Comparative Cross-sectional Study

It was a hospital-based comparative and cross-sectional study conducted in the Department of Obstetrics and Gynaecology,S.M.S Medical College, Jaipur, Rajasthan, India. Approval was obtained from the Ethics Committee, S.M.S MedicalCollege, Jaipur, Rajasthan, India. Those women who did not have any menstrual period for the last one year were screened.Demographic characteristics of these postmenopausal women were noted which included age, occupation of self and family,educational status, the total income of family, smoking or alcohol intake was noted. These were then subjected to a detailedhistory taking regarding any illness and drug intake including calcium and vitamin D supplementation. A thorough clinicalexamination including BMI and biochemical tests were done on those with no such history or treatment records. These testsincluded a complete blood count, erythrocyte sedimentation rate, C-reactive protein, fasting blood sugar, renal and liverfunction tests, thyroid profile, vitamin D levels, parathyroid hormone levels, calcium levels. Those women who fulfilledthe inclusion and exclusion criteria were included in the study. The sample size was calculated at 80% study power and analpha error of 0.05. For a minimum detectable mean difference of 23.2 mg/dL in total cholesterol between the two groups, 51patients in each group were required as sample size which was enhanced and rounded off to 55 patients as final sample sizeexpecting 10% dropouts/attrition. Thus, the study included 110 postmenopausal women fulfilling the inclusion and exclusioncriteria. Two groups were made. Group 1 consisting of postmenopausal females who had been diagnosed with osteoporosiswhile Group 2 consisted of a similar number of postmenopausal females who did not show osteoporosis.

Postmenopausal women (atleast 1 year without menses) with body mass index (BMI) in the range 18.5 to 25 kg/m2, willingto participate in the study and give written informed consent were included in the study

• Malignant disease
• Women who were suffering from diseases like diabetes, thyroid, parathyroid and adrenal gland disorders, chronic renalfailure, inflammatory arthritis and diseases of the gastrointestinal tract
• Women using drugs like statins, corticosteroids, hormones and diuretics for more than three months
• Secondary osteoporosis due to endocrine diseases
• History of peptic ulcer surgery
• Osteoporosis induced by medications

These women were subjected to detailed menstrual and obstetric history. Detailed clinical examination was done. For assessinglipid profile, samples were taken from a peripheral vein after 12 hours of fasting and were immediately centrifuged at 4^°C.Plasma was used to analyse the lipid profile-total cholesterol, LDL, TG and HDL

Lipid profile was estimated by using the enzyme calorimetric technique. It was considered abnormal if cholesterol >200mg/dL; triglycerides ≥150 mg/dL and HDL ≤50 mg/dL.

Along with that, a DEXA scan was done at the lumbar spine (L2-L4) and at the neck of the femur to assess the bonemineral density to diagnose osteoporosis. T-score measured in standard deviation showed the difference between a patient’sBMD and that of healthy young adults of the same sex. A positive score indicated bone to be stronger than normal.¹² Z-scoreshowed the amount of bone, compared with other people in same age group and of the same size and gender.¹²

Results were interpreted graphically and osteoporosis was diagnosed when the T score was less than or equal to 2.5.

A correlation between lipid profile and osteoporosis was done in both the groups

The data obtained was tabulated, compared and analysed by χ² test to identify differences in baseline characteristicsbetween both the groups. Data were presented as mean±standard error values for continuous variables and aspercentage±standard error for categorical variables. Statistical analysis was performed. A p-value <0.05 was considered tobe statistically significant.

A total of 110 postmenopausal women were included in the study, with 55 each in the two groups. The mean age of womenin Group 1 (with osteoporosis ) was 53.7±5.07 years while it was 54.47±4.64 years in Group 2 (p=0.354). There was nostatistically significant difference in the mean age of the two groups. Most of the women in both the groups belonged tothe middle class (78.18% in Group 1 and 72.72% in Group 2). No statistically significant difference was found when thetwo groups were compared for socio-economic status.None of the women included had a history of calcium or vitamin Dintake in the past six months. 76.36% of osteoporotic postmenopausal women (Group 1) were multiparous while 81.82% ofwomen in group 2 were multiparous. When this factor was compared between the two groups, the difference was not foundstatistically significant.

Postmenopausal women in the BMI range of 18.5 to 25 kg/m² only were included in the study. Others were excludedfrom the study to avoid confounding factors. The mean BMI in women with osteoporosis was 22.16±1.88 kg/m² and ingroup 2 was 21.98±2.18 kg/m². This difference was insignificant (Table 1). It was observed in many studies that a fewernumber of menstrual years was associated with an increased incidence of osteoporosis, hence the two groups were comparedfor age at menarche. No statistically significant difference was observed in the two groups when age at menarche wascompared (Table 1). 24 women in Group 1 and 27 women in Group 2 attained menopause during 51-55 years of age. Whenwomen in the two groups were compared for age at which menopause was achieved, no statistically significant differencewas observed (Table 1). Similarly, there was no difference between the two groups when the time since the last deliverywas compared (Table 1).

Table 1 shows that in group 1, 42 women (76.36%) were parity ≥3 or more while in Group 2, their number was 45(81.8%). When this factor was compared, this difference was not found statistically significant. None of the women in bothgroups was smokers or consumed alcohol and none had a history of spontaneous fracture in the past. Hypertension was seenin 8 (14.5%) women in Group 1 and 7 (12.7%) in Group 2. The difference in the number of hypertensives in the two groupswas not statistically significant. These women were on anti-hypertensives other than those mentioned in the exclusioncriteria (Table 1).

Our study aimed at finding an association between atherogenic lipid profile and the development of osteoporosis. Manystudies have suggested that hyperlipidemia has a role in the development of both atherosclerosis and osteoporosis. Our resultswere similar to many studies. BMI is one of the factors which affects the development of osteoporosis, so only those patientswere included in the study whose BMI was normal. Sadat Ali et al. found a statistically significant difference in BMD with adifference of 10 in mean BMI among postmenopausal women.¹³ Skrzek A et al. suggested that 26.9 kg/m² is the optimal valueof BMI which would indicate the most favourable preservation of the bone mineral density in postmenopausal women.¹⁴ Wealso found that early menarche and late menopause was protective against osteoporosis. Mendoza-Romo MA et al. found thatwomen who attained menarche at an age more than 13 years were more prone for osteoporosis in postmenopausal age (OR4.46; p=0.035).¹⁵ Parker SE et al. observed that women who attained menarche at 11 years of age or less were associated witha reduced incidence of osteoporosis.¹⁶ They also found an incidence rate ratio for the association between age at menopause(≥50 years) and osteoporosis risk and it was 0.61 (CI 0.40, 0.92). Women who menstruated for ≤25 years were more stronglyassociated with osteoporosis than women who had menses for ≥35 years (IRR 1.80; CI 1.14, 2.86). Sioka C et al. studied thatthe women who attained their menopause at ≤45 years of age had decreased bone mineral density (p=0.034).¹⁷ We JS et al.found that the age at last childbirth significantly influenced the prevalence of osteoporosis irrespective of BMI ≥25 kg/m2 (p<0.001) in postmenopausal women.¹⁸

When levels of serum cholesterol in the two groups were compared, there was a statistically significant difference withincreased values in women with osteoporosis. Similar findings were observed by Shukla J et al.who found that postmenopausalwomen with osteoporosis had significantly increased values of total cholesterol (mean=137.11 mg/dL, SD=7.28) andtriglycerides (mean=137.11 mg/dL, SD=7.28).¹⁹

YY Chen et al. found that postmenopausal women with osteoporosis had a significantly higher total cholesterol levelcompared to those with the normal bone mineral density.20 Garg MK et al. observed that BMD at femur (0.887±0.152)decreased significantly with increasing quartiles of total cholesterol (<200 mg/dL, p=0.024).²¹

Few studies have dismissed any association between these two. Adami and colleagues found no significant associationof elevated serum cholesterol with a decrease in bone mineral density at the hip level in women aged 68-75 years.22 Li et al.observed the same.²³

Sivas et al. found that the mean serum cholesterol of women with vertebral fractures was significantly lower than thepatients without fractures (mean=214.4±4.3 mg/dL with p<0.05).The results of this study are in contrast to our study.²⁴However, they suggested a significant correlation between serum triglycerides and women prone to fractures (mean=139.4±7.8mg/dL with p <0.05) which is by our study results.

Adami and colleagues found a strong positive correlation of lumbar spine BMD-Z score values and triglycerides levelin postmenopausal women (mean=1.50 mmol/L, SD=0.71).²² Bijelic R et al. found that elevated serum triglyceride levels(p=0.033) were significantly associated with osteoporosis.²⁵

We did not find any significant difference in HDL values between the two groups as did Adami and colleagues andSivas et al. who also found no significant association of decreased serum HDL cholesterol with a decrease in bone mineraldensity.22,24 However, YY Chen et al. showed that osteoporosis group had a significantly higher HDL level compared to thenormal density group.20 Yamaguchi et al. evaluated the relationships between plasma levels of HDL-cholesterol and observedthat it was significantly and positively correlated (p<0.05) with BMD values and hence associated with the presence ofvertebral fractures in postmenopausal women.²⁶

In the study conducted by Bijeclic R et al., the results of univariate logistic regression analysis show that the totalcholesterol (p=0.000, OR=1.006, 95% CI=1.003 to 1.0009), LDL (p=0.005, OR=1.005, 95% CI=1.001 to 1.008) andtriglycerides (p=0.033, OR=1.004, 95% CI=1.000 to 1.008) are significant risk factors for osteoporosis, although in themultivariate logistic regression, LDL cholesterol and TG were not identified as independent risk factors.²⁵ Results ofmultivariate regression analysis showed that the increased value of total cholesterol is a significant independent risk factor forosteoporosis in postmenopausal women (p=0.018, OR=1.006, 95% CI=1.001 to 1.010).24 This is similar to the results of ourstudy which also suggests increased total cholesterol values in postmenopausal women with osteoporosis.