Effect of systemic glucocorticoid therapy on bone metabolism and the osteoprotegerin system in patients with active Crohn's disease.

BACKGROUND AND AIMS: 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. CONCLUSION: 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.

Management of osteoporosis in patients with gastrointestinal diseases.

Osteoporosis is a frequent complication in the course of various gastrointestinal disorders. Since its pathogenesis is complex, and incompletely understood in comparison to the well-known pathomechanism of postmenopausal osteoporosis, adequate management is difficult. We first summarize those therapeutic options which have strong evidence in postmenopausal osteoporosis and, thereafter, we review those in the context of different gastrointestinal diseases. Treatment of the underlying intestinal disorder seems to be most important to normalise altered bone metabolism and to prevent osteoporosis in patients with coeliac disease. In patients with osteoporosis associated with Crohn's disease, various treatment strategies (such as vitamin D, sodium fluoride, bisphosphonates) are discussed. In contrast to postmenopausal osteoporosis, interventional studies in secondary osteoporosis are often limited by the small study population and data about the efficacy of any treatment in prevention of fractures are therefore lacking. Well-conducted, controlled studies with the endpoint of preventing fractures are therefore required to optimise the treatment of osteoporosis in these patients.