[Effects of oral administration of various non-steroidal anti-inflammatory drugs on bone growth and bone wound healing in mice]

Abstract

Morphometric and microdensitometric studies on normal bone growth and bone wound healing in growing ICR strain male mice were carried out as preliminary investigations. Then the effects of oral administration of non-steroidal anti-inflammatory drugs on bone growth and bone wound healing were studied. Femur length and width, and bone mineral contents in the femur as judged by microdensitometry of the soft x-ray films of the cortical portion of the femur showed time-dependent linear increase between 3 and 6 weeks of age. Wound holes were made in the parietal bones of mice with a dental bar at 4 weeks of age, and uncalcified area in the holes was determined by image analysis of soft x-ray films. The area decreased their size with the advance in age, especially a marked decrease was observed 2 weeks after the operation. From the above results, 4 week-old male mice were employed and 8 kinds of non-steroidal anti-inflammatory drugs (indomethacin, 1 mg/kg; mefenamic acid, 10 mg/kg; flufenamic acid, 10 mg/kg; diclofenac sodium, 1 mg/kg; ibuprofen, 10 mg/kg; naproxen, 10 mg/kg; phenylbutazone, 10 mg/kg and aspirin, 50 mg/kg) and dexamethasone (1 mg/kg), a steroidal anti-inflammatory drugs were administered orally every day for 9 or 11 days except Sunday, and 15 days after the initial administration, the length and width of the femur were measured. The bone mineral contents were determined by microdensitometry of the soft x-ray film of the femur. Hydroxyproline contents of the femur were also determined. Wound holes were made in the parietal bones at 4 week-old and administered the drugs from one day before the operation for 9 days and the uncalcified area in the wound hole was determined 2 weeks after the operation with an image analyzer. The results obtained were as follows: 1. A significant inhibition of the growth in length of the femur was observed by dexamethasone, diclofenac sodium and naproxen administration for 9 and 11 days. A significant inhibition of the growth in width was also observed by dexamethasone and diclofenac sodium administration for 9 days and by dexamethasone administration for 11 days.(ABSTRACT TRUNCATED AT 400 WORDS)