Journal of Bone and Mineral Metabolism

, Volume 26, Issue 1, pp 93-100

First online:

Nonenzymatic collagen cross-links induced by glycoxidation (pentosidine) predicts vertebral fractures

  • Masataka ShirakiAffiliated withDepartment of Internal Medicine, Research Institute and Practice for Involutional Diseases Email author 
  • , Tatsuhiko KurodaAffiliated withDepartment of Obstetric and Gynecology, Tokyo Women's Medical University
  • , Shiro TanakaAffiliated withDepartment of Epidemiology and Biostatistics, Tokyo University
  • , Mitsuru SaitoAffiliated withDepartment of Orthopedic Surgery, Jikei University School of Medicine
  • , Masao FukunagaAffiliated withDepartment of Nuclear Medicine, Kawasaki Medical School
  • , Toshitaka NakamuraAffiliated withDepartment of Orthopedic Surgery, University of Occupational and Environmental Health

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Advanced glycation end products (AGE) in collagen have been reported to decrease the mechanical property of bone. However, there are no available data on the relation between fracture risk and levels of glycoxidative (nonenzymatic) cross-links of collagen in clinical samples. A total of 432 Japanese elderly women who were not receiving any drug treatment for osteoporosis were selected and followed for 5.2 ± 3.3 (mean ± SD) years for this observational study. Vertebral fractures and bone mineral density were assessed at baseline and then at 1- to 2-year intervals or at indication of any symptom. Two types of collagen metabolites were measured at baseline: urinary N-terminal telopeptide of type I collagen (NTX), a marker of pyridinium cross-link, and urinary pentosidine, a nonenzymatic collagen cross-link produced by AGEs. A total of 97 incident vertebral fractures on 72 subjects were observed. Simple regression analysis using Cox's hazards model showed that log-transformed urinary NTX and pentosidine are significant risk factors for time-dependent incidence of vertebral fractures, in addition to the traditional risk factors (age, lumbar bone mineral density, and number of prevalent vertebral fractures). However, urinary excretion of pentosidine (hazard ratio, 1.33; 95% CI, 1.01–1.76, P = 0.04) was a significant predictor of incident vertebral fracture after adjustment for other traditional risk factors. The present data suggest that AGE-related collagen cross-link is a novel risk for vertebral fracture.

Key words

osteoporosis vertebral fracture collagen cross-link pentosidine