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Bone Mineral Density in Estrogen-Deficient Young Women

Integrative Reproductive Medicine Unit (V.B.P., K.A.C., V.H.V., L.M.N.), Intramural Research Program on Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892-1103; Radiology Department (J.C.R.), and Nutrition Department (N.S.), Mark O. Hatfield Clinical Research Center, National Institutes of Health, Bethesda, Maryland 20892-1103; Clinical Endocrinology Branch (G.C.), National Institute of Diabetes and Digestive Diseases, National Institutes of Health, Bethesda, Maryland 20892-1103; and Biostatistics and Bioinformatics Branch (J.F.T.), Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892-1103

Address all correspondence to: Vaishali Popat, M.D., M.P.H., Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, CRC, Room 1-3330, 10 Center Drive, Bethesda, Maryland 20892. E-mail: popatv{at}mail.nih.gov.

Context: Osteoporosis primarily affects postmenopausal women. However, young women with estrogen deficiency also are at increased risk for low bone density.

Objective: The aim of the study was to assess bone density and associated risk factors for reduced bone density in young, estrogen-deficient women using primary ovarian insufficiency (POI) as the disease model.

Design and Setting: We conducted a cross-sectional study at a tertiary care research center.

Participants: We studied women with POI (n = 442), concurrent controls (n = 70), and matched controls from NHANES III (n = 353).

Primary Outcome Measure: We measured bone mineral density (BMD) using dual-energy x-ray absorptiometry.

Results: Patients on average had 2–3% lower BMD at L1–L4, femoral neck, and total hip (P < 0.01 at all sites). The modifiable risk factors for BMD below the expected range for age (Z-score <–2) were: more than 1-yr delay in diagnosis of estrogen deficiency (P = 0.018), low (<32 ng/ml) vitamin D levels (P = 0.002), estrogen replacement nonadherence (P = 0.002), low calcium intake (P = 0.005), and lack of exercise (P = 0.005). As compared to Caucasians, African-American and Asian women with POI were 3.18 and 4.34 times more likely, respectively, to have Z-scores below –2 (P = < 0.0001 for both). Race was an overall risk factor, but on regression modeling, not an independent predictor of low bone density.

Conclusions: Women with POI have lower bone density compared to regularly menstruating women. Compared to Caucasians, minority women with estrogen deficiency are more likely to have BMD below the expected range for age. This racial disparity appears to be related to a combined effect of several modifiable risk factors. Delay in diagnosis of POI also contributes to reduced bone density by delaying proper therapy.