Nilsson O S, Bauer F C, Broström L A, Nilsonne U
Cancer Res. 1984 Apr;44(4):1653-6.
Heterotopic new bone formation was induced by implanting pieces of demineralized bone matrix in the abdominal wall of 22 growing Sprague-Dawley rats. The animals were divided into three groups and were given, 24 hr after initiation of the bone induction process, a single i.v. injection of methotrexate, 100 or 250 mg/kg body weight, or placebo, followed after 2 hr by leucovorin rescue. A slight and transient arrest in weight gain was noted in the methotrexate-treated animals. New bone formation during 3 weeks after implantation was analyzed by the amount of ash in implants, and as a measure of bone formation at the end of the experiment, short-time incorporation of 45Ca and [3H]proline was used. The ash content of implants was reduced by 56 and 68% in the two methotrexate groups. Uptake of both nucleotides was also greatly reduced in heterotopic bone, whereas metaphysial and diaphysial tibia and teeth were not affected. The results indicate a pronounced inhibition of methotrexate on bone induction, persisting for at least 3 weeks. Methotrexate reduces the bone-forming potential, with possible consequences for the success of limb-saving surgery and fracture healing.
通过在22只生长中的斯普拉格-道利大鼠腹壁植入脱矿骨基质片诱导异位新骨形成。将动物分为三组，在骨诱导过程开始24小时后，静脉注射一次甲氨蝶呤，剂量为100或250毫克/千克体重，或注射安慰剂，2小时后给予亚叶酸救援。甲氨蝶呤治疗的动物体重增加略有短暂停滞。通过植入物中的灰分量分析植入后3周内的新骨形成情况，作为实验结束时骨形成的指标，使用45Ca和[3H]脯氨酸的短期掺入情况。两个甲氨蝶呤组植入物的灰分含量分别降低了56%和68%。异位骨中两种核苷酸的摄取也大大减少，而胫骨近端和骨干以及牙齿未受影响。结果表明甲氨蝶呤对骨诱导有明显抑制作用，至少持续3周。甲氨蝶呤降低了骨形成潜力，可能对保肢手术和骨折愈合的成功产生影响。
