Risk Factors for Osteoporosis: Prevalence, Change, and Association With Bone Density

Janet R. Guthrie, MSc, Dip Ed, PhD, Peter R. Ebeling, MB BS, MD, FRACP, Lorraine Dennerstein, AO, MB BS, PhD, FRANZP, DPM, John D. Wark, MB BS, PhD, FRACP

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The study was approved by the Human Ethics Committee of the University of Melbourne, and approval to carry out the BMD measurements at the Bone Densitometry Unit of the Royal Melbourne Hospital was granted by the Royal Melbourne Hospital Board of Medical Research.

The subjects of this report were identified from a cross-sectional survey of a randomly selected population-based sample of 2001 Melbourne women[4] who were Australian born and aged 45-55 years at the time of the first interview. Women who were prepared to be contacted again, had menstruated in the previous 3 months, and were not taking hormone replacement therapy (HRT) were invited to take part in a longitudinal study on women's health during midlife (The Melbourne Women's Midlife Health Project). Of these 779 women, 438 (56%) accepted.

BMD of the lumbar spine (2nd to 4th lumbar vertebrae) and of the femoral neck was measured by dual x-ray absorptiometry (DXA) with a Hologic QDR-1000 W densitometer in the Bone Densitometry Unit, Department of Medicine, The Royal Melbourne Hospital. The within-subject coefficient of variation was 1% at the lumbar spine and 1.7% at the femoral neck.[5] The long-term in vitro precision was 0.37% for the lumbar spine and 0.47% for the proximal femur using Hologic anthropomorphic phantoms. The reference value for BMD measurements was provided by Hologic[6] and consisted of a population sample of 650 North American Caucasian women aged 20-85 years.

For each subject, the following were recorded annually: height, weight, waist and hip circumference, and skin-fold measurements, as has been described previously.[7] Body mass index (BMI) was calculated as weight/height2 (kg/m2). A short self-administered food frequency questionnaire[8] was used to estimate calcium intake, and a physical activity questionnaire[9] was used to determine the total physical activity of participants during the previous 12 months. The calcium intake reported on the food frequency questionnaire accounts for 60% of the total calcium intake in Australian women,[10] and this was allowed for in the calculations. The use of calcium supplements was documented and included in the calcium intake estimations. Gynecologic variables and current and past smoking habits were obtained at interview.

Fasting blood samples were drawn between the 4th and 8th days of the menstrual cycle or after 3 months of amenorrhea. Hormone levels (eg, follicle-stimulating hormone [FSH], estradiol, testosterone, and sex-hormone binding globulin [SHBG]) were measured as previously described.[11,12] Free androgen index (FAI) was calculated as the ratio of the measured level of testosterone to the measured level of SHBG x 100.

Menopausal Status. Menopausal status was determined by menstrual history reported at the time of the interview. Women were defined as premenopausal if they reported no change in menstrual frequency in the prior 12 months and perimenopausal if they reported changes in menstrual frequency. Women in the latter group were divided into "early perimenopausal" if they had menstruated in the prior 3 months but reported changes in menstrual frequency and "late perimenopausal" if they reported 3-11 months of amenorrhea. Women were defined as naturally postmenopausal if they reported amenorrhea for at least 12 consecutive months. Women who had experienced a hysterectomy (with or without oophorectomy) or an endometrial ablation or bilateral oophorectomy were classified as having a surgical menopause. HRT use was recorded at the time of interview.

Frequency distributions of all variables were used to identify skewness of distribution and for error checks. Hormone levels and time since final menstrual period (FMP) were log transformed, and physical activity measures (hours/week) were square root transformed for all analyses. Baseline and follow-up measures were compared using paired t tests. Continuous variables of parity, age at menarche, and oral contraceptive pill (OCP) use were also analyzed as categorical variables. For parity, the groups were 0, 1-2, 3, and 4 or more children; for age at menarche, the groups were less than or equal to 11years, 11.5-13.5 years, and greater than or equal to 14 years; for OCP use, the groups were none, less than or equal to 5, and greater than 5 years. Statistical comparisons between menopausal and menopausal transition groups were made using analysis of variance. Unless otherwise noted, a nominal level of significance of P < .05 was used, and all statistical tests were two-tailed. SPSS software[13] was used for all analyses.


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