Antonio Dueñas

Effect of Quinapril, Quinapril-Hydrochlorothiazide, and Enalapril on the Bone Mass of Hypertensive Subjects: Relationship With Angiotensin Converting Enzyme Polymorphisms

BACKGROUND Many alterations in extracellular metabolism of calcium have been associated to hypertension, but the number of studies relating this disease with osteoporosis is extremely low. This study clarifies the therapeutic effect of three treatments-quinapril, quinapril + hydrochlorothiazide (HCTZ), enalapril-on bone remodeling markers, bone mineral density (BMD) in hypertensive patients, and relationship with angiotensin converting enzyme (ACE) polymorphism. METHODS This open, prospective study included 134 patients with low-to-moderate hypertension and stable BMD according to Joint National Committee criteria and 96 patients completed the study. After a washout period, patients were randomized to one of the three treatments, which they received for 1 year. Analyses of blood and urine samples and densitometric studies on lumbar spine were performed. RESULTS Calcium and 25-hydroxyvitamin D levels increased (9.5 +/-0.3 and 9.6 +/-0.3 mg/dL, P =.01 and 46 +/-22 and 58 +/-22 nmol/L, P =.026, respectively) in the quinapril-treated group and calcium levels increased (9.4 +/-0.6 and 9.8 +/-0.4 mg/dL, P =.001) in the quinapril-HCTZ-treated group. The 1, 25-dihydroxyvitamin D levels, calciuria, and calcium/creatinine ratio decreased (64 +/-23 and 43 +/-16 nmol/L, P =.0001;209 +/-93 and 161 +/-93 mg/24 h, P =.0022;0.21 +/-0.09 and 0.17 +/-0.11, P =.04, respectively). In the enalapril-treated group 1, 25-dihydroxyvitamin D levels (61 +/-27 and 42 +/-19 nmol/L, P =.0022) decreased. Only women presented a statistical significance (1.064 +/-0.16 g/cm(2), P =.034) between ID+II polymorphism and BMD decrease, and between DD polymorphism with less BMD under baseline conditions and a BMD increase (1.070 +/-0.16 g/cm(2), P =.017) after ACE inhibitor treatment. CONCLUSIONS The ACE inhibitors have a beneficial effect on BMD and calcium metabolism alterations in hypertensive subjects. Concerning BMD response, women presenting with the II+ID polymorphism had a poor response to antihypertensive drug treatment, whereas women with the DD polymorphism responded better. This is the first study demonstrating a relationship between ACE polymorphism and BMD response and antihypertensive ACE inhibitor treatment.

Relationship Between Bone Mineral Density and Angiotensin Converting Enzyme Polymorphism in Hypertensive Postmenopausal Women

BACKGROUND The purpose of this study was to assess the relationship between bone mineral density and insertion/deletion (I/D) angiotensin converting enzyme polymorphism (ACE) in hypertensive postmenopausal women. METHODS Blood and urine samples from the study subjects were analyzed for calcium metabolism related parameters. Densitometry studies were conducted in the lumbar spine (L2 to L4). The ACE polymorphism was analyzed by polymerase chain reaction. RESULTS Women with II genotype showed a higher intact parathyroid hormone (76 +/- 33 v 55 +/- 27 pg/mL and 52 +/- 26 pg/mL, P =.034) without a decrease in calciuria, and higher bone mineral density than women with ID and homozygotus deletion genotype (1.138 +/- 0.08 v 1.051 +/- 0.16 pg/mL and 1.053 +/- 0.16 pg/mL). CONCLUSIONS The ACE polymorphism could be one of the factors causing bone mass variations.

Effect of the Antihypertensive Treatment on the Bone Mineral Density and Osteoporotic Fracture

The financial and social cost of hypertension and osteoporosis, clinically silent diseases, are determined by the consequences, such as a vascular disease and fractures. The relationship between these illnesses has not been clearly established, although many alterations in extracellular metabolism of calcium, which could determine the level of bone mineral density (BMD) in these patients, have been associated to hypertension. Despite these alterations, the lack of studies relating these two important diseases is surprising, and hypertension is not identified as a risk factor for osteoporosis. Interestingly, there is a lack of information of the long-term effects of antihypertensive treatment on bone mineral density, although 50 % of the hypertensive population is made up of postmenopausal women. Most studies analyzed the effects of thiazides and, to a lesser degree, the effects of calcium antagonist. The purpose of this review is evaluate the effect of the antihypertensive therapeutic group (diuretics, β-blockers, calcium antagonists, angiotensin converting enzyme) on the bone mineral density (BMD) and osteoporotic fracture.

Ghrelin and Bone Mass in Postmenopausal Hypertensive Women

Background: Ghrelin, a recently discovered peptide mainly secreted by the stomach, has an orexigenic effect which stimulates secretion of the growth hormone. It also has vasodilator effects which reduce blood pressure and stimulate in vitro, bone formation. Objectives: To evaluate the effect of ghrelin on bone mass and bone remodeling markers in postmenopausal hypertensive women. Material and Methods: 25 postmenopausal hypertensive women, light to moderate based on the JNC-VII criteria, were studied. They had a mean age of 58 ± 8 years, a body mass index of 28 ± 6 and a hypertension development time of 65 ± 84 months. Osteocalcin, PTHi, 25-vitamin D, ghrelin in serum and deoxypiridinoline in urine were determined in all patients. A lumbar spine densitometer was made (DXP Lunar, Madison, Wisc., USA). Results: Diminished levels of ghrelin were observed in the osteoporotic group (40 ± 19 vs. 78 ± 40, p = 0.027). When the patients were separated according to ghrelin tertiles, a greater bone mass was observed in the upper tertiles, which was associated with a decrease in the urinary deoxypiridinoline. When the total population was analyzed, no relation between the ghrelin and bone mass was found, nor with any of the parameters of calcium metabolism. Only a statistically significant relation between ghrelin and deoxypiridinoline was observed (r = –0.428, p = 0.026). Conclusions: In postmenopausal hypertensive women, ghrelin may produce a protecting effect over bone mass through an anticatabolic mechanism manifested by a decrease of bone resorption.