Effect of Etidronate on Aortic Calcification and Bone Metabolism in Calcitoriol-Treated Rats With Subtotal Nephrectomy

Tamura, Kazuhiro; Suzuki, Yusuke; Hashiba, Hirotake; Tamura, Hiroshi; Aizawa, Sumio; Kuroda, Hiroshi

doi:10.1254/jphs.fpj05019x

Cited by 28 publications

(17 citation statements)

References 29 publications

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“…21 Accumulating evidence suggests that bisphosphonates also have the potential to induce the regression of atherosclerotic plaques and vascular calcification in experimental studies [22][23][24] and small clinical studies. [14][15][16] They are grouped into 2 classes according to their chemical structure and the molecular mechanism by which they inhibit osteoclast activity.…”

Section: Discussionmentioning

confidence: 99%

Atorvastatin, Etidronate, or Both in Patients at High Risk for Atherosclerotic Aortic Plaques

et al. 2013

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Background-Statins are not effective in reducing atherosclerotic plaques of the abdominal aorta, and accumulating evidence suggests that bisphosphonates have the potential to induce the regression of atherosclerotic plaques of the abdominal aorta. Methods and Results-A prospective, randomized, open-label, blinded-end-point trial involving 108 participants with hypercholesterolemia was conducted. Participants received 20 mg atorvastatin daily, 400 mg etidronate daily, or both drugs daily. The primary end point was the percent change in maximal vessel wall thickness of atherosclerotic plaques in the thoracic and abdominal aortas as measured by magnetic resonance imaging after 12 months of treatment. In both the combination therapy and atorvastatin groups, maximal vessel wall thickness of the thoracic aorta was reduced by 13.8% (95% confidence interval, −16.4 to −11.3) and 12.3% (95% confidence interval, −14.9 to −9.7), respectively. These reduction rates were comparable between groups (P=0.61). Meanwhile, in the etidronate group, maximal vessel wall thickness of the thoracic aorta remained unchanged (2.2%; 95% confidence interval, −0.3 to 4.8). Conversely, maximal vessel wall thickness of the abdominal aorta was reduced more effectively in the combination therapy group (−11.4%) than in the atorvastatin group (−0.9%; P<0.001) and the etidronate group (5.5%; P=0.006). Conclusions-Atorvastatin plus etidronate combination therapy for 12 months significantly reduced both thoracic and abdominal aortic plaques, whereas atorvastatin monotherapy reduced only thoracic aortic plaques and etidronate monotherapy reduced only abdominal aortic plaques. The effectiveness of combination therapy in reducing atherosclerotic plaques in the abdominal aorta was significantly greater than for both atorvastatin and etidronate monotherapy.

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Section: Discussionmentioning

confidence: 99%

Atorvastatin, Etidronate, or Both in Patients at High Risk for Atherosclerotic Aortic Plaques

et al. 2013

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“…In fact, the significantly reduced mineral apposition rates in ibandronate-treated rats observed in our study support this notion. Etidronate and pamidronate have recently been shown to prevent vascular calcification in uremic rats and, concomitantly, to affect bone formation and mineralization [10,11]. Although a comparison of these studies, including the present one, is hampered by different experimental designs (e.g.…”

Section: Discussionmentioning

confidence: 97%

“…Beyond this, individual bisphosphonates of either class differ with respect to the biological half-life, route of administration, side effects, and relative potencies to inhibit bone resorption and formation [7]. In this context it is worth mentioning that a recent study in experimental chronic uremia revealed that the etidronate dosage required to prevent arterial calcification also impaired bone mineralization [10]. In a more recent animal study, etidronate and pamidronate were shown to attenuate ectopic calcification and to reduce bone formation while leaving bone resorption virtually unaffected [11,12].…”

Section: Introductionmentioning

confidence: 99%

Ibandronate affects bone growth and mineralization in rats with normal and reduced renal function

et al. 2010

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Bisphosphonates have been shown to attenuate ectopic calcification in experimental uremia. While they are known to reduce bone turnover, the effects on endochondral bone formation have not yet been addressed. To address this issue, we administered male Sprague-Dawley rats weekly subcutaneous injections of either vehicle or ibandronate (1.25 μg/kg body weight) for a total of 10 weeks. The rats were randomly allocated into one of four groups: (1) vehicle-treated, sham-operated rats; (2) ibandronate-treated, sham-operated rats; (3) vehicle-treated, 5/6 nephrectomized rats; (4) ibandronate-treated, 5/6 nephrectomized rats. Bones were double labeled with tetracycline and demeclocycline in vivo, and tibiae were removed for analysis. Weight gain was similar in all groups. Ibandronate reduced body length gain and tibial growth rate in the sham-operated animals but not in the rats showing chronic renal failure (CRF). The height of the proliferative zone of the epiphyseal growth plate was reduced in the ibandronate-treated controls and tended to be reduced in CRF rats. A significant correlation between tibial growth rate and height of the proliferative zone was observed. Mineral apposition rates were significantly reduced in ibandronate-treated, sham-operated rats and tended to be reduced in CRF rats. In conclusion, ibandronate interferes with tibial growth and bone mineralization in young rats with normal and reduced renal function.

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“…In rodents with renal failure and severe medial calcification, which was induced by 5/6 nephrectomy and treatment with high doses of calcitriol [40,41], etidronate inhibited aortic calcification at a dose (5 mg/kg) but did not significantly affect bone metabolism; consequently, the effects of etidronate on aortic calcification are unrelated to its effects on bone formation and serum calcium levels. …”

Section: Bisphosphonatesmentioning

confidence: 99%

Anti-Osteoporotic Drugs and Vascular Calcification: The Bidirectional Calcium Traffic

Yavropoulou¹,

Pikilidou

Yovos³

2013

J Vasc Res

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During the last years, numerous epidemiological studies have demonstrated a direct relationship between vascular calcification and low bone mineral density. This observation is in line with experimental data demonstrating the osteogenic characteristics of calcified arteries. Various common risk factors have been suggested to link vascular calcification and bone loss, including aging, estrogen deficiency, vitamin D and K deficiency, diabetes mellitus, renal failure, smoking, chronic inflammation and oxidative stress. Although the underlying pathogenetic mechanisms are not yet clear, current research is focusing on anti-osteoporotic agents that could potentially affect the deposition of calcium in the arterial wall and thus provide an additional therapeutic strategy in elderly osteoporotic women prone to calcific cardiovascular disease.

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Effect of Etidronate on Aortic Calcification and Bone Metabolism in Calcitoriol-Treated Rats With Subtotal Nephrectomy

Cited by 28 publications

References 29 publications

Atorvastatin, Etidronate, or Both in Patients at High Risk for Atherosclerotic Aortic Plaques

Atorvastatin, Etidronate, or Both in Patients at High Risk for Atherosclerotic Aortic Plaques

Ibandronate affects bone growth and mineralization in rats with normal and reduced renal function

Anti-Osteoporotic Drugs and Vascular Calcification: The Bidirectional Calcium Traffic

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