Increase in C‐Reactive Protein Predicts Increase in Rate of Bone Mineral Density Loss: The Study of Women's Health Across the Nation

This longitudinal cohort study's aim was to detect whether larger increases in C‐reactive protein (CRP) predict greater amounts of subsequent bone loss in women transitioning from premenopause to postmenopause. Participants were initially 42 to 52 years of age and premenopausal or early perimenopausal. The sample included 1431 women who were not using hormone therapy and whose CRP values were not consistent with acute inflammation. Individual fixed effects (IFE) models estimated the association of log(2) CRP with subsequent bone mineral density (BMD) decline rate, adjusted for menopause transition (MT) stage (1: premenopausal or early perimenopausal; 2: late perimenopausal or early postmenopausal; or 3: late postmenopausal), body mass index, diabetes, smoking, alcohol, bone active medications, and anti‐inflammatory medications. BMD decline at both the lumbar spine (LS) and femoral neck (FN) was faster for observations made in MT stage 2 than that during other stages (all p < .001). In adjusted IFE models, MT stage modified the relation between increase in CRP and BMD decline rate (interaction p values <.05). Each within‐woman doubling of CRP was associated with a 0.09% faster yearly decline in FN BMD in MT stages 1 (p = .006) and 3 (p = .03), and 0.10% faster decline in LS BMD in MT stage 3 only (p = .007). Within‐woman increases in CRP in premenopause and early perimenopause and in late postmenopause predict faster BMD decline in the next ~2 years, but the magnitude of CRP's effect is small. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.