Background H2 - antagonists belong to wildly used drugs. Results of epidemiological studies assessing the influence of long-term therapy with H2-antagonists on bone mineral density (BMD) and fractures risk are ambiguous [1,2].
Objectives The aim of the study was top evaluate influence of ranitidine, a H2 antagonist, on bone turnover and bone mineral density (BMD) in growing rats.
Methods The experiment was carried out on 24 young (8-week-old) male Wistar rats. Rats were randomly assigned to one of two groups (12 animals in each group): group R – rats receiving ranitidine (10 mg /kg) in saline solution (4ml/kg), and group C (control group) – rats receiving saline solution (4ml/kg). Saline solution and ranitidine were given intraperitoneally once daily for 84 days. On day 85 blood samples for serum isolation were collected. After animal scarification right femurs were obtained from each animal and femur index defined as ratio of femur weight and body weight (15 femur mass [g] body mass [g] x 100%'>) was calculated. Serum calcium and phosphate levels were assessed in certified laboratory. Markers of bone turnover were assessed with commercial ELISA kits according to producers' instruction. Bone mineral density (BMD) of right femur was measured by dual-energy X-ray absorptiometry (DXA) with Hologic DXA equipment (Hologic Dicovery W 81507) using a small animal software. The experiment was performed with the approval of the First Local Ethics Committee for Experiments on Animals in Wroclaw.
Results Femur index and BMD were significantly decreased in rats receiving ranitidine comparing co control group (0.36% ±0.03% vs. 0.03% ±0.02%, p=0.02 and 0.263±0.008 g/cm2 vs. 0.272±0.007 g/cm2, p=0.01, respectively). Serum phosphate level was significantly increased in rats receiving ranitidine comparing to control group (5.06±1.21 mg/dl vs. 4.14±0.39 mg/dl, p=0.02). No significant difference in serum calcium levels between analyzed groups was detected (10.15±0.38 mg/dl in group R vs. 10.34± 0.21 mg/dl in group C, p>0.05). C-terminated telopeptide of type I collagen (CTX) level was increased in group R comparing to group C (140.5± 35.1vs. 102.2±50.0 pg/mL, p=0.04). No significant differences between analyzed groups in serum osteocalcin (OC), osteoprotegerin (OPG) and receptor activator of nuclear factor kappa B ligand (RANKL) levels were detected (342.5±123.3 pg/ml vs. 269.3±76.6 pg/ml, p>0.05; 0.42±0.25 ng/ml vs. 0.30±0.18 ng/ml, p>0.05 and 227.4±57.3 pg/ml vs. 214.7±50.5 pg/ml, p>0.05, respectively).
Conclusions In young growing rats receiving ranitidine we observed decreased BMD and femur index. It seems to be the consequence of increased bone resorption in rats receiving ranitidine.
Adachi Y, Shiota E, Matsumata T et al. 1998.Bone mineral density in patients taking h2-receptor antagonist. Calcif. Tissue Int. 62: 283–285.
Eom C, Park SM, Myung S et al. 2011.Use of acid-suppressive drugs and risk of fracture: a meta-analysis of observational studies. Ann Fam Med 9: 257–267.
Acknowledgement Grant for Young Researcher Wroclaw Medical University Pbmn138
Disclosure of Interest None declared