Diversity of Femoral Neck and Spine Bone Mineral Density - Surrogate Marker of Aortic Calcification in Postmenopausal Women

Abstract

Background/Aims: Osteoporosis and Abdominal Aortic Calcification (AAC) are major causes of morbidity and mortality in postmenopausal women. The aim of this study was to determine the accuracy of Anterior-Posterior (AP) Dual-energy X-ray Absortiometry (DXA) in detecting and scoring the AAC compared with x-ray Lateral Lumbar Radiography (LLR).

Methods: We estimated femoral neck and lumbar spine Bone Mineral Density (BMD) by AP DXA and AAC by x-ray LLR in 55 postmenopausal female-aged 59.01 ± 9.27 years. We hypothesized that subtracted femoral neck BMD (BMD_FN) from lumbar spine BMD (BMD_LS) presented as ΔBMD = BMD_LS – BMD_FN would have predictable diagnostic value in detection of abdominal vascular calcification.

Results: The mean BMD_FN was 0.744 ± 0.184 g /cm² and the mean BMD_LS was 0.833 ± 0.157 g /cm², P < 0.0001; the mean ΔBMD was 0.089 ± 0.077 g / cm² and the mean AAC score was 2.182 ± 1.982. Bivariate Pearson’s revealed significant positive correlation between AAC and ΔBMD (r = 0.449, p = 0.0006); by linear regression analysis: R2 = 0.2019, coefficients β: b0 = 1.151 (P = 0.003) and b1 = 11.5049 (P = 0.0006) and by multiple regression analysis: βst = 13.5244 (P < 0.0001). We found sensitivity of 64.3% and specificity of 82.9% by receiver operating characteristic (AUC = 0.759) in prediction of AAC by ΔBMD.

Conclusions: This AP subtracting BMD DXA method provides a useful tool for detecting and scoring subclinical and extensive AAC in postmenopausal women, using simple, semiquantitative, accuracy scoring system, with minimal radiation exposure and low cost.

Keywords: Osteoporosis; Aortic calcification; Postmenopausal women; Dual-energy x-ray absortiometry; Lateral lumbar radiography

Abbreviations

AAC: Abdominal Aortic Calcification; AP: Anterior-Posterior; DXA: Dual Energy X-Ray Absortiometry; LLR: Lateral Lumbar Radiograph; BMD: Bone Mineral Density; BMD_FN: Femoral Neck Bone Mineral Density; BMD_LS: Lumbar Spine Bone Mineral Density; ΔBMD: Delta Bone Mineral Density; Std. error: Standard Error; AUC: Area Under Curve; BMI: Body Mass Index; SD: Standard Deviation; WHO: World Health Organization; CI: Confidence Interval; ROC: Receiver Operating Characteristics; CHP: Chronic Hemodialysis Patients; GPP: General Population Patients

Introduction

Osteoporosis and atherosclerosis are major causes of morbidity and mortality in postmenopausal women [1]. Calcification is a common feature of atherosclerotic plaques and is regulated in a way similar to bone mineralization [2]. There are not enough studies that examined whether presence of atherosclerotic calcification is associated with bone loss.

The term osteoporosis is used to define a group of clinical disorders characterized by reduced bone mass without defect in mineralization. Osteoporosis occurs when bones lose an excessive amount of their protein and mineral content (calcium). Bone is living tissue that is constantly being renewed in two-stage process (resorption and formation) that occurs throughout life. After mid- 30s, bone mass is lost at a faster pace than it is formed, so the bone mineral density in the skeleton begins to slowly decline. Most cases of osteoporosis occur as an acceleration of this normal aging process, which is referred to as primary osteoporosis [3].

Bone mineral loss is most often in older people and in women after menopause. They lose bone mineral mass more rapidly after menopause (usually around age 50), when they stop producing a bone-protecting hormone called estrogen. Seven years following menopause, women can lose more than of 20% of their bone mineral mass. Women are about five times more likely to be affected than men to develop osteoporosis [4].

Vascular calcification and osteoporosis are common age-related processes. AAC is displayed on routine lateral lumbar spine radiographs as dense calcium mineral deposits of the aorta that lies adjacent to vertebrae. The two processes may represent independent age-related phenomena, or mobilization of calcium in developing atherosclerotic plaque. It means that, vascular compromise due to aortic calcification might, in itself, results in bone loss [5]. Atherosclerosis calcification has long been considered a late stage, unregulated sequel of atherosclerotic process. Aortic calcification occurs more early with rapid progress and arterial narrowing. Recent studies implicated several possible metabolic linkages between aortic calcification and bone mineral density loss, including estrogen, vitamin D and K, lipid oxidation products and osteoprotegerin (protein that regulates osteoclast activity and proliferation).

Our hypothesis was that the value of subtracted femoral neck BMD from lumbar spine BMD (ΔBMD) should be greatest in those individuals with more vascular calcification of the abdominal aorta. The aims of this study were:

1. To find association between AAC and femoral neck BMD; between AAC and spine BMD; AAC and ΔBMD;
2. To determine the accuracy of AP DXA scan in detecting and scoring AAC compared with detected AAC by LLR.

Materials and Methods

Patients

This cross-sectional study was conducted from October to December 2013. The study group included volunteer sample of 55 white postmenopausal women with mean age of 59.01 ± 9.27 years, their mean Body Mass Index (BMI) of 27.7 ± 3.65 kg/m2. Fourteen women were smokers, 12 were diabetic, and 30 were hypertensive. Exclusion criteria were chronic renal disease, insulin-dependent diabetes, malignancy, rheumatoid arthritis, liver disease, or any chronic disease that might affect the skeleton. They signed an informed consent and the Ethics Committees of our institution approved the study. Menopausal state was assessed by a self-administered questionnaire that asked whether the menses had stopped. Women were classified as postmenopausal once they had experience at least 12 consecutive months of amenorrhea.

Demographic and clinical data were collected from the patient’s chart and included age, weight, height, history of diabetes mellitus, smoking habit, hypertension, and above mentioned disease that might affect the bone mass. BMD of the femoral neck and the lumbar spine was assessed by Dual Energy X-Ray Absorptiometry (DXA). Lateral Lumbar Radiography (LLR) of the abdominal aorta was used to determine the overall Abdominal Aortic Calcification (AAC) score.

Assesment

Bone mineral density

Bone density scanning, also called Dual-Energy X-Ray Absorptiometry (DXA) or bone densitometry, is an enhanced form of X-ray technology that is used to measure bone density. DXA is today’s established standard for measuring BMD [6].

We conducted BMD testing using DXA by Hologic QDR4500SL system (Hologic Inc., Bedford, MA, USA). BMD was measured by DXA in the lumbar spine and femoral neck. Two X-ray beams with differing energy were used for measurement of BMD. The BMD was determined based on the absorption of each beam by bone after subtraction of the absorption of soft tissue. For assessment of the spine, the patient’s legs were supported on a padded box to flatten the pelvis and lower the (lumbar) spine. For assessment of the femoral neck, the patient’s foot was placed in a brace that rotates the hip inward. In both cases, the detector was passed slowly over the area, generating images on a computer monitor [7].

Absolute BMD values and T-scores (number of SDs below the BMD of a young reference group) of the lumbar spine and femoral neck were recorded as BMD (g/cm²) and T-score (for femoral neck, total and L1 to L4 region). The WHO (World health organization) defined the following categories based on bone density in Caucasian females: normal bone, T-score greater than -1; osteopenia, T-score between -1 and -2.5; osteoporosis, T-score less than -2.5.

Abdominal aortic calcification

We performed lateral lumbar radiographs to determine AAC in the standing position using standard radiographic equipment (Shimadzu RADSpeed 324-DK, Nishinokyo-Kuwabarachou. Nakagyo-ku. Kyoto 604-8511. Japan. The film distance was 1 m and estimated dose of radiation was no more than 15 mGy. Abdominal aortic calcification is often seen as linear thin-film tracks at the anterior or posterior wall of the abdominal aorta with linear edge corresponding to the aortic wall beside lumbar vertebral segments L1 to L4.

We estimated aortic score using a previously validated system [6- 8]. The measure for the unit AAC score is the linear length of aortic calcification compared with 1/3 of aortic longitudinal wall projected near the vertebral segment beside it: score 0 – no calcific deposits in front of the vertebra; score 1 – small scattered calcific deposits filling less than 1/3 of the longitudinal wall of the aorta; score 2 – 1/3 or more, but less than 2/3 of the longitudinal wall of the aorta calcified; score 3 – 2/3 or more of the wall calcified. The scores were summarized using the composite score for anterior and posterior wall severity (range score 0–3), where the scores of individual aortic segment calcifications, both for the anterior and posterior walls (max. 2 x 12) were summed (maximum score 24) [8,9].

Statistical analysis

The data were analyzed using MedCalc version 13.0.6.0 (Acacialaan 22, 8400 Ostend, Belgium). Results were expressed as mean ± SD or percentage. Student’s t test for paired data was used to compare the femoral neck BMD and lumbar spine BMD. Pearson’s correlations were calculated to explore the relationship between femoral neck BMD, spine BMD and ΔBMD and other variables, as appropriate. Simple linear regression analysis was performed to assess the associations between dependent and independent variables and to create the equation of linear regression. We conducted a multiple backward regression analysis to determine the effect on the dependent variable (AAC) of variations in one of the independent variables (femoral neck BMD, diabetes, hypertension, spine BMD, smoking, age and BMI) while the other independent variables were fixed. All tests were two-sided. A value of p < 0.005 was considered to indicate a significant difference.

Results

During the 3-month period from October to December 2013, DXA and Lateral lumbar X-ray radiography measurements and other demographic examinations were successfully conducted on 55 postmenopausal female participants aged 59.01 ± 9.27 years and body mass index 27.7 ± 3.65 kg/m2. The demographic and clinical characteristics of the patients studied are presented in Table 1.