title: Effect of systemic glucocorticoid therapy on bone metabolism and the osteoprotegerin system in patients with active Crohn's disease.
abstract: OBJECTIVE
  Osteoporosis may occur in 25-30% of patients with Crohn's disease. Its pathogenesis is not completely understood. Both systemic inflammation in acute disease and treatment with systemic glucocorticoids have been implicated. The aim of the present study was to investigate changes in bone density and biochemical markers of bone metabolism before and during a 3-month period of high-dose glucocorticoid treatment for acute flare-up of Crohn's disease.
  
  
  METHODS
  Twenty-five patients with active Crohn's disease requiring systemic glucocorticoid treatment (prednisolone, 60 mg/day) were investigated. Lumbar spine and femoral neck bone mineral densitometry was performed at baseline and again after 3 months. Clinical examinations including evaluation of the Crohn's disease activity index and measurement of the biochemical markers osteocalcin, deoxypyridinoline, osteoprotegerin and the soluble receptor activator of NF-kappaB ligand were performed prior to, and at 1, 2 and 12 weeks following steroid administration. RESULTS Median lumbar bone mineral density decreased significantly during the observation period by 1.04% from -0.84 (t score; range, -2.8 to +0.57) to -0.95 (range, -3.1 to +0.40; P = 0.022), while bone density of the total femur decreased by 2.9% from -0.83 (range, -2.61 to +1.86) to -0.90 (range, -2.65 to +0.19; P = 0.01). Serum levels of osteocalcin, a bone formation marker, and osteoprotegerin, an anti-resorptive cytokine produced by osteoblasts, decreased after the first 2 weeks of treatment and reached baseline levels after 3 months. No significant change was found for the bone resorption marker deoxypyridinoline, while soluble receptor activator of NF-kappaB ligand, a cytokine promoting bone resorption, tended to increase during steroid treatment.
  
  
  CONCLUSIONS
  A decrease in bone mineral density in patients with Crohn's disease appears to result, at least in part, from a short-term effect of systemic glucocorticoid. Modulation of osteoclastogenesis by the receptor activator of NF-kappaB ligand/osteoprotegerin cytokine system and decreased osteoblastic function may be the underlying molecular basis.
authors.affiliation: Department of Medicine I, University of Ulm, Germany. christian.tirpitz@medizin.uni-ulm.de
authors.forename: Christian
authors.initials: C
authors.lastname: von Tirpitz
authors.forename: Sonja
authors.initials: S
authors.lastname: Epp
authors.forename: Jochen
authors.initials: J
authors.lastname: Klaus
authors.forename: Richard
authors.initials: R
authors.lastname: Mason
authors.forename: Gerhard
authors.initials: G
authors.lastname: Hawa
authors.forename: Natascha
authors.initials: N
authors.lastname: Brinskelle-Schmal
authors.forename: Lorenz C
authors.initials: LC
authors.lastname: Hofbauer
authors.forename: Guido
authors.initials: G
authors.lastname: Adler
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Kratzer
authors.forename: Max
authors.initials: M
authors.lastname: Reinshagen
mesh_terms: D000208:Acute Disease; D000328:Adult; D000469:Alkaline Phosphatase / Q000097:blood / Q000652:urine; D015415:Biomarkers / Q000097:blood / Q000652:urine; D015519:Bone Density / Q000187:drug effects; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism; D003424:Crohn Disease / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D004334:Drug Administration Schedule; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage* / Q000627:therapeutic use; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D008297:Male; D015675:Osteocalcin / Q000097:blood / Q000652:urine; D053244:Osteoprotegerin; D010865:Pilot Projects; D011239:Prednisolone / Q000008:administration & dosage* / Q000627:therapeutic use; D011446:Prospective Studies; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor
chemical_list: D015415:Biomarkers; D005938:Glucocorticoids; D006023:Glycoproteins; D053244:Osteoprotegerin; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C506030:TNFRSF11B protein, human; D015675:Osteocalcin; D011239:Prednisolone; D000469:Alkaline Phosphatase