The effect of diabetes mellitus on rat mandibular bone formation and microarchitecture

Abbassy MA, Watari I, Soma K. The effect of diabetes mellitus on rat mandibular bone formation and microarchitecture. Eur J Oral Sci 2010; 118: 364–369. © 2010 The Authors. Journal compilation © 2010 Eur J Oral Sci The aim of this study was to assess the effect of type 1 diabetes mellitus (DM) on the structure of mandibular bone and on the changes of alveolar/jaw bone formation. Experimental DM was induced in 3‐wk‐old male Wistar rats by a single dose of 60 mg/kg body weight of streptozotocin. All rats were injected with calcein on days 21 and 28. The rats were killed when 8 wk of age. Bone structure was analyzed by bone histomorphometry, microcomputed tomography (micro‐CT), and histological section. Histomorphometric analysis showed that the mineral apposition and the bone formation rates in most of the mandibular regions were significantly decreased in the DM group compared with the control group. Micro‐CT analysis showed significant deterioration of the bone quality in rats with DM. For a histometric measure of bone resorption, the number of osteoclasts along the distal surface of the alveolar wall was counted. The number of osteoclasts was significantly lower in the rats with DM than in the controls. These findings suggest that uncontrolled DM decreases mandibular bone formation, reduces the rate of bone turnover in the alveolar wall surrounding the root, and affects the quality of bone structure resulting in retardation of its skeletal development.     

胰岛素样生长因子I对糖尿病大鼠拔牙后牙槽骨改建的影响

目的研究胰岛素样生长因子I（IGF—I）对糖尿病大鼠拔牙后牙槽骨改建的影响,为糖尿病性牙周病的治疗提供依据。方法对四氧嘧啶诱导的糖尿病大鼠拔牙后进行胰岛素和胰岛素样生长因子I治疗,通过X线、组织切片苏木精一伊红染色和四环素双标记的方法观察牙槽骨改建情况。结果与正常组相比,糖尿病大鼠拔牙创骨愈合减慢,骨形成减少,牙槽骨高度和牙槽骨骨形成率显著降低。IGF—I的治疗不仅能控制糖尿病大鼠的血糖保持在正常范围内,还可以增加牙槽骨高度和提高骨形成率。结论IGF-I的治疗可以促进糖尿病大鼠拔牙创骨愈合和增加骨形成量,且与胰岛素治疗之间没有明显差别。     

Effects of insulin‐like growth factor I on alveolar bone remodeling in diabetic rats

Fang Y, Wang L‐P, Du F‐L, Liu W‐J, Ren G‐L. Effects of insulin‐like growth factor I on alveolar bone remodeling in diabetic rats. J Periodont Res 2013; 48: 144–150. © 2012 John Wiley & Sons A/S Background and Objective: Diabetes is a chronic hyperglycemic disorder and results in a tendency to develop osteoporosis. Furthermore, the delayed healing of tooth‐extraction wounds, the activation of alveolar resorption and the suppressed formation of bone around implants are difficult for dentists to resolve. In diabetes, insulin‐like growth factor I (IGF‐I) appears to enhance the differentiation of osteoblasts and to activate the mineralization of bone. Hence, the aim of this study was to investigate the effects of insulin‐like growth factor I on the remodeling of alveolar bone in diabetic rats. Material and Methods: Diabetes was induced in 40 male Sprague‐Dawley rats by intravenous administration of alloxan. The teeth of the rats were extracted to investigate remodeling of alveolar bone. Insulin‐like growth factor I was administered, via intraperitoneal injection, to diabetic rats following tooth extraction. The remodeling of alveolar bone was determined using radiographic data, histological analyses and tetracycline fluorescence labeling. Results: Compared with the control group, diabetes decreased alveolar bone formation. The height of alveolar bone and the bone‐formation rate was significantly lower in the untreated diabetic group than in the control group or in the treated rats. Treatment with insulin‐like growth factor I not only regulated abnormal blood glucose levels but also increased the height of the alveolar bone and increased the bone‐formation rate relative to the results in diabetic animals. Furthermore, the expression of glucose transporter‐1, the main transporter of glucose, was changed by hyperglycemia. Conclusion: The results suggest that insulin‐like growth factor I treatment increases the volume of newly formed bone following tooth extraction and normalizes the expression of glucose transporter‐1 in diabetic rats, which may play an important role in bone formation and mineralization.     

糖尿病大鼠牙槽骨骨密度的变化

为了评价糖尿病大鼠牙槽骨代谢情况，采用放射免疫分析检测其血清骨钙素浓度，以双能量Ｘ线骨密度测量仪测量牙槽骨骨密度并结合组织学观察。结果表明，糖尿病大鼠血清骨钙素浓度升高，股骨与上、下牙槽骨骨密度降低，牙槽骨骨小梁变细变疏、骨吸收活跃，新骨形成减少。本研究结果提示，糖尿病大鼠牙槽骨骨吸收活跃，骨形成缓慢，有骨质疏松倾向。     

糖尿病大鼠牙槽骨骨密度与全身骨密度变化的相关实验研究

目的比较雌、雄性糖尿病大鼠牙槽骨骨密度的改变以及雄性糖尿病大鼠全身骨密度的改变。方法将40只Wistar大鼠分为糖尿病组（雌、雄性大鼠各15只）和对照组（雌、雄性大鼠各5只）。腹腔注射链脲佐菌素（STZ）制备糖尿病大鼠模型,检测糖尿病组和对照组大鼠血糖、血清胰岛素和骨代谢指标,检测下颌牙槽骨、股骨和腰椎的骨密度。结果对照组和糖尿病组雄性大鼠下颌牙槽骨骨密度均高于雌性大鼠（P<0.05）;糖尿病组雌、雄性大鼠下颌牙槽骨骨密度分别低于对照组雌、雄性大鼠（P<0.05）。对照组雄性大鼠的骨密度由高至低依次为股骨、下颌牙槽骨、腰椎;糖尿病组雄性大鼠的骨密度由高至低依次为下颌牙槽骨、股骨、腰椎。结论糖尿病雌、雄性大鼠下颌牙槽骨发生了糖尿病性骨质疏松,且雌性大鼠骨质疏松更严重;雄性糖尿病大鼠下颌牙槽骨、股骨和腰椎骨密度较对照组低,下颌牙槽骨骨密度变化与股骨和腰椎的变化相一致,或是糖尿病组大鼠下颌牙槽骨骨密度变化滞后于股骨和腰椎骨密度的变化。     

The influence of short-term diabetes mellitus and insulin therapy on alveolar bone loss in rats

BACKGROUND: It is well known that the multiple direct and indirect consequences of hyperglycemia in diabetic individuals have been linked to a number of abnormal host effector mechanisms that could lead to an increased risk of developing periodontal disease. OBJECTIVE: The aim of this study was to investigate the effect of short-term experimental diabetes and insulin therapy on the severity of alveolar bone loss in rats, and the effect of experimental periodontitis on glycemic control. METHODS: Seventy-two male Wistar rats were divided into four groups: group I animals were submitted to dental ligature around lower right first molars (ligated); group II consisted of streptozotocin (STZ)-diabetic, ligated rats; group III represented STZ-diabetic, unligated rats; and group IV consisted of insulin-treated (6 U/day), STZ-diabetic, ligated rats. Blood glucose of all diabetic rats was monitored at regular intervals. Standardized digital radiographs were taken after killing at 7, 15 and 30 days to measure the amount of bone loss about the mesial root surface of the first molar tooth in each rat. Results: No significant (p < 0.05) changes in plasma glucose levels of insulin-treated diabetic rats were found among the different examinations after the beginning of insulin therapy. Rats from group II showed significantly greater increases in mean plasma glucose levels at 15 and 30 days after ligature placement compared with rats from group III (p < 0.05). Furthermore, in spite of the significant alveolar bone loss progression that was observed in groups I, II and IV (p < 0.00001; two-way anova), no significant differences among these groups regarding the severity of bone loss (p = 0.77) and no significant interaction between treatment group and time (p = 0.81) were found. CONCLUSIONS: Within the limits of this study, it can be suggested that the severity of periodontal disease was not affected by short-term diabetes, and that experimental periodontitis increased blood glucose levels in uncontrolled diabetic rats.     

Effect of age on alveolar bone turnover adjacent to maxillary molar roots in male rats: A histomorphometric study

OBJECTIVE: The effect of age on alveolar bone turnover adjacent to maxillary molar roots of male rats was assessed histomorphometrically with special focus on bone formation and resorption. DESIGN: A total of 110 male Wistar rats ranging in age from 6 to 100 weeks were used for this study. Histomorphometric parameters were measured in fluorescence-labeled undecalcified ground and paraffin-embedded decalcified sections of the alveolar wall around the disto-lingual roots of the maxillary first molars. Bone formation was measured statically by determining the percentage of the bone surface that was double-labeled surface (dLS/BS), bone formation rate (BFR/BS), and mineral apposition rate (MAR). Bone resorption was quantified statically in terms of the number of osteoclasts (N.Oc/BS) and the percentage of the bone surface covered with osteoclasts (Oc.S/BS). RESULTS: For the total surface of the alveolar wall, the values obtained for all parameters of both bone formation and resorption decreased with advancing age. All these values rapidly decreased during the early part of the life span, from 6 to 30-40 weeks of age, of the rats. A site-specific difference between the distal and mesial sides of the alveolar wall was found for each age group. dLS/BS and BFR/BS were significantly greater (p < 0.0001) on the mesial side than on the distal one. On the other hand, the distal side showed significantly greater (p < 0.0001) value for N.Oc/BS and Oc.S/BS did the mesial one. However, there were no significant age-related changes in dLS/BS and BFR/BS on the distal side or in N.Oc/BS and Oc.S/BS on the mesial side throughout observation period. CONCLUSION: The results of the present study demonstrate that alveolar bone turnover of male rats decreased rapidly with advancing age but that in order to maintain the integrity of the tooth function mechanical stress may still have participated in bone formation and resorption of the alveolar wall even in rats 100-week old.     

Orthodontically induced root and alveolar bone resorption: inhibitory effect of systemic doxycycline administration in rats

The aim of the present study was to investigate the effect of systemic administration of low-dose doxycycline (DC) on orthodontic root resorption. The effect on alveolar bone, the cell population involved, and the amount of tooth movement were also evaluated.Fifty-six 40-50-day-old male Wistar rats were used. Six animals served as untreated controls. Six animals were only administered DC for 7 days, by means of a mini-osmotic pump implanted subcutaneously. In 44 animals the maxillary first molar was mesialized by a fixed orthodontic appliance exerting 50 g force upon insertion. In 28 of these animals DC was administered at the time of appliance insertion and throughout the experiment. The animals were sacrificed 7, 10 or 14 days after force application and block sections processed for analysis. An area including the mesial aspect of the distopalatal root and the adjacent inter-radicular alveolar bone was histomorphometrically evaluated. The root resorption area, absolute alveolar bone area, distance between first and second molars, number of odontoclasts, osteoclasts, mononuclear cells on the root, tartrate-resistant acid phosphatase (TRAP)-positive cells on the root, bone, and in the periodontal ligament (PDL) were compared between DC-treated and non-DC-treated animals.The results revealed a significant reduction in root resorption, the number of odontoclasts, osteoclasts, mononuclear cells on the root surface, and TRAP-positive cells on the root and bone for the DC-administered group. The absolute alveolar bone area was greater, whereas the distance between the first and second molars did not differ between groups. In conclusion, systemic administration of low-dose DC in rats may have an inhibitory effect on orthodontically induced resorptive activity.     

Effect of diabetes on orthodontic tooth movement in a mouse model

Orthodontic tooth movement is achieved by the remodeling of alveolar bone in response to mechanical loading. Type 1 diabetes results in bone remodeling, suggesting that this disease might affect orthodontic tooth movement. The present study investigated the effects of the diabetic state on orthodontic tooth movement. An orthodontic appliance was placed in normoglycemic (NG), streptozotocin-induced diabetes (DB), and insulin-treated DB (IT) C57BL6/J mice. Histomorphometric analysis and quantitative PCR of periodontium were performed. The DB mice exhibited greater orthodontic tooth movement and had a higher number of tartrate-resistant acid phosphate (TRAP) -positive osteoclasts than NG mice. This was associated with increased expression of factors involved in osteoclast activity and recruitment (Rankl, Csf1, Ccl2, Ccl5, and Tnfa) in DB mice. The expression of osteoblastic markers (Runx2, Ocn, Col1, and Alp) was decreased in DB mice. Reversal of the diabetic state by insulin treatment resulted in morphological findings similar to those of NG mice. These results suggest that the diabetic state up-regulates osteoclast migration and activity and down-regulates osteoblast differentiation, resulting in greater orthodontic tooth movement.     

Alendronate therapy in cyclosporine-induced alveolar bone loss in rats

BACKGROUND AND OBJECTIVE: Cyclosporine A is an immunosuppressive drug that is widely used in organ transplant patients as well as to treat a number of autoimmune conditions. Bone loss is reported as a significant side-effect of cyclosporine A use because this can result in serious morbidity of the patients. As we have shown that cyclosporine A-associated bone loss can also affect the alveolar bone, the purpose of this study was to evaluate the effect of the concomitant administration of alendronate on alveolar bone loss in a rat model. MATERIAL AND METHODS: Forty Wistar rats (10 per group) were given cyclosporine A (10 mg/kg, daily), alendronate (0.3 mg/kg, weekly), or both cyclosporine A and alendronate, for 60 d. The control group received daily injections of sterile saline. The expression of proteins associated with bone turnover, including osteocalcin, alkaline phosphatase and tartrate-resistant acid phosphatase (TRAP), and also the calcium levels, were evaluated in the serum. Analysis of the bone volume, alveolar bone surface, the number of osteoblasts per bone surface and the number of osteoclasts per bone surface around the lower first molars was also performed. RESULTS: The results indicate that cyclosporine A treatment was associated with bone resorption, represented by a decrease in the bone volume, alveolar bone surface and the number of osteoblasts per bone surface and by an increase in the number of osteoclasts per bone surface and TRAP-5b. These effects were effectively counteracted by concomitant alendronate administration. CONCLUSION: It is concluded that concomitant administration of alendronate can prevent cyclosporine A-associated alveolar bone loss.     

Diabetes enhances periodontal bone loss through enhanced resorption and diminished bone formation

Using a ligature-induced model in type-2 Zucker diabetic fatty (ZDF) rat and normoglycemic littermates, we investigated whether diabetes primarily affects periodontitis by enhancing bone loss or by limiting osseous repair. Diabetes increased the intensity and duration of the inflammatory infiltrate (P < 0.05). The formation of osteoclasts and percent eroded bone after 7 days of ligature placement was similar, while four days after removal of ligatures, the type 2 diabetic group had significantly higher osteoclast numbers and activity (P < 0.05). The amount of new bone formation following resorption was 2.4- to 2.9-fold higher in normoglycemic vs. diabetic rats (P < 0.05). Diabetes also increased apoptosis and decreased the number of bone-lining cells, osteoblasts, and periodontal ligament fibroblasts (P < 0.05). Thus, diabetes caused a more persistent inflammatory response, greater loss of attachment and more alveolar bone resorption, and impaired new bone formation. The latter may be affected by increased apoptosis of bone-lining and PDL cells.     

糖尿病大鼠正畸牙齿移动及组织学变化

目的 探讨糖尿病大鼠正畸牙移动对牙周组织的影响。方法 选用80只雄性SD大鼠，牵引左上颌第一磨牙近中移动。实验组以STZ腹腔注射制备Ⅰ型糖尿病模型，对照组注射柠檬酸缓冲液，3周后开始实验。分别在加力0、3、7、14、21天处死大鼠，记录上颌第一磨牙移动距离，组织HE染色后，观察牙周组织形态学的改变。结果 ①实验组大鼠牙齿移动距离在移动末期明显大于对照组；②实验组骨质疏松；③实验组大鼠压力侧破骨细胞数在骨吸收期少于对照组，3、7、14天有统计学意义；④实验组大鼠在骨形成期张力侧成骨细胞数少于对照组，14、21天有统计学意义。结论 ①糖尿病性骨质疏松导致正畸牙齿移动末期牙齿移动速度加快；②糖尿病骨质反应能力降低，牙齿移动过程中破骨活动和成骨过程均受抑制。     

The effects of colony-stimulating factor-1 on tooth eruption in the toothless (osteopetrotic) rat in relation to the critical periods for bone resorption during tooth eruption.

The toothless (tl) rat is an osteopetrotic mutation characterized by a generalized skeletal sclerosis, reduced bone resorption, few osteoclasts and a total absence of erupted teeth. This mutation is not cured by bone marrow transplants from normal littermates. It is known that the skeletal defects in tl rats are greatly improved after treatment with colony-stimulating factor-1 (CSF-1). This investigation concerns the effects of CSF-1 on the development and eruption of the dentition of tl rats. Untreated tl rats had no erupted teeth by 56 days after birth, and the roots of incisors and molars were severely distorted by compression against bone. The apex of the mandibular incisor did not extend past the first molar and continued growth of its apical end produced odontoma-like masses consisting of distorted dentine and enamel matrices. In addition, few osteoclasts were seen on alveolar bone surfaces surrounding the developing teeth. Mutants given CSF-1 were characterized by delayed eruption of all molars and sometimes incisors. The incidence of incisor eruption was related inversely to the age at which CSF-1 treatment began. Molars of treated tl rats had well-developed roots similar to those in normal rats. Treated mutants had numerous osteoclasts in alveolar bone and well-developed haemopoietic marrow spaces in the mandible. Histochemical staining for both tartrate-resistant acid phosphatase and tartrate-resistant acid ATPase was reduced or negligible in osteoclasts of untreated tl rats, heavy in normal osteoclasts and of intermediate intensity in CSF-1-treated mutants.(ABSTRACT TRUNCATED AT 250 WORDS)     

糖尿病大鼠牙周组织改变的实验观察

目的 探索大鼠发生糖尿病后对其牙周组织的影响.方法 建立糖尿病大鼠动物模型,分别在1、3和6个月三个不同时期,用光镜观察和免疫组织化学染色方法研究大鼠的牙周组织改变.结果 糖尿病大鼠1个月时即有牙槽骨的吸收破坏, 3个月至6个月时骨吸收范围扩大,牙周纤维排列紊乱和断裂.骨吸收仅位于牙槽骨侧,而牙体侧牙骨质和牙周膜无破坏.结论 大鼠在发生糖尿病后,出现特异性牙槽骨吸收为主要特征的病理性改变.     

A quantitative study of osteoclastic bone resorption during experimental periodontal disease in the golden hamster

The aim of this study was to measure the osteoclastic resorption of alveolar bone during an experimental periodontal disease. Twenty golden hamsters were used: 10 animals were fed a normal diet and served as controls and 10 animals were fed the Keyes hyperglucidic diet during 6 months to induce periodontal disease. The results show that the different surfaces of alveolar bone do not react in the same proportion: the number of osteoclasts is greatly and significantly increased (p < 0.001) along the periosteum, significantly increased (p < 0.01) along the endosteum, and not modified along the alveolar wall.The number of osteoclasts along the alveolar wall is negatively correlated with the number of osteoclasts along the endosteum and the periosteum.     

二膦酸盐对骨质疏松大鼠下颌牙槽骨牙本质基质蛋白1表达的影响

目的 :观察二膦酸盐对去卵巢骨质疏松大鼠下颌牙槽骨内破骨细胞以及牙本质基质蛋白1(dentin matrix protein1,DMP1)表达的影响。方法 :取6月龄SD大鼠30只,随机分为假手术组(Sham)、去卵巢模型组(OVX)和二膦酸盐药物治疗组(RIS),每组10只。Sham组大鼠仅术中暴露卵巢不切除,OVX组大鼠行"双侧卵巢切除术+生理盐水皮下注射",RIS组行"双侧卵巢切除术+利塞磷酸钠(2.4μg/kg)皮下注射"。术后3个月取各组大鼠下颌骨常规脱钙,甲苯胺兰染色观察下颌第一磨牙(M1)区域牙槽骨组织学结构,抗酒石酸酸性磷酸酶(tartrate-resistant acid phosphatase,TRAP)染色观察M1区域牙槽纵隔破骨细胞的骨吸收情况,免疫组化染色观察各组M1牙槽骨DMP1分布表达情况,并进行相关半定量图像分析。结果:与Sham组相比,OVX组TRAP阳性细胞数增加;而较OVX组而言,RIS组TRAP阳性细胞数显著减少(P<0.05)。免疫组化染色显示,各组DMP1不仅表达在牙槽骨骨细胞内,牙槽间隔的松质骨骨基质、牙周韧带中均可见其表达,OVX组M1牙槽骨DMP1表达较Sham组减少(P<0.05),而RIS组表达较OVX组有升高。结论:二膦酸盐能减少骨质疏松大鼠下颌牙槽骨破骨细胞数量,并上调DMP1表达,从而影响下颌牙槽骨矿化。     

Quantitative analyses of osteoclasts, bone loss and inflammation in human periodontal disease

Human autopsy specimens bearing posterior teeth with interproximal areas were studied by quantifying various histological parameters. Osteoclasts were found to be equally frequent on the crestal, alveolar wall and endosteal alveolar bone surfaces. Evidence of previous resorption in the form of scalloping suggested that osteoclastic activity had also occurred in the past. The size of the inflammatory infiltrate was significantly correlated with the degree of bone loss, but not with the number of osteoclasts. However, the distance from the apical border of the inflammatory infiltrate to the alveolar bone crest was significantly correlated with both the number of osteoclasts on the alveolar crest, as well as their total number. These findings in the human periodontitis lesion support those from the animal model system which have indicated that the proximity of the inflammatory infiltrate to the bone surface is a significant factor in the osteoclastic resorption of alveolar bone.     

细胞凋亡及其相关基因Bcl-2和 Bax在大鼠正畸牙槽骨改建中的作用

目的：观察大鼠正畸牙齿移动中牙槽骨的细胞凋亡现象以及凋亡相关基因Ｂｃｌ－２和Ｂａｘ的表达,初步探讨细胞凋亡在牙槽骨改建中的作用。方法：选用２５只健康雄性ＳＤ大鼠,用单簧圈别针簧矫治器推上颌切牙侧向移动,于加力后１、３、５、７ｄ系列观察牙槽骨中细胞凋亡及其相关基因Ｂｃｌ－２和Ｂａｘ的表达,以正常组为对照,用免疫组织化学方法和ＴＵＮＥＬ法进行检测。结果：正常牙槽骨组织中存在凋亡细胞,主要见于骨细胞,呈散在性分布,数量较少。牙齿移动时,压力侧牙槽骨改建活跃,凋亡细胞有增多趋势,而张力侧牙槽骨凋亡细胞呈减少趋势。在成骨细胞、破骨细胞、透明性变区未检测到凋亡细胞。Ｂｃｌ－２和Ｂａｘ在正常牙槽骨细胞均有表达,在压力侧Ｂａｘ的表达强于Ｂｃｌ－２,在成骨细胞和破骨细胞Ｂｃｌ－２的表达强于Ｂａｘ。结论：细胞凋亡及其相关基因Ｂｃｌ－２和Ｂａｘ参与了正畸牙齿移动过程中牙槽骨的改建过程。     

S100A9在糖尿病大鼠牙周组织中的表达及其作用研究

目的 研究S100A9蛋白在糖尿病大鼠牙周组织中的表达,探讨其在糖尿病诱发的牙周病变中可能的作用机制。方法 本实验通过对SD大鼠腹腔注射链脲佐菌素（STZ）构建糖尿病大鼠模型,通过苏木精-伊红（HE）染色观察糖尿病大鼠牙周结构的变化,免疫组织化学染色观察糖尿病大鼠牙周组织中S100A9的表达与分布,同时检测其配体Toll受体4（TLR4）和核转录因子κB（NF-κB）/p-P65蛋白的表达。通过分析上述蛋白的表达规律,探讨S100A9蛋白在糖尿病诱发的牙周病变中的作用机制。结果 糖尿病大鼠的牙槽骨骨小梁结构稀疏,硬骨板消失;免疫组织化学染色显示牙周膜、牙槽骨及牙龈上皮中S100A9的表达水平比对照组明显上调,TLR4在牙槽骨、牙周膜、牙龈中的表达水平相较于对照组也显著增强;p-P65在对照组中没表达,但在糖尿病组中牙周膜和牙槽骨中呈阳性表达。结论 糖尿病导致大鼠牙周组织结构病变,其原因可能与S100A9介导的TLR4和NF-κB信号通路的活化有关。     

Bone formation around titanium implants in the rat tibia: role of insulin

BACKGROUND AND PURPOSE: Clinical and experimental studies show, with few exceptions, that type 1 diabetes mellitus is associated with a delay in bone repair around endosseous implants. The effect of insulin in bone repair/remodeling is not completely understood. The aim of this study was to investigate the course of histological and ultrastructural changes of the osseointegration process under the influence of insulin. MATERIALS AND METHODS: Titanium implants were inserted into the tibiae of male Wistar rats. Animals were divided into three groups: 1) rats with alloxan-induced diabetes; 2) diabetic rats treated with isophane insulin (2 IU/day); and 3) matching controls. Histological and histomorphometric analysis of bone-implant sections were performed 10 and 21 days after implant placement. RESULTS: Relative to control values, rats with alloxan-induced diabetes exhibited a 50% reduction in the area of formed bone (P < 0.001) and in the surface of contact between bone and implant (P < 0.01) 21 days after implant placement. There were no significant differences between groups 10 days after surgery. Values returned to normal levels in diabetic rats after insulin treatment. Presence of chondrocyte-like cells surrounded by a cartilaginouslike matrix in diabetic rats suggests a delay in the process of bone repair. Ultrastructural characteristics of bone-implant interface in diabetic rats treated with insulin resembled those observed in controls. CONCLUSION: The data presented suggest that bone repair around endosseous implants is regulated, at least in part, by insulin. The results imply that the control of the metabolic status of the diabetic patient is essential for a successful osseointegration.