title: High bone turnover is associated with low bone mass and spinal fracture in postmenopausal women.
abstract: A group of 366 healthy, white postmenopausal women, aged 50-81 years, mean age 66 years, were selected from the screened population of Scandinavians who were part of a multicenter study of the efficacy of tiludronate, a new bisphosphonate, in established postmenopausal osteoporosis. Eighty-eight women had a lumbar spine bone mineral density (BMD) above 0.860 g/cm2, and 278 women had a BMD below 0.860 g/cm2. Spinal fracture was diagnosed from lateral spine X-ray studies and defined as at least 20% height reduction (wedge, compression, or endplate fracture) in at least one vertebra (T4-L4). Bone resorption was assessed by measurement of the urinary excretion of type I collagen degradation products by the CrossLaps enzyme-linked immunoassay (ELISA). Bone formation was assessed by ELISA measurement of the N-terminal-midfragment as well as the intact serum osteocalcin (OCN-MID), thus omitting the influence of the instability of osteocalcin caused by the labile 6 amino acid C-terminal sequence. The women were divided into groups with high or low bone turnover according to the concentrations of urinary Cross-Laps or OCN-MID. Women in the quartiles with the highest concentrations of CrossLaps [519 +/- 119 micrograms/mmol (SD)] or OCN-MID [44.6 +/- 7.5 ng/ml (SD)] had 10-16% lower spinal BMD compared with women in the lowest quartiles (CrossLaps 170 +/- 48 micrograms/mmol (SD), and OCN-MID [22.1 +/- 3.0 ng/ml (SD)] (P < 0.0004). The prevalences of spinal fracture were 25 to 29% in the lowest quartiles, whereas the prevalences in the highest quartiles were almost double-53-54% (P < 0.006). If the women were subgrouped according to spinal BMD and prevalence of spinal fracture, corresponding results were found. Women with a BMD less than 0.860 g/cm2, without or with spinal fracture (n = 136 and n = 142), had 36-43% higher concentration of Cross-Laps (P = 0.0001) and 11-15% higher concentration of OCN-MID (P < 0.02), as compared with women with a BMD above 0.860 g/cm2 and no spinal fracture (n = 84). In conclusion, the results indicate a strong association among high bone turnover, low bone mass, and prevalence of spinal fracture, which supports the theory that high bone turnover is a risk factor for spinal fracture and osteoporosis.
authors.affiliation: Center for Clinical and Basic Research, Ballerup, Denmark.
authors.forename: P
authors.initials: P
authors.lastname: Ravn
authors.forename: M
authors.initials: M
authors.lastname: Rix
authors.forename: H
authors.initials: H
authors.lastname: Andreassen
authors.forename: B
authors.initials: B
authors.lastname: Clemmesen
authors.forename: M
authors.initials: M
authors.lastname: Bidstrup
authors.forename: M
authors.initials: M
authors.lastname: Gunnes
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000032:analysis; D015519:Bone Density / Q000187:drug effects / Q000502:physiology*; D001846:Bone Development / Q000187:drug effects; D001862:Bone Resorption / Q000503:physiopathology; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism*; D003430:Cross-Sectional Studies; D004164:Diphosphonates / Q000494:pharmacology / Q000627:therapeutic use; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007118:Immunoassay; D008159:Lumbar Vertebrae / Q000293:injuries*; D008875:Middle Aged; D015675:Osteocalcin / Q000097:blood / Q000276:immunology; D015663:Osteoporosis, Postmenopausal / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology*; D011933:Reagent Kits, Diagnostic; D016103:Spinal Fractures / Q000209:etiology* / Q000517:prevention & control; D013904:Thoracic Vertebrae / Q000293:injuries*
chemical_list: D015415:Biomarkers; D004164:Diphosphonates; D011933:Reagent Kits, Diagnostic; D015675:Osteocalcin; C058651:tiludronic acid