title: A cross-sectional study of bone turnover markers in healthy premenopausal women.
abstract: BACKGROUND
  Biochemical markers of bone turnover (BTMs) provide useful information in the diagnosis and management of metabolic bone diseases. Currently, there exist few published reference ranges for bone markers in healthy premenopausal women using the newer, automated assays of bone turnover. This cross-sectional study of healthy premenopausal women was performed to determine reference ranges for four different markers of bone turnover and to compare reference ranges in users and non-users of oral contraceptives (OCs).
  
  
  METHODS
  Urinary N-telopeptide of type 1 collagen (NTX) was determined from fasting second morning-void urine of healthy premenopausal women. In addition, fasting serum was collected for determination of C-telopeptide of type I collagen (CTX), bone-specific alkaline phosphatase (bone ALP), and N-terminal propeptide of type 1 procollagen (PINP). Subjects underwent central dual energy X-ray absorptiometry and completed a questionnaire regarding medical history and activities known to affect bone health.
  
  
  RESULTS
  Serum and urine samples were collected from 237 healthy premenopausal women (119 OC users and 118 non-users) between the ages of 28 and 45 years. The mean age of subjects was 37 years, with a mean bone mineral density T-score of -0.1 at the lumbar spine and 0.0 at the total hip. Logarithmic transformation produced normal distributions for all markers but NTX. Mid-95% ranges for each marker were generally consistent with those reported by manufacturers. For each BTM examined, values were skewed toward the lower end of the range. Median NTX levels for OC users and non-users were 16.0 and 29.0 nmol/mmol creatinine, respectively. The mid-95% ranges for NTX in OC users and non-users were 3-60 and 4-64 nmol/mmol creatinine, respectively. Median levels of CTX, bone ALP, and PINP were also lower in OC users than non-users. The mean level of each BTM was significantly lower in OC users than non-users (P<0.01), whereas reference ranges (geometric mean+/-2 SD) were somewhat similar for the two groups.
  
  
  CONCLUSIONS
  Values obtained from this well-characterized population provide reference ranges for BTMs in healthy premenopausal women. Median and mean BTM levels for OC users were consistently lower compared with non-users; thus, separate reference ranges are required for these two groups of premenopausal women. The relevance of premenopausal reference ranges for postmenopausal women remains uncertain.
authors.affiliation: Merck and Co., Inc., 351 N. Sumneytown Pike, North Wales, PA 19454-2505, USA. anne_depapp@merck.com
authors.forename: Anne E
authors.initials: AE
authors.lastname: de Papp
authors.forename: Henry G
authors.initials: HG
authors.lastname: Bone
authors.forename: Michael P
authors.initials: MP
authors.lastname: Caulfield
authors.forename: Risa
authors.initials: R
authors.lastname: Kagan
authors.forename: Anna
authors.initials: A
authors.lastname: Buinewicz
authors.forename: Erluo
authors.initials: E
authors.lastname: Chen
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Rosenberg
authors.forename: Richard E
authors.initials: RE
authors.lastname: Reitz
mesh_terms: D000328:Adult; D017677:Age Distribution; D000469:Alkaline Phosphatase / Q000097:blood; D015415:Biomarkers / Q000097:blood / Q000652:urine; D001842:Bone and Bones / Q000378:metabolism*; D024042:Collagen Type I / Q000097:blood / Q000652:urine; D003430:Cross-Sectional Studies; D005260:Female; D006262:Health; D006801:Humans; D008875:Middle Aged; D017697:Premenopause; D011347:Procollagen / Q000097:blood; D011795:Surveys and Questionnaires
chemical_list: D015415:Biomarkers; D024042:Collagen Type I; D011347:Procollagen; D000469:Alkaline Phosphatase