Prolyl-hydroxyproline dipeptide in non-hydrolyzed morning urine and its value in postmenopausal osteoporosis

Clin Chem Lab Med. 2008;46(10):1391-7. doi: 10.1515/CCLM.2008.259.


Background: Owing to the high correlation between the level of prolyl-4-hydroxyproline dipeptide in non-hydrolyzed urine and that of 4-hydroxyproline in hydrolyzed urine, we examined whether the dipeptide might function as a valuable marker of bone turnover.

Methods: Based on densitometric measurements, 68 postmenopausal women were divided into groups of non-osteopathic, osteopenic and osteoporotic subjects. The dipeptide and current urinary resorption markers were assayed in morning urine, the former using liquid chromatography, the others plus serum formation markers by means of immunoassay procedures. Together with the assay of basal levels, diet-related changes and healing effect of yearly alendronate therapy were assessed.

Results: Concentration levels in controls and osteoporotic subjects differed significantly; receiver operating characteristics yielded sensitivity of 0.743, specificity of 0.908, area under curve of 0.903, and cut-off of 10.2 micromol/mmol of creatinine. Spearman rank correlation showed the highest pair coefficient between the dipeptide and osteocalcin. Diet-related changes were not found. Following therapy, a significant decline occurred already within a trimester, whilst with the other resorption markers not until 6 months.

Conclusions: The ease of the dipeptide assay in non-hydrolyzed urine surpasses that of hydroxyproline, and the results present the compound as a real competition to other commonly assessed markers in osteopathies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Alendronate / therapeutic use
  • Biomarkers / urine
  • Bone Resorption / urine
  • Bone and Bones / pathology
  • Bone and Bones / physiopathology
  • Dipeptides / urine*
  • Female
  • Humans
  • Hydrolysis
  • Hydroxyproline / urine
  • Middle Aged
  • Osteoporosis, Postmenopausal / drug therapy
  • Osteoporosis, Postmenopausal / physiopathology
  • Osteoporosis, Postmenopausal / urine*
  • Time Factors


  • Biomarkers
  • Dipeptides
  • prolyl-4-hydroxyproline
  • Hydroxyproline
  • Alendronate