Correlates of osteoprotegerin and association with aortic pulse wave velocity in patients with chronic kidney disease

Clin J Am Soc Nephrol. 2011 Nov;6(11):2612-9. doi: 10.2215/CJN.03910411. Epub 2011 Sep 22.


Background and objectives: Osteoprotegerin (OPG), a cytokine that regulates bone resorption, has been implicated in the process of vascular calcification and stiffness.

Design, setting, participants, & measurements: Serum OPG was measured in 351 participants with chronic kidney disease (CKD) from one site of the Chronic Renal Insufficiency Cohort Study. Cortical bone mineral content (BMC) was measured by quantitative computed tomography in the tibia. Multivariable linear regression was used to test the association between serum OPG and traditional cardiovascular risk factors, measures of abnormal bone and mineral metabolism, and pulse wave velocity.

Results: Higher serum OPG levels were associated with older age, female gender, greater systolic BP, lower estimated GFR, and lower serum albumin. OPG was not associated with measures of abnormal bone or mineral metabolism including serum phosphorus, albumin-corrected serum calcium, intact parathyroid hormone, bone-specific alkaline phosphatase, or cortical BMC. Among 226 participants with concurrent aortic pulse wave velocity measurements, increasing tertiles of serum OPG were associated with higher aortic pulse wave velocity after adjustment for demographics, traditional vascular risk factors, and nontraditional risk factors such as estimated GFR, albuminuria, serum phosphate, corrected serum calcium, presence of secondary hyperparathyroidism, serum albumin, and C-reactive protein or after additional adjustment for cortical BMC in a subset (n = 161).

Conclusions: These data support a strong relationship between serum OPG and arterial stiffness independent of many potential confounders including traditional cardiovascular risk factors, abnormal bone and mineral metabolism, and inflammation.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Analysis of Variance
  • Aorta / physiopathology*
  • Biomarkers / blood
  • Bone Density
  • Cardiovascular Diseases / blood
  • Cardiovascular Diseases / diagnostic imaging
  • Cardiovascular Diseases / etiology*
  • Cardiovascular Diseases / physiopathology
  • Chi-Square Distribution
  • Chronic Disease
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Kidney Diseases / blood
  • Kidney Diseases / complications*
  • Kidney Diseases / diagnostic imaging
  • Kidney Diseases / physiopathology
  • Linear Models
  • Male
  • Middle Aged
  • Osteoprotegerin / blood*
  • Pulsatile Flow*
  • Regional Blood Flow
  • Risk Assessment
  • Risk Factors
  • Tibia / diagnostic imaging
  • Tibia / metabolism
  • Tomography, X-Ray Computed
  • United States
  • Up-Regulation


  • Biomarkers
  • Osteoprotegerin
  • TNFRSF11B protein, human