A 12-Month Evaluation of Nitrite Oxide Metabolism Around Immediate and Conventionally Loaded Dental Implants Gu ¨ liz N. Gu ¨ ncu ¨ , DDS, PhD,* Tolga F. To ¨ zu ¨ m, DDS, PhD,† M. Barı ¸ s Gu ¨ ncu ¨ , DDS, PhD,‡ Nermin Yamalik, DDS, PhD, MS,§ and Celal Tu ¨ mer, DDS, PhD B one is a living tissue that is remodeled throughout life by bone resorbing osteoclasts and bone forming osteoblasts. 1 It is well documented that bone actively remod- els in response to various signals in- cluding mechanical signs. 1,2 During remodeling, alignment of new bone is along the dominant local loading di- rection, suggesting local regulation of bone formation by mechanical stim- uli. 3 It has been shown that mechanical loading modulates bone remodeling by provoking the cellular response via loading-induced flow of interstitial fluid through the lacuno-canalicular network of osteocytes. 4 Many vari- ables, such as systemic hormones, 5 mechanical stimulus, 1,6 and nitric ox- ide (NO), 7,8 were reported that involve the bone metabolism. 2,4,9,10 NO is a free radical produced from L-arginine through the action of isoen- zymes, named NO synthases. 11 As well as vascular regulation, homeostasis, neurotransmission, immune function, 12 and defense against certain bacterial in- fections, 13 NO is also involved in bone formation and resorption. 12 Its dual ef- fect includes some harmful cytotoxic and cytostatic actions. 14,15 Endothelial cells and macrophages 16 and the inflam- matory cells in the oral cavity 17 are important sources of inducible NO syn- thases (iNOS). Inflamed periodontal tis- sues are shown to exhibit increased NO synthesis, 16 iNOS 18 –20 and arginase ac- tivity. 20 High-level expression of iNOS from macrophages is suggested to be related to periodontal destruction. 15 NO metabolism is also suggested to be asso- ciated with the clinical inflammatory state of peri-implant tissues. 21 NO has a role in bone metabo- lism, in which orthodontic models or in vitro study designs 2,4,6,7,9,22 provide considerable amount of data suggest- ing the effect of NO metabolism on bone cell function, bone maintenance, and remodeling. 9,12,19 Evidence from the literature revealed that the applica- tion of NO precursor increased and NO inhibitors reduced orthodontic tooth movements. 7,8 Moreover, in- creasing iNOS activity in periodontal tissues with tooth movement 23 pointed out the association of NO production with bone metabolism in rats. More- over, mechanical strain and shear stress have been shown to cause rapid increase in the production of NO. 6,22 Based on peri-implant sulcular fluid (PISF) nitrite level, a stable end- *Clinical Instructor, Department of Periodontology, Faculty of Dentistry, Hacettepe University, Ankara, Turkey. †Associate Professor, Department of Periodontology, Faculty of Dentistry, Hacettepe University, Ankara, Turkey. ‡Prosthodontist, Private Practice, Ankara, Turkey. §Professor, Department of Periodontology, Faculty of Dentistry, Hacettepe University, Ankara, Turkey. Professor, Department of Oral Surgery, Faculty of Dentistry, Hacettepe University, Ankara, Turkey. ISSN 1056-6163/09/01801-027 Implant Dentistry Volume 18 • Number 1 Copyright © 2009 by Lippincott Williams & Wilkins DOI: 10.1097/ID.0b013e318195aaa3 Background: During bone re- modeling, alignment of bone is affected by loading direction. Con- siderable amount of data also sug- gest nitric oxide (NO) to be involved in bone metabolism. This study was conducted to evaluate the potential changes in NO metab- olism in relation to the loading style of dental implants by analyz- ing the nitrite content of peri- implant sulcus fluid. Methods: Dental implants were placed in 12 patients who had first molar loss bilaterally in the mandibu- lar area. One site of the patient deter- mined as immediately loaded and the other side were conventionally loaded. Clinical parameters were recorded and peri-implant sulcus fluid samples were obtained. Peri-implant sulcus fluid nitrite levels were spectrophoto- metrically determined. Clinical mea- surements and nitrite analysis were repeated at 1, 3, 6, 9, and 12 months. Results: In both groups, there was a reduction between baseline and 12 months in all clinical parameters, ex- cept probing depth. Although, steady decrease was noticed in total nitrite levels during the whole experimental period in immediately loaded im- plants, more fluctuations were ob- served in conventionally loaded ones. Conclusions: The findings of this 12-month follow-up study support the association of NO in the bone metab- olism around dental implants and fur- ther suggest the impact of different loading regimens on NO metabolism. (Implant Dent 2009;18:27–37) Key Words: dental implants, nitric oxide, loading, peri-implant sulcular fluid, nitrite IMPLANT DENTISTRY /VOLUME 18, NUMBER 1 2009 27