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Re: Chronic inflammatory intestinal diseases and bone loss

Dear Editor,

We were very interested in the recent article by Moschen et al. on the activation of RANKL/OPG system in inflammatory bowel disease (IBD). Until recently, osteoporosis secondary to gastrointestinal diseases was mainly considered a direct consequence of malabsorption [2,3]. The article of Moschen et al. [1] and a previous one of our group on bone loss in celiac disease [4], a disorder similarly characterized by intestinal inflammation, offer a new perspective on the pathogenesis of bone loss and reveal a more complex picture. Moschen et al. [1] demonstrated the overproduction of OPG in the cells of colonic mucosa in IBD whereas Taranta et al. [4] showed the direct role of the soluble cytokines in the serum of celiac patients on bone cells. In fact, they found an increased RANKL/OPG ratio in untreated celiac patients and different effects of the sera of untreated celiac patients with respect to those on gluten-free diet, on cultured bone cells. These effects included an increased in vitro osteoclastogenesis, and lower IL-18 and OPG expression in osteoblasts.

In both studies, these biochemical observations were translated in a reduction of bone mass. Moschen et al. [1] found a negative correlation between OPG plasma levels and spine and femoral neck bone mineral density (BMD). Taranta et al. [4] observed a significant negative correlation between BMD Z-score and IL-6 levels and RANKL/OPG ratio. In the discussion, Moschen et al. [1] observed that "studies of OPG/RANKL and BMD are required to validate" his model.

We think that our study may be a first step to understand at least in part the relative contribution of inflammation to bone loss in intestinal diseases. These results are also in accordance with recent studies on primary osteoporosis, which are beginning to show a relevant role of local and systemic factors on bone cell activity [5-7]. Finally, these studies might also open the way to different therapeutic approaches - namely, drugs specifically acting on cytokines release and/or activity - for bone loss secondary to "inflammatory intestinal diseases".

Maria Teresa Bardella, MD, Chair of Gastroenterology, Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, IRCCS, Milano (Italy)

Maria Luisa Bianchi, Bone Metabolism Unit, Istituto Auxologico Italiano, IRCCS, Milano (Italy)

Anna Teti, Department of Experimental Medicine, University of L’Aquila, L’Aquila (Italy)

References

1) Moschen AR, Kaser A, Enrich B, et al. The RANKL/OPG system in activated in inflammatory bowel disease and relates to the state of bone loss. Gut 2005;54:479-87.

2) Selby PL, Davies M, Adams JE at al. Bone loss in celiac disease is related to secondary hyperparathyroidism. J Bone Mineral Res 1999;4:652-7.

3) Bianchi ML, Bardella MT. Bone and celiac disease. Calcif Tissue Int 2002;71:465-71.

4) Taranta A, Fortunati D, Longo M, et al. Imbalance of osteoclastogenesis regulating factors in patients with celiac disease. J Bone Miner Res 2004;19:1112-21

5) Wei S, Kitaura H, Zhou P, et al. IL-1 mediates TNF-induced osteoclastogenesis. J Clin Invest 2005 Feb;115:282-90.

6) Shen F, Ruddy MJ, Plamondon P, Gaffen SL. Cytokines link osteoblasts and inflammation: microarray analysis of interleukin-17- and TNF-alpha-induced genes in bone cells. J Leukoc Biol 2005;77:388-99.