of study subjects according to study groups and gender
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Inclusion and exclusion criteria for patient selection
- Patients with moderate sized periapical cystic lesion of anterior maxilla involving one or more teeth confirmed by clinical and radiological evaluation were included in the study
- All cases were meticulously screened through routine blood and urine examination to rule out any systemic diseases such as diabetes, hypertension etc., and medically compromised patients were exempted from the study to eliminate bias
- Patients with gross mobility of involved teeth due to moderate bone loss were not included in the study
- Patients with frankly infected cysts were excluded in the study
- Patients who are readily available for periodic recalls and reviews were included.
Operative procedures
An infraorbital nerve block and an incisive canal nerve block were induced by 2% lignocaine with adrenaline. After securing anesthesia, a mucoperiosteal flap was created and reflected under completely aseptic conditions. The underlying bone was removed and the apical lesion was curetted. The surgical site was irrigated with sterile saline and bleeding if present, was arrested by application of a gauze pack. In Groups 1 and 2 the graft material was packed inside the bony defect, with no over contouring. Care was taken to ensure that no graft particles were placed outside the cavity under the mucoperiosteal flap. The flap was repositioned and sutured. Gentle pressure with a sterile gauze pack was applied postoperatively to the surgical flap to facilitate reattachment of the flap to the underlying bone. In all cases, postoperative antibiotics and an antiinflammatory agent were prescribed.
Clinical evaluation
Follow-up examinations were conducted 1 st day, 7 th day (at the time of suture removal), and 4, 12, and 24 weeks postsurgery. Mucosal color and any postoperative pain or swellings were noted during clinical evaluations.
Intraoral digital radiographic imaging
At 1 st , 4 th , 12 th , and 24 th week postsurgery, the mean density of the image of the surgical defect was measured using a Digora unit. The mean density values and standard deviations were calculated using Quatro Pro software (Corel Corporation, Ottawa, Ontario, Canada).
Radiological examination carried out postoperatively by taking standard intra-oral periapical radio-visiograph, immediate postoperatively and at each follow-up visit to determine graft consolidation, graft resorption and new bone formation with radiographic parameters as:
• Density of bone formation
• Surgical site margin
• Bone formation characteristics.
Both oral and maxillofacial surgeon and radiologist evaluated the radiological healing of bone. To avoid observer bias both examiners were blinded.
Postsurgical radiographic pattern of the surgical margins evaluated as
• Unchanged - when the original radioopaque margin of the lesion was unaltered. Seen immediately in postoperative radiograph
• Slightly changed - when the clarity and width of original margin were reduced that is, <1/4 th of the circumference of the lesion
• Partly reduced - when the clarity of the original margin had partially disappeared or was partly displaced inward toward the center of the surgical area
• Entirely absent - when the entire margin of the lesion was completely absent, indicating the merging of material margin and bony margin.
Postsurgical radiographic appearance of the internal portion of surgical site (bone formation) evaluated as
• Changed - as the graft material placed in the surgical site that changes the internal portion. This immediate postoperative radiograph taken as standard for further bone formation characteristics
• Ground glass - increase in radioopacity as noted with immediate grafting
• Spicular - when bone spicules are visible from periphery to center of the surgical site
• Trabecular - when radiating trabecule enclosing marrow spaces were observed uniformly.
Statistical analysis
Statistical comparison was made using Mann-Whitney U-test, Wilcoxon matched pairs test and paired t-test. The mean values and standard deviations of each parameter were calculated. The differences between means were evaluated using the Student's t-test; P < 0.05 was considered as significant. The kappa (κ) correlation taken in to consideration to assess the degree of observer agreement for radiological assessment.
| Results | | |
0Clinical observation
First day postsurgery clinical examination showed similar edema among patients in both groups. The overlying mucosa had the same reddish color in all patients. At the time of suture removal, the mucosa of all patients had regained normal color and contour. Moreover, no flap dehiscence was observed. Except in one patient having >5 cm cystic defect and sinus tract in the flap in Group-2 required regular irrigation because of particle migration through existing sinus tract, which healed 2 weeks postoperatively with gingival dressing.
Digital radiographic observations
Surgical site out line [Figure 1]a and b evaluation at 3 rd month intervals in BHA is 156 and SHA 144, with P = 0.72 indicating both materials have similar margin blend with material margin, whereas similar results seen at 6 th month intervals also [Figure 2]. But, the sum of ranks of BHA is 113 and SHA is 187 at 3 rd month interval with significant P = 0.032 indicating bone formation pattern [Figure 3]a and b is different in both [Table 3]. | Table 3: Comparison of groups (BHA and SHA) with radiological evaluation of bone formation at 1st week, 1st month, 3rd month and 6th months by Mann-Whitney U-test
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 | Figure 1: (a) Schematic diagram showing radiological evaluation of surgical site outline (b) Intraoral periapiacal radiographs showing radiological evaluation of surgical site outline
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The mean radiographic density of grafted cystic bone defects were continued to increase until it reached its maximum at week 24 [Figure 4] and [Table 4]. The mean density of BHA and SHA group at 3 rd month interval and at 6 months interval is statistically not significant suggesting both achieved similar density. Other characteristics like bone formation and blending of bone margin and material margin were well correlated with density of bone formation. The kappa correlation of observations of bone healing parameters by examiners was in very good agreement with each other (with κ - 0.81-0.92). | Table 4: Comparison of groups (BHA and SHA) with mean bone density at 1st week, 1st month, 3rd month and 6th month by t-test
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 | Figure 2: Comparison of bovine derived hydroxyapatite and synthetic hydroxyapatite groups with radiological evaluation surgical site outline at 1st week, 1st month, 3rd month and 6th month
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 | Figure 3: (a) Schematic diagram showing radiological evaluation of bone formation characteristics. (b) Intraoral periapiacal radiographs showing radiological evaluation of bone formation characteristics
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 | Figure 4: Comparison of groups (bovine derived hydroxyapatite and synthetic hydroxyapatite) with mean bone density at 1st week, 1st month, 3rd month and 6th month
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| Discussion | | |
Hydroxyapatite is an osteoconductive material that is, it acts as a scaffold for bony ingrowth and gradually replaced by new bone. [1],[2],[3],[4],[5] HA is unique biocompatible ceramic substance that is beginning to find its rightful place as a useful and versatile biomaterial. This study showed that the biologic regeneration can be improved by grafting without any undue complications. Implantation promoted bone tissue regeneration and graft material resorption in bone defects of maxillary cystic cavities.
Density is the degree of darkening of exposed and processed X-ray film, expressed as the logarithm of the opacity of a given area of the film. Radio-visiography has a program to measure bone density. [10],[11],[12] In the present study, measurements of density of the grafted cystic cavities suggested that bone deposition continued to dominate inside the defect up to 24 weeks postsurgery. The mean density of BHA and SHA group at 3 rd month interval and at 6 months interval is statistically not significant suggesting both achieved similar density, which shows both are equally efficient in bone formation.
Surgical site out line [12],[13] is surgical margin after cystic enucleation. In the present study surgical site out line evaluation at 3 rd and 6 th month intervals with insignificant P value indicating both materials have similar margin blend with material margin. This indicates both materials are showing equal efficacy in surgical site margin blending with material margin.
The rapid bone regeneration associated with graft could be explained by the ability of the HA to enhance the selective adsorption of attachment proteins and growth factors which stimulate osteoblast adhesion and bone deposition. [7] Another mechanism by which the graft could enhance bone formation is through ion release, as supported by the work of Matsuoka and associates. [14] Results of the present study was associated with a significantly greater rate of bone regeneration both in BHA and SHA implantation sites.
The radiological evaluation of bone formation [12],[13],[14],[15] after grafting in cystic defects is the initiation of bone formation marked by radioopacity and pattern of bone formation. In our study sum of ranks of BHA is 113 and SHA is 187 at 3 rd month interval with significant P = 0.032 indicating bone formation pattern is different in both. This may be attributed to the material properties like early or late resorption of graft particles. However, at 6 th month interval it remains the same. Which indicates the pattern of bone formation is similar in both materials.
The grafting showed superior results over the traditional ungrafting, by accelerating bone tissue regeneration in cystic bone defects. [16],[17] The change in density measurements inside the cystic bone defects correlates well with bone regeneration and graft material resorption observed in vivo. [18],[19] . After 12 weeks, the density continued to increase until week 24, indicating new bone tissue formation. This healing phase is similar to the so-called "trabecular pattern," which occurs after 6 months with partial filling of the defect with bone. [20]
Use of HA in combination with platelet rich plasma, autogeneous bone, recombinant human bone morphogenic protein-2 (rhBMP-2) showed good results in bone formation. [21] The HA acts as a scaffold for bony ingrowth, even showed osteoinductive activity. [22],[23] But HA alone cannot be used in load bearing area for reconstruction. [21] It can be used with collagen matrix to have good strength. Recent advances in bone regeneration includes BMP, transforming growth factor-β, platelet derived growth factor, amino acids chain peptides-P-15 and OSA-117MV, stem cells. [21] While many of these particular concepts were regarded a visionary a few years ago, they have now reached clinical reality, in planned phased clinical trials. [24],[25],[26],[27],[28],[29] The reconstruction of atrophic alveolar ridges with allogenic bone graft, distraction and exotic autogenous bone graft for crater defects also showed good results. [30],[31],[32] Recently, demineralized bone matrix (DBM) incorporated into various carriers such as collagen or selected polymers for bone regeneration [33],[34],[35] The major disadvantage of this technique is the cost of the DBM material. [33],[34],[35]
Hydroxyapatite is a ceramic. HA can be divided into two groups depending upon its ability to resorb. [36],[37],[38],[39] Some refer to the internal pore size as a means of differentiating between various types of HA. [40],[41],[42] The porous form of HA allows rapid fibrovascular tissue ingrowth, which may stabilize the graft and help resist micromotion. [43],[44] HA can be machined to many shapes or consistencies. [45],[46],[47] HA has several potential clinical applications including the filling of bony defects, the retention of the alveolar ridge form following tooth extraction and as a bone expander when combined with autogenous bone during ridge augmentation and sinus grafting procedures. [48],[49],[50],[51],[52] One important advantage related to all xenogenic and allogenic materials is that they could potentially be used as bone graft expanders by mixing them with autogenous bone chips. This mixing could decrease the volume of autogenous bone graft needed, which in turn could convert an extra-oral harvesting procedure to an intra-oral harvesting procedure potentially reducing donor site morbidity. [53],[54] HA have been used to deliver BMP including other noncollagenous proteins, DBM, collagen, polylactic acid and or polyglycolic acid combinations, calcium carbonate, calcium sulphates and fibrin glue. [55],[56],[57],[58],[59],[60],[61],[62]
Many products are being marketed today as bone grafts. Several of these products capitalize on the necessities of an ideal substitute. As more materials are adapted and discovered, preexisting products are finding new applications and effectiveness in combination with newly emerging technology. In addition, further research is going on to use it in combination with collagen and others for bone repair. The very favorable results of our study warrant further multi-centric investigations as the study is limited to smaller sample size and moderate defects using only two types of materials.
| Conclusion | | |
Hydroxyapatite is a versatile biocompatible graft substitute that does not cause any chronic inflammatory, allergic, or toxic reaction. It has been primarily used as ceramic formulation. The ideal graft material for reconstruction of bone defects should allow host bone formation in a relatively short span of time. HA provides a means of achieving this goal. Results of both densitometric and radiographic studies suggested that the use of HA graft material has the potential to accelerate bone formation. Both materials are equally efficient in bone regeneration.
| Acknowledgement | | |
The study is registered in Clinical Trail Registry-India with registration no- CTRI/2014/05/004578.
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Correspondence Address:
Vivekanand S Kattimani
Department of Oral and Maxillofacial Surgery, SIBAR Institute of Dental Sciences, Guntur, Andhra Pradesh
India
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/0970-9290.147100
[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2], [Table 3], [Table 4] |
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