Altered osteoprotegerin/RANKL ratio and low bone mineral density in celiac patients on long-term treatment with gluten-free diet

Horm Metab Res. 2006 Jun;38(6):417-22. doi: 10.1055/s-2006-944548.


Skeletal demineralization and mineral metabolism derangement are well-recognized features of untreated celiac disease (CD). Although treatment with a gluten-free diet appears to prevent bone loss while correcting skeletal demineralization in childhood, there is evidence that bone mineral density does not return to normal in celiacs diagnosed in adulthood. Osteoprotegerin (OPG), a member of the tumor necrosis factor receptor family, and ligand of receptor activator of NFkB (RANKL) are involved in the process of bone turnover and have been implicated in the pathogenesis of osteoporosis and other metabolic bone diseases. We measured OPG, RANKL, bone mineral density (BMD), and biochemical markers of bone turnover in 32 adult female premenopausal celiac patients on a gluten-free diet, and thirty age-matched healthy women. We correlated the OPG/RANKL ratio with the severity of bone loss. Celiac patients had a mean BMD lower than controls in lumbar spine and in the femoral neck. Serum levels of bone alkaline phosphatase (BAP, marker of bone formation), and urinary excretion of telopeptides of type I collagen (a marker of bone resorption) were significantly higher than in controls. Serum OPG and RANKL levels were significantly higher in CD patients than in controls, while the OPG/RANKL ratio was significantly lower in CD patients than in controls and was positively correlated with BMD at the spine. The role of elevated OPG in CD patients is unclear, but it might represent a compensatory mechanism against other factors that promote bone damage. Further studies are required to assess a possible therapeutic potential of osteoprotegerin in optimally treated celiacs with persistent osteopenia.

Publication types

  • Comparative Study
  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers / analysis
  • Bone Density*
  • Bone Resorption / etiology
  • Carrier Proteins / blood*
  • Case-Control Studies
  • Celiac Disease / blood
  • Celiac Disease / diet therapy*
  • Celiac Disease / metabolism
  • Female
  • Follow-Up Studies
  • Glutens*
  • Glycoproteins / blood*
  • Humans
  • Long-Term Care
  • Membrane Glycoproteins / blood*
  • Osteoprotegerin
  • RANK Ligand
  • Receptor Activator of Nuclear Factor-kappa B
  • Receptors, Cytoplasmic and Nuclear / blood*
  • Receptors, Tumor Necrosis Factor / blood*


  • Biomarkers
  • Carrier Proteins
  • Glycoproteins
  • Membrane Glycoproteins
  • Osteoprotegerin
  • RANK Ligand
  • Receptor Activator of Nuclear Factor-kappa B
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Tumor Necrosis Factor
  • TNFRSF11A protein, human
  • TNFRSF11B protein, human
  • TNFSF11 protein, human
  • Glutens