Elsevier

Maturitas

Volume 65, Issue 4, April 2010, Pages 396-402
Maturitas

Bone turnover markers and bone mineral density in hypertensive postmenopausal women on treatment

https://doi.org/10.1016/j.maturitas.2010.01.007Get rights and content

Abstract

Objective

To evaluate bone mineral density (BMD) and bone metabolism in hypertensive postmenopausal women, and to differentiate the effect of thiazides from that of other antihypertensive agents.

Subjects and methods

A community-based population of 636 postmenopausal women, 293 with hypertension (160 receiving thiazides, and 133 receiving other antihypertensive treatments), and 343 control women, were evaluated. Serum levels of aminoterminal propeptide of type I collagen (P1NP), C-terminal telopeptide of type I collagen (β-CTX), 25-hydroxivitamin D, and intact parathyroid hormone were measured by electrochemiluminiscence. BMD was determined by DXA, and heel quantitative ultrasound measurements (QUS) with a gel-coupled device.

Results

BMD expressed as Z-score was higher in both groups of hypertensive women at all locations. Expressed as g/cm2, it was also higher in patients on thiazides at femoral neck and lumbar spine. Only in the latter site, differences remained significant after adjusting for potential confounding variables, including BMI. Bone turnover markers were lower in both groups of hypertensive women, although the difference was greater in those on thiazides. After adjusting for potential confounders, differences remained significant only in the thiazide group.

Conclusions

Our results add evidence to the idea that thiazides are beneficial to prevent bone loss.

Introduction

Osteoporosis is a disease characterized by an increase in bone fragility, resulting in fractures induced by low-energy trauma or even of a spontaneous nature. It is estimated that more than one-third of all Caucasian women over the age of 50 will suffer a fracture of the spine, hip or wrist in their life-time [1], [2]. Dual X-ray absorptiometry (DXA) is recognized as the reference method for measuring bone mineral density (BMD), and for each standard deviation decrease in BMD, fracture risk approximately doubles [2]. In recent years, quantitative ultrasound (QUS) measurements have been proposed as an alternative method for the non-invasive assessment of skeletal status, as they reflect not only the BMD but also qualitative aspects of bone such as elasticity, structure and geometry [3].

On the other hand, hypertension is a chronic disease characterized by progressive damage to target organs, such as the heart, kidney and brain. Its prevalence increases with age, as osteoporosis does [4]. However, the relationship between both disorders has not been clearly established. Thus, in several studies, hypertension has been shown to be inversely correlated with bone mineral content [5], whereas a direct relation [6] or no significant association [7] with BMD has also been described in others. Moreover, information about the long-term effects of antihypertensive treatment on BMD is scarce, except in the case of thiazides. It has been suggested that thiazide diuretics, which are commonly used to treat hypertension, may be of benefit in the prevention of osteoporosis. As a matter of fact, large epidemiologic studies, either prospective or case-control designs, have consistently shown that thiazides are associated with a risk reduction in osteoporotic fractures [8], [9], [10], [11], [12]. In addition, in most, but not all, studies, the use of thiazides has been associated with higher BMD in both sexes [13], [14], [15], [16], [17]. Moreover, a decrease in bone turnover markers has also been reported [13], [14], [16], [17], [18]. However, no significant changes have been described in QUS parameters in postmenopausal women treated with thiazides [19].

A number of mechanisms have been proposed to explain the positive effects of thiazides on osteoporosis. These diuretics reduce renal calcium excretion and may cause a positive calcium balance, decreasing plasma levels of parathyroid hormone (PTH) and thus, reducing bone turnover [13], [14], [16], [20]. Nevertheless, experimental data do not fully support this hypothesis, since conflicting results have been reported on the effect of thiazides on calciotropic hormones. Both 1,25(OH)2D and PTH levels have been reported as being decreased, unchanged, and even increased in response to thiazide treatment [17], [18], [21], [22], [23], [24], [25], [26], suggesting that these agents might have a direct action on bone [17], [26].

The aim of the present study was to evaluate bone turnover markers and BMD, estimated by DXA and QUS, in a population-based study of hypertensive postmenopausal women on treatment, and to determine the effect of thiazides and other antihypertensive drugs on calcium homeostasis and bone mass.

Section snippets

Study design and participants

The study population was set up with postmenopausal women included in the Camargo Cohort Study. The Camargo Cohort is a community-based study established to evaluate the prevalence of metabolic bone diseases as well as the prevalence of risk factors for osteoporosis and fragility fractures in postmenopausal women and men older than 50 in our region. Blood analysis, including parameters related to bone metabolism (PTH, 25OHD, and bone turnover markers), DXA and QUS measurements, as well as

Results

A total of 793 postmenopausal women were initially included in the study. However, 157 of them were excluded because of having metabolic diseases (primary hyperparathyroidism, hyperthyroidism, serum creatinine > 151 μmol/l), or because they were on drugs known to affect bone metabolism. Of the remaining 636 women, 160 were receiving thiazide diuretics (hydrochlorothiazide: 12.5–50 mg/day) for more than 1 year, due to hypertension, whether alone (32 women) or in combination with other

Discussion

In the present study we have compared BMD and bone turnover markers in women with essential hypertension with those of a control group, in the setting of a cohort of postmenopausal women established to assess the prevalence of bone and calcium metabolism disorders. Treated hypertensive women were divided into two groups according to whether they were (or were not) on thiazide treatment, irrespective of whether they were also on other antihypertensive drugs. The percentage of women on

Conflict of interest

No conflict of interest was declared.

Funding

This study was supported by grants from the “Fondo de Investigación Sanitaria”, Ministerio de Sanidad y Consumo, Spain (FIS: PI05 0125 and FIS: PI08 0183) and “Instituto de Formación e Investigación Marqués de Valdecilla”, Santander, Spain (IFIMAV: API/07/13).

Contributors

José M. Olmos: Conception, design, interpretation, and coordination of the work, as well as to write the manuscript. José L. Hernández, Execution of the statistical analysis and interpretation of the study. Revision of the manuscript. Josefina Martínez: Execution of biochemical studies and interpretation of the results. Jesús Castillo: Recruitment of subjects, interpretation of the study. Carmen Valero: Execution of BMD and ultrasound studies and interpretation of the results of the study.

Ethical approval

The study protocol was approved by the local Ethical Committee.

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