Angiotensin-I Converting Enzyme Genotype-Dependent Benefit from Hormone Replacement Therapy in Isometric Muscle Strength and Bone Mineral Density¹

Abstract

Low bone mineral density (BMD) and muscle weakness are major risk factors for postmenopausal osteoporotic fracture. Hormone replacement therapy (HRT) reverses the menopausal decline in maximum voluntary force of the adductor pollicis and reduces serum angiotensin-I converting enzyme (ACE) levels. The insertion (I) allele of the ACE gene polymorphism is associated with lower ACE activity and improved muscle efficiency in response to physical training. Therefore, we examined whether the presence of the I allele in postmenopausal women would affect the muscle response to HRT. Those taking HRT showed a significant gain in normalized muscle maximum voluntary force slope, the rate of which was strongly influenced by ACE genotype (16.0 +/- 1.53%, 14.3 +/- 2.67%, and 7.76 +/- 4.13%, mean +/- SEM for II, ID, and DD genotype, respectively; P = 0.017 for gene effect, P = 0.004 for I allele effect). There was also a significant ACE gene effect in the response of BMD to HRT in Ward's triangle (P = 0.03) and a significant I allele effect in the spine (P = 0.03), but not in the neck of femur or total hip. These data suggests that low ACE activity associated with the I allele confers an improved muscle and BMD response in postmenopausal women treated with HRT.

Effects of 1,25-dihydroxyvitamin D3 on the local bone renin-angiotensin system in a murine model of glucocorticoid-induced osteoporosis

“…This finding is supported by previous studies (28,29). The present study demonstrated that high bone turnover increased the RANKL/OPG ratio, followed by activation of the local bone RAS, which is supported by previous research (22).…”

A prolonged hiatus in postmenopausal HRT, does not nullify the therapy’s positive impact on ageing related sarcopenia

“…In parallel and as expected, the grouping comparison and the correlation between age and Estradiol were statistically significant (rho = -0.773, p<0.001). These findings are consistent with previous research comparing pre-menopausal to post-menopausal [40], or post-menopausal Used_HRT vs No_HRT [15,16,48]. Our current, results are even more striking when one considers that in the HRT group, therapy had been ceased 10.6 ± 8.9 years prior to the current study and the levels of estrogen were now within expected post-menopausal levels [49,50].…”

“…In fact, work using amenorrheic [13] or post-menopausal females [14], is especially relevant here in demonstrating the theorem that estrogen is important for skeletal muscle structure and function. Indeed a substantial body of work shows a link between lowered circulating estrogen levels, and muscle atrophy as well as poor physical performance [15,16]. Also of note, is the previous research showing that obesity is one of the key factors linked to an overall increase in concentrations of free circulating biologically active estradiol (17β-estradiol).…”

Lack of association of the ACE genotype with the muscle strength response to resistance training

“…A higher proportion of the DD genotype has been reported in elite sprint athletes when compared to endurance athletes and controls (Jones, Montgomery, & Woods, 2002;Myerson et al, 1999;Nazarov et al, 2001;Woods, D. et al, 2001). This genotype has been associated with a greater proportion of fast twitch fibres (Zhang et al, 2003), suggesting that this polymorphism may influence skeletal muscle function, although contradictory evidence also exists (Akhmetov et al, 2006).…”