The 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.