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

Abstract

Osteoprotegerin (OPG) and receptor activator of nuclear factor-kappa B ligand (RANKL) have been revealed in the pathogenesis of primary osteoporosis and other metabolic bone diseases. This study was designed to assess the effect of 17-β estradiol (E2) treatment and angiotensin converting enzyme inhibitor (ACEI), captopril, on osteoporosis induced by ovariectomy in rats and discussing the role of OPG/RANKL ratio in their action. Thirty two adult female rats were divided into four equal groups. Group I: control group, Group II: ovariectomized (OVX) non treated group, Group III: OVX rats treated with E2, Group IV: OVX rats treated with captopril. OVX rats showed a significant decrease in serum Ca2+ and OPG levels with significant increase in serum RANKL, osteocalcin, alkaline phosphatase activity and urinary hydroxyproline levels. Treatment with captopril as well as E2 led to a significant improvement in bone markers levels with a significant increase in OPG/RANKL ratio. Image analysis technique revealed that there was a significant improvement in cortical bone thickness (CBT) and mean trabecular bone density (TBD) in OVX rats treated with either E2 or ACEI. So, we can conclude that the protective effect of E2 and ACEI on osteoporosis may be mediated by influencing OPG/RANKL signaling.

Inhibition on angiotensin-converting enzyme exerts beneficial effects on trabecular bone in orchidectomized mice

“…Treatment of ORX mice with captopril significantly suppressed these changes of CAII, MMP-9 and OPG/RANKL. Similar results were reported by others that captopril increased the ratio of OPG/RANKL in bone [18] and serum [33] of OVX rats. Both MMP-9 and CAII, produced from osteoclasts, are enzymes to dissolve organic component and inorganic substance of bone, respectively [27].…”

“…Of noted, the recent studies demonstrated that captopril repaired cortical morphometric features [18] and improved cortical bone thickness [33] in OVX rats, while, the potential effect of captopril on cortical bone in ORX animals, such as the middle-shaft of tibia and femur, require further investigation.…”

Long-term use of angiotensin-converting enzyme inhibitors protects against bone loss in African-American elderly men

“…Increased osteoprotegerin (OPG)/receptor activator of nuclear factor-kappa B ligand (RANKL) ratio was reported after ACEi in ovariectomized rats [27]. Anti-resorptive effects of ACEi through anti-osteoclastogenic activities reported in other [8–9] along with the increased OPG/RANKL ratio explains why use of ACEi would be associated with decreased bone loss, as observed in our study.…”

Advanced Progress of the Relationship Between Antihypertensive Drugs and Bone Metabolism

“…ACE inhibitors have been widely used in the treatment of hypertension and are the first drugs of interest to focus on the effects of RAAS inhibitors on bone metabolism. Numerous animal experiments 11,[13][14][15][16][17] and clinical studies 9,[18][19][20][21][22][23][24][25] have shown that ACE inhibitors reduce bone loss, improve BMD, increase bone biomechanical strength, reduce fracture risk, and accelerate fracture healing.…”