prednisolone-hemisuccinate and Osteoporosis

Glucocorticoid-induced osteoporosis is the most frequently occurring type of secondary osteoporosis. Antagonists of β-adrenergic receptors are now considered to be potential drugs under investigation for osteoporosis. The aim of the present study was to investigate the effects of propranolol, a nonselective β-receptor antagonist, on the skeletal system of mature male rats and on the development of bone changes induced by glucocorticoid (prednisolone) administration. The experiments were performed on 24-week-old male Wistar rats. The effects of prednisolone 21-hemisuccinate sodium salt (7 mg/kg, sc daily) or/and propranolol hydrochloride (10 mg/kg, ip daily) administered for 4 weeks on the skeletal system were studied. Bone and bone mineral mass in the tibia, femur and L-4 vertebra, length and diameter of the long bones, mechanical properties of tibial metaphysis, femoral diaphysis and femoral neck, bone histomorphometric parameters and turnover markers in serum were determined. Prednisolone-induced unfavorable skeletal changes led to disorders in bone mechanical properties. Propranolol not only did not improve bone parameters, but even caused deleterious effects on the skeletal system. Concurrent administration of propranolol with prednisolone did not counteract the changes induced by prednisolone. The results of this study may help to understand the equivocal results of human studies on the effects of β-blockers on the skeletal system. It is possible that the drugs exert biphasic effects on the skeletal system, both favorable and deleterious, depending on the dose or individual susceptibility.

Topics: Adrenergic beta-Antagonists; Animals; Bone and Bones; Bone Density; Glucocorticoids; Male; Osteoporosis; Prednisolone; Propranolol; Rats; Rats, Wistar

The influence of glucocorticoid (GC) on bone in rats at different ages was investigated in order to provide insight into human glucocorticoid induced osteoporosis (GCOP). Three-, 6-, and 12-month-old female Wistar rats were divided into four groups: Zero-time control (ZT), vehicle (Cont), prednisolone (PSL) 2 mg/kg (P-L), PSL 20 mg/kg (P-H). PSL was subcutaneously administered every day for 4 weeks. Bone mineral density (BMD) at the proximal metaphysis and diaphysis of the tibia was measured by peripheral quantitative computed tomography. Histomorphometry of the tibia was performed for 3- and 6-month-old rats. GC increased trabecular and cortical BMD at the metaphysis in all 3-month-old rats with time. Trabecular BMD at the metaphysis in the P-L and P-H groups was significantly higher than in the control group. Histomorphometric parameters for both bone formation and resorption were also increased by GC treatment. In the 6-month-old rats, the metaphyseal trabecular BMD did not significantly change in any group, but the diaphyseal trabecular BMD significantly increased in the control group with time. The trabecular BMD of the metaphysis and diaphysis was significantly lower in the P-L and P-H groups than in the control group at week 4. Histomorphometric parameters for bone formation and resorption were both reduced by GC treatment. The BMD remained unchanged in all 12-month-old rats. Six-month-old rats treated with 20 mg/kg GC are suitable models for GC-induced osteoporosis with dominant cancellous bone decrease and reduced bone turnover. The pathology induced by 20 mg/kg prednisolone in 6-month-old female rats seems to be most similar to glucocorticoid-induced osteoporosis in humans.

Topics: Animals; Bone Density; Bone Remodeling; Bone Resorption; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Glucocorticoids; Osteogenesis; Osteoporosis; Prednisolone; Rats; Rats, Wistar; Tibia; Tomography, X-Ray Computed