Effects of Administration of Amlodipine and Lacidipine on Inflammation-Induced Bone Loss in the Ovariectomized Rat

Karakuş, Emre; Halıcı, Zekai; Albayrak, Abdulmecit; Bayır, Yasin; Demirci, Elif; Aydın, Ali; Ozturkkaragoz, Berna; Çadırcı, Elif; Ayan, Arif Kürşad; Şahin, Ali; Ünal, Deniz

doi:10.1007/s10753-015-0254-6

Cited by 9 publications

(10 citation statements)

References 89 publications

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“…Interestingly, these findings contradict previous studies investigating the effect amlodipine on bone metabolism and osteoporosis (Karakus et al, 2016;Ushijima et al, 2010). Ushijima et al (2010) postulated that amlodipine prevents a reduction in bone mineral density in stroke-prone spontaneously hypertensive rats through an inhibition of osteoclast activity.…”

Section: Discussioncontrasting

confidence: 80%

“…Halici et al (2008) demonstrated that amlodipine protects against ovariectomyinduced bone loss. Furthermore, Karakus et al (2016) showed in an experimental ovariectomised and inflammation-induced osteoporosis rat model that amlodipine does not only prevent the ovariectomyand inflammation-induced loss of the osteogenic factors runt-related transcription factor 2 (Runx2) and type I collagen 1a1 (Col1a1) but even induces a 3-to 4-fold elevation of Runx2 and Col1a1 expression when compared to non-osteoporotic controls. Accordingly, the authors proposed that amlodipine may be used as a therapeutic agent for osteoporosis treatment in hypertensive patients (Karakus et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

“…Drugs that are among the primary choices of hypertension treatment include calcium channel blockers (CCBs). They act by blocking the voltagedependent calcium channels in arteriolar smooth muscle cells, thus reducing the peripheral vascular resistance and, as a consequence, blood pressure (Katz et al, 1984). However, since CCBs interfere with the transportation of calcium through cell membranes, they may affect a range of metabolic processes, including bone metabolism (Duriez et al, 1990).…”

Section: Introductionmentioning

confidence: 99%

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Amlodipine accelerates bone healing in a stable closed femoral fracture model in mice

Menger

Merscher²,

Scheuer³

et al. 2021

eCM

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Calcium channel blockers (CCBs), which are widely used in the treatment of hypertension, have been shown to influence bone metabolism. However, there is little information on whether CCBs also influence the process of fracture healing. Therefore, the effect of the CCB amlodipine on bone healing was studied in a stable closed fracture model in mice using intramedullary screw fixation. Bone healing was investigated by radiology, biomechanics, histomorphometry and Western blot analysis 2 and 5 weeks after fracture healing. Animals were treated daily (post operatively) per per os using a gavage with amlodipine low dose (1 mg/ kg body weight, n = 20), amlodipine high dose (3 mg/kg body weight, n = 20) or vehicle (NaCl) (control, n = 20) serving as a negative control. At 2 and 5 weeks, histomorphometric analysis revealed a significantly larger amount of bone tissue within the callus of amlodipine low-dose- and high-dose-treated animals when compared to controls. This was associated with a smaller amount of cartilaginous and fibrous tissue, indicating an acceleration of fracture healing. Biomechanics showed a slightly, but not significantly, higher bending stiffness in amlodipine low-dose- and high-dose-treated animals. Western blot analysis revealed a significantly increased expression of bone morphogenetic protein (BMP)-2 and vascular endothelial growth factor (VEGF). Moreover, the analysis showed a 5-fold higher expression of osteoprotegerin (OPG) and a 10-fold elevated expression of the receptor activator of NF-κB ligand (RANKL), indicating an increased bone turnover. These findings demonstrated that amlodipine accelerated fracture healing by stimulating bone formation, callus remodelling and osteoclast activity.

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Section: Discussioncontrasting

confidence: 80%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Amlodipine accelerates bone healing in a stable closed femoral fracture model in mice

Menger

Merscher²,

Scheuer³

et al. 2021

eCM

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“…It is now known that IL-17 production can occur independently of IL-23 stimulation [87] and that IL-1β is capable of driving maturation of IL-17 producing cells [88,89]. This supports a role for the IL-1 family in AS especially since IL-23 blockade is ineffective for spinal disease progression [90,91]. IL-1β is capable of inducing the expression of other inflammatory cytokines from CD4+ and CD8+ cells; this allows for an initiation of an inflammatory response seen in tissue repair.…”

Section: Il-17a and Other Il-17 Family Cytokines In Tissue Repairmentioning

confidence: 72%

Cytokine “fine tuning” of enthesis tissue homeostasis as a pointer to spondyloarthritis pathogenesis with a focus on relevant TNF and IL-17 targeted therapies

et al. 2021

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A curious feature of axial disease in ankylosing spondylitis (AS) and related non-radiographic axial spondyloarthropathy (nrAxSpA) is that spinal inflammation may ultimately be associated with excessive entheseal tissue repair with new bone formation. Other SpA associated target tissues including the gut and the skin have well established paradigms on how local tissue immune responses and proven disease relevant cytokines including TNF and the IL-23/17 axis contribute to tissue repair. Normal skeletal homeostasis including the highly mechanically stressed entheseal sites is subject to tissue microdamage, micro-inflammation and ultimately repair. Like the skin and gut, healthy enthesis has resident immune cells including ILCs, γδ T cells, conventional CD4+ and CD8+ T cells and myeloid lineage cells capable of cytokine induction involving prostaglandins, growth factors and cytokines including TNF and IL-17 that regulate these responses. We discuss how human genetic studies, animal models and translational human immunology around TNF and IL-17 suggest a largely redundant role for these pathways in physiological tissue repair and homeostasis. However, disease associated immune system overactivity of these cytokines with loss of tissue repair “fine tuning” is eventually associated with exuberant tissue repair responses in AS. Conversely, excessive biomechanical stress at spinal enthesis or peripheral enthesis with mechanically related or degenerative conditions is associated with a normal immune system attempts at cytokine fine tuning, but in this setting, it is commensurate to sustained abnormal biomechanical stressing. Unlike SpA, where restoration of aberrant and excessive cytokine “fine tuning” is efficacious, antagonism of these pathways in biomechanically related disease may be of limited or even no value.

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“…Accordingly, the N/L-type CCB has a probability of less activation of the renin-angiotensin system [18]. Moreover, the administration of AML suppresses an inflammatory response by reducing the production of TNF-alpha, IL-1beta, and IL-6 [19], all of which are osteoclastogenic [20, 21]. Lin demonstrated that AML compared to the control group significantly increased the testosterone level in male SHR without affecting the levels of the follicle-stimulating and luteinizing hormone [21].…”

Section: Discussionmentioning

confidence: 99%

Effects of Amlodipine on Bone Metabolism in Orchidectomised Spontaneously Hypertensive Rats

et al. 2018

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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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Effects of Administration of Amlodipine and Lacidipine on Inflammation-Induced Bone Loss in the Ovariectomized Rat

Cited by 9 publications

References 89 publications

Amlodipine accelerates bone healing in a stable closed femoral fracture model in mice

Amlodipine accelerates bone healing in a stable closed femoral fracture model in mice

Cytokine “fine tuning” of enthesis tissue homeostasis as a pointer to spondyloarthritis pathogenesis with a focus on relevant TNF and IL-17 targeted therapies

Effects of Amlodipine on Bone Metabolism in Orchidectomised Spontaneously Hypertensive Rats

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