Aim: Our study aimed to investigate the effect of amlodipine on bone metabolism in orchidectomized rats. Methods: Eight-week-old rats were divided into three groups. The sham-operated control group (SHAM) and the control group after orchidectomy (ORX) received the standard laboratory diet (SLD). The experimental group after orchidectomy (ORX+AML) received SLD enriched with amlodipine for 12 weeks. Bone marker concentrations in serum of PINP, OPG and IGF-1, and the levels of CTX-I, BAP and BMP-2 in a bone homogenate were measured using enzyme-linked immunosorbent assay. Bone mineral density (BMD) was measured by dual energy X-ray absorptiometry. The femurs were used for biomechanical testing. Results: Bone markers (CTX-I, BAP, BMP-2) in ORX were higher versus SHAM. In ORX+AML there was a decrease in PINP, CTX-I, BAP, BMP-2 and OPG versus ORX. IGF-1 was decreased in ORX versus SHAM. In ORX+AML it was increased versus ORX. In ORX, a decrease was demonstrated versus SHAM in BMD of the whole body, in the lumbar vertebrae and in both femurs. In ORX+AML there was an increase in BMD of the whole body versus ORX. Three-point bending test revealed a decrease in maximal load values in ORX versus SHAM. After amlodipine administration there was an increase in the left femur versus ORX. Conclusions: Amlodipine is capable of mitigating the negative effects of orchidectomy and could be a good prevention of osteoporosis.
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
Spontaneously hypertensive rats (SHR) represent a model of essential hypertension. We studied the effect of amlodipine (AML) on bone markers, bone mineral density (BMD), and biomechanical properties of osteopenic bone induced by orchidectomy in male SHR. Rats were allocated to 3 groups and were sacrificed after 12 weeks: sham-operated control; orchidectomised control; and orchidectomised receiving a diet supplemented with AML. Indicators of bone turnover were assessed in bone homogenate, BMD was measured by dual energy X-ray absorptiometry, and the femurs were subjected to biomechanical testing. Long-term AML administration does not have a negative impact on bone metabolism and density in male SHR.
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