Department of Orthodontics, School of Dentistry, Aichi-Gakuin University, Nagoya 464-8651, Japan.
J Bone Miner Metab. 2009;27(6):663-72. doi: 10.1007/s00774-009-0090-6. Epub 2009 May 13.
Bisphosphonates (BPs) are clinically used for the treatment of bone metabolic abnormalities because they are powerful inhibitors of bone resorption. Osteonecrosis of the jaw has been observed after tooth extraction in a considerable number of BP-treated cancer patients, but the reason for this is not known. We studied the effects of BP on extraction socket healing in rats that were pretreated with BP prior to tooth extraction. Male Wistar rats (approximately 5 weeks old) were divided into experimental (BP) and control groups. In both groups, maxillary right second molars were extracted under general anesthesia. BP group rats were injected with 50 microl (1.0 mg/kg) alendronate into the right buccal alveolar bone every 4 days for 14 days, starting 2 days before tooth extraction. Control group rats were injected with physiological saline instead of alendronate. Rats were euthanized 3, 7, 10 or 14 days after tooth extraction, and maxillary bones were collected. Bone morphometric analysis using microfocus X-ray CT images and calculation of bone-resorption parameters based on hematoxylin and eosin or TRAP-stained pathological sections of the molar region showed that new bone formation in the extraction socket was delayed in the BP group relative to the control group during the first 7 days after extraction. A subsequent increase in new bone formation showed that bone resorption in the BP rats was eventually inhibited. This delay in initial healing may explain the jaw osteonecrosis observed in some BP-treated cancer patients.
双膦酸盐 (BPs) 临床上用于治疗骨骼代谢异常，因为它们是强大的骨吸收抑制剂。在相当数量的接受 BP 治疗的癌症患者中，拔牙后观察到下颌骨坏死，但原因尚不清楚。我们研究了 BP 对接受 BP 预处理的大鼠拔牙窝愈合的影响。雄性 Wistar 大鼠（约 5 周龄）分为实验组（BP）和对照组。在两组中，均在全身麻醉下拔除上颌右侧第二磨牙。BP 组大鼠在拔牙前 2 天开始，每 4 天向右侧颊牙槽骨注射 50 微升（1.0mg/kg）阿仑膦酸钠，共 14 天。对照组大鼠注射生理盐水代替阿仑膦酸钠。拔牙后 3、7、10 或 14 天处死大鼠，采集上颌骨。使用微焦点 X 射线 CT 图像进行骨形态计量学分析，并根据摩尔区域的苏木精和伊红或 TRAP 染色病理切片计算骨吸收参数，结果显示，与对照组相比，BP 组拔牙窝内新骨形成在拔牙后前 7 天延迟。随后新骨形成增加表明 BP 大鼠的骨吸收最终受到抑制。这种初始愈合的延迟可能解释了一些接受 BP 治疗的癌症患者中观察到的下颌骨坏死。
