Effect of angiotensin II receptor blockers, candesartan, on osteoprotegerin level in hypertensive patients: Link between bone and RAAS

Abstract

Introduction: The renin-angiotensin-aldosterone system (RAAS) has recently been considered as a possible link between bone and vascular disease. The present study was designed to determine the effect of the angiotensin II receptor blocker candesartan on circulating osteoprotegerin (OPG) in hypertensive patients with multiple cardiovascular risk factors. Material and methods: A total of 69 hypertensive patients were randomized to two groups: Group 1 included patients treated with oral candesartan in doses of 16 mg to 32 mg per day in addition to routine standard of care (routine care + ARB), and Group 2 included patients who received routine standard of care other than ARBs or ACEIs, with no change to their treatment (routine care). Patients were evaluated for lipid profile, HbA1C, insulin, C-peptide, CRP, aldosterone, renin, homeostasis model assessment-insulin resistance (HOMA-IR) and OPG. Results: Baseline OPG levels did not differ significantly by treatment group. Post-treatment serum OPG levels were marginally lower in Group1 compared with Group 2; however, this decrease did not reach statistical significance (p = 0.077). Conclusions: In the present study, treatment with the ARB candesartan had no significant effect on circulating OPG levels in hypertensive patients with multiple cardiovascular risk factors. To the best of our knowledge, the present study is the first to estimate an effect of candesartan on bone remodeling marker such as OPG.

A comparative study between the effect of 17-β estradiol and angiotensin converting enzyme inhibitor on osteoporosis in ovariectomized rats

“…These results are similar to that of Shuai et al (2015) who evidenced that the role of local RAS is related to bone mineral density in glucocorticoid-induced osteoporosis patients, and suggested that local RAS might influence OPG/RANKL signaling to modulate bone metabolism. Only one study showed that inhibition of the RAS caused non-significant changes in circulating OPG levels in hypertensive patients (Oz et al 2015). In addition, AngII significantly induced the expression of receptor activator of NF-κB ligand (RANKL) in osteoblasts, leading to the activation of osteoclasts, whereas these effects were completely blocked by an AngII type 1 receptor blocker (Kaneko et al 2011) and Quantitative RT-PCR using RNA isolated from the tibia and femur of mice lacking the gene encoding the major Ang II receptor isoform, AngII type 1A receptor (AT1a) revealed that the OPG/RANKL ratio was increased (Gebru et al 2013).…”

The Relationship between Renin–Angiotensin–Aldosterone System (RAAS) Activity, Osteoporosis and Estrogen Deficiency in Type 2 Diabetes

“…The renin-angiotensin-aldosterone system is positively correlated with T2D and hypertension [196][197][198][199]. Anti-hypertensive medications that block the RAAS have been evidenced to have osteoprotective effects [3,[200][201][202][203][204][205]. Furthermore, RAAS blockers are directly correlated with improved glucose handling and inhibition of progressive insulin resistance [199,206].…”