Abstract
ABSTRACTThe menopause transition (MT) is a period of rapid bone loss and has been proposed to be a time‐limited window for early intervention to prevent permanent microarchitectural damage and reduce the risk of subsequent fracture. To intervene early, however, we first need to be able to determine whether menopause‐related bone loss is about to begin, in advance of substantial bone loss. The objective of this study was, therefore, to assess whether urinary N‐telopeptide (U‐NTX) in pre‐ or early perimenopause can predict the onset of menopause‐related bone loss. Repeated U‐NTX measurements were obtained during pre‐ and early perimenopause in 1243 participants from the Study of Women's Health Across the Nation (SWAN). We examined the ability of U‐NTX to predict the onset of significant menopause‐related bone loss (categorical outcome, yes versus no) at the lumbar spine (LS) and femoral neck (FN), defined as annualized bone mineral density (BMD) decline at a rate faster than the smallest detectable change in BMD over the 3 to 4 years from the time of U‐NTX measurement. Adjusting for age, race/ethnicity, body mass index, urine collection time, starting BMD, and study site in multivariable, modified Poisson regression, every standard deviation increment in U‐NTX, measured at baseline in early perimenopausal women, was associated with an 18% and 22% greater risk of significant bone loss at the LS (p = 0.003) and FN (p = 0.003), respectively. The area under the receiver‐operator curve for predicting LS and FN bone loss was 0.72 and 0.72, respectively. In mixed‐effects analysis of all repeated measures of early perimenopausal U‐NTX over follow‐up, U‐NTX predicted onset of bone loss at the LS (p = 0.002) but not at the FN. We conclude that U‐NTX can be used early in the MT to determine if a woman is about to experience significant LS bone loss before there has been substantial skeletal deterioration. © 2018 The Authors. JBMR Plus is published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research.
Highlights
Osteoporosis is characterized by skeletal fragility resulting from decreased bone mineral density (BMD) and impaired bone quality.(1) In women, menopause transition (MT)-related BMD decline accelerates 1 year before the final menstrual period (FMP) and slows slightly in postmenopause.(2) This loss in BMD during the menopause transition (MT) is accompanied by damage to trabecular microarchictecture that may increase fracture risk.(3,4) Within the first decade after menopause, vertebral fracture incidence increases.(5,6) This suggests that the MT is a critical period to intervene to prevent rapid bone loss and permanent microarchitectural deterioration.(7) To do so, we first need to be able to recognize when women are about to lose a significant amount of bone so that they can be targeted for intervention before substantial loss
The r majority (57.9%) were premenopausal (Table 1). {TBL 1} Mean decline in BMD was faster in sc the lumbar spine (LS) than in the femoral neck (FN), and more women experienced significant bone loss in the LS over the u 3 to 4 years from Study of Women’s Health Across the Nation (SWAN) baseline than in the FN, regardless of which BMD decline rate n threshold was used to categorize the onset of bone loss (LSC-based or distribution-based). a U-NTX at baseline was normally distributed
A greater proportion of early perimenopausal than premenopausal women was categorized as losing significant bone using either threshold: 28.3 versus 15.1% (p < 0.001) in the LS, 10.8 versus 5.0% (p < 0.001) in the FN using least significant change (LSC)-based thresholds, and 21.4 versus 11.0% in the LS (p < 0.001), 12.3 versus 5.5% in the FN (p < 0.001) using distribution-based thresholds (Figs.[1] and 2). {FIG1}{FIG2} U-NTX as predictor of onset of MT-related bone loss; SWAN baseline analyses
Summary
Participant characteristics at SWAN baseline t In the baseline U-NTX analytic sample, mean age was 46.0 years (range 42.0 to 52.8 years). ip Nearly half were white, 17.8% African American, 14.7% Chinese, and 6.4% Japanese. Greater U-NTX at SWAN baseline (when participants were aged 42 to 52 years and pre- or early perimenopause) was independently associated with greater risk of bone loss onset over the 3 to 4 years, after adjusting for MT stage, age, BMI, race/ethnicity, urine collection time, starting BMD, and study site in modified Poisson regression (Table 2). Repeated measures analysis stratified by MT stage In mixed-effects, modified Poisson regression, after adjusting for age, BMI, race/ethnicity, urine collection time, starting BMD, and study site, premenopausal U-NTX was not associated with risk of onset of significant bone loss over the 3 to 4 years (Table 4). Combining early perimenopausal U-NTX with relevant clinical covariates (age, race/ethnicity, and BMI) provided good discrimination between women who were more versus less likely to begin losing significant bone at the LS over the 3 to 4 years (AUC >0.7). Losing bone from baseline to 3 to 4 years later (least significant change-based threshold)c r Lumbar spine
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