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Table of Contents   
ORIGINAL RESEARCH  
Year : 2010  |  Volume : 21  |  Issue : 4  |  Page : 557-563
Comparison of the regenerative potential of an allograft used alone and that in conjunction with an immunosuppressive drug in the treatment of human periodontal infrabony defects: A clinical and radiological study


1 Department of Periodontology, National Dental College and Hospital, Derabassi, India
2 Department of Conservative Dentistry and Endodontics, National Dental College and Hospital, Derabassi, India
3 Department of Periodontology, Surendera Dental College, Shri Ganganager, Rajasthan, India
4 Department of Periodontology, Seema Dental College, Rishikesh, India

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Date of Submission16-Jan-2009
Date of Decision03-Oct-2009
Date of Acceptance23-Jan-2010
Date of Web Publication24-Dec-2010
 

   Abstract 

Background: Experimentation confirmed the conclusion that bone allografts, like other tissue and organ allografts, are immunogenic. These immune responses cause resorption of allograft, thus lowering the bone formation capacity of the graft. An attempt has been made in this study to prevent immune reactions and achieve enhanced regeneration of allograft-demineralized freeze-dried bone matrix by incorporating it with an immunosuppressive drug Cyclosporine-A (CsA) in the treatment of human periodontal infrabony defects.
Materials and Methods: Fifteen patients showing clinical evidence of almost bilateral infrabony defects requiring bone grafting procedures were selected. In each patient, the infrabony defect of one side of the arch was designated as Group A (control site) and the infrabony defect of the contralateral side of the same arch was designated as Group B (test site).
Results: On comparative evaluation of the two groups (by Student t-test), the mean values of reduction in probing depth (P=0.81 NS ) and gain in clinical attachment level (P=1.00 NS ) of Group B were found to be greater than that of Group-A, but the differences were statistically non-significant. The mean linear bone fill (P=0.010 ** ) of Group B was also detected to be higher than that of Group A, and the difference was found to be statistically significant.
Conclusion: Increase in linear bone fill in Group B signifies the role of CsA in augmenting the regenerative potential of allograft by eliminating immune reactions.

Keywords: Allografts, immune reactions, immunosuppression, regeneration

How to cite this article:
Dhawan S, Dhawan R, Gill AS, Sikri P. Comparison of the regenerative potential of an allograft used alone and that in conjunction with an immunosuppressive drug in the treatment of human periodontal infrabony defects: A clinical and radiological study. Indian J Dent Res 2010;21:557-63

How to cite this URL:
Dhawan S, Dhawan R, Gill AS, Sikri P. Comparison of the regenerative potential of an allograft used alone and that in conjunction with an immunosuppressive drug in the treatment of human periodontal infrabony defects: A clinical and radiological study. Indian J Dent Res [serial online] 2010 [cited 2020 Jan 25];21:557-63. Available from: http://www.ijdr.in/text.asp?2010/21/4/557/74220
The ultimate aim of periodontal therapy is regeneration. Historically, bone grafts have been utilized to achieve regeneration. The use of allogenic human bone allografts overcome the problems associated with autografts [1] as these are usually derived from bone harvested at autopsy [2] and from amputation.

Among allografts, the most commonly used bone graft is demineralized freeze-dried bone matrix (DFDBM) and is known to stimulate bone formation through osteoinduction. [2],[3] Demineralization of bone exposes the bone morphogenetic proteins (BMP) located in the bone matrix and, in fact, may activate them. These BMPs incite new bone formation during the healing process [4] by irreversibly inducing differentiation of perivascular mesenchymal type cells into osteoprogenitor cells. [3] DFDBM induces bone formation in non-orthotopic sites such as muscles and connective tissues [5] around implants, [6] in localized alveolar ridge augmentation procedures, in sinus elevation, etc. DFDBM-implanted periodontal defects usually result in decreased probing depth and a gain in the clinical attachment level and show a potential to promote regeneration of the periodontal attachment apparatus. [7],[8],[9],[10]

However, tissue inflammation and foreign body reactions after DFDBM transplantation have been reported, which reduce the bone formation capacity. [11] The inflammation has been found to be suppressed with enhanced endochondral bone formation when bone substitutes are implanted in immunosuppressed animals. [11],[12]

The immunosuppressant, Cyclosporine-A (CsA), has been used to prevent the organ transplant rejection through its suppressive action on specific T-cell populations. [13] Augmenting these results is the morphometric finding in a study on rats that suggested an increased quantity of bone formation induced by DFDBM with CsA administration. [14],[15]

Taking a clue from the above observations, it may appear logical that if CsA is incorporated into DFDBM, it may ward off any possible immune reaction to the graft and produce better results. A very small dose in the form of local drug delivery could be used to minimize any possible side-effect of CsA. Thus, the aim of this study is to evaluate the relative efficacy of allograft (DFDBM) used alone and that in conjunction with an immunosuppressive drug (CsA) in the treatment of human periodontal infrabony defects.


   Materials and Methods Top


Study population

A controlled, single-blind study was designed with 15 patients (10 males and five females) in the age group of 30-50 years. Patients older than 50 years were not included in this study due to the reported decreased regenerative potential in these patients. [4] The patients were selected from among those reporting at the Department of Periodontology, Government Dental College, Amritsar. The patients selected were suffering from chronic generalized periodontitis (based on criteria established by AAP,1999), [16] having at least two or more bilateral two-walled or three-walled infrabony defects, with a pocket depth ≥7 mm and radiographic evidence of infrabony (vertical) defects. The exclusion criteria for selection of the patients were as follows:

  • Smokers and alcoholic patients
  • Patients with any clinical signs and symptoms of trauma from occlusion
  • Patients suffering from any systemic disease
  • Patients with a known history of allergy
Before surgery, all these patients received supragingival scaling and oral hygiene instructions. Patients were reviewed after a period of 2 weeks and were evaluated for optimal oral hygiene. For each patient, two interproximal sites, one in each quadrant of the same arch were selected based on periodontal pocket, measuring about 5-7 mm and with a radiographic evidence of infrabony (vertical) defects. Sites were selected by the simple random sampling technique and assigned as control site (Group A) and test site (Group B). In each patient, the infrabony defect of one side of the arch was designated as Group A and the infrabony defect of the contralateral side of the same arch was designated as Group B. Group A was treated by the placement of DFDBM alone and Group B was treated by the placement of DFDBM and then loading it with CsA. Patients were subjected to occlusal equilibration if required and routine laboratory investigations were performed.

Parameters

Clinical parameters assessed were probing depth and attachment level (to ascertain the clinical attachment loss). The clinical measurements were obtained by one examiner using the Goldman-Fox/Williams color-coded probe. Pre-fabricated acrylic occlusal stents were fabricated so that measurement made post-surgically could be at the same position and angulation as that made pre-surgically. The stents were stored on the cast to minimize distortion.

Radiographic assessment was made to measure the amount of linear bonefill using intraoral periapical films (size 32 mm×41 mm) (E speed plus). Radiographically, the infrabony defect depth was ascertained using a standardized radiographic technique and by measuring from a fixed reference point (the adjacent cuspal tip) to the most apical point of the base of the defect. A grid was used as an adjunct to the X-ray film to ensure accuracy in the measurements.

Materials

DFDBM used in this study was prepared from the bones obtained from the Department of Orthopaedics, Government Medical College, Amritsar. The DFDBM used in this study is prepared from the cortical bones as they contain more BMPs than the cancellous bone. [10]

CsA used in this study is Cyclosporine-A (Panimun-Bioral® ) 100 mg capsules. The patient's body weight was recorded and CsA as per dosage of 2 mg/kg body weight was packed in a pre-weighed ampule a day before surgery. This specific amount of drug was to be loaded on the DFDBM after its placement in the infrabony defect.

Surgical procedure

This study has been conducted in accordance with the principles laid down by the Declaration of Helsinki. [17] After an explanation of the proposed study criteria, including treatments and the potential risks and benefits, the participants were asked to sign consent form prior to the periodontal surgery. The study was conducted after receiving clearance from the ethical clearance committee of the institute. Each patient was pre-medicated using 10 mg diazepam and 0.3 mg glycopyrrolate intramuscularly 45 min before the surgical procedure.

The area to undergo surgery was anesthetized with lignocaine hydrochloride 2% with adrenaline 1:200,000. Envelop flaps were reflected and the operated area was debrided so that the interproximal defects (infrabony defects) are clear and prepared prior to the placement of graft either alone or in combination with CsA. Flaps were repositioned and approximated with interrupted interdental sutures using 3-0 black braided silk.

Antibiotic therapy (amoxicillin 250 mg + cloxacillin 250 mg + lactobacillus 60 million spores) for 5 days along with an anti-inflammatory agent for 3 days was prescribed post-operatively. The patients were asked to follow dietary instructions strictly and perform adequate plaque control by rinsing with 10 ml of 0.2 chlorhexidine gluconate twice daily for 2 weeks post-operatively. Sutures were removed 1 week after surgery


   Results Top


All subjects tolerated the surgical procedures well, experienced no post-operative complications, complied with the study protocol and completed the 24-weeks follow-up. The post-operative assessments for the parameters were performed at 12 weeks and at 24 weeks. The observations recorded were subjected to statistical analysis. No difference in results was found between male and female patients. Similarly, with regard to age, periodontal regenerative potential was found to be samilar in all patients (30-50 years).

The mean values of probing depth [Table 1], clinical attachment level [Table 2] and infrabony defect depth [Table 3] at three points in time were evaluated. The efficacy of the two treatment modalities at 12 and 24 weeks post-operatively were evaluated using the paired Student's t-test because the observations at the two points in time were expected to be closely related to each other. The two Groups A (DFDBM) and B (DFDBM with CsA) were then comparatively evaluated over the three time intervals using the independent Student's t-test.
Table 1: Probing depth using demineralized freeze-dried bone matrix alone (Group A) and demineralized freeze-dried bone matrix loaded with cyclosporine-A (Group B) (in mm)

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Table 2: Clinical attachment loss using demineralized freeze-dried bone matrix alone (Group A) and demineralized freeze-dried bone matrix loaded with cyclosporine-A (Group B) (in mm)

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Table 3: Infrabony defect depth (ascertained radiographically) using demineralized freeze-dried bone matrix alone (Group A) and demineralized freeze-dried bone matrix loaded with cyclosporine-A (Group B) (in mm)

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On analyzing the clinical criteria of reduction in probing depth of the two groups, it was seen that there had been a significant reduction in probing depth with DFDBM loaded with CsA at all the three points in time. DFDBM used alone provided a significant reduction in probing depth at 12 weeks and 24 weeks post-operatively, and non-significant reduction in probing depth between 12 and 24 weeks post-operatively [Table 4].
Table 4: Reduction in probing depth of Group A (demineralized freeze-dried bone matrix alone) and Group B (demineralized freeze-dried bone matrix loaded with cyclosporine-A) (in mm)

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Regarding gain in attachment level, DFDBM loaded with CsA provided significant gain in attachment level at 12 weeks and 24 weeks post-operatively, but non-significant gain in attachment level between 12 and 24 weeks post-operatively. With DFDBM used alone, there had been a significant gain in the attachment level at all the three points of time [Table 5].
Table 5: Gain in attachment level of Group A (demineralized freeze-dried bone matrix alone) and Group B (demineralized freeze-dried bone matrix loaded with cyclosporine-A) (in mm)

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The linear bonefill level for both the groups was statistically significant at all the three points of time [Table 6].
Table 6: Linear bonefill (ascertained radiographically) of Group A (demineralized freeze-dried bone matrix alone) and Group B (demineralized freeze-dried bone matrix loaded with cyclosporine-A) (in mm)

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On comparative evaluation between the two groups, results indicated that DFDBM loaded with CsA exhibited greater reduction in the probing depth (P=0.81) [Table 7] and mean a gain in the clinical attachment level (P=1.00) [Table 8] than DFDBM used alone over the entire span of the study, although the difference was found to be statistically non-significant.
Table 7: Comparative reduction in probing depth between Group A (demineralized freeze-dried bone matrix alone) and Group B (demineralized freeze-dried bone matrix loaded with cyclosporine-A) for the chosen parameters in mm

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Table 8: Comparative gain in clinical attachment level between Group A (demineralized freeze-dried bone matrix alone) and Group B (demineralized freeze-dried bone matrix loaded with cyclosporine-A) for the chosen parameters in mm

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DFDBM loaded with CsA provided greater linear bonefill than DFDBM used alone over the entire span of the study, with statistically significant linear bonefill between 12 weeks post-operative to 24 weeks post-operative than DFDBM used alone (P=0.01) [Table 9].
Table 9: Comparative linear bonefill (ascertained radiographically) between Group A (demineralized freeze-dried bone matrix alone) and Group B (demineralized freeze-dried bone matrix loaded with cyclosporine-A) for the chosen parameters in mm

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   Discussion Top


Recent thrust is to regenerate the lost attachment apparatus, which is one of the primary goals for the treatment of periodontitis.

Bone grafting is the most common form of regenerative therapy.

Autogenous grafts are considered to be the gold standard among grafts as they contain live osteoblasts and stimulate bone formation by osteogenesis. However, the need for a second operative site, resultant patient's morbidity lead to the development of allografts and xenografts as alternative graft materials.

Among allografts, DFDBM is the most widely used allograft in periodontics today because of safety, ease of use and purported osteoinductive and osteoconductive properties. [2] Histologic evaluation reveals a new attachment apparatus in humans by DFDBM. [18],[19] DFDBM used in this study is prepared from cortical bones as it retain less antigenicity than cancellous bone after deep freezing. [20]

Studies have clearly demonstrated that new bone formation in allografts is curtailed due to immunological reactions. [11],[21],[22] It is necessary to quantitate bone biology to understand the important antigens in graft and, most importantly, to understand the direct relationships between bone remodelling and the immune system (immunocompetent cells and their products). The immune system is complex and is capable of development of activated cells (such as helper T-cells, cytotoxic T-cells and plasma cells) as well as cell products (immunoglobulins and cytokines, including interleukin [IL-1] and tumor necrosis factor [TNF-α], granulocyte-macrophage colony-stimulating factor (GM-CSF) and other ILs). Products of immunocompetent cells play a major role in modulating, if not controlling, bone remodelling.

In allografts, cell surface antigens (Class-I and Class-II) controlled by the major histocompatibility complex (MHC) are considered to be the primary source of bone graft immunogenicity. Both Class-I and Class-II antigens of cells in an allograft are the major alloantigens that are recognized by host CD4+ helper T-cells and CD8+ cytotoxic T-cells, respectively. [21],[23] These T-cells activate macrophages. [21],[22] T-cells and macrophages further result in release of a cascade of cytokines, as shown in [Figure 1], [24] causing destruction of graft antigens. Cytokines such as IL-1 and TNF-α are direct activators of osteoclast, causing bone resorption. IL-2 activates cytotoxic T-cells and B-lymphocytes, which produce antigraft antibodies. IFN-γ causes upregulation of MHC antigen expression on the graft and thus provokes accelerated rejection response. More specifically, the greater the incompatibility, the less new bone formation by graft [Figure 1].
Figure 1: Mechanism of graft rejection and inhibitory action of cyclosporine

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Histologically, Bonfiglio and Jeter [21] studied the immune response against autografts and allografts in rabbits and found no evidence of immune response in the autograft. Whereas increased necrosis and resorption of allograft was observed that reached maximum intensity at 3 weeks and persisted up to 12-18 weeks, suggesting cell-mediated immunity as the major culprit. Elves ,[25] using uptake of strontium-85 to label and quantitate new bone formation in rats, demonstrated round cells, plasma cells and macrophages on the allograft, with diminished osteogenesis that proved more profound with greater degrees of genetic disparity.

Inflammatory and immunological response have been found to be decreased and bone formation is found to be increased in immunosuppressed animals, suggesting immunological response as a major culprit in reducing the osteogenic capacity of the allogenic and xenogenic bone grafts. [11],[12],[22]

The immunosuppressant CsA is the most effective drug for the prevention and treatment of graft rejection reaction. In this study, the systemic side-effects of CsA, such as nephrotoxicity, hypertension, tremor, gingival hyperplasia and liver dysfunction that occur at very high doses [26] have been avoided by the local administration of low-dose CsA. Applied locally, high-dose CsA 15-30 mg/kg body weight also produces trabecular bone loss [27] in comparison to enhanced bone formation at a low dose (0.5-2 mg/kg body weight). [14],[15] Treatment with low-dose CsA is unlikely to disturb post-surgical wound healing and thus can be safely incorporated. [28],[29]

CsA abrogates proliferation of T-lymphocytes (cell-mediated immunity) induced by either antigen or mitogens during graft rejection by acting at various levels [Figure 1]:

  • CsA inhibit T-cell-dependent IL-1 secretion from macrophages [30],[31],[32]
  • CsA prevent the IL-2 producer T-cell from expressing receptors for IL-1 and thus suppressing the synthesis of IL-2 from these cells [30]
  • Suppression of synthesis of IL-2 from T-helper cells inhibited the activation of cytotoxic T-cells, B-cells, macrophages and their subsequent destructive effects on the graft [33]
  • CsA inhibit antigen presenting cell (APC) activity through abrogation of MHC Class-II expression. It is mediated through inhibition of IFN-γ and IL-4 from T-cells.[34]
  • CsA inhibited bone resorption by suppressing IL-1-stimulated prostaglandin (PG)E 2 production. [35] At higher concentrations, there is a direct inhibitory action of CsA on osteoclasts. [36]
CsA causes reversible inhibition by blocking the ability of the intact host immune apparatus from responding to stimulation by donor antigen. Once the drug is discontinued, an unmodulated and intact host immune apparatus would be left in place, thus safer in use.

In periodontitis, bacterial lipolysaccharide (LPS) is a potent stimulus for IL-1 and TNF-α production from macrophages. IL-1β and TNF-α are the major cytokines in causing allograft bone resorption,[37] with IL-1β being more potent than TNF-α.[38] The level of these cytokines increases in GCF in periodontal disease and decreases after treatment. [39] CsA inhibited bone resorption produced by this bacterial LPS, IL-1 and PGE 2 , [34],[40] decreasing the intensity of periodontitis.

Additionally, CsA potentiate osseous regeneration in periodontal defects as it has a direct activating effect on osteoblasts. Increase in bone formation is seen with CsA, as indicated by an increase in the bone alkaline phosphatase levels. [41],[42]

Routinely, various allografts and xenografts are being used for periodontal regenerative procedures. The advantage of this study is that augmentation of the regenerative potential of these grafts can be achieved by incorporating them with low-dose CsA. The results of this study are in accordance with studies of Ekelund and Nilsson (1996) [14],[43] and Fu et al. (2003), [15] who demonstrated additional bonefill when CsA was added locally to DFDBM in rats than when DFDBM was used alone.

However, the disadvantage of this study is its short duration and small study sample size. Also, what was not determined by this study is characterization of the relationship between two previously perceived separate systems: bone remodelling and the immune response. If immune responses are deleterious for allografts, these are also essential for bone remodelling by graft. What percentage of allograft regeneration is affected by immune reactions? These are the questions that remain unanswered. The application of objective methods are awaited to evaluate correlations between bone physiology, immunology and clinical outcome in humans.


   Conclusion Top


Within the constraints of this study, CsA has been shown to potentiate the regenerative capacity of allografts and, hence, brightens its futuristic aspect regarding its use with various allografts in the treatment of periodontal infrabony defects. As immunologic responses against these grafts are inevitable, the results obtained from this study present a valid premise for further long-term studies with larger study samples to determine measures for manipulation of the immune response to enhance or maximize the biologic potential of bone allografts and xenografts.


   Acknowledgment Top


We express special thanks to Dr. A. S. Sethi, Professor, Punjab School of Economics, Guru Nanak Dev University, Amritsar, for his help with the statistical analysis of the data and its interpretation.

 
   References Top

1.Froum SJ, Ortiz M, Witkin RT, Thaler R, Scopp IW, Stahl SS. Osseous autografts III, Comparison of osseous coagulum-bone blend implants with open curettage. J Periodontol 1976;47:287-94.  Back to cited text no. 1
    
2.Libin BM, Ward HL, Fishman L. Decalcified, lyophilized bone allografts for use in human periodontal defects. J Periodontol 1975;46:51-6.  Back to cited text no. 2
    
3.Urist MR, DeLange RJ, Finerman GA. Bone cell differentiation and growth factors: formation by autoinduction. Science 1983;220:680-6.  Back to cited text no. 3
    
4.Schwartz Z, Somers A, Mellonig JT, Carnes DL Jr, Dean DD, Cochran DL, et al. Ability of commercial demineralized freeze-dried bone allograft to induce new bone formation is dependent on donor age but not gender. J Periodontol 1998;69:470-8.  Back to cited text no. 4
    
5.Urist MR, Hay PH, Dubuc F, Buring K. Osteogenetic competence. Clin Orthop Relat Res 1969;64:194-220.  Back to cited text no. 5
    
6.Hall EE, Meffert RM, Hermann JS, Mellonig JT, Cochran DL. Comparison of bioactive glass to demineralized freeze-dried bone allograft in the treatment of intrabony defects around implants in the canine mandible. J Periodontol 1999;70:526-35.  Back to cited text no. 6
    
7.Meadows CL, Gher ME, Quintero G, Lafferty TA. A comparison of polylactic acid granules and decalcified freeze-dried bone allograft in human periodontal osseous defects. J Periodontol 1993;64:103-9.  Back to cited text no. 7
    
8.Pearson GE, Rosen S, Deporter DA. Preliminary observations on the usefulness of a decalcified, freeze-dried cancellous bone allograft material in periodontal surgery. J Periodontol 1981;52:55-9.  Back to cited text no. 8
    
9.Quintero G, Mellonig JT, Gambill VM, Pelleu GB Jr. A six-month clinical evaluation of decalcified freeze-dried bone allografts in periodontal osseous defects. J Periodontol 1982;53:726-30.  Back to cited text no. 9
    
10.Sonis ST, Kaban LB, Glowacki J. Clinical trial of demineralized bone powder in the treatment of periodontal defects. J Oral Med 1983;38:117-22.  Back to cited text no. 10
    
11.Kόbler N, Reuther J, Kirchner T, Priessnitz B, Sebald W. Osteoinductive, morphologic, and biomechanical properties of autolyzed, antigen-extracted, allogeneic human bone. J Oral Maxillofac Surg 1993;51:1346-57.  Back to cited text no. 11
    
12.Marusiζ A, Dikiζ I, Vukiceviζ S, Marusiζ M. New bone induction by demineralized bone matrix in immunosuppressed rats. Experientia 1992;48:783-85.  Back to cited text no. 12
    
13.Kaufmann Y, Chang AE, Robb RJ, Rosenberg SA. Mechanism of action of Cyclosporine-A: Inhibition of lymphokine secretion studied with antigen-stimulated T-cell hybridomas. J Immunol 1984;133:3107-11.  Back to cited text no. 13
    
14.Ekelund AL, Nilsson O. Effects of Cyclosporin - A on bone turnover and on resorption of demineralized bone matrix. Clin Orthop Relat Res 1996;326:127-34.  Back to cited text no. 14
    
15.Fu E, Tseng YC, Shen EC, Hsieh YD, Chiang CY. Effects of low-dose Cyclosporine on osteogenesis of human demineralized bone grafts in a surgically created mandibular defects in rats. J Periodontol 2003;74:1136-42.  Back to cited text no. 15
    
16.Novack MJ. Classification of diseases and conditions affecting the periodontium. In: Carranza, editor. Clin Perio. 10 th ed. Philadelphia: Saunders; 2006. p. 100-6.   Back to cited text no. 16
    
17.World Medical Organization. Declaration of Helsinki. Br Med J 1996;313:1448-9.  Back to cited text no. 17
    
18.Bowers GM, Chadroff B, Carnevale R, Mellonig J, Corio R, Emerson J, et al. Histologic evaluation of new attachment apparatus formation in humans (Part II). J Periodontol 1989;60:675-82.  Back to cited text no. 18
    
19.Bowers GM, Chadroff B, Carnevale R, Mellonig J, Corio R, Emerson J, et al. Histologic evaluation of new attachment apparatus formation in humans (Part III). J Periodontol 1989;60:683-93.  Back to cited text no. 19
    
20.Langer F, Gross AE. Immunogenicity of allograft articular cartilage. J Bone Joint Surg Am 1974;56:297-304.  Back to cited text no. 20
    
21.Bonfiglio M, Jeter WS. Immunological responses to bone. Clin Orthop Relat Res 1972;87:19-27.  Back to cited text no. 21
    
22.Horowitz MC, Friedlaender GE. Induction of specific T-cell responsiveness to allogeneic bone. J Bone Joint Surg Am 1991;73:1157-68.  Back to cited text no. 22
    
23.Stevenson S, Davis D. The immune response to osteochondral allografts in dogs. J Bone Joint Surg Am 1987;69:573-82.  Back to cited text no. 23
    
24.Newman MG, Takei HH. Immunity and Inflammation:Basic Concepts. In: Carranza FA, editor. Clin perio. 9 th ed. Philadelphia: Saunders; 2003. p.128.  Back to cited text no. 24
    
25.Elves MW. Studies of the behaviour of allogeneic cancellous one grafts in inbred rabbits. Transplantation 1975;19:416-23.  Back to cited text no. 25
    
26.Calne RY, Rolles K, White DJ, Thiru S, Evans DB, McMaster P, et al. Cyclosporin-A initially as the only immunosuppressant in 34 recipients of cadaveric organs: 32 kidneys, 2 pancreases, and 2 livers. Lancet 1979;2:1033-6.  Back to cited text no. 26
    
27.Movsowitz C, Epstein S, Fallon M, Ismail F, Thomas S. Cyclosporine-A in vivo produces severe osteopenia in the rat. Effect of dose and duration of administration. Endocrinology 1988;123:2571-7.  Back to cited text no. 27
    
28.Petri JB, Schurk S, Gebauer S, Haustein UF. Cyclosporine A delays wound healing and apoptosis and suppresses activin beta-A expression in rats. Eur J Dermatol 1998;8:104-13.  Back to cited text no. 28
    
29.Okubo T. Influences of cyclosporin A on wound healing. Hokkaido Igaku Zasshi 1993;68:665-82.  Back to cited text no. 29
    
30.Britton S, Palacios R. Cyclosporin-A-usefulness, risks and mechanism of action. Immunol Rev 1982;65:5-22.  Back to cited text no. 30
    
31.Bunjes D, Hardt C, Rφllinghoff M, Wagner H. Cyclosporin-A mediates immunosuppression of primary cytotoxic T cell responses by impairing the release of interleukin-I and interleukin-2. Eur J Immunol 1981;11:657-61.  Back to cited text no. 31
    
32.Wagner H. Cyclosporine-A: Mode of action. Transplant Proc 1983;15:523-6.  Back to cited text no. 32
    
33.Thomson AW, Whiting PH, Simpson JG. Cyclosporine: Immunology, Toxicity and Pharmacology in experimental animals. Agents Actions 1984;15:306-27.  Back to cited text no. 33
    
34.Russell RG, Graveley R, Coxon F, Skjodt H, Pozo ED, Elford P, et al. Cyclosporine-A. mode of action and effects on bone and joint tissues. Scand J Rheumatol 1992;21:9-18.  Back to cited text no. 34
    
35.Skjodt H, Crawford A, Elford PR, Ihrie E, Wood DD, Russell RG. Cyclosporine -A modulates interleukin-1 activity on bone in vitro. Br J Rheumatol 1985;24:165-9.  Back to cited text no. 35
    
36.Chowdhury MH, Shen V, Dempster DW. Effects of Cyclosporine-A on chick osteoclasts in vitro. Calcif Tissue Int 1991;49:275-9.  Back to cited text no. 36
    
37.Evans DB. Activities in vitro which include the stimulation of bone resorption. Biochem. Biophys Res Commun 1989;159:1243-8.  Back to cited text no. 37
    
38.Carranza FA Jr, Newman MG. Clin Perio, 8th ed; Philadelphia: WB Saunders; 1996. p. 142.  Back to cited text no. 38
    
39.Tatakis DN. Interleukin-1 and bone metabolism: A review. J Periodontol 1993;64:416  Back to cited text no. 39
    
40.Klaushofer K, Hoffmann O, Stewart PJ, Czerwenka E, Koller K, Peterlik M, et al. Cyclosporine - A inhibits bone resorption in cultured neonatal mouse calvaria. J Pharmacol Exp Ther 1987;243:584-90.  Back to cited text no. 40
    
41.Bonnin MR, Gonzalez MT, Griρσ JM, Cruzado JM, Bover J, Martinez JM, et al. Changes in serum osteocalcin levels in the follow-up of kidney transplantation Ann Clin Biochem 1997;34:651-5.  Back to cited text no. 41
    
42.Wilmink JM, Bras J, Surachno S, van Heyst JL, van der Horst JM. Bone repair in cyclosporin treated renal transplant patients. Transplant Proc 1989;21:1492-4.  Back to cited text no. 42
    
43.Ekelund A, Nilsson OS. Effects of Cyclosporin A on experimental new bone formation in rats. Clin Orthop Relat Res 1992;284:288-98.  Back to cited text no. 43
    

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Correspondence Address:
Shivani Dhawan
Department of Periodontology, National Dental College and Hospital, Derabassi
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0970-9290.74220

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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8], [Table 9]

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