Evaluations of bone turnover in a sample of Iraqi postmenopausal hypertensive obese women

Isam Noori Salman, Noor Ulhuda G. Mohammed, Safaa Ehs-san Atta, Baydaa Ahmed Abed, Hussein Hatam omran. Evaluations of Bone turnover in a sample of Iraqi Postmenopausal Hypertensive Obese Women. Cardiometry; Issue No. 32; August 2024; p. 55-59; DOI: 10.18137/cardiometry.2024.32ю5559; Available from:

The number of hypertensive patients is increasing. Pure systolic or combined systolic and diastolic hypertension occurs in about 50% of people aged more than 65 years. The number of hypertensive individual’s increase as the obesity incidence increase.1,2

Control of hypertension and its complications (premature cardiovascular disease, stroke and cerebrovascular accident) until now is not enough , and only 34% of hypertensive patients are under control where their blood pressure is below 140/90mmHg, and this was blamed to be the main risk factor for heart attack and stroke.3

Hypertension with obesity cause an increase in cardiac output with relatively normal systemic vascular resistance, while obesity alone without hypertension shows a normal cardiac output but low systemic vascular resistance than those with normal weight .The main mechanism by which obesity leads to an increase in blood pressure is still not clear, but peripheral insulin resistance that ends with impaired glucose tolerance and hyper-insulinemia and increased sympathetic activity which leads to volume expansion as renal sodium reabsorption increased may play a main role.1,4

Also a sleep apnea syndrome which is a sequel of obesity activates sympathetic nervous system and enhanced secretion of aldosterone and increase level of endothelin due to repeated hypoxia episodes that leads to increase in blood pressure.5

Menopause defines as a cessation of menstrual periods (Amenorrhea) in women about the age of 50 years due to decrease the function of ovaries with symptoms of hot flashes and a high level of follicular stimulating hormone (FSH). The incidence of coronary artery disease in pre-menopausal females are less than in males at the same age, while after menopause , the coronary artery disease events become equal to that in males or even more which indicates the pro- tective role of female sex hormones against the risk of coronary artery disease.6,7

The mechanism in which hypertension, overweight and obesity are seen more in postmenopausal females than in males at the same age is still not clear. The underlying cause of association of obesity with hypertension may be due to the sympathetic nervous system and rennin- angiotensin-aldosterone system over activity; insulin and leptinresistance.8,9

Osteoporosis is mainly a sequel of bone turnover changes with aging that leads to bone loss which recognized at the time of menopause affecting the balance of bone resorption and formation Bone alkaline phosphatase is a bone-specific isoform of the enzyme serum alkaline phosphatase that reflects the activity of the cells in bone mineralization and considered as a reliable biomarker of bone formation.10,11 aim of this study to estimate the effect of hypertension and obesity on bone turnover markers in Iraqi postmenopausal women with hypertension and obesity.

PATIENTS AND METHODS:

The research was done from April 2022 – July 2022 A verbal consent was applied by each patient and approved by the Scientific Committee of the National diabetes center NDC /Mustansiriyah University. Ninety-nine female patients with menopause for the last 3 to 5 years with no history of hormonal therapy and no calcium or any other supplement usage that affect bone metabolism were considered as patients group and divided as group one which includes patients with the presence of both hypertension and obesity (obese-BMI ≥ 30kg/m2 and hypertensive with blood pressure ≥ 140/90 mmHg, n=65, age 56.02±4.37, BMI 35.68±4.78). And group two which includes subjects who are not hypertensive and not obese considered as controls (BMI<30 kg/m2 and blood pressure<140/90 mmHg, n = 34, age 56.44±3.17, BMI 26.02±3.05).

Table (1)

Number of study subjects according to hypertension and obesity.

Hypertension
Normotensive Non obese	Hypertensive obese	Total
34	65	99

A full history regarding age, duration of menopause, family history of hypertension, and drug in-

56 | Cardiometry | Issue 32. August 2024

take. A clinical examination was performed for all participants.

The exclusion criteria including smoking, alcoholism, calcium supplementation within the last 6 months, a bone fracture within the previous 6 months; hypo- or hyperthyroidism ,any abnormal renal or liver function; any prior treatment with a bisphosphonate. The parameters, including serum calcium (Ca), phosphorus (Pi), and alkaline phosphatase were evaluated using commercially available kits.

STATISTICAL ANALYSIS:

Statistical analysis was done using (SPSS) version 15.0 for data analysis, the results are presented as the mean (SD) and P < 0.05 was considered significance.

RESULTS:

Table(1) shows no significant difference in mean age, calcium, phosphorous between hypertensive obese and normotensive control group (p>0.05).non-obese

Table (1)

Demographic characteristics in obese hypertensive (n=65) and non-obese normotensive (n=34) subjects.

Characteristic obese hypertensive n=65 Non-obese normotensive (Controls) n=34 P value Age(years) 4.579±57.02 3.27±55.44 0.658 BMI(kg/m2) 4.78±35.68 3.05±26.06 <0.0001 WC (Cm) 8.66±112.06 13.72±87.43 <0.0001 Ca++(mg/dl) 0.89±9.04 0.58±9.35 0.074 Phosphorous (mg/dl) 0.73±3.411 0.52±3.356 0.707 Cholesterol(mg/dl) 216.17±34.3 198.81±28.3 <0.05 HDL(mg/dl) 50.31±7.35 53.64±5.081 <0.05 LDL(mg/dl) 137.91±33.87 117.91±25.73 <0.05 TG (mg/dl)) 135.75±53.33 127.88±48.70 0.49 Alkaline Phosphatase (KA units/dl) 4.32±8.98 1.85±4.69 <0.0001 p <0.05

Mean BMI is significantly highly elevated in the case group compared tocontrols (p<0.001). Mean Waist circumference is higher in the case group compared to control group (p<0.001).Total cholesterol is significantly higher in the case group compared to controls (p < 0.05). Mean HDL is highly lower in case group than the control group (p < 0.05). Mean LDL is higher in the patients group than controls (p < 0.05).

Triglycerides is elevated in the patients group compared to the controls but the difference is not statically significant (p=0.48). Alkaline phosphatase is significantly elevated (high normal) in case group compared to the controls(low normal) (p<0.001).

DISCUSSION:

The present study showed that there was a highly significant increase in the serum levels ALP in patients group was highly significant with. These findings were in correspondence with a study done by Schutte R et a l on 79 South African men reported that 24-hour systolic blood pressure was positively correlated with serum ALP.^12,13

The results obtained in this study explored that obesity (BMI ≥ 30) was seen more in hypertensive females among hypertensive and non-hypertensive controls. The study approved an opposite correlation between serum calcium level and BMI in hypertensive patients ,and this may be explain by that the body fat percentage and body mass are correlated inversely with the level of calcium in the body that mostly extra-cellularly distributed.14,15

The finding in the same group that the normal level of serum calcium and phosphorus in hypertensive obese subjects with the highest level of alkaline phosphatase could be the greater and new finding of this research as an independent predictor of osteoporosis .The result declared that postmenopausal patients with normal serum calcium (9.04 ± 0.89 mg/dl) but with high alkaline phosphatase level had both ,higher BMI and high systolic and diastolic hypertension.16,17

The only high level of bone alkaline phosphatase pointed that the Resorption of the bone in Iraqi females with postmenopausal and controlled or uncontrolled hypertension are very high, which leads to increase incidence of bone fracture. The whole findings and observations in this study approved the presence of clear correlation between hypertension and postmenopausal women with obesity and dislipidemia which constitute accumulative risk factors.18,19

At menopause, the average of bone remodeling increases precipitously. This fact may be explained by evidence that loss of estrogen postmenop ausual-ly will encourage the bone marrow cells (osteoclasts and osteoblasts) formation and this will raise a suggestion that measurement of serum total ALP alone may provides a good and adequate diagnostic tool with cost-benefit value.20,21

The explanation why bone resorption is increasing with aging in female may be due to reduced conception of calcium and also because of inhibition of bone formation to keep the serum calcium at optimal level. The results showed that the level of serum total calcium was in the low level in postmenopausal female compared to those premenopausal controls and was statistically nonsignificant (p =0.074).22 These findings were in accordance with the studies of other investigators, but there were no significant changes in serum total calcium in postmenopausal cases compared to premenopausal controls.23

Estrogen deficiency after menopause leads to high bone turnover which elevate the rate of bone remodeling due to the osteoblasts receptors dysfunction because of lack of hormones. Bone markers monitoring is of great benefit as a screening tool of osteoporo-sis. 24,25

Postmenopausal bone changes is induced by the effect of estrogen deficiency on the bone, and this leads to quick bone turnover with predominance of osteoclastic activity which can be estimated by a sensitive bone marker which is easily available named alkaline phosphatase enzyme which monitories the mineralization of the bone.26

The significant increase of ALP levels ( p <0.001) in the hypertensive and obese postmenopausal women in this study is also seen in studies conducted by Gjin Ndrepepa who observed the increment patterns for ALP levels.^27,28

In contrast to finding in the current study, Onyeuk-wu et al demonstrated that the serum ALP levels have no significant changes in patients with post menopause and this finding because of the dissimilarity in the study population and geographical variations. In spite of that ALP is labeled as bone marker , it is also known as non specific marker of bone, So a measurement of bone specific alkaline phosphatase (BAP) is valid to differentiate between hepatic disease from osteoporotic activity.²⁹

The study concluded that changes in the bone markers is contributed to osteoporosis and affected by presence of hypertension and obesity.