Osteoporosis and cardiovascular disease cause increased morbidity and mortality in elderly females. Several epidemiological studies have demonstrated that these two conditions are closely related [
A high total cholesterol (TC) concentration is related to the risk of cardiovascular disease. Lipid levels are also used to assess the risk of coronary heart disease, as cutoffs indicating that the commencement of treatment is appropriate and as goals in patient outcomes [
A possible association between lipid profile and osteoporosis has also been investigated. Some researchers have demonstrated that an atherogenic lipid profile is associated with a lower bone mineral density (BMD) [
Apart from the lipid levels, a possible role for inflammation has also been suggested in both conditions. Increased level of high-sensitivity C-reactive protein (hsCRP) is tightly correlated with an increased incidence of coronary heart disease in healthy individuals [
In this study, we aim to investigate the association among lipid profiles, hsCRP, and bone turnover markers (BTMs) in healthy pre- and postmenopausal women to identify possible biomarkers that might predict osteoporosis.
The study population consisted of 759 Korean women older than 20 years of age who visited the Health Promotion Center of Asan Medical Center, Seoul, Korea, from January 2006 to December 2008, and in whom BMD and serum BTMs were measured. A self-administered questionnaire explored their medical, medication, and behavioral history. The height and weight of each subject were measured, while the subjects were dressed in light clothing without shoes, and the body mass index (BMI, kg/m2) was calculated. Following an overnight fasting, venous blood was drawn from each subject for laboratory tests. Women were excluded if they had undergone a hysterectomy or if they had taken drugs such as HMG-CoA reductase, estrogen, or bisphosphonate, which could affect lipid levels and BMD.
The concentrations of TC, calcium, alkaline phosphatase, phosphorus, triglyceride, and HDL cholesterol were measured by colorimetric methods using a Toshiba 200FR automated analyzer (Toshiba Medical Systems, Tokyo, Japan). The serum hsCRP concentration was determined using the CRP immunoturbidimetric method (Roche Diagnostics, Basel, Switzerland) on a COBAS Integra 800 analyzer (Roche Diagnostics). The serum concentrations of CTX and osteocalcin were measured using a chemiluminescence immunoassay (Roche Diagnostics) on an Elecsys 2010 automated analyzer (Roche Diagnostics).
The BMD (g/cm2) was measured at the nondominant femoral neck and the anterior-posterior lumbar spine (L1–L4) using dual energy X-ray absorptiometry (Prodigy Advance with ver. 11.4 software; GE Lunar, Madison, WI, USA). The
The measurements for pre- and postmenopausal women were compared using Student’s
The characteristics of the study subjects were summarized in Table
Clinical characteristics of the subjects based on menopausal status.
Variable | Premenopausal ( |
Postmenopausal ( |
|
---|---|---|---|
Age (years) |
|
|
<0.001 |
Height (cm) |
|
|
<0.001 |
Weight (kg) |
|
|
NS |
BMI (kg/m2) |
|
|
<0.001 |
Spine |
|
|
<0.001 |
Femur |
|
|
<0.001 |
Calcium (mmol/L) |
|
|
<0.001 |
ALP (U/L) |
|
|
<0.001 |
Phosphorus (mmol/L) |
|
|
<0.001 |
Total cholesterol (mmol/L) |
|
|
<0.001 |
Triglycerides (mmol/L) |
|
|
<0.001 |
HDL-C (mmol/L) |
|
|
<0.05 |
hsCRP (mg/L) |
0.39 (0.26–0.73) | 0.59 (0.36–1.21) | <0.001* |
CTX ( |
|
|
<0.001 |
Osteocalcin ( |
|
|
<0.001 |
ALP: alkaline phosphatase; BMI: body mass index; CTX: cross-linked C-terminal telopeptide; HDL-C: high density lipoprotein cholesterol; NS: not significant; TC: total cholesterol. Values are expressed as means ± standard deviations if not otherwise specified. *Analyzed using the Mann-Whitney
We categorized subjects based on BMD status (using the WHO definition) into three groups: normal, with osteopenia, and with osteoporosis. Among the 759 studied subjects, 425 women were normal, 287 had osteopenia, and 47 had osteoporosis. Owing to the small number of subjects with osteoporosis, we combined the osteopenia and osteoporosis groups into the “low BMD” group to give a total of 334 subjects and compared the marker levels between normal and low BMD groups. The CTX and osteocalcin levels were significantly higher in low BMD group than that of normal group (both
Serum CTX (a) osteocalcin, (b) total cholesterol, (c) log10hsCRP, and (d) concentrations in normal and low BMD subjects. The low BMD group was defined as those with osteopenia or osteoporosis as defined by the WHO classification. There were significant differences in the serum CTX (
In a stratified analysis by menopausal status, both CTX and osteocalcin levels showed similar results (Figure
Serum CTX (a) osteocalcin, (b) total cholesterol, (c) log10hsCRP, and (d) concentrations in normal and low BMD subjects based on menopausal status. The low BMD group was defined as those with osteopenia or osteoporosis as defined by the WHO classification. CTX, cross-linked C-terminal telopeptide; hsCRP, high sensitivity C-reactive protein.
Multivariate logistic regression analysis revealed that the BMI (OR, 0.817; 95% CI, 0.756–0.884), TC (OR, 1.647; 95% CI, 1.190–2.279), and osteocalcin (OR, 1.044; 95% CI, 1.002–1.088) had an increased risk of low BMD in premenopausal women (Table
Stepwise multiple logistic regression analysis to assess the association between bone mineral density as a dependent variable and other covariables based on menopausal status.
Variable | Odds ratio | 95% confidential interval |
|
---|---|---|---|
Premenopause | |||
BMI | 0.817 | 0.756–0.884 | 0.001 |
TC | 1.647 | 1.190–2.279 | <0.05 |
Osteocalcin | 1.044 | 1.002–1.088 | <0.05 |
Postmenopause | |||
Age | 1.094 | 1.064–1.126 | <0.001 |
BMI | 0.882 | 0.826–0.942 | <0.001 |
TC | 0.649 | 0.521–0.809 | <0.001 |
CTX | 1.001 | 1.000–1.002 | <0.05 |
Analyzed independent variables: age, BMI, TC, hsCRP, CTX, and osteocalcin.
See Table
We found that the TC levels were significantly higher in the low BMD group compared to the normal BMD group in premenopausal women and were also positively correlated with the serum concentrations of CTX and osteocalcin. These results suggest that the pathogenesis of osteoporosis is related to cholesterol metabolism. An atherogenic lipid profile is thought to be associated with osteoporosis. It has been speculated that oxidized lipid is the common trigger of atherosclerosis and osteoporosis. Oxidized lipid stimulates atherosclerosis by promoting mineralization of the arterial wall and can cause osteoporosis by reducing bone mineralization and inhibiting osteoblast differentiation [
Hormone-replacement therapy prevents cardiovascular disease by reducing the level of low-density lipoprotein (LDL) cholesterol and inhibits osteoporosis in postmenopausal women [
The importance of other lipid markers and the levels of HDL cholesterol and triglyceride, with respect to BMD, has been debated [
Biochemical BTMs offer a dynamic measure of bone metabolism. BTMs arereleased into the circulation during bone formation or resorption and respond more rapidly and profoundly to changes in bone turnover than the BMD. In addition, BTMs are easily measured in the blood or urine and are increasingly assessed in clinical settings. Both osteocalcin and CTX are well documented, sensitive, and specific biomarkers for bone metabolism [
The hsCRP concentration showed no correlations with BTM levels. hsCRP is the most sensitive marker for detecting subclinical inflammation, so this finding is inconsistent with the previous report [
Our study has several limitations. This is a cross-sectional analysis with no prospective follow-up of patients. And we have no information on the incidence of fracture and the ultimate clinical endpoint of osteoporosis. More well-controlled prospective studies would be needed to elucidate the relationship between candidate serum markers and the risk of osteoporosis.
In conclusion, our results indicate that a high TC level is associated with low BMD and atherosclerosis, suggesting that dyslipidemia is the common mechanism triggering osteoporosis and atherosclerosis in premenopausal women. However, the changes in the level of the inflammation marker hsCRP were not sufficiently prominent to be useful as a predictor of osteoporosis, despite the suggested association of inflammation with osteoporosis.
The authors declare that there is no conflict of interests regarding the publication of this paper.