Osteoporosis, vertebral fractures and metabolic syndrome in postmenopausal women

A total of 270 caucasian postmenopausal women (age range: 50–90 yr) living in the Rabat area participated in the present study. Women were recruited through advertisements and “word of mouth” from june 2012 to march 2013. Original inclusion criteria were age > 50, menopause > 1 year and no previous osteoporotic fracture or known diagnosis of osteoporosis. Women with liver or renal disease, endocrine or metabolic abnormalities, and receiving medicine known to influence bone mineralization, such as corticosteroids, heparin, anticonvulsants, vitamin D, bisphosphonates, were excluded. Our institutional review board (Comité d’éthique et de recherche de l’hôpital Militaire Mohammed V) approved this study. The procedures of the study were in accordance with the Declaration of Helsinki, and local ethics committee approval was obtained for the study (Comité d’éthique de la Faculté de Médecine et de Pharmacie de Rabat). All the participants gave an informed and written consent. Each subject completed a standardized questionnaire designed to document putative risk factors of osteoporosis. The questionnaire collected information on current medication use, history of peripheral traumatic fractures, smoking habits, and level of physical activity in leisure time, along with calcium consumption and the use of vitamins and medications. Height and weight were measured in light indoor clothes without shoes. Body mass index (BMI)] was calculated by dividing weight in kilograms by height in meters squared. Waist was measured in centimeters at the bending point using a flexible tape measure, with the participant wearing single-thickness clothing and standing in an erect position with feet together. Although this is not a population-based cohort, care was taken to ensure representativeness of the general population with a particular regard to the inclusion of a wide range of age categories, body sizes and activities. We did not exclude individuals using inhalation steroids or with certain lifestyle habits such as heavy smoking, being sedentary, being athletic, or having a high or low calcium intake, which are examples of voluntary factors that may have some impact on bone metabolism.

The women were asked whether they usually drank milk or alcohol; if they ate cheese or yogurt; if they did gymnastics or jogging/walking and if they smoked tobacco. If the answer was positive, they were asked to quantify their average current consumption (evaluated on the 7 day prior to the interview) of milk or yogurt (mL/day), cheese (g/day) and wine and/or spirits (mL/day). Tobacco smoking was quantified as average number of cigarettes (smoked/day) multiplied by the number of years of smoking, gymnastics as min/week, or jogging/walking as min/day. Finally, patients were categorized as never smokers, ex-smokers and current smokers; high, normal and low calcium intake (more than 1500 mg/day, between 800 and 1500 day − 1 and below 800 mg/day, respectively); high, moderate and low physical activity (more than 3, 2–3 and below 1 hour/week, respectively).

BMD was determined by a Lunar Prodigy Vision DXA system (Lunar Corp., Madison, WI). The DXA scans were obtained by standard procedures supplied by the manufacturer for scanning and analysis. All BMD measurements were carried out by 2 experienced technicians. Daily quality control was carried out by measurement of a Lunar phantom. At the time of the study, phantom measurements showed stable results. The phantom precision expressed as the coefficient of variation was 0.08%. Moreover, reproducibility has been assessed in clinical practice and showed a smallest detectable difference of 0.04 g/cm²(spine) and 0.02 (hips) [15, 16]. Patient BMD was measured at the lumbar spine (anteroposterior projection at L1-L4) and at the femurs (i.e., femoral neck, trochanter, and total hip). Using the Moroccan female normative data [17], the World Health Organization (WHO) classification system was applied, defining osteoporosis as T-score ≤ −2.5 and osteopenia as −2.5 < T-score < −1. Study participants were categorized by the lowest T-score of the L1–4 lumbar spine, femur neck, or total femur.

VFs was classified using a combination of Genant [18] semiquantitative (SQ) approach and morphometry in the following manner: each VFA image was inspected visually by two trained clinicians (IG and AM) to decide whether it contained a fracture in any of the visualized vertebrae and assigned by consensus a grade based on Genant SQ scale, where grade 1 (mild) fracture is a reduction in vertebral height of 20-25%, grade 2 (moderate) a reduction of 26-40%, and grade 3 (severe) a reduction of over 40%. In case of doubt regarding fracture grade, the vertebrae in question was measured using built-in morphometry. Automatic vertebral recognition by the software was used. Positioning of the six morphometry points was modified by one of the two clinicians only when the software failed to correctly recognize vertebral heights. The intra-rater reproducibility of this method was evaluated using the kappa score to 0.90 (p < 0.0001). Subjects with no fractures were included in the non-fracture group, whereas those with grade 1 or higher fractures were included in the fracture group. However, as many studies rarely report mild deformities as “fractures”, and to realize comparisons with the literature, we distinguished the group of women with grade 1 fractures from the grade 2/3 fracture group. The spinal deformity index (SDI), as described by Kerkeni et al. [19], was then calculated by summing in each patient the grade of each vertebra from T4 to L4. In theory, the SDI value can vary between 0 (no fracture) and 39 (all the assessed vertebrae are grade 3).

The prevalence of MS and its components were defined by NCEP-ATP III criteria [2]. Participants were classified as having the MS if any three of the following were present: abdominal obesity (waist circumference greater than 88 cm), triglycerides of 150 mg/dL (1.7 mmol/L) or greater, HDL cholesterol levels less than 50 mg/dL (1.29 mmol/L), fasting glucose of 110 mg/dL (6.1 mmol/L) or greater, or blood pressure of 130/85 mmHg or greater. Participants with documented use of antihypertensive medication were categorized as meeting the blood pressure criteria. Diabetes was defined by the American Diabetes Association 1998 guidelines [20] (fasting plasma glucose equal or greater than 126 mg/dL or 2-h plasma glucose in 75 g oral glucose tolerance test equal or greater than 200 mg/dL).

Results are presented as means (SD) for continuous variables and as frequencies for categorical variables. To compare patients with and without MS and patients with or without osteoporosis, chi-square test and Student t-test were used. To compare patients with and without VFs, chi-square test and analysis of variance ANOVA were used.Potential risk factors for osteoporosis were finally entered to a stepwise conditional binary logistic regression analysis and the resulted odds ratios with 95% confidence intervals were reported. The level for significance was taken as p ≤ 0.05. Excel 2010 and SPSS 20.0 were used for statistical analysis.

In this series of 270 women, the mean ± SD (range) age, weight and BMI were 61.0 ± 7.8 (50 to 90) years, 75.5 ± 11.7 (45 to 106) Kg and 32.3 ± 6.5 (19.1 to 54.8) kg/m², respectively (Table 1). Only 4 women (0.4%) were current smokers. Sixty nine (25.6%) women reported a history of traumatic peripheral fracture before the age of 50. Diabetes was present in 79 women (29.3%), hypertension in 94 (34.8%) and dyslipidemia (hypercholesterolemia and/or hypertriglyceridemia) in 66 (24.4%). The MS as defined by the NCEP-ATP IIIwas present in 62 women (23.0%).

The mean BMD was 0.98 (0.17) g/cm² at the lumbar spine, 0.85 (0.14) g/cm² at the femoral neck and 0.92 (0.12) g/cm² at the total hip. The mean T-scores were −1.45 (1.3), −1.42 (1.01) and −0.85 (1.04) respectively. According to the WHO classification, 82women had osteoporosis at any site (30.4%).

In these 270 women, 85.7% of vertebrae from T4–L4 and 96.2% from T8–L4 were adequately visualized on VFA. The percentage of vertebrae not visualized at T4, T5, and T6 levels was 51.9%, 40.7, and 26.7% respectively. VFs were identified in 116 (43.0%): 80 (29.6%) had grade 1 and 36 (13.3%) had grade 2 or 3. Among the latter group, 52 (19.2%) women had multiples VFs. Fractures were most common in the mid-thoracic spine and at the thoracolumbar junction (Figure 1). The mean SDI was 1.20 ± 2.2 (0–12).

Comparison between patients with and without MS (Table 2) showed that those with MS were older, had more pregnancies and longer period since menopause. They had a significantly higher BMD (lumbar spine, femoral neck and total hip) and lower prevalence of osteoporosis as the defined by the WHO criteria (17.7% vs. 34.1%; p = 0.029). No significant statistical difference was noted in prevalence of VFs (14.5 vs. 13.0%; p = 0.672).

Comparison between patients with and without osteoporosis (T-score below −2.5 in any of the lumbar spine, femoral neck or total hip) showed that those with osteoporosis were older, had lesser weight, height, BMI, and total body fat percentage and had longer period since menopause (Table 3). There were significantly less women with MS among the group of osteoporotic women (13% vs. 27%; p = 0.018).

Comparison between patients without VFs and patients with VFs grade 1 and grade 2/3 (Table 4) showed that women with VFs were older, have a longer period since menopause, were more likely to have history of traumatic peripheral fracture and had a lower BMD at the lumbar spine, femoral neck and total hip. Prevalence of MS was similar between the three groups.

Conditional regression binary analysis assessing the presence of osteoporosis as the dependent variable showed that women with a MS had a significant 71% decrease in the odds of being osteoporotic by BMD compared with women who had not MS accounting for age, BMI, number of parities and years since menopause. The predictive variables significantly associated to the osteoporotic status were the presence of MS, BMI, and number of parities (Table 5).