CLINICAL EFFICACY OF LOCALLY INJECTED CALCITRIOL IN ORTHODONTIC TOOTH MOVEMENT Research Article NOOR R. Al-HASANI 1 , ALI I. AL-BUSTANI 2 , MOAFAQ M. GHAREEB 3 , SAAD A. HUSSAIN 4 * 1 Department of Clinical Pharmacy, College of Pharmacy, 2 Department of Orthodontics, College of Dentistry, 3 Department of Pharmaceutics, 4 Received: 1 Jul 2011, Revised and Accepted: 27 Sep 2011 Department of Pharmacology and Toxicology, College of Pharmacy, Baghdad University, Baghdad, Iraq. Email: saad_alzaidi@yahoo.com ABSTRACT Orthodontic treatment has two major problems: being lengthy and costly procedure. The present study was designed to evaluate the clinical efficacy of locally injected vitamin D3 Keywords: Orthodontic, Calcitriol, Local injection, OTM (calcitriol) in accelerating orthodontic teeth movement (OTM) and reducing treatment time and cost in humans. The study was performed on 15 Iraqi adult orthodontic patients within the age range 17-28 years, they are randomly allocated into three groups, each of five patients and treated with either 15 pg, 25 pg, or 40 pg/0.2ml calcitriol diluted with 10% dimethylsulfoxide (DMSO). The maxillary arch of every patient was divided into control (right) and experimental (left) sides. In addition to force application, the right canine received 0.2 ml DMSO injections while the left canine received the calcitriol injections. The follow up period for every patient included five visits at one week intervals through which they received two injections three times and evaluated for OTM, GCf collection and radiographic examination. Statistically non- significant differences were reported for OTM between control and experimental sides, and among the three groups. However, on clinical efficacy basis, the dose of 25 pg calcitriol produced about 51% faster rate of experimental canine movement compared to control, while each of the 15 pg and 40 pg doses resulted in about 10% accelerated OTM. Further more, the periapical radiographs showed no any damaging effect of calcitriol to the surrounding tissues. In conclusion, for the first time we reported that locally injected calcitriol, in dose dependent pattern, is clinical and cost effective in humans. INTRODUCTION Application of mechanical forces to teeth causes tooth movement as a result of the biological responses of the periodontal tissues. In orthodontic tooth movement, mechanical stress appears to evoke biochemical and structural responses in a variety of cell types both in vivo and in vitro 1,2 . Although current clinical systems in orthodontics use mechanical forces to induce bone remodeling, several researchers have suggested that there might be ways to increase cellular activity with agents more potent than mechanical force alone. Considerable scientific interest has been focused on chemical 3,4 or electrical stimuli in combination with mechanical forces for more rapid bone turnover and faster orthodontic tooth movement 5 . One of the most commonly studied agents in animal and clinical models is prostaglandin E 6,7 . Klein and Raisz reported that prostaglandin E1 (PGE 1 ) and prostaglandin E 2 (PGE 2 ) stimulated bone resorption, directly acting on osteoclasts, and had effects similar to those of parathyroid hormone. The role of vitamin D in the maintenance of calcium homeostasis in human beings has been well documented 8 . In particular, the active form of vitamin D, 1, 25- dihydroxycholecalciferol, is one of the most potent stimulators of osteoclastic activity known. It is also involved in the formation of osteoclasts from precursor monocytes and may produce these effects at much lower doses than other hormones such as prostaglandins. Collins and Sinclair 9 as well as Kale et al. have reported that the local administration of vitamin D increases the rate of tooth movement in cats and rats respectively; they have emphasized that administration of vitamin D results in a good balance between deposition and resorption of bone and well- modulated bone turnover compared to prostaglandin administration 10 . It has been shown to be a potent stimulator of bone resorption by inducing differentiation of osteoclasts from their precursors, as well as increasing activity of existing osteoclasts 11 . In vitro studies have shown that, upon administration of 1, 25-DHCC, osteoblast cell cultures demonstrate a two- to fourfold increase in osteoclastic bone resorption compared to controls. The same results are seen when 1, 25-DHCC is added to osteoclasts incubated alone. But upon administration of actinomycin D, a known inhibitor of osteoblast activity, 1,25-DHCC was unable to stimulate osteoclastic resorption 12 . Moreover, in vivo studies appearing in the orthodontic literature have shown increased levels of orthodontic tooth movement upon daily PDL injections of 1, 25-DHCC. The amount of increased tooth movement compared to controls has been reported to be as high as 60% in experimental animal models 9,13 . According to literature survey, no data available about using vitamin D in human trials; so, the present study was designed to evaluate the effect of locally injected 1,25-Dihydroxy-cholecalciferol (Vitamin D3 MATERIALS AND METHODS , Calcitriol) in accelerating orthodontic tooth movement in humans. Subjects Selection and Study Design The present open label study was conducted at Baghdad Teaching Hospital- College of Dentistry/Baghdad University, during the period from October 2010 to April 2011. The study protocol was in accordance with the ethics of the clinical research and approved by the committee of graduate studies in the College of Pharmacy/Baghdad University. After getting consent of the Orthodontic Department at Baghdad Teaching Hospital, sample selection was started by examining patients seeking orthodontic treatment at the postgraduate clinic. Selection of subjects has been done according to that they are orthodontic patients within the age range 17-28 years, with class I and II malocclusion cases that require bilateral maxillary 1 st Instruments, Chemicals and Methods premolars extraction and bilateral maxillary canines retraction (distalization). They should not have any history of chronic systemic illness, syndromes, craniofacial deformities; i.e. clinically healthy subjects, no previous orthodontic treatment, and no history of chronic drug intake; they should have vital teeth with healthy periodontium and no root resorption (examined by dental panoramic radiographs). After clinical examination of 48 patients indicated for the sample criteria and full interpretation of the research aims, signed consents were obtained only from 22 patients and/or their parents to participate as volunteers. Of those 22 patients, only 15 patients completed the research requirements. All subjects received Pre-adjusted Fixed Appliance treatment (Stainless Steel Roth 0.022" System, Dentaurum Co., Germany), and finished the 1 st (leveling and alignment) phase. Maxillary Canine retraction started in the 2 nd phase using stainless steel round 0.018" base archwire with a distalizing force of 150 g measured by a pressure gauge 14 . The anchorage for canine retraction included stoppers mesial to 1 st molars, 3 orders bends, ligation of 2 nd International Journal of Pharmacy and Pharmaceutical Sciences ISSN- 0975-1491 Vol 3, Suppl 5, 2011 A A c c a a d d e e m mi i c c S S c c i i e e n n c c e e s s