Effects of Various Antihypertensive Drugs on the Function of Osteoblast.

Nishiya, Yoichi; Sugimoto, Seiji

doi:10.1248/bpb.24.628

Cited by 40 publications

(38 citation statements)

References 52 publications

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“…The effect of amlodipine on bone metabolism has not yet been sufficiently investigated; so far only a few studies have examined this problem (Nishiya and Sugimoto 2001;Halici et al 2008;Ushijima et al 2010).…”

Section: Discussionmentioning

confidence: 99%

“…Most studies have demonstrated a somewhat positive effect on bone tissue resulting in a decrease in bone resorption, an increase in bone mineral density (BMD) and a reduction of risk for fractures (Ritchie et al 1994;Rejnmark et al 2006;Ushijima et al 2010). So far, little information has been published on the effect of amlodipine on bone metabolism (Nishiya and Sugimoto 2001;Halici et al 2008;Ushijima et al 2010). …”

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confidence: 99%

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Effects of amlodipine on bone metabolism in male albino Wistar rats

et al. 2011

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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

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Effects of amlodipine on bone metabolism in male albino Wistar rats

et al. 2011

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“…Benidipine blocks calcium influx through L-type voltage dependent calcium channel greatly potentiate mineralization, calcium influx and alkaline phosphates (ALP) activity. Amlodipine partially elevate ALP activity and block the calcium influx at 10 µM in osteobalst-like cell (MC3T3-E1 cell) line (Nishiya and Sugimoto, 2001). Also benidipine blocks calcium influx more strongly than other CCBs by high affinity to calcium channel and has strong osteoblast differentiating ability.…”

Section: Discussionmentioning

confidence: 97%

The Change of Bone Mineral Density by Bisphosphonates Therapy with Calcium-Antagonists in Osteoporosis

Kim¹,

La²,

Kang³

2008

Biomolecules and Therapeutics

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− Imbalance in calcium and phosphorous metabolism due to aging or menopause leads to osteoporosis. In contrast to patients with normal blood pressure, hypertensive patients have a higher loss of calcium in the urine with its attendant risk of osteoporosis. The high blood pressure is associated with the risk of bone loss and abnormalities in calcium metabolism leading to calcium loss. So we retrospectively investigated the changes of bone mineral density (BMD) which drugs can have clinical influences over osteoporosis treatments of patients with calcium-antagonists as common antihypertensive drugs and with bisphosphonates which causes a most effective inhibition of osteoclasts resorption. As a result over 70 years of age group and within bisphosphonates group, alendronate 70 mg once-weekly group showed significant increase of BMD in lumbar area. Combination group of cilnidipine and maxmarvil ® showed very significant decrease of BMD. In conclusion, it is desirable that combination therapy with calcium-antagonists is used carefully in the treatment of osteoporosis with high blood pressure.

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“…Another ARB, losartan, enhanced bone mass in adult mice and this effect was based on the stimulation of bone formation and the inhibition of bone resorption (14). On the contrary, no effect of ARBs has been found on bone loss in several other animal studies (7,12,26). Clinically, it was reported that use of ARBs was not associated with bone loss in elderly men (27).…”

Section: Discussionmentioning

confidence: 99%

“…Increasing evidence showed that CCB use is linked to decreased risk of falls and fractures (6). CCBs were found to stimulate osteoblast differentiation or inhibit osteoclast functions (7,8). Recent experimental studies also suggested that amlodipine exerts favorable effects on bone by decreasing bone turnover (9,10).…”

Section: Introductionmentioning

confidence: 99%

Influences of Treatment with Amlodipine and Valsartan on Bone Turnover Markers and OPG/RANKL/RANK System in Newly Diagnosed Hypertensive Adults; Which is more Beneficial?

Naharci¹,

Karaman²,

Ay³

et al. 2014

Turk Neph Dial Transpl

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We aimed to investigate the effects of treatment with amlodipine and valsartan, on markers of bone remodeling in newly diagnosed hypertensive adults. Forty-three subjects with newly diagnosed were included in the study. Patients were also randomly divided into two groups, and each group received monotherapy with amlodipine or valsartan. Blood levels of bone turnover markers and osteoprotegerin (OPG) / receptor activator of nuclear factor-κB ligand (RANKL) / RANK system were measured. Amlodipine reduced sRANKL levels and sRANKL/OPG ratio more than valsartan, and this decrease was statistically signifi cant (p<0.001, p=0.002, respectively). Although blood OPG concentration did not change after treatment in both groups, sRANKL/OPG ratio decreased signifi cantly (p<0.001). Amlodipine also caused some reduction in CTx blood levels compared to valsartan. So we can suggest that amlodipine may be a better option than valsartan in patients with osteoporosis or terms of prevention of bone loss in hypertensive adults. KEY WORDS:Hypertension, Amlodipine, Valsartan, Osteoporosis, Bone remodeling ÖZBu çalışmada amacımız; yeni tanı almış, yetişkin hipertansif hastalarda Amlodipin ve Valsartan tedavisinin kemik yeniden şekillendirilmesi (remodeling) üzerine olan etkisini araştırmaktır. Çalışmaya daha önce tedavi almamış 43 yeni tanılı hasta alındı.Hastalar rastgele iki gruba ayrıldı. Her bir gruba monoterapi şeklinde Amlodipin ve Valsartan verildi. Kemik yapım-yıkım belirteçleri yanında osteoprotegerin (OPG) / nükleer faktör kappa-B reseptör aktivatörü ve ligand(sRANKL) / RANK sistemi çalışıldı. Amlodipin kolunda sRANKL düzeyinin ve sRANKL/OPG oranınının valsartandan daha fazla azaldığı ve bunun istatistiki açıdan anlamlı olduğu görüldü (p<0.001, p=0.002, sırasıyla). Tedavi sonrası her iki grupta da OPG konsantrasyonu değişmemekle birlikte sRANKL/OPG oranının anlamlı şekilde azaldığı görüldü (p<0.001). Yine Amlodipinin C-telopeptide of type I collagen(CTx ) düzeyini Valsartana göre daha fazla azalttığı görüldü. Bu veriler ışığında, osteoprotik hastalarda veya kemik kaybı yönünden risk taşıyan hastalarda amlodipin tedavisinin valsartan tedavisine göre daha iyi bir seçim olabileceğini söyleyebiliriz.

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Effects of Various Antihypertensive Drugs on the Function of Osteoblast.

Cited by 40 publications

References 52 publications

Effects of amlodipine on bone metabolism in male albino Wistar rats

Effects of amlodipine on bone metabolism in male albino Wistar rats

The Change of Bone Mineral Density by Bisphosphonates Therapy with Calcium-Antagonists in Osteoporosis

Influences of Treatment with Amlodipine and Valsartan on Bone Turnover Markers and OPG/RANKL/RANK System in Newly Diagnosed Hypertensive Adults; Which is more Beneficial?

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