Brook A. Niemiec
DVM, DAVDC, DEVDC, FAVD
Dr. Niemiec is chief of staff of Veterinary Dental Specialties & Oral Surgery, with 14 offices throughout the United States. He is a regular speaker on local, national, and international levels and was elected Clinical Instructor of the Year for the 2016 Western Veterinary Conference. He has authored many articles, chapters, and books and founded the veterinary dental telemedicine website vetdentalrad.com. Finally, he coordinates the San Diego Vet Dental Training Center, with 3 to 4 meetings per year covering basic and intermediate veterinary dentistry.Read Articles Written by Brook A. Niemiec
Periodontal disease is the number one diagnosed problem in small animal veterinary medicine.1,2 Therefore, treatment and prevention of this malady are the subject of significant research, which has resulted in numerous new products and procedures—in addition to current therapies—to prevent and treat periodontal disease (Table 1).
These methods and products can be grouped into 4 different treatment areas:
- Removal of infectious agents (pathogen control)
- Reduction of inflammation and/or bone destruction by the host (host modulation)
- Regeneration of lost alveolar bone (guided tissue regeneration)
- Consideration of implants.
It is well known that periodontal disease is initiated by plaque bacteria.3 Therefore, the basis for periodontal therapy is, and likely always will be, plaque control. This is best achieved by a combination of thorough professional therapy and home care.
Veterinary Oral Health Council
The VOHC is not a regulatory agency. Submission of clinical trial results to VOHC on behalf of a product is voluntary. If the data submitted demonstrate the required dental efficacy, the VOHC awards its Seal of Acceptance to the product.
On the professional side, there are several barrier sealants available, with evidence that they decrease periodontal disease.4-6
The other form of professional pathogen control should be periodontal surgery. As discussed in Proper Diagnosis of Periodontal Disease (January/February 2015, available at tvpjournal.com), pockets greater than 3 mm in dogs and 0.5 mm in cats are pathologic and require therapy.7-10
In dogs and cats, treat all pockets with closed root planing and, ideally, administration of a sustained-release antimicrobial agent into the pocket if the pockets (Figures 1 to 3):11-14
- Are between 4 and 6 mm in dogs and 1 to 3 mm in cats
- Do not have mobility (Table 2), Stage 2 or 3 furcation exposure (Table 3), or other forms of disease (eg, tooth resorption, endodontic infection).
The sustained-release perioceutic doxirobe has antibacterial, anticollagenase, and antiprostaglandin properties, and also assists in gingival reattachment.
In dogs, pockets greater than 6 mm (Figure 4A) or furcation Stage 2 (Figure 4B) or 3 (Figure 4C) require periodontal flap surgery to effectively clean the root surface and allow for reattachment and infection control.10,15-20 Figure 5 demonstrates that periodontal flaps are necessary for thorough cleaning of deep pockets.
These procedures can be learned by general practitioners and require minimal investment in equipment. If such procedures are not an option, these teeth should be extracted.
- Toothbrushing is still considered the gold standard for dental home care. Acceptable standards for toothbrushing are at least every other day for nonactive periodontal disease to daily brushing for advanced periodontal disease. If clients are educated early about the benefits of brushing, compliance will increase.
- Topical antiseptics, such as chlorhexidine and zinc ascorbate, are antimicrobial agents that have been shown to decrease plaque and gingivitis and can be used as adjunct therapy.21-25
- A dental diet—Prescription Diet t/d Canine and Feline (hillsvet.com)—has shown true effectiveness in the treatment of gingivitis. While a claim for gingivitis is no longer allowed, evidence suggests that this and other specifically designed dental diets decrease plaque and calculus accumulation.26-28
- Rawhide chews and other chew treats are also effective at decreasing plaque and calculus.29,30
However, many products are not supported by published peer-reviewed studies. For a list of approved products, please visit the Veterinary Oral Health Council’s (VOHC) website, vohc.org.
It has long been thought that traditional dry dog food is good for oral health, and one study appeared to support these claims.31 However, an additional study showed that dry food was not superior to moist foods with regard to improving oral health.32
As stated previously, plaque has been identified as the etiologic agent of periodontal disease.
- Bacteria and their byproducts create inflammatory changes that may result in alveolar bone loss in susceptible individuals.
- The inflammation is caused by bacteria; however, the patient’s immune response to the inflammation determines (or controls) the progression of the disease.33-36
- If the acute inflammatory response is resolved quickly, tissue injury is prevented. However, inadequate resolution and failure to return tissue to homeostasis result in neutrophil-mediated destruction and chronic inflammation of the periodontal ligament and alveolar bone.8,34-37
Host modulation is a new technique for treating periodontal disease that controls the patient’s response to infection and inflammation. Numerous preparations have shown promise in decreasing the amount of inflammation and osteoclastic bone resorption in cases of chronic periodontitis. In addition, several drug therapies have good efficacy in slowing the progression of periodontal disease.38-52
Many of these preparations have substantial adverse effects, which make their use questionable.53 However, an increasing number of products are natural products or nutraceuticals with minimal to no adverse effects.
As stated earlier, resolution of inflammation (and return to homeostasis) prevents osteoclastic bone resorption.
Nonsteroidal Anti-inflammatory Drugs. Control through classic anti-inflammatory pathways is effective but typically associated with significant adverse effects. Numerous nonsteroidal anti-inflammatory drugs (eg, cyclooxygenase-1 and -2 inhibitors) have been helpful in decreasing periodontal disease and alveolar bone loss.54-61 However, these products appear most effective in the short term.38,39
Antimicrobials. Antimicrobials are another group of medications with significant promise both locally and systemically; in particular, the tetracycline class and especially doxycycline (2 mg/kg PO Q 24 H life long62). These are typically used below the antimicrobial dose needed for their anti-inflammatory properties. Numerous human studies now support long-term administration of low-dose doxycycline after periodontal therapy has been performed.40-42
Bioactive Products. Lipoxins, resolvins, and protectins are a new family of bioactive products of fatty acids, such as eicosapentaenoic acid, that may decrease periodontal inflammation.43–51 Topical application of resolvin E1 (RvE1) in rabbit periodontitis protected against inflammation-induced tissue and bone loss associated with periodontitis.44
An additional study showed that topical application of RvE1 in rabbits had dramatic effects on the regeneration of periodontal tissues destroyed by periodontal disease.52 These products may represent a future option for the control of periodontal inflammation and secondary alveolar bone loss.
Several recent studies have linked chronic oxidative stress with periodontal disease (Table 4).63-67 Furthermore, antioxidant capacity is decreased in patients with established periodontal disease (particularly those with diabetes mellitus).68,69 Finally, proper equilibrium between free radicals and antioxidants is now thought to be the main prerequisite for healthy periodontal tissue.70 Therefore, antioxidants appear to be an important aspect of periodontal health, and supplementation may have protective qualities.71
Numerous methods and products are available for increasing antioxidant capacity. These can range from simple vitamin supplementation (vitamins C and E)72,73 to specific products that more effectively increase total antioxidant capacity.
- Topical application of antioxidants improves periodontal health.74,75 In addition, a veterinary- specific formulation (Antioxidant Oral Gel and Breath Renewal System, toothtotail.com) decreases halitosis in dogs.76
- On the systemic side, Nrf2 (see What Is Nrf2?) triggers production of superoxide dismutase, gluthathione, and catalase, which helps protect against free radicals, and may have benefits for treating periodontal disease.77,78 A natural product with a veterinary-specific formulation (LifeVantage Canine Health, lifevantage.com/IVS) stimulates antioxidant production in the body and in humans increases the levels of natural antioxidants far more than vitamin supplementation alone.79,80
What Is Nrf2?
Nrf2 is a protein messenger in cells that regulates the expression of antioxidant proteins that protect against oxidative damage triggered by injury and inflammation. Several drugs that stimulate the Nrf2 pathway are being studied for treatment of diseases that are caused by oxidative stress.
Fatty Acids. Recent studies on the use of fatty acid supplements have shown beneficial results in periodontal inflammation.81-86 However, because of the high epithelial penetration of fatty acids, topical application may be favorable for the treatment of local oral inflammatory diseases, including periodontitis.44
A particular fatty acid, 1-tetradecanol complex, is an esterified monounsaturated fatty acid with positive effects in rabbits. In 2 in vivo studies on New Zealand rabbits, topical administration stopped the progression of periodontal disease and significantly reduced macroscopic periodontal inflammation, attachment, and bone loss.87,88 Histologic assessment demonstrated that it also inhibited inflammatory cell infiltration and osteoclast activity.
Other Nutraceuticals. Milk basic protein (MBP) supplementation is effective in increasing bone mineral density (BMD), and this increase in BMD may be primarily mediated through the promotion of bone formation and inhibition of bone resorption.89 When administered at high doses, it has been shown in experimental rat models to aid in the recovery of periodontally lost alveolar bone.90,91
Coenzyme Q10 deficiency has been shown in humans with periodontal disease.92,93 Conversely, supplementation (systemic or topical) may have a beneficial effect on periodontal health in humans.94-96 Studies in humans have also demonstrated that folic acid is effective in preserving gum tissue and reducing risk for gingivitis and periodontitis.97
Finally, proper nutrition (see Home Care), including vitamin supplementation, appears to be an important aspect of periodontal care.98,99 Studies have found that vitamin supplementation provides beneficial effects for periodontal patients.100-102
Regenerating bone lost via periodontal disease is another targeted therapy. Guided tissue regeneration (GTR) has been used for decades, but recent advances in barriers and bone grafting have markedly improved the success rates.103-106
Regardless, only a handful of conditions carry a good prognosis for bone regeneration. The best prognosis is seen with:107
- 3-walled periodontal pockets typically seen on the palatal aspect of the maxillary canine (Figure 6A) and distal aspect of the distal root of the mandibular first molar (Figure 6B)
- Lesions with Stage 2 furcation (Figure 6C).
Because these are common conditions in small breed dogs, many patients may benefit from these procedures.
The theory of GTR is that the downward growth of faster healing soft tissue must be prevented to allow the slower growing bone and periodontal ligament to repopulate the periodontally induced bony defect (Figure 7 and Figure 8).108,109 The procedure involves:107
- Creating a periodontal flap
- Performing open root planing (the first 2 steps create a clean root surface for healing)
- Filling the defect with bone augmentation
- Placing a barrier membrane.
Numerous products are used in humans, but the products of choice for most veterinary dentists are cancellous freeze-dried demineralized bone for the graft and demineralized laminar bone sheets as the membrane.107, 110-114
While rare (and controversial)115 in veterinary dentistry, implantology is exceedingly common in human dentistry (Figure 9). It is increasingly being used in place of traditional methods, such as periodontal surgery and even endodontics.
The main reason for the use of implants is that they are associated with a better long-term prognosis than periodontal surgery or endodontics in advanced disease. Therefore, they provide a good option for maintaining teeth and removing a potentially infected or painful tooth earlier in the course of disease. If an implant could be performed in a pet with advanced disease, it may convince the client to remove an infected tooth.
Some have voiced concerns that there is minimal clinical evidence that these procedures work in veterinary patients. However, most research for humans was performed on dogs, and the results were very positive. The other issue with this form of therapy is the numerous anesthesias required, but advances in technology and techniques will likely improve this in the near future. Adequate bone density is needed to accommodate this type of therapy.
- New passive pathogen (plaque) control measures are coming out all the time. For many of these, no research exists, so look beyond the advertisements for research, or use the VOHC for confirmation before making your recommendations.
- Deep periodontal pockets require periodontal flap surgery or extraction, and some of these teeth can be saved with GTR.
- Host modulation therapy is likely the future of periodontal therapy.
- Nutraceuticals, antioxidants, vitamins, and proper nutrition all play a role in supporting good periodontal health. These treatments, in combination with new local bone regenerating products (such as BMP) and implantology, will dramatically change the way we treat periodontal disease.
Without mechanical removal of the causative agent of periodontal disease, these treatments are not effective. However, if proper pocket augmentation is accomplished, these therapies provide the opportunity to re-establish bone attachment and minimize inflammatory reactions associated with all phases of periodontal disease.
BMD = bone mineral density; GTR = guided tissue regeneration; MBP = milk basic protein; RvE1 = resolvin E1; VOHC = Veterinary Oral Health Council
- University of Minnesota Center for Companion Animal Health. National companion animal study. Uplinks 1996; p 3.
- Lund EM, Armstrong PJ, Kirk CA, et al. Health status and population characteristics of dogs and cats examined at private veterinary practices in the United States. JAVMA 1999; 214:1336-1341.
- Van Dyke TE, Serhan CN. Resolution of inflammation: A new paradigm for the pathogenesis of periodontal diseases. J Dent Res 2003; 82:82-90.
- Gengler WR, Kunkle BN, Romano D, Larsen D. Evaluation of a barrier sealant in dogs. J Vet Dent 2005; 22:157-159.
- Homola AM, Dunton RK. Methods, compositions, and dental delivery systems for the protection of the surfaces of teeth. U.S. patent no. 5,665,333 issued September 9, 1997, and U.S. patent no. 5,961,958 issued October 5, 1999.
- Sitzman C. Evaluation of a hydrophilic gingival dental sealant in beagle dogs. J Vet Dent 2013; 30:150-155.
- Wiggs RB, Lobprise HB. Oral exam and diagnosis. Veterinary Dentistry, Principals and Practice. Philadelphia: Lippincott Raven, 1997, pp 87-103.
- Debowes LJ. Problems with the gingiva. In Niemiec BA (ed): Small Animal Dental, Oral and Maxillofacial Disease: A Color Handbook. London: Manson Publishing, 2010, pp 159-181.
- Niemiec BA. Veterinary dental radiology. In Niemiec BA (ed): Small Animal Dental, Oral and Maxillofacial Disease: A Color Handbook. London: Manson Publishing, 2010, pp 63-87.
- Bellows J. Periodontal equipment, materials, and techniques. Small Animal Dental Equipment, Materials, and Techniques: A Primer. Ames, IA: Blackwell, 2004, pp 115-173.
- Niemiec BA. Advanced non-surgical therapy. In Niemiec BA (ed): Veterinary Periodontology. Ames, IA: Wiley Blackwell, 2013, pp 154-169.
- Cobb CM. Non-surgical pocket therapy: Mechanical. Ann Periodontol 1996; 1:443-490.
- Pattison AM, Pattison GL. Scaling and root planing. In Newman M (ed): Carranza’s Clinical Periodontology, 10th ed. St. Louis: WB Saunders, 2007, pp 749-797.
- Wiggs RB, Lobprise HB. Periodontology. In Wiggs RB, Lobprise HB (eds): Veterinary Dentistry: Principles and Practice. Philadelphia: Lippincott-Raven, 1997, pp 186-231.
- Jensen L, Logan E, Finney O, et al. Reduction in accumulation of plaque, stain, and calculus in dogs by dietary means. J Vet Dent 1995; 12:161-163.
- Carranza FA, Takei HH. Phase II periodontal therapy. In Newman M (ed): Carranza’s Clinical Periodontology, 10th ed. St. Louis: WB Saunders, 2007, pp 881-886.
- Perry DA, Schmid MO, Takei HH. Phase I periodontal therapy. In Newman M (ed): Carranza’s Clinical Periodontology, 10th ed. St. Louis: WB Saunders, 2007, pp 722-727.
- Caffesse RG, Sweeney PL, Smith BA. Scaling and root planing with and without periodontal flap surgery. J Clin Periodontol 1986; 13:205-210.
- Holmstrom SE, Frost P, Eisner ER. Periodontal therapy and surgery. In Holmstrom SE, Frost P, Eisner ER (eds): Veterinary Dental Techniques for the Small Animal, 2nd ed. Philadelphia: Saunders, 1998, pp 167-213.
- Niemiec BA. Periodontal therapy. Top Companion Anim Med 2008; 23:81-90.
- Hamp SE, Emilson CG. Some effects of chlorhexidine on the plaque flora of the beagle dog. J Periodontol Res 1973; 12:28-35.
- Hull PS, Davies RM. The effect of a chlorhexidine gel on tooth deposits in beagle dogs. J Small Anim Pract 1972; 13:207-212.
- Maruniak J, Clark WB, Walker CB, et al. The effect of 3 mouthrinses on plaque and gingivitis development. J Clin Periodontol 1992; 19:19-23.
- Overholser CD, Meiller TF, DePaola LG, et al. Comparative effects of 2 chemotherapeutic mouthrinses on the development of supragingival dental plaque and gingivitis. J Clin Periodontol 1990; 17:575-579.
- Clarke DE. Clinical and microbiological effects of oral zinc ascorbate gel in cats. J Vet Dent 2001; 18:177-183.
- Logan EI, Finney O, Hefferren JJ. Effects of a dental food on plaque accumulation and gingival health in dogs. J Vet Dent 2002; 19:15-18.
- Logan EI, Proctor V, Berg ML, et al. Dietary effect on tooth surface debris and gingival health in cats. Proc Am Vet Dent Forum, 2001, p 377.
- Brown WY, McGenity P. Effective periodontal disease control using dental hygiene chews. J Vet Dent 2005; 22:16-19.
- Hennet P, Servet E, Venet C. Effectiveness of an oral hygiene chew to reduce dental deposits in small breed dogs. J Vet Dent 2006; 23:6-12.
- Gorrel C, Bierer TL. Long-term effects of a dental hygiene chew on the periodontal health of dogs. J Vet Dent 1999; 16:109-113.
- Gawor JP, Reiter AM, Jodkowska K, et al. Influence of diet on oral health in cats and dogs. J Nutr 2006; 136:2021S-2023S.
- Harvey CE, Shofer FS, Laster L. Correlation of diet, other chewing activities, and periodontal disease in North American client-owned dogs. J Vet Dent 1996; 13:101-105.
- Niemiec BA. Host modulation therapies. In Niemiec BA (ed): Veterinary Periodontology. Ames, IA: Wiley Blackwell, 2013, pp 299-304.
- Lang NP, Mombelli A, Attstrom R. Dental plaque and calculus. In Lindhe J, Karring T, Lang NP (eds): Clinical Periodontology and Implant Dentistry, 3rd ed. Denmark: Munksgaard, 2002, pp 102-134.
- Thoden Van Velzen SK, Abraham-Inpijin L, Modrer WDR. Plaque and systemic disease: A reappraisal of the focal infection concept. J Clin Periodontol 1984; 11:209-220.
- Scannapieco FA. Periodontal inflammation: From gingivitis to systemic disease? Compend Contin Educ Pract Vet 2004; 25 (suppl 1):16-25.
- Nisengard RJ, Kinder Haake S, Newman MG, Miyasaki KT. Microbial interactions with the host in periodontal diseases. Carranza’s Clinical Periodontology. St. Louis: WB Saunders, 2006, pp 228-250.
- Nassar CA, Nassar PO, Nassar PM, Spolidorio LC. Selective cyclooxygenase-2 inhibition prevents bone resorption. Braz Oral Res 2005; 19:36-40.
- Queiroz-Junior CM, Pacheco CM, Maltos KL, et al. Role of systemic and local administration of selective inhibitors of cyclo-oxygenase 1 and 2 in an experimental model of periodontal disease in rats. J Periodontal Res 2009; 44:153-160.
- Emingil G, Atilla G, Sorsa T, et al. Effectiveness of adjunctive low-dose doxycycline therapy on clinical parameters and gingival crevicular fluid laminin-5 gamma2 chain levels in chronic periodontitis. J Periodontol 2004; 75:1387-1396.
- Gürkan A, Cinarcik S, Hüseyinov A. Adjunctive subantimicrobial dose doxycycline: Effect on clinical parameters and gingival crevicular fluid transforming growth factor-beta levels in severe, generalized chronic periodontitis. J Clin Periodontol 2005; 32:244-253.
- Gürkan A, Emingil G, Cinarcik S, Berdeli A. Post-treatment effects of subantimicrobial dose doxycycline on clinical parameters and gingival crevicular fluid transforming growth factor-beta1 in severe, generalized chronic periodontitis. Int J Dent Hyg 2008; 6:84-92.
- Serhan CN, Gotlinger K, Hong S, Arita M. Resolvins, docosatrienes, and neuroprotectins, novel omega-3-derived mediators, and their aspirin-triggered endogenous epimers: An overview of their protective roles in catabasis. Prostaglandins Other Lipid Mediat 2004; 73:155-172.
- Hasturk H, Kantarci A, Ohira T, et al. RvE1 protects from local inflammation and osteoclast-mediated bone destruction in periodontitis. FASEB J 2006; 20:401-403.
- Arita M, Yoshida M, Hong S. Resolvin E1, an endogenous lipid mediator derived from omega-3 eicosapentaenoic acid, protects against 2,4,6-trinitrobenzene sulfonic acid-induced colitis. Proc Natl Acad Sci USA 2005; 102:7671-7676.
- Arita M, Bianchini F, Aliberti J, et al. Stereochemical assignment, antiinflammatory properties, and receptor for the omega-3 lipid mediator resolvin E1. J Exp Med 2005; 201:713-722.
- Arita M, Ohira T, Sun YP, et al. Resolvin E1 selectively interacts with leukotriene B4 receptor BLT1 and ChemR23 to regulate inflammation. J Immunol 2007; 178:3912-3917.
- Arita M, Clish CB, Serhan CN. The contributions of aspirin and microbial oxygenase to the biosynthesis of anti-inflammatory resolvins: Novel oxygenase products from omega-3 polyunsaturated fatty acids. Biochem Biophys Res Commun 2005; 338:149-157.
- Serhan CN, Savill J. Resolution of inflammation: The beginning programs the end. Nat Immunol 2005; 6:1191-1197.
- Bannenberg GL, Chiang N, Ariel A, et al. Molecular circuits of resolution: Formation and actions of resolvins and protectins. J Immunol 2005; 174:4345-4355.
- Schwab JM, Chiang N, Arita M, Serhan CN. Resolvin E1 and protectin D1 activate inflammation-resolution programmes. Nature 2007; 447:869-874.
- Hasturk H, Kantarci A, Goguet-Surmenian E, et al. Resolvin E1 regulates inflammation at the cellular and tissue level and restores tissue homeostasis in vivo. J Immunol 2007; 179:7021-7029.
- Van Dyke TE. The management of inflammation in periodontal disease. J Periodontol 2008; 79 (suppl 8):1601-1608.
- Gurgel BC, Duarte PM, Nociti FH Jr, et al. Impact of an anti-inflammatory therapy and its withdrawal on the progression of experimental periodontitis in rats. J Periodontol 2004; 75:1613-1618.
- Oliveira TM, Sakai VT, Machado MA, et al. COX-2 inhibition decreases VEGF expression and alveolar bone loss during the progression of experimental periodontitis in rats. J Periodontol 2008; 79:1062-1069.
- Buduneli N, Buduneli E, Cetin EO, et al. Clinical findings and gingival crevicular fluid prostaglandin E2 and interleukin-1-beta levels following initial periodontal treatment and short-term meloxicam administration. Exp Opin Pharmacother 2010; 11:1805-1812.
- Holzhausen M, Rossa Júnior C, Marcantonio Júnior E, et al. Effect of selective cyclooxygenase-2 inhibition on the development of ligature-induced periodontitis in rats. J Periodontol 2002; 73:1030-1036.
- Holzhausen M, Spolidorio DM, Muscará MN, et al. Protective effects of etoricoxib, a selective inhibitor of cyclooxygenase-2, in experimental periodontitis in rats. J Periodontal Res 2005; 40:208-211.
- Bezerra MM, de Lima V, Alencar VB, et al. Selective cyclooxygenase-2 inhibition prevents alveolar bone loss in experimental periodontitis in rats. J Periodontol 2000; 71:1009-1014.
- Paquette DW, Fiorellini JP, Martuscelli G, et al. Enantiospecific inhibition of ligature-induced periodontitis in beagles with topical (S)-ketoprofen. J Clin Periodontol 1997; 24:521-528.
- Offenbacher S, Williams RC, Jeffcoat MK, et al. Effects of NSAIDs on beagle crevicular cyclooxygenase metabolites and periodontal bone loss. J Periodontal Res 1992; 27:207-213.
- Kim SE, Kim S, Jeong M, et al. Experimental determination of a subantimicrobial dosage of doxycycline hyclate for treatment of periodontitis in beagles. Am J Vet Res 2013; 74(1):130-135.
- Waddington RJ, Moseley R, Embery G. Reactive oxygen species: A potential role in the pathogenesis of periodontal diseases. Oral Dis 2000; 6:138-151.
- Sculley DV, Langley-Evans SC. Periodontal disease is associated with lower antioxidant capacity in whole saliva and evidence of increased protein oxidation. Clin Sci (Lond) 2003; 105:167-172.
- Takane M, Sugano N, Iwasaki H, et al. New biomarker evidence of oxidative DNA damage in whole saliva from clinically healthy and periodontally diseased individuals. J Periodontol 2002; 73:551-554.
- Pendyala G, Thomas B, Kumari S. The challenge of antioxidants to free radicals in periodontitis. J Indian Soc Periodontol 2008; 12:79-83.
- D’Aiuto F, Nibali L, Parkar M, et al. Oxidative stress, systemic inflammation, and severe periodontitis. J Dent Res 2010; 89:1241-1246.
- Pendyala G, Thomas B, Joshi SR. Evaluation of total antioxidant capacity of saliva in type-2 diabetic patients with and without periodontal disease: A case-control study. N Am J Med Sci 2013; 5:51-57.
- Pendyala G, Thomas B, Joshi S. Periodontitis, diabetes mellitus, and the lopsided redox balance: A unifying axis. J Indian Soc Periodontol 2013; 17:338-344.
- Dahiya P, Kamal R, Gupta R, Puri A. Oxidative stress in chronic periodontitis. Chron Young Scientists 2011; 2:178-181.
- Pavlica Z, Petelin M, Nemec A, et al. Measurement of total antioxidant capacity in gingival crevicular fluid and serum in dogs with periodontal disease. Am J Vet Res 2004; 65:1584-1588.
- Parrish JH Jr, DeMarco TJ, Bissada NF. Vitamin E and periodontitis in the rat. Oral Surg Oral Med Oral Pathol 1977; 44:210-218.
- Kim JE, Shklar G. The effect of vitamin E on the healing of gingival wounds in rats. J Periodontol 1983; 54:305-308.
- Chandra RV, Srinivas G, Reddy AA, et al. Locally delivered antioxidant gel as an adjunct to nonsurgical therapy improves measures of oxidative stress and periodontal disease. J Periodonal Implant Sci 2013; 43:121-129.
- Chandra RV, Sandhya YP, Nagarajan S, et al. Efficacy of lycopene as a locally delivered gel in the treatment of chronic periodontitis: Smokers vs nonsmokers. Quintessence Int 2012; 43:401-411.
- Low SB, Peak RM, Smithson CW, et al. Evaluation of a topical gel containing a novel combination of essential oils and antioxidants for reducing oral malodor in dogs. Am J Vet Res 2014; 75:653-657.
- Hybertson BM, Gao B, Bose SK, et al. Oxidative stress in health and disease: The therapeutic potential of Nrf2 activation. Mol Aspects Med 2011; 32:234-236.
- Davis K. Understanding antioxidants: Using various arsenals to impact the oral environment. Dent Today 2012; 31:92, 94, 96-97.
- Nelson SK, Bose SK, Grunwald GK, et al. The induction of human superoxide dismutase and catalase in vivo: A fundamentally new approach to antioxidant therapy. Free Radic Biol Med 2006; 40:341-347.
- Bogaard HJ, Natarajan R, Henderson SC, et al. Chronic pulmonary artery pressure elevation is insufficient to explain right heart failure. Circulation 2009; 120:1951-1960.
- Kesavalu L, Vasudevan B, Raghu B, et al. Omega-3 fatty acid effect on alveolar bone loss in rats. J Dent Res 2006; 85:648-652.
- Kesavalu L, Bakthavatchalu V, Rahman MM, et al. Omega-3 fatty acid regulates inflammatory cytokine/mediator messenger RNA expression in Porphyromonas gingivalis-induced experimental periodontal disease. Oral Microbiol Immunol 2007; 22:232-239.
- Vardar S, Buduneli E, Türkoglu O, et al. Therapeutic versus prophylactic plus therapeutic administration of omega-3 fatty acid on endotoxin-induced periodontitis in rats. J Periodontol 2004; 75:1640-1646.
- Vardar S, Buduneli E, Baylas H, et al. Individual and combined effects of selective cyclooxygenase-2 inhibitor and omega-3 fatty acid on endotoxin-induced periodontitis in rats. J Periodontol 2005; 76:99-106.
- Nauroth JM, Liu YC, Van Elswyk M. Docosahexaenoic acid (DHA) and docosapentaenoic acid (DPAn-6) algal oils reduce inflammatory mediators in human peripheral mononuclear cells in vitro and paw edema in vivo. Lipids 2010; 45:375-384.
- Naqvi AZ, Buettner C, Phillips RS, et al. n-3 fatty acids and periodontitis in US adults. J Am Diet Assoc 2010; 110:1669-1675.
- Hasturk H, Goguet-Surmenian E, Blackwood A. 1-Tetradecanol complex: Therapeutic actions in experimental periodontitis. J Periodontol 2009; 80:1103-1113.
- Hasturk H, Jones VL, Andry C, Kantarci A. 1-Tetradecanol complex reduces progression of Porphyromonas gingivalis-induced experimental periodontitis in rabbits. J Periodontol 2007; 78:924-932.
- Uenishi K, Ishida H, Toba Y, et al. Milk basic protein increases bone mineral density and improves bone metabolism in healthy young women. Osteoporos Int 2007; 18(3):385-390.
- Seto H, Nagata T. Prevention of osteoporosis by foods and dietary supplements. Milk basic protein (MBP) induces alveolar bone formation in rat experimental periodontitis. Clin Calcium 2006; 16:1639-1645.
- Seto H, Toba Y, Takada Y, et al. Milk basic protein increases alveolar bone formation in rat experimental periodontitis. J Periodontal Res 2007; 42:85-89.
- Littarru GP, Nakamura R, Ho L, et al. Deficiency of coenzyme Q 10 in gingival tissue from patients with periodontal disease. Proc Natl Acad Sci USA 1971; 68:2332-2335.
- Nakamura R, Littarru GP, Folkers K, Wilkinson EG. Study of CoQ10-enzymes in gingiva from patients with periodontal disease and evidence for a deficiency of coenzyme Q10. Proc Natl Acad Sci USA 1974; 71:1456-1460.
- Wilkinson EG, Arnold RM, Folkers K, et al. Bioenergetics in clinical medicine. II. Adjunctive treatment with coenzyme Q in periodontal therapy. Res Commun Chem Pathol Pharmacol 1975; 12:111-123.
- Hanioka T, Tanaka M, Ojima M, et al. Effect of topical application of coenzyme Q10 on adult periodontitis. Mol Aspects Med 1994; 15:s241-248.
- Wilkinson EG, Arnold RM, Folkers K. Bioenergetics in clinical medicine. VI. Adjunctive treatment of periodontal disease with coenzyme Q10. Res Commun Chem Pathol Pharmacol 1976; 14:715-719.
- Stein GM, Lewis H. Oral changes in a folic acid deficient patient precipitated by anticonvulsant drug therapy. J Periodontol 1973; 44:645-650.
- Indrei LL. Nutrition and periodontal disease. Rev Med Chir Soc Med Nat Iasi 2006; 110:195-197.
- Klokkevold PR, Mealey BL. Influence of systemic disorders and stress on the periodontium. In Newman M (ed): Carranza’s Clinical Periodontology, 10th ed. St. Louis: WB Saunders, 2007, pp 228-250, 284-310.
- Muñoz CA, Kiger RD, Stephens JA, et al. Effects of a nutritional supplement on periodontal status. Compend Contin Educ Pract Vet 2001; 22:425-428.
- Parrish JH Jr, DeMarco TJ, Bissada NF. Vitamin E and periodontitis in the rat. Oral Surg Oral Med Oral Pathol 1977; 44:210-218.
- Kim JE, Shklar G. The effect of vitamin E on the healing of gingival wounds in rats. J Periodontol 1983; 54:305-308.
- Needleman IG, Worthington HV, Giedrys-Leeper E, Tucker RJ. Guided tissue regeneration for periodontal infra-bony defects. Cochrane Database Syst Rev 2006; 19(2).
- Donos N, Sculean A, Glavind L, et al. Wound healing of degree III furcation involvements following guided tissue regeneration and/or Emdogain. A histologic study. J Clin Periodontol 2003; 30:1061-1068.
- Murphy KG, Gunsolley JC. Guided tissue regeneration for the treatment of periodontal intrabony and furcation defects. A systematic review. Ann Periodontol 2003; 8:266-302.
- Reynolds MA, Aichelmann-Reidy ME, Branch-Mays GL, Gunsolley JC. The efficacy of bone replacement grafts in the treatment of periodontal osseous defects. A systematic review. Ann Periodontol 2003; 8:227-265.
- Niemiec BA. Osseous surgery and guided tissue regeneration. In Niemiec BA (ed): Veterinary Periodontology. Ames IA: Wiley Blackwell, 2013, pp 254-288.
- Melcher AH. On the repair potential of periodontal tissues. J Periodontol 1976; 47:256-260.
- Aukhil I, Patterson E, Suggs C. Guided tissue regeneration. An experimental procedure in beagle dogs. J Periodontol 1986; 57:7727-7734.
- Scott TA, Towle HJ, Assad DA, Nicoll BK. Comparison of bioabsorbable laminar bone membrane and non-resorbable ePTFE membrane in mandibular furcations. J Periodontol 1997; 68:679-686.
- Fugazzotto PA. The use of demineralized laminar bone sheets in guided bone regeneration procedures: Report of three cases. Int J Oral Maxillofac Implants 1996; 11:239-244.
- Bowers GM, Chadroff B, Carnevale R, et al. Histologic evaluation of new attachment apparatus formation in humans. Part III. J Periodontol 1989; 60:683-693.
- Bowers G, Felton F, Middleton C, et al. Histologic comparison of regeneration in human intrabony defects when osteogenin is combined with demineralized freeze-dried bone allograft and with purified bovine collagen. J Periodontol 1991; 62:690-702.
- Mellonig JT. Freeze-dried bone allografts in periodontal reconstructive surgery. Reconstruct Periodont 1991; 35:505-521.
- Tannenbaum J, Arzi B, Reiter AM. The case against the use of dental implants in dogs and cats. JAVMA 2013; 243:1680-1685.