Effects of Alendronate and Strontium Ranelate on Cancellous and Cortical Bone Mass in Glucocorticoid-Treated Adult Rats

We studied the effects of alendronate (Aln) and strontium ranelate (SrR) administration on cancellous and cortical bone in glucocorticoid (GC)-treated rats. Thirty-two 3.5-month male Sprague-Dawley rats were randomized into four groups: age-matched normal control (Nrm), methylprednisolone (Met; 5.0 mg/kg/day, sc, for 5 days/week), Met plus Aln orally (1.0 mg/kg/day), and Met plus SrR orally (900 mg/kg/day). The study period was 9 weeks. DXA was used to evaluate the femoral diaphysis and fifth lumbar vertebra (L5). Histomorphometry was performed in the proximal tibial metaphysis and tibial diaphysis. Met significantly decreased body weight and bone mineral density (BMD) compared with Nrm. Aln and SrR significantly increased body weight and BMD compared with Met. SrR resulted in significantly higher BMD than Aln. Met markedly decreased BV/TV, Tb.Th, and Tb.N and increased Tb.Sp compared with Nrm. Aln and SrR showed significantly increased of BV/TV, Tb.Th, and Tb.N and improved bone architecture. Moreover, Met reduced %Ct.Ar, enlarged %Ma.Ar, and decreased bone formation indices in the periosteum as well as increased ES/BS in the endosteum compared with Nrm. Aln significantly decreased endosteal ES/BS compared with Met. SrR significantly increased %Ct.Ar and bone formation indices in the periosteum as well as the endosteum and decreased endosteal ES/BS compared with Met. Furthermore, SrR led to a significantly higher cancellous and endocortical MS/BS and endocortical bone formation compared with Aln. Our findings suggest SrR at a dose of 900 mg/kg has a greater effect than Aln at 1.0 mg/kg, according to BMD and histomorphometric analysis, in preventing GC-induced osteopenia. Therefore, SrR might be applicable as a bone therapeutic agent to treat secondary osteoporosis in the clinic.