Methotrexate effects on heterotopic bone in rats.

We studied the effects of high-dose methotrexate on heterotopic bone formation induced by implants of demineralized bone matrix in the abdominal wall of growing rats. Methotrexate induced an arrest in normal weight gain of the animals, more pronounced the younger the animals were. The youngest animals had reduced ash weight and decreased isotope uptake in the tibiae and teeth. However, implants from these animals, given methotrexate 10 days before implantation of bone matrix, had a 33 per cent increase in ash content. When methotrexate was given at, or 10 days after, implantation, heterotopic bone formation was reduced by 40 and 22 per cent, respectively, whereas orthotopic bone was considerably less affected in these older animals. In a second experiment, no difference in elimination rates of 45Ca between methotrexate-treated and control rats in implants, teeth, or tibiae were found. It appears that a less detrimental effect of methotrexate on new bone formation can be expected if the drug is given before, or a substantial period after, surgery requiring bone formation for healing.