Bone Abstracts

Results of epidemiological studies indicate that paracetamol use may be a risk factor for fracture. The exact mechanism of paracetamol action remains unclear, but it is known to inhibit COX-2. Orchidectomy-induced androgen deficiency was reported to increase COX-2 expression and prostanoid release in rats. The aim of the present study was to investigate the effect of paracetamol on bone mechanical properties in rats with normal androgen levels and with androgen deficiency induced by orchidectomy.

Three-month-old Wistar rats were orchidectomized (ORX) or sham-operated (Sham), and, after 7 days, divided into six groups (n=10): sham-operated control rats, sham-operated rats receiving paracetamol (70 or 210 mg/kg), ORX control rats, ORX rats receiving paracetamol (70 or 210 mg/kg). Paracetamol was administered by a gastric tube once daily, for 7 weeks (6 days a week). Mechanical properties of the proximal tibial metaphysis, femoral diaphysis and femoral neck, as well as histomorphometric parameters: transverse cross-section area of the cortical bone and width of trabeculae in the distal epiphysis and metaphysis in the femur were determined 8 weeks after ORX or sham operation.

The paracetamol effect on bone strength was dose- and androgen level-dependent. Paracetamol at 70 mg/kg did not significantly affect the skeletal system in Sham rats and tended to unfavorably affect it in ORX rats. At 210 mg/kg, paracetamol non-significantly worsened mechanical properties of cancellous bone (the tibial metaphysis) in Sham rats, whereas it counteracted the orchidectomy-induced worsening of histomorphometric parameters and mechanical properties of both cancellous and compact bone (the tibial metaphysis, and femoral diaphysis and neck) in ORX rats.

In conclusion, long-term use of high-dose paracetamol (210 mg/kg for 7 weeks) favorably affected the skeletal system of androgen-deficient rats.