Effects of amlodipine on bone metabolism in male albino Wistar rats

Abstract

Amlodipine (dihydropyridine-type calcium channel blocker) is a widely used agent for the treatment of hypertension in human and veterinary medicine but detailed information about its effects on bone metabolism are missing. Therefore, the aim of our study was to investigate the effect of amlodipine on bone metabolism in male albino Wistar rats. Amlodipine (0.3 mg/100 g body weight; gavage) was administered to 8 rats for 8 weeks. Control group (n = 8) received aqua pro inj. (0.2 ml/100 g body weight; gavage). Bone marker concentrations of carboxy-terminal cross-linking telopeptide of type I collagen (CTX-I) and aminoterminal propeptide of procollagen type I in serum, and of bone alkaline phosphatase (BALP) in both serum and bone homogenate were measured by enzyme immunoassay. We investigated the expression of bone morphogenetic protein 2 (BMP-2) in proximal tibia using Western blotting, and bone mineral density was measured by Dual-energy X-ray Absorptiometry in lumbar and caudal vertebrae and in femoral areas. Mechanical properties of the femurs were measured by three-point bending of the shaft and compression testing of the femoral neck. After 8 weeks of amlodipine administration there was a significant decrease in serum concentrations of BALP (p = 0.0009) and CTX-I (p = 0.003), and the content of BALP in bone homogenate (p = 0.026) compared to the control. In addition, Western blot analysis indicated increased BMP-2 protein concentration after amlodipine administration. Our findings suggest that amlodipine has a retarding influence on bone metabolism in rats by decreasing bone turnover, which probably in consequence increases expression of BMP-2. Bone markers, Western blotting, bone mineral density, biomechanical testingCardiovascular diseases are one of the leading causes of death for people in developed countries world-wide. The most common form is arterial hypertension, which can be reduced by several groups of drugs. At the present, not much attention has been paid to whether or how these drugs affect bone metabolism.Hypertension and osteoporosis are frequent diseases among people of higher age. Both are induced by interaction of many genetic and environmental factors (Shimizu et al. 2008). The first-choice antihypertensive drugs include the calcium channel blockers. Amlodipine is a derivate of dihydropyridine and is one of the 3 rd generation calcium channel blockers. Amlodipine is effectively used in human and veterinary medicine. Its principal action is to inhibit calcium entry through voltage-gated transmembrane L-type channels, thus decreasing intracellular calcium concentration and inducing smooth muscle relaxation (Devabhaktuni et al. 2009).Osteoblasts are derived from mesenchymal stem cells and play a pivotal role in bone formation. Osteoblasts have been also found to exprimate voltage-gated calcium channels (Duncan et al. 1998). L-type calcium channels have been shown in a rat osteoblast-like cell line (Morain et al. 1992). Vitamin D 3 , parathyroid hormone

Assessment of femoral bone osteoporosis in rats treated with simvastatin or fenofibrate

“…These results are consistent with other studies which concluded that to a certain extent, statins inhibit bone resorption and promote bone formation, but have no significant effect on bone mineral density in healthy rats [37,38]. In osteoporotic bone, studied by analysis of histological images and 1 H NMR relaxometry, both treatments showed a positive effect by increasing the percentage of femoral diaphysis trabecular bone.…”

Effects of Amlodipine on Bone Metabolism in Orchidectomised Spontaneously Hypertensive Rats

“…The ORX + AML rats had a higher concentration of BALP compared to that of the SHAM group, but rather less than that of the ORX group. These results are again in agreement with experiments carried out on normotensive Wistar rats [26]. We consider that AML affects the metabolism of osteoblasts by reduction of phosphatase activity in bone tissues.…”

“…The results of this study are similar to those of a previous study with Wistar rats, in which AML induces the suppression of bone turnover, in particular by decreasing osteoformation, and to a lesser extent osteoresorption [26]. In SHR, AML decreases bone turnover, specifically by the modification of osteoformation and depression of osteoresorption.…”

Protective Effect of Amlodipine on Rat Bone Tissue after Orchidectomy

“…These methods were described in detail in our previous report [14] . Prior to testing, the diameter of the midshaft of the femurs and the length from the top of the femur head to the distal point of the medial condyle were measured.…”