use of orthodontic mini - implants is gaining popularity due to providing absolute anchorage without reactive tooth movement . with skeletal anchorage such as osseous dental implants , miniplates , miniscrews , or microscrews , clinicians can expect reliable anchorage while depending less on patient compliance [ 17 ] . most current orthodontic mini - implants have untreated screw surfaces , and mini - implants achieve primary stability through mechanical retention [ 5 , 8 ] . in the field of prosthodontics , surface - treated dental implant is preferred due to its improved osseointegration [ 912 ] . a few surface - treated orthodontic mini - implants are available and their removal torque is higher than smooth surface mini - implant . surface - treated mini - implants are reported to have less failure and can support heavier and more dynamic forces [ 13 , 14 ] . recently , the number of adult orthodontic patients is increasing in the past few years . diabetes mellitus is a group of metabolic diseases in which a person has high blood sugar , either because the body does not produce enough insulin or because cells do not respond to the insulin that is produced . two fasting glucose measurements above 126  mg / dl ( 7.0  mmol / l ) are considered diagnostic for diabetes mellitus . according to u.s . department of health and human services , 14.7 million people are diagnosed with diabetes from the age of 20 to 65 . 15,600 youth ( younger than 20 years of age ) were newly diagnosed with type 1 diabetes annually in the usa . although there has been some conflicting evidence , diabetic patients seem to be more prone to infection and delayed healing after surgery . furthermore , some animal studies report that diabetes interferes with the process of osseointegration [ 1519 ] . clinical application and prognosis of implants in healthy patients have been studied extensively and long - term success of prosthodontic implant has been documented . however , it is not known whether diabetes increases risk of mini - implant failure . in diabetic patients , comparative study between surface - treated implants and machine - surfaced implants has not been performed . this study aimed to investigate effect of surface - treated orthodontic mini - implants in diabetic patients . osseointegration on both the surface - treated and smooth surface mini - implants was examined . streptozotocin and alloxan , having specific cytotoxic effects on pancreatic beta - cells , are widely used to induce diabetes mellitus in animal studies . there have been many studies to induce diabetes in rats [ 20 , 21 ] . but few studies were performed in rabbits and this study was novel in inducing diabetes in rabbits . there was trial and error when finding the dosage of alloxan and timing of glucose injection . after the pilot animal study to clarify the adjustment of diabetic induction , 12 new zealand white rabbits , weighing approximately 3  kg , were used . eighteen rabbits were assigned to diabetic group and single intravenous injection of 150  mg / kg body weight 10% alloxan monohydrate ( sigma co. , st . after injection of alloxan , 20  ml of 5% glucose ( jw pharmaceutical , seoul , republic of korea ) was injected 5 times subcutaneously to prevent hypoglycemic shock . blood glucose was monitored by the glucose - oxidase method one week after the injection of alloxan . tail - nicked blood samples were obtained and rabbits were also monitored for weight loss or gain as an indicator of overall health weekly . if the glucose level was over 200  mg / dl , a diagnosis of diabetes was made [ 20 , 21 ] . blood glucose levels in diabetic rabbits were more than 300  mg / dl throughout the entire experiment ( figure 1 ) . experiment protocol was approved by the institutional animal care and use committee ( the catholic university of korea , st . mary 's hospital , seoul , republic of korea ) ( cumc-2010 - 0094 - 04 ) . a total of 48 orthodontic mini - implants were used in this study ( 24 sla surface - treated , 24 smooth surface implants ) . the mini - implants were 1.8  mm in diameter and 8.5  mm in length . they were two - component system composed of screw and head portion ( threaded portion 6.5  mm ) ( cimplant co. , seoul , republic of korea ) . the mini - implants were self - tapping and dull - pitched modified cylinder type and they were the same for both diabetic and control groups except for the surface treatment of one group . because blood glucose level increased significantly after injection and steadily maintained during 4 weeks and body weight decreased in diabetic group from 3 weeks ( figure 2 ) ; the implants were placed on six healthy controls and six diabetic rabbits 4 weeks after the induction of diabetes . two anesthetics were intramuscularly administered for general anesthesia , tiletamine - zolazepam ( 10  mg / kg , zoletil , virbac korea co. , seoul , republic of korea ) and xylazine ( 2  mg / kg , rompun , bayer korea , seoul , republic of korea ) . to obtain local anesthesia and hemostasis , 1.8  ml of local anesthetic ( 2% lidocaine with 1  :  100,000 epinephrine ) was injected in the surgical site . the dissection was performed with a number 15 blade through skin and subcutaneous tissue to the periosteum and fascia . mini - implants were placed according to the randomized balanced complete block design to maintain sufficient distance between each other and minimize the position difference and variation [ 13 , 23 ] . predrilling was carried out with 1.5  mm diameter guide drill under profuse irrigation to penetrate 3.5  mm into the bone . mini - implants were placed to penetrate through the first cortical layer and reach approximately 6.5  mm . a surgical engine ( elcomed sa 200  c , w&h , burmoos , austria ) was used to record insertion torque in every 0.125 second during insertion of mini - implants . insertion depth was controlled by fully embedding surface - treated area into bone [ 23 , 24 ] . analgesics ( ketoprofen 1  mg / kg , q.d . ) and antibiotics ( gentamicin 4  mg / kg , q.d . ) were subcutaneously administered for 3 days . six diabetic and six control rabbits were randomly sacrificed following four weeks of healing period with overdose of anesthetics . bone metabolism in rabbit is three times faster than human and four weeks in rabbit correspond to 3 months in human . a total of 32 implants were removed from 4 control rabbits and 4 diabetic rabbits . removal torque was measured with the surgical engine , during counterclockwise rotation . for mechanical analysis , torque was measured continuously during insertion and removal of mini - implants , and maximum torque was extracted from these measures . specimens for the histomorphometric evaluation were prepared with 16 mini - implants around tibia in remaining two control rabbits and 2 diabetic rabbits . tibia containing mini - implants were dehydrated in step gradients of ethanol ( 70% , 80% , 90% , and 100% ) and infiltrated and embedded in a mixture of ethanol and technovit 7200 resin ( exakt gmbh , germany ) . samples were sectioned by exakt diamond cutting system after hardening of resin and the sections were polished to a final thickness of 40  5  m by exakt grinding system . ccd camera ( spot insight 2  mp scientific ccd digital camera system , diagnostic instrument , inc . , usa ) , attached to light microscope ( bx51 , olympus , japan ) , was used to obtain images . digitized images were evaluated histomorphometrically using spot software v 4.0 ( diagnostic instrument , usa ) and image pro plus ( media cybernetics , usa ) . the percentage of bone to implant contact ( bic % ) was calculated as total bic divided by total circumference of mini - implant  100 . the amount of total energy during placement and removal was calculated using a computer program . statistical analysis was performed with the language r. two - way anova ( analysis of variance ) was calculated to compare the results according to the presence of diabetes and surface treatment . figure 1(a ) shows the weights of the rabbits ( mean  standard deviation ( sd ) ) in both groups . the diabetic group showed a significant decrease in weight from 3 weeks in comparison with the control group ( p < 0.05 ) . one week after injection of 10% alloxan monohydrate , the glucose - oxidase method showed that the blood glucose levels showed hyperglycemic state throughout the entire experiment and sustained weight loss was observed in diabetic rabbits as in previous studies [ 20 , 21 ] . no significant inflammation was found at the surgical site . in both diabetic and control groups , all the mini - implants remained stable and did not fail until removal . there was no significant difference between diabetic and control groups in maximum insertion torque , regardless of surface treatment . total insertion energy was higher in control group than diabetic group . in maximum removal torque total removal energy was greater in diabetic group but difference was not clinically significant . in the diabetic group , maximum removal torque and total removal energy were significantly higher in the surface - treated group than in the smooth surface group . in the healthy control group , however , there was no significant difference in total removal energy between the surface - treated group and the smooth surface group . bic was increased in the control group compared with the diabetic group without statistical significance . similarly , in both control and diabetic groups , bic was increased in surface - treated group compared with non - surface - treated group but there was no significantly statistical difference ( table 1 ) . previous literatures have reported that diabetic state led to more bone loss and reduced bone formation . long - term increase in blood glucose concentration alters the response to parathyroid hormone that suppresses osteoblast differentiation and regulates the metabolism of calcium and phosphate . hyperglycaemia leads to increased formation and accumulation of advanced glycation end products ( ages ) in the blood . these molecules develop microvascular complications and reduce the number of osteoblasts and the level of osteocalcin and hence have an effect on bone matrix and slow bone formation [ 2729 ] . the diabetic hyperglycemic state also has a negative impact on mineral deposition and bone density and delays bone healing and metabolism . maximum insertion and removal torque and total insertion and removal energy were used to evaluate osseointegration and stability of the mini - implant . total insertion energy is the total energy recorded from the beginning of insertion to the point at which the maximum insertion torque is reached . the pressure exceeding the normal limit can cause complications such as blood circulation blockage and microfracture . contact area and removal torque between bone and implant were increased over time and highly correlated . to minimize measuring error , a surgical engine , which can record the torque in every 0.125 second during insertion and removal of mini - implants , was used to measure maximum insertion and removal torque and total insertion and removal energy . in maximum insertion torque , there was no significant difference between diabetic and control groups . total insertion energy , however , was higher in the control group than the diabetic group . total insertion energy is the area below the graph of continuous torque measured during placement . the slope of the graph to maximum insertion torque is steeper in control group than diabetic group . therefore , total insertion energy , the area below the steep graph , is greater in control group than diabetic group . the stress applied to adjacent bone at the time of implantation is thought to be less in diabetic group due to compromised bone quality . total removal energy was greater in diabetic group but the amount of difference was not clinically significant . these findings were interesting , since the authors had anticipated that maximum removal torque and total removal energy would be higher in the normal group than in the diabetic group . this result can be interpreted that there is not much difference between control and diabetic groups in mechanical interlocking between bone and implant surface . currently , most of available orthodontic mini - implants are not surface - treated . in this study , the difference in osseointegration between the surface - treated group and the non - surface - treated group was investigated through the placement of implants in healthy controls and diabetic rabbits , respectively . since the mini - implants in this study are in same shape , the amount of load to surrounding bone during placement was not significantly different ; thus total insertion energy was similar between smooth surface group and sla treated group . and because the moment of disosseointegration is maintained very shortly and decreases rapidly to zero , degree of osseointegration is represented in maximum removal torque rather than total removal energy . the maximum removal torque of the surface - treated group was significantly higher than that of the smooth surface group in both the diabetic and control groups . surface - treated mini - implants showed more resistance by showing higher maximum removal torque in both diabetic ( 6.13  ncm > 3.94  ncm ) and control groups ( 5.31  ncm > 3.75  ncm ) . this result means that the surface treatment enhances the osseointegration of mini - implants even in a diabetic patient . thus , 4 weeks in rabbit indicates 3 months in human . both maximum removal torque and total removal energy were greater in sla mini - implants than smooth surface mini - implants in diabetic group . total removal energy is the total energy recorded from the point at which the maximum removal torque is reached to the end of the removal procedure . this was higher in sla treated mini - implant than smooth surface mini - implants in diabetic group . therefore , in diabetic patient , sla treated mini - implants can be recommended . in a previous study where osseointegration was histometrically analyzed 12 weeks after implantation , bic had no significant difference between diabetic and normal groups . however , small sample size due to high mortality rate of rabbits during diabetes induction may be one of the reasons that bic is not being significantly different . another reason can be wide range of standard deviation resulting in less accurate bic measurement . the tibia in rabbit is a site more abundant in bone marrow than in rats . since the mini - implants were not loaded during the healing process , it can be assumed that the bone healing showed no significant difference at the interface between the mini - implant and bone in the diabetic group or the control group . further study needs to be performed when orthodontic forces are applied on mini - implants . moreover , type 1 diabetes was induced in this study , whereas type 2 diabetes is more clinically prevalent . in prolonged type 2 diabetes , however , the insulin deficiency can be advanced as in type 1 diabetes , so the result of this study may have relevance to many clinical situations . to understand the effective use of orthodontic mini - implants in the diabetic patient , a study was performed comparing normal rabbits to rabbits with intentionally induced diabetes . it can be concluded that the use of orthodontic mini - implants in a diabetic patient is likely to show results similar to the healthy patient . various literatures reported that surface - treated mini - implants had improved osseointegration than smooth surface mini - implants . this applies to diabetic state as well in terms of surface treatment . in conclusion ,
introduction . 
 the purpose of this study was to investigate effects of surface treatment of mini - implants in diabetes - induced rabbits by comparing osseointegration around mini - implants . 
 methods . 
 twelve new zealand white rabbits were divided into two groups ( alloxan - induced diabetic group and control group ) . 
 a total of 48 mini - implants were placed after four weeks of diabetic induction . 
 24 mini - implants were surface - treated with sla ( sandblasted with large grit , and acid etched ) and the remaining 24 mini - implants had smooth surfaces . 
 four weeks after placement , 32 mini - implants were removed from 4 control and 4 diabetic rabbits . 
 insertion and removal torques were measured . 
 the remaining 16 mini - implants from the two groups were histomorphometrically analyzed . 
 results . 
 maximum insertion torque showed no difference between diabetic and control groups , but total insertion energy was higher in control group . in surface - treated mini - implants , 
 maximum removal torque was higher in both diabetic and control groups . 
 bone - implant contact ( bic ) was increased in the control group when compared to the diabetic group . 
 surface - treated group had higher bic than smooth surface group in both control and diabetic groups 
 . however , there was no significantly statistical difference . conclusions . 
 type 1 diabetes mellitus and surface treatment method of mini - implant affected primary stability of mini - implants . 
 in addition , the use of orthodontic mini - implants in a diabetic patient is likely to show results similar to the healthy patient .