Exercise prevents the lansoprazole-induced weakening of antiresorptive activity of alendronate in orchidectomized rats

U Cegieła, J Folwarczna, M Pytlik, R Miozga, D Nowak, A Janas. Department of Pharmacology, Medical University of Silesia, Katowice, 41-200 Sosnowiec, Poland

Proton pump inhibitors (PPIs) are commonly used in elderly patients with gastroesophageal reflux disease, often concurrently with alendronate, an antiresorptive drug used in the treatment of osteoporosis. Clinical studies indicate that PPIs, used long-term in elderly patients increase the risk of hip fracture, and decrease the antifracture efficacy of alendronate. Orchidectomized rats serve as a model of androgen deficiency-induced osteoporosis. Physical activity is necessary to maintain good bone health. Exercise improve bone mass mainly due to increasing bone formation.

The aim of the present study was to examine the effect of exercise on the antiosteoporotic efficacy of alendronate administered concurrently with lansoprazole, a PPI, on the skeletal system of rats with orchidectomy-induced bone changes.

The experiments were carried out on 3-month-old male Wistar rats, divided into following groups (n = 8): I – non-orchidectomized (sham-operated) control rats, II – orchidectomized control rats, III – orchidectomized rats receiving alendronate, IV – orchidectomized rats receiving alendronate and lansoprazole, V – orchidectomized rats receiving alendronate and submitted to exercise, VI – orchidectomized rats receiving alendronate and lansoprazole and submitted to exercise. The orchidectomy or sham-operation were performed, under ketamine-xylazine anaesthesia, 7-8 days before the start of drug administration. The rats were submitted to the exercise on the treadmill 1 hour/day for 7 weeks (6 days a week). Alendronate sodium (3 mg/kg po) and lansoprazole (4 mg/kg po) were administered once daily for 7 weeks (6 days a week). Mechanical properties of tibial metaphysis and femoral diaphysis (in three-point bending tests) and femoral neck (in a compression test), bone turnover markers (serum osteocalcin and C-terminal telopeptide of type I collagen fragments), histomorphometric parameters in the tibial diaphysis (transverse cross-section area of the cortical bone and the marrow cavity, periosteal and endosteal transverse growth, width of osteoid) and in the femur (width of trabeculae in the distal epiphysis and metaphysis), as well as mass and mass of bone mineral in the tibia and femur were studied.

Androgen deficiency induced by orchidectomy increased bone turnover, causing a decrease in bone mass and mass of bone mineral, and decreasing the width of trabeculae in the femoral epiphysis and metaphysis. The weakening of bone mechanical properties, statistically significant in the tibial metaphysis, was also observed. Alendronate decreased bone turnover and counteracted the development of orchidectomy-induced bone changes. Lansoprazole weakened the alendronate effect on bone mass, mass of bone mineral and width of epiphyseal and metaphyseal trabeculae, causing significant weakening of mechanical properties of tibial metaphysis in comparison with the alendronate-treated rats. Implementation of exercise increased the alendronate effect on bone mass, mass of bone mineral, the mechanical properties of tibial metaphysis and femoral neck in the orchidectomized rats. Similar changes were observed in the orchidectomized rats treated with lansoprazole and alendronate, submitted to exercise; no deleterious effects of lansoprazole were observed.

In conclusion, exercise prevented the lansoprazole-induced decrease in the efficacy of alendronate in orchidectomized rats.