Serrão Caroline Ribeiro, Bastos Marta Ferreira, Cruz Daniele Ferreira, de Souza Malta Fernando, Vallim Paolla Camacho, Duarte Poliana Mendes
Int J Oral Maxillofac Implants. 2017 May/Jun;32(3):547-554. doi: 10.11607/jomi.5754.
There is interest in establishing hypoglycemiant agents able to contain/revert the impact of diabetes mellitus on osseointegration. The purpose of this study was to assess the possible effect of metformin in reversing the negative effects of hyperglycemia on the healing of bone surrounding implants inserted in rats.
Rats (10 per group) were assigned to one of the following groups: DM group: type 2 diabetic rats deprived of metformin (M) treatment; MDM group: type 2 diabetic rats under M treatment (40 mg/kg/day, starting on the 15th day after implant placement); control group: nondiabetic rats without M treatment. At 30 days after streptozotocin injection, titanium implants were placed in tibiae. Animals were euthanized 30 days after implant surgery. Bone-to-implant contact (BIC), bone area (BA), and the number of receptor activator of nuclear factor κB ligand (RANKL)- and osteoprotegerin (OPG)-stained cells were assessed in cortical and medullary areas.
The percentages of BIC and BA in the cortical bone were reduced in the DM and MDM groups compared with the control group (P < .05). The percentage of BA in the medullary region was reduced in the DM group compared with the control group (P < .05). The MDM group showed the greatest number of OPG-stained cells, while the DM group presented the greatest ratio of RANKL/OPG in the medullary area (P < .05).
Metformin did not modulate the damaging effect of hyperglycemia on bone healing around implants at histometric levels, but increased the expression of OPG and decreased the RANKL/OPG ratio in the medullary area, yielding some molecular benefits in the osseointegration of implants under the hyperglycemic state.
人们对于建立能够抑制/扭转糖尿病对骨整合影响的降血糖药物很感兴趣。本研究的目的是评估二甲双胍在逆转高血糖对大鼠植入物周围骨愈合的负面影响方面的可能作用。
将大鼠（每组10只）分为以下几组：糖尿病组：未接受二甲双胍（M）治疗的2型糖尿病大鼠；二甲双胍治疗糖尿病组：接受M治疗（40mg/kg/天，从植入物放置后第15天开始）的2型糖尿病大鼠；对照组：未接受M治疗的非糖尿病大鼠。在链脲佐菌素注射30天后，将钛植入物植入胫骨。植入手术后30天对动物实施安乐死。评估皮质和髓质区域的骨与植入物接触（BIC）、骨面积（BA）以及核因子κB受体激活剂配体（RANKL）和骨保护素（OPG）染色细胞的数量。
与对照组相比，糖尿病组和二甲双胍治疗糖尿病组皮质骨中的BIC和BA百分比降低（P < 0.05）。与对照组相比，糖尿病组髓质区域的BA百分比降低（P < 0.05）。二甲双胍治疗糖尿病组显示OPG染色细胞数量最多，而糖尿病组在髓质区域的RANKL/OPG比值最高（P < 0.05）。
二甲双胍在组织计量学水平上并未调节高血糖对植入物周围骨愈合的破坏作用，但增加了髓质区域OPG的表达并降低了RANKL/OPG比值，在高血糖状态下对植入物的骨整合产生了一些分子层面的益处。
