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Association between Hypertension, Antihypertensive Drugs, and Osteoporosis in Postmenopausal Syrian Women: A Cross-Sectional Study.

1. Introduction

The diagnosis of both osteoporosis and HTN has been increasing globally due to the increased number of people aged over 50 yrs driven by the increasing longevity [1-3].

It has been estimated that 50% of women over 50 yrs had low bone mass according to the national health nutrition examination survey, and about 25% of women over 60 yrs had osteoporosis [4], and 20% to 40% is the worldwide prevalence of hypertension [5, 6].

The increased comorbidities and mortality associated with these two diseases illustrate their clinical risk.

On one hand, HTN is a major risk factor for ischemic heart disease, renal failure, and other ischemic vascular diseases [7-9], and as a result, it accounts for 1-4% of all causes of death [6-10].

On the other hand, osteoporotic fractures are important causes of disability [3]. Hip fracture is associated with a 20% excess mortality one year following the fracture [11].

Recently, many epidemiological and biological studies suggested that both HTN and osteoporosis share the same etiopathology, involving low calcium intake and level, vitamin D and vitamin K deficiency, and low or very high levels of nitric oxide [12].

The prevalence of low bone mass, osteoporosis, and hypertension among postmenopausal Syrian women was determined in this study, and the association between osteoporosis, hypertension, and antihypertensive drugs was explored.

2. Methods

2.1. Study Population. A cross-sectional study was performed between November 2018 and March 2019 at AlMouwasat University Hospital, Damascus, Syria. Participants were postmenopausal women aged [greater than or equal to] 40 yrs. Subjects who were previously diagnosed with osteoporosis, chronic kidney disease (glomerular filtration rate (GFR) <30 mL/ min/1.73 [m.sup.2]), chronic liver disease, advanced heart disease, metabolic or inherited bone disease, such as hyperparathyroidism or hypoparathyroidism, Paget disease, osteomalacia, or osteogenesis imperfecta, Cushing syndrome, hyperthyroidism, or took medication that proved to increase bone mineral density (such as bisphosphonate, hormone replacement therapy, selective estrogen receptor modulator, strontium ranelate, calcitonin, and PTH Analog) were excluded.

HTN was defined as blood pressure [greater than or equal to] 130/85 mmHg or a history of hypertension medication.

Information was collected by a questionnaire included age, menopause duration, work, exercise, cigarette smoking, and regular alcohol consumption.

Weight (with light clothes) and barefoot height were measured using the Seca Scale Model 713 device (Boian Surgical, Padstow, Australia). Body mass index was calculated by the equation (BMI = weight (kg)/height ([m.sup.2])). Participants were categorized according to the criteria by the World Health Organization (WHO) as follows: BMI <25 kg/ [m.sup.2] for normal weight, 25 [less than or equal to] BMI < 30 kg/[m.sup.2] for overweight, and BMI [greater than or equal to] 30 kg/[m.sup.2] for obesity.

Total body measurement of BMD was made using a dual-energy X-ray absorptiometry (Medilink, MEDIX DR VER v4.0.3) at the total lumbar spine (L1-L4) and left hip. If a fracture or degeneration was recorded at one or two lumbar vertebrae, those vertebrae were excluded from the DXA report, and the diagnosis was made according to the rest of the lumbar vertebrae. If three or more vertebrae were affected, the lumbar BMD was excluded from the report, and the participant was excluded from the study [13]. The left hip was not scanned when a positive history of fracture or surgery was present, and the right hip was scanned instead. The scanner was used by the same well-trained nurse and calibrated daily against the standard calibration block supplied by the manufacturer. Osteoporosis was diagnosed according to the WHO criteria, using T-score values shown in Table 1.

Data were analyzed using the SPSS software version 23.0 (IBM, Armonk, New York, USA), p values <0.05 were considered statistically significant. Mean and standard deviation were calculated. The chi-square test was used for nominal data and independent-samples T-test for continuous normally disturbed variables.

3. Results

813 postmenopausal women were included, their mean age was 58.92 [+ or -] 8.6 yr, and their mean menopause duration was 10.1 [+ or -] 8.3 yr, with an average height of 152.16 cm [+ or -] 6.38 cm, weight 77.09 kg [+ or -] 14.51kg, BMI 33.35 kg/[m.sup.2] [+ or -] 6.13 kg/[m.sup.2], total lumbar BMD 0.905 g/[cm.sup.2] [+ or -] 0.162 g/[cm.sup.2], and femoral neck BMD 0.928 g/[cm.sup.2] [+ or -] 0.148 g/[cm.sup.2] (Table 2). 182(22.3%) women were smokers, 288 (35.42%) women regularly exercised, and 232 (28.5%) were workers. None of the participants consumed alcohol regularly as it is an unpopular habit in the Syrian community. Osteoporosis was found in 195 women (24%), and low bone mass was found in 368 women (45.2%) while normal bone density was found in 250 women (30.8%). Table 3 shows the general characteristics of the participants of the study.

The incidence of osteoporosis and low bone mass increased significantly with age and menopause duration (p: 0.0001) (Table 4).

Obesity, overweight, and normal weight prevalence were 69.6%, 23.1%, and 7.3%, respectively. The normal weight group had the highest osteoporosis incidence with a significant difference (p: 0.0001) Table 4.

Among the 813 women included, 387 (47.7%) had HTN. (93.1%) Of them were treated with one or more antihypertensive drugs and (6.9%) did not have any treatment for HTN.

Figure 1 shows the distribution of participant according to the type of antihypertensive drug.

The prevalence of osteoporosis and low bone mass were almost equal among women who had or did not have HTN, and no significant difference was found (p: 0.351) (Table 4 and Figure 2).

Independent-samples T-test was used to evaluate the relationship between the total hip BMD, the total lumbar BMD, and antihypertensive drugs.

The median total lumbar BMD was found to be increased significantly among women who took thiazide or beta blockers (BBs) compared with women who did not take either of them. Table 5.

4. Discussion

HTN and osteoporosis are very common diseases among elderly population [6]. Many previous studies had suggested that HTN is an independent risk factor for fractures, but it was not clear if HTN affects BMD significantly [12].

The association between osteoporosis, HTN, and antihypertensive drugs was discussed in this study.

Among the 813 postmenopausal women, (45.2%) had low bone mass and nearly the fourth (24%) had osteoporosis. These results were in alignment with the results of many other studies in the Middle East and the west [14-20].

The prevalence of osteoporosis and low bone mass and osteoporosis increased significantly as the age and menopause duration prolonged, as previous other prospective studies showed that rates of bone loss from the spine and hip were 1% to 2% of its total mass during the early post-menopause phase and about 35% to 55% slower loss during the late menopause phase [21, 22].

A significantly negative relationship between BMI and the prevalence of osteoporosis was found in our study; this could be explained by the anabolic effect of adipokines secreted by adipose tissue [23, 24].

There was no association between HTN and osteoporosis according to the results of our study. This was consisted with the results of Fahad Javed F and colleague's study which found that the prevalence of low bone mass and osteoporosis were similar in those with or without HTN [25]. However, these results did not support the results of Li and colleague's meta-analysis, which demonstrated that HTN was associated with increased odds of having osteoporotic fractures, especially in women [26].

The exact mechanism underlying the effect of HTN on osteoporosis in humans has not been clear yet. Several mechanisms have been proposed. Although many studies had shown that high blood pressure is associated with increased loss of calcium in the urine, leading to a negative calcium balance of bone remodeling and increased levels of parathyroid hormone, which accelerate bone turnover and decrease bone mass [27, 28], recent studies had shown that hypertensive subjects had an increased levels of ghrelin [29, 30], which affect bone directly by inhibiting bone resorption and enhancing bone formation [31]. These counteracting mechanisms may ultimately lead to stabilization of BMD in hypertensive patients, which could explain the results of our study.

Moreover, antihypertensive drugs may have an add-on effect on bone. The results of our study showed that the use of thiazide or beta blocker drugs was significantly associated with increased levels of total lumbar BMD.

Several studies had investigated the effects of beta blockers on the bone to explore how beta blockers may improve BMD. Studies on animal models suggested that inactivation of the sympathetic nervous system impairs osteoclastic bone resorption and thus increases bone formation. [32]. And while many studies had not proven any improvements on BMD with beta blocker treatment [12,33], others showed beneficial effects of beta blockers on osteoporotic subjects [33].

Similarly, thiazides may have an important role in preventing bone loss.

On one hand, thiazides decrease urinary calcium excretion by inhibiting the sodium chloride cotransporter in the distal tubule. [34]. And on the other hand, recent studies suggested that thiazides may have a direct effect on bone cells by enhancing osteoblast differentiation [35] and decreasing acid production through inhibition of carbonic anhydrase activity in the osteoclasts [34].

5. Conclusion

The results of our study show that there is no association between osteoporosis and hypertension in elderly postmenopausal Syrian women. However, our study shows a positive role of thiazide diuretics and beta blockers on the bone mineral density of the lumbar spine in osteoporotic hypertensive postmenopausal women. Further prospective studies with larger sample sizes and narrow age range are needed to evaluate the relationship between BMD and hypertension.

BMD:   Body mineral density;
BMI:   Body mass index;
DXA:   Dual-energy X-ray absorptiometry;
HTN:   Hypertension;
ACE-I: Angiotensin-converting enzyme inhibitor;
CCB:   Calcium channel blockers;
BB:    Beta blockers.

Data Availability

The data file (in EXCEL or SPSS) used to support the findings of this study are available from the corresponding author upon request.

Conflicts of Interest

Authors declare no conflicts of interest.


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Nermeen Hijazi [ID],(1) and Zaynab Alourfi (1,2)

(1) Internal Medicine Department--Endocrinology, Damascus University, Damascus, Syria

(2) Faculty of Medicine, Syrian Private University (SPU), Damascus, Syria

Correspondence should be addressed to Nermeen Hijazi;

Received 5 November 2019; Accepted 21 January 2020; Published 19 February 2020

Academic Editor: Noureddin Nakhostin Ansari

Caption: Figure 1: Distribution of the participant in the study according to the type of antihypertensive drug. ACE-I, angiotensin-converting enzyme inhibitor; CCB, calcium channel blocker; BB, beta blocker.

Caption: Figure 2: Distribution of low bone mass and osteoporosis between hypertensive and nonhypertensive participants.
Table 1: T-score values and diagnosis by the WHO.

Diagnosis                      T-Score

Osteoporosis       T [less than or equal to] -2.5
Low bone mass   -2.5 < T [less than or equal to] - 1
Normal                         T > -1

Table 2: Description of numeric variables of the participants
of the study.

Parameter            Mean [+ or -] standard deviation

Age                         58.92 [+ or -] 8.6
Menopause duration           10.1 [+ or -] 8.3
Weight                     77.09 [+ or -] 14.51
Height                     152.16 [+ or -] 6.38
BMI                         33.35 [+ or -] 6.13
Total lumbar BMD           0.905 [+ or -] 0.162
Total neck BMD             0.928 [+ or -] 0.148

Table 3: The general characteristics of the participants
of the study (N = 813).

                      Variable      Frequency   Percent (%)

                       Normal          250         30.8
Diagnosis           Low bone mass      368         45.2
                    Osteoporosis       195          24
Hypertension        Hypertensive       387         47.61
                    Normotensive       426         52.39
                       Normal          59           7.3
BMI                  Overweight        188         23.1
                       Obesity         566         69.6
Cigarette smoking        Yes           182         22.3
                         No            631         77.7
Work                     Yes           232         28.5
                         No            581         71.5
Regular exercise         Yes           288         35.42
                         No            525         64.57

BMI, body mass index.

Table 4: Distribution of low bone mass and osteoporosis among the
participant according to their age, menopause duration, BMI, and
hypertension diagnosis.

                               Normal      Low bone mass

                     40-50   52 (47.7%)     44 (40.4%)
Age group            50-60   129 (32.2%)    179 (44.6%)
                     60-70   50 (23.3%)     108 (50.2%)
                     >70     19 (21.6%)      37 (42%)
                     <10     167 (38.7%)     186 (43%)
Menopause duration   10-20   68 (22.5%)     152 (50.3%)
                     >20      15 (19%)       30 (38%)
                     <25      1 (1.7%)      25 (42.4%)
BMI                  25-30   46 (24.5%)     91 (48.4%)
                     >30     203 (35.9%)    252 (27.1%)
Exercise             Yes     103 (35.8%)    126 (43.7%)
                     No       147 (28%)     242 (46.1%)
Cigarette smoking    Yes     43 (23.6%)      80 (44%)
                     No      207 (32.8%)     288 (45%)
Work                 Yes      79 (34%)      103 (44.4%)
                     No      171 (29.4%)    265 (45.6%)
Hypertension         Yes     128 (33.1%)    172 (44.4%)
                     No      122 (28.6%)     196 (46%)

                     Osteoporosis        p value

                      13 (11.9%)    0.0001 ([dagger])
Age group             93 (23.2%)
                      57 (26.5%)
                      32 (36.4%)
                      79 (18.3%)    0.0001 ([dagger])
Menopause duration    82 (27.2%)
                       34 (43%)
                      33 (55.9%)    0.0001 ([dagger])
BMI                   51 (27.1%)
                     111 (19.6%)
Exercise              59 (20.5%)    0.046 ([dagger])
                     136 (26.9%)
Cigarette smoking     59 (32.4%)    0.004 ([dagger])
                     136 (21.6%)
Work                  50 (21.6%)          0.367
                      145 (25%)
Hypertension          87 (22.5%)          0.351
                     108 (25.4%)

BMI, body mass index. ([dagger]) Statistically significant.

Table 5: Comparison of mean BMD among hypertensive patients according
to the type of used antihypertensive drug.

                      Mean of    p value   Mean of    p value
                      femoral               total
                      neck BMD             lumbar

ACE-I or ARBs   No     0.926      0.726     0.899      0.08
                Yes    0.930                0.922
CCB             No     0.930      0.146     0.904      0.907
                Yes    0.909                0.906
Thiazide        No     0.926      0.653     0.899      0.019
                Yes    0.933                0.935
BB              No     0.925      0.491     0.895     0.0001
                Yes    0.939                0.949

BMD, bone mineral density; ACE-I, angiotensin-converting enzyme
inhibitor; CCB, calcium channel blocker; BB, beta blocker.
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Title Annotation:Research Article
Author:Hijazi, Nermeen; Alourfi, Zaynab
Publication:Advances in Medicine
Article Type:Clinical report
Geographic Code:7SYRI
Date:Mar 31, 2020
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