Mechanical properties of bone and skin during recovery after cyclophosphamide administration

Abstract

The effects of cyclophosphamide were studied 2, 5 and 9 days after terminating a two-week every-second-day intraperitoneal medication in young, male rats. The cytostatic effect was assessed by counting white blood cells (WBC) in arterial blood. WBC counts were reduced by 72% of control values at 2 days and regained normal values at 9 days after an overshooting leucocytosis at 5 days. Compared to control animals, the treated rats had significantly reduced body weights, metaphyseal bending strength and longitudinal growth of the femur at all time intervals observed. The torsional strength of the femur diaphysis and the strength of wounded skin were not affected at 2 days, but significantly reduced at 5 and 9 days. The tensile strength of intact skin was not found to be affected by the drug. From the 5th to the 9th day after ending medication, the curves for control and treated animals were assuming parallel slopes regarding metaphyseal bone strength, longitudinal bone growth and tensile strength of wounds. This may indicate reversion of the drug effects approximately one week after terminating medication.

Synthesis and Solubility of Collagen in Rats during Recovery after High‐dose Cyclophosphamide Administration

“…Earlier investigations have shown that high intraperitoneal doses of cyclophosphamide causes significantly reduced synthesis and solubility of collagen in bones and in skin wounds of rats (Wie & Beck 1980). These findings were confirmed by the present observations as far as collagen solubility of implant connective tissue and collagen formation in bone and implants are concerned.…”

“…Fourty-eight male, outbred Wistar/Af/Han/Mol SPF rats aged 27 days, with a median initial weight of 72 (71-75) g were used. This is the same material as that used in a previous paper dealing with the mechanical properties of bone and skin during recovery after cyclophosphamide treatment (Wie et al 1980).…”

“…Death followed by exsanguination. Cytostatic effect of the medication was evaluated by electronical counting of white blood cells (Wie et al 1980).…”

“…Immediately after death of the animals the implants were dissected free from adjacent tissues and transferred to acetone for defatting for 7 days before drying to constant weight at 35". Biochemical analyses were performed as described by Wie & Beck (1979& 1980. Soluble collagen was extracted in 0.5 M NaCl at 4 ' for 20 hours in a shaking machine.…”

“…The haematopoiesis following administration of cyclophosphamide in therapeutic a n d toxic doses has been found t o exhibit a leucocytopenia, followed by a transitory leucocytosis i n the recovery period before returning t o normal blood values (Hast 1966;Valeriote et al 1968;Wie et al 1980). A corresponding reversibility seems to be indicated by the observation that 'H-labelling of DNA in wound granulation tissue attained normal values in rats 5 days after terminating medication (Wie et al.…”