Retracted (01 Sept 2021): Metabolic syndrome in Saudi women with low bone mineral density

Retraction notice (01 September 2021)

This article has been retracted according with request from author Dr Mubashir Zafar and by agreement between the journal Editor in Chief, Anton Kiselev and LLC Science and Innovations. The retraction has been agreed due to conflict of interest between authors and this article duplicate published in Medical Journal of the Islamic Republic of Iran.

Data about both versions of article:

• Russian Open Medical Journal — Received 2 April 2020, Accepted 6 October 2020, https://romj.org/2020-0412, Corresponding author: Dr Mubashir Zafar, E-mail: researchmubshir@outlook.com. 
• Medical Journal of the Islamic Republic of Iran — Received 14 May 2020, Published 18 Feb 2021, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8214043/, Corresponding author: Mubashir Zafar, E-mail: researchmubshir@outlook.com. 

Dr Mubashir Zafar informed us that his email (researchmubshir@outlook.com) was hacked  and recovered only in August 2021. As a result, unknown persons, illegally acting on behalf of the authors via this email, performed a series of actions (the ORCID of first author was faked, author's signatures in copyright form was faked, unknown persons corresponded with the editorial board and approved the draft of the article for publication) that violated the rights of the authors and resulted in a duplicate publication.

Introduction

The prevalence of metabolic syndrome (MetS) is expanding at an alarming rate in developed and developing nations throughout the world [1]. M‏etS is a cluster of the most dangerous heart attack risk factors including raised fasting plasma glucose, abdominal obesity, high cholesterol and high blood pressure [2]. Epidemiologic researches indicate that metabolic syndrome is a major risk factor for various number of chronic diseases mainly cardiovascular disease and type II diabetes [3]. According to the International Diabetes Federation (IDF) it is estimated to have MetS in around 20-25% of the world’s adult population and are twice as probable to die from and three times as likely to have a heart attack or stroke compared to individuals without the syndrome [3]. A survey published in 2018 shows that the prevalence of MetS in Saudi Arabia was found to be 39.8% (34.4% in men and 29.2% in women) and 31.6% (45.0% in men and 35.4% in women), according to the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) and IDF criteria, respectively [4]. Moreover, per International Osteoporosis Foundation (IOF), osteoporosis affects an estimated 200 million people worldwide which is responsible for more than 8.9 million fractures yearly, resulting in an osteoporotic fracture every 3 seconds.

The high prevalence for both diseases prompts a need to understand the relationship between the two conditions. Epidemiological studies achieve inconclusive outcomes on the relationship between bone health and MetS, whereby this relationship is beneficial, adverse or non-significant [5]. conducted a cross-sectional study to determine the association among menopausal Korean women between risk factors of MetS and bone mineral density (BMD). The findings showed that MetS risk factors did not differ significantly, while waist circumference showed a significant association with body surface area (BSA) (r=-0.242, P<0.001), BSA (r=0.186, P<0.01) and bone mineral content (BMC) (r=0.161, P<0.05) correlated significantly with diastolic blood pressure in correlation test. This result was similar to a cross sectional study conducted by [6] that included 2007 participants (1045 males and 962 females) over 50 years of age who were examined by a preventive examination agency in urban Taiwan to examine the link between MetS and osteoporosis among Taiwanese middle-aged and elderly participants. A population-based survey in China consisting of 9930 Chinese adolescents aged 40 years or older in the district of Chongming, Shanghai was performed to assess the connection between MetS and osteoporotic fracture between middle-aged and elderly Chinese [7].

Although MetS and osteoporosis were earlier thought to be two unrelated diseases, latest studies have shown that both conditions share several genetic, nutritional and hormonal factors [8]. While the relationship between cardiovascular disease and osteoporosis has been widely studied, the specific association between MetS, a powerful risk factor for cardiovascular disease, and osteoporosis has not been discussed so extensively and several studies have shown inconsistent outcomes [9-15].

The prevalence of metabolic syndrome has increased in Saudi Arabia, forcing such a need to determine the causal factors that led MetS among aged population. Life expectancy also rises, which raises Saudi women's risk of osteoporosis. Only limited studies have focused on explaining the relationship between MetS and BMD in Saudi Arabia, these studies cover all populations including expatriated which did not determine the actual problem among Saudi women. Also, these studies are cross sectional studies which did not determine the temporality (causal association). This research will also be the first case-control study undertaken in Saudi Arabia in order to determine a possible causal relationship between the two conditions. Furthermore, only Saudi females will be included as survey respondents estimating the real issue among Saudi women.

Objectives: The aim of this study is to determine the relationship between MetS and BMD among Saudi menopausal women in Eastern Province – Saudi Arabia.

Material and Methods

Study setting and participants

Study setting: The study was conducted at Safwa General Hospital, one of the Eastern Province's main government facilities consisting of nearly 30 beds and serving approximately 150-200 patients daily in the outpatient departments (OPD). And also, patients were included from one of the biggest primary healthcare centers in Qatif that serve about 80-100 patients daily.

Study participants: All menopausal women (age 45-75 years old) who had got BMD scans by Dual-Energy X-ray Absorptiometry (DEXA) and were diagnosed as osteoporotic as cases and without osteoporotic as control by their physicians who visits the hospital for regular checkup

Menopausal status is defined as cessation of menstruation for at least 1 year.

Study design

It is a case control study.

For cases: Inclusion criteria: all menopausal women age (45-75 years old) who in their general physician visits had been advised of a bone mineral density (BMD) scan owing to their being at risk associated with bone loss and were diagnosed with osteoporosis with MetS. Exclusion criteria: perimenopausal women, participants with liver or renal diseases, inflammatory diseases, vascular diseases or with evident endocrine disorders or drug treatment with possible effect on bone metabolism like bisphosphonate, or estrogen replacement therapy.

For controls: Inclusion criteria: all menopausal women age (45-75 years old) who were free of osteoporosis with MetS Exclusion criteria: perimenopausal women, being above 75 years of age or on estrogen replacement therapy. Hormonal replacement therapy is defined as the therapeutic use of hormones typically to increase diminished levels in the body.

Sample size and sampling technique

Sample size: Sample size was calculated by WHO sample size calculator for health studies based on 95% confidence level, relative precision 0.25, probability to exposure given to disease 0.6, probability to exposure given to no disease 0.4 and anticipated Odd Ratio is 1.5, the sample size is 380 for this study. Divide the sample size as 190 participants for cases and 190 for control and participants were selected through stratified random sampling.

Data collection tool and technique

Structured questionnaire was used. The questionnaire is divided into four section first sociodemographic characteristic including smoking habit, physical exercise, exposure to sunlight and family history of MetS, anthropometric measurement, Biochemical measurement including FBG, RBG, lipid profile and DEXA measurement.

Anthropometry, blood sample and analysis

Height and weight were measured using an automatic anthropometer in participants wearing light clothing and no shoes. Body mass index (BMI) was calculated as body weight (in kilograms) divided by height (in meters squared) and then classified according to WHO classes: Normal (18.50–24.99 kg/m²), Overweight (25.00–29.99 kg/m²) , Obese (≥30 kg/m²), The waist circumference was measured at the midpoint between the lowest rib and the upper iliac crest using a tape measure on exhalation.

Blood pressure was measured using an automatic blood pressure monitor after resting for 10 minutes in a sitting position before measurement as the average of 2 consecutive measurements after at least 5 minutes of sitting.

Blood sample after 8-12 hours fasting was collected for the measurement of fasting blood sugar, high density lipoprotein cholesterol, and triglycerides.

Criteria for diagnosis of metabolic syndrome

Participants were diagnosed with MetS using the criteria set in the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) which states MetS being present if at least three of the following five components are present.

1. Central obesity: waist circumference (WC) ≥102 cm (males), ≥88 cm (females).

2. Hyperglycemia: fasting blood sugar (FBS) ≥100 mg/dl

3. Hypertriglyceridemia: serum triglycerides (TG) ≥150 mg/dl

4. Serum HDL-cholesterol (HDL-C) <50 mg/dl

5. Systolic blood pressure (SBP) ≥130mmHg and/or diastolic blood pressure (DBP) ≥85 mmHg.

Criteria for diagnosis of osteoporosis

The bone mineral density of the total hip were measured using dual-energy X-ray absorptiometry (DEXA). The T score was calculated, and the diagnosis of osteoporosis were made according to the World Health Organization (WHO) criteria

·           T-score between −1 and −2.5 is indicative of osteopenia

·           T-score of −2.5 and below reflects osteoporosis

·           T-score of −1 and above is considered normal T-Score Tertiles

·           Data were divided into T-score tertiles with tertile1 having the lowest T-score and tertile 3 having the highest T-score.

Ethical consideration

Ethical approval were obtained from Imam Abdulrahman Bin Faisal University Research Ethical Review Board. Permission were taken from the hospital. Informed consent were obtained from all subjects who agree to participate in the study before the interview. Participation is voluntary, and participants are free to withdraw at any time without any explanation. The confidentiality and privacy of the subjects were maintained and there were no financial benefit to either the subjects or the researcher.

Statistical analysis

All Statistical analysis were performed with SPSS windows version 23. Continuous data were presented as mean ± standard deviation (SD). Statistical significance between the groups were evaluated using Students t-test while categorical data were compared by Chi square test. Correlation between MetS and BMD were determined by Pearson’s correlation test. A Confident Interval (CI) of 95% and a P-value of less than 0.05 (two-sided) was consider statistically significant. Multinomial logistic regression were performed using the T-score tertile as a dependent variable (with lowest tertile as reference) and full MetS or its individual components (present vs. absent) as independent variables. Different models were formed with model “a” as univariate, and all other models were adjusted accordingly for + age (model “b”), + BMI (model “c”), + other components of MetS (model “d”) and + risk factors associated with bone loss like type II diabetes mellitus.

Results

Table 1 shows the socio-demographic characteristics of study participants. The mean age of all subjects is 63.8±7.1 years. The data shows a statistically significant difference in age categories between women with osteoporosis compared to their counterparts, i.e. those with osteoporosis are older (P<0.001).

Table 1. Socio-demographic characteristics of study participants (n=380)

There is no statistical significance in baseline characteristics between all participants except for physical activity. Physical inactivity is more prevalent among women with osteoporosis than those without osteoporosis (57.9% vs. 42.1, P=0.016). Whereas more women without osteoporosis are exercising 1-2 times per week more than their counterparts with osteoporosis (58.3% vs. 41.7%, P<0.05). 

Table 2 shows the difference in anthropometric and biochemical parameters of all participants. Women with higher BMI have significantly less cases of osteoporosis compared to their counterparts (58% vs. 42%, P=0.001). In addition, participants with higher Serum TG have significantly higher cases of osteoporosis compared with their counterparts (P<0.001). Moreover, women with lower mean levels of HDL-C have significantly less cases of osteoporosis compared to their counterparts (P<0.001).

Table 2. Anthropometric and biochemical characteristics of study participants (n=380)

Data are given as the mean ± SD or as the number of subjects with percentages given in parentheses, as appropriate. Categorical data were compared by χ2 test. WHO criteria: a T-score between −1 and −2.5 is indicative of osteopenia, while a T-score of −2.5 and below reflects osteoporosis; a T-score of −1 and above is considered normal. 

Table 3 shows the prevalence of MetS in participants with tertile according to the T-score (L1-L4 spine). The lowest T-score (least BMD represents the tertile 1 and the highest T-score represents the tertile 3. The prevalence of the five components is more or less similar in different tertiles of T-score and this is seen in both groups. The data does not show significant statistical difference in either groups.

Table 3 Prevalence of metabolic syndrome (MetS) components in tertile of T-score (n=380)

Categorical data were compared by χ2 test. WHO criteria: a T-score between −1 and −2.5 is indicative of osteopenia, while a T-score of −2.5 and below reflects osteoporosis; a T-score of −1 and above is considered normal. P-value <0.05 significant.

Table 4 shows the results of the correlation between MetS and BMD in both groups. A very weak negative correlation was observed between BMD and SBP (r=-0.072), TG (r=-0.069) and HDL (R=-0.065) in women with osteoporosis , and between BMD and WC (r=-0.091), TG (r=-0.025) and HDL (r=-0.061) in their control counterparts. No statistical significance was found in either group (P-value >0.05).

Table 4 Correlation between bone mineral density and features of the metabolic syndrome in 380 postmenopausal women

Table 5 shows the association of socio-demographic characteristics with osteoporosis. All the socio-demographic characteristics were associated of osteoporosis but none of them were statistically significant.

Table 5 Associations of osteoporosis with metabolic syndrome other risk factors among women in Dammam

Odds ratio with 95% confidence interval. BMI, body mass index. The reference category is: T1. b: this parameter is reference category. 

Table 6 shows the association of metabolic syndrome characteristics with osteoporosis in multiple regression analysis. Triglyceride is the only component of metabolic syndrome were statically significant associated with osteoporosis. Every unit change of triglycerides the -0.004 unit decreased in the osteoporosis.

Table 6 Multiple regression analysis of the effect of metabolic syndrome risk factors on T-score

B, unstandardized beta; SE, standard error; β, standardized beta; WC, waist circumference; SBP, systolic blood pressure; DBP, diastolic blood pressure; TG, triglyceride; HDL-C, high density lipoprotein cholesterol; FBS, fasting blood sugar. 

Discussion

The study results revealed osteoporosis was significantly associated with a metabolic syndrome in Saudi women. This association was unbiassed of other covariates.

Metabolic syndrome (MetS) is a group of cardiovascular hazards which have been clustered under one umbrella because they exist together much more often than would be expected by probability. This result is consistent with other studies results [16-18]. Moreover, some universal mechanisms for both illnesses have been related. For example, low HDL levels are considered preemptive risk factors for osteoporosis, and it also have been suggested to progress of MetS [19-22].

This study results found that metabolic syndrome components prevalence was more in osteoporosis patients compare to non-osteoporosis patients. These results were consistent with other studies results, previous studies have revealed that higher blood pressure in osteoporosis patients with increased chance of bone loss [23]. Furthermore, low HDL level was observed among those who have osteoporosis [24]. Case control study was conducted, result found that high blood pressure was major contributor to bone loss [25]. other components of MetS is TG level, our study found that high level in osteoporosis patients and definitely, TG level increase with age.

This study also found that WC and obesity is strongly associated with MetS. This result consistent with other study results. Even Though the pathophysiological systems connecting obesity to osteoporotic fracture have not been well recognized, it is plausible to consider disproportionate growth of visceral fat could affect in a higher emission of proinflammatory cytokines, with a harmful outcome on bone [26-28].

Physical activity was also associated with osteoporosis in this study results. This results contrast of other study results. Previous study found that those who have more physical active was less chance of osteoporosis fracture [29]. The reason for this conclusion is the when person more active which increased the bone mineral replacement and good for health.

The study results also found that those women who cover the body had more association of osteoporosis. The reason for this association is that sunlight is important predictor for bone mineral. This result is consistent with other study results [30-31].

This study had few limitations. First, this study recruited only two centres, therefore it is difficult to generalize the findings to women. Second, ages of the study subjects were limited to those in their 75s, results for oldest post-menopausal women were not analyzed. Third, bone-metabolism-associated factors such as vitamin D, blood levels of calcium, eating behavior, smoking, alcohol consumption all of which may affect BMD of menopausal women, were not examined in this study, which may confound the explanation of the results of this study.

Conclusion

This study found that presence of MetS was significantly associated with osteoporosis Saudi women. Further experimental studies were needed to generating the strong evidence.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Declaration of Helsinki and its later amendments, or comparable ethical standards.

Conflict of interest

None declared.