title: Bone resorption and fracture across the menopausal transition:  the Study of Women's Health Across the Nation.
abstract: OBJECTIVE
  Bone turnover markers (BTMs) predict fracture in older women, whereas data on younger women are lacking. To test the hypothesis that BTMs measured before and after menopause predict fracture risk, we performed a cohort study of 2,305 women.
  
  
  METHODS
  Women attended up to nine clinic visits for an average of 7.6 ± 1.6 years; all were aged 42 to 52 years and were premenopausal or early perimenopausal at baseline. Incident fractures were self-reported. Serum osteocalcin and urinary cross-linked N-telopeptide of type I collagen (NTX) were measured at baseline. NTX was measured at each annual follow-up. Interval-censored survival models or generalized estimating equations were used to test whether baseline BTMs and changes in NTX, respectively, were associated with fracture risk. Hazard ratios (HRs) or odds ratios were calculated with 95% CIs.
  
  
  RESULTS
  Women who experienced fractures (n = 184) had about a 10% higher baseline median NTX (34.4 vs 31.5 nanomoles of bone collagen equivalents per liter per nanomole of creatinine per liter; P = 0.001), but there was no difference in osteocalcin. A 1-SD decrease in lumbar spine bone mineral density (BMD) measured premenopausally was associated with a higher fracture risk during menopause (HR, 1.50; 95% CI, 1.28-1.68). Women with a baseline NTX greater than the median had a 45% higher risk of fracture, multivariable-adjusted (HR, 1.46; 95% CI, 1.05-2.26). The HR of fracture among women with both the lowest spine BMD (quartile 1) and the highest NTX (quartile 4) at baseline was 2.87 (95% CI, 1.61-6.01), compared with women with lower NTX and higher BMD. Women whose NTX increased more than the median had a higher risk of fracture (odds ratio, 1.51; 95% CI, 1.08-2.10). Women who had baseline NTX greater than the median experienced greater loss of spine and hip BMD.
  
  
  CONCLUSIONS
  A higher urinary NTX excretion measured before menopause and across menopause is associated with a higher risk of fracture. Our results are consistent with the pathophysiology of transmenopausal changes in bone strength.
authors: Department of Epidemiology, University of Pittsburgh, 130 DeSoto Street, Pittsburgh, PA 15261, USA. jcauley@edc.pitt.edu
authors: Jane A
authors: JA
authors: Cauley
authors: Michelle E
authors: ME
authors: Danielson
authors: Gail A
authors: GA
authors: Greendale
authors: Joel S
authors: JS
authors: Finkelstein
authors: Yue-Fang
authors: YF
authors: Chang
authors: Joan C
authors: JC
authors: Lo
authors: Carolyn J
authors: CJ
authors: Crandall
authors: Robert M
authors: RM
authors: Neer
authors: Kristine
authors: K
authors: Ruppert
authors: Leslie
authors: L
authors: Meyn
authors: Beth A
authors: BA
authors: Prairie
authors: MaryFran R
authors: MR
authors: Sowers
mesh_terms: D000328:Adult; D001862:Bone Resorption / Q000150:complications / Q000175:diagnosis*; D015331:Cohort Studies; D024042:Collagen Type I / Q000652:urine; D005260:Female; D050723:Fractures, Bone / Q000453:epidemiology* / Q000209:etiology / Q000652:urine; D006801:Humans; D008593:Menopause / Q000502:physiology* / Q000652:urine; D008875:Middle Aged; D015675:Osteocalcin / Q000097:blood; D015663:Osteoporosis, Postmenopausal / Q000150:complications; D010455:Peptides / Q000652:urine; D012307:Risk Factors; D016387:Women's Health
chemical_list: D024042:Collagen Type I; D010455:Peptides; C052929:collagen type I trimeric cross-linked peptide; D015675:Osteocalcin