ReviewOsteoporosis in Inflammatory Bowel Disease
Section snippets
Pathophysiology of Osteoporosis in Inflammatory Bowel Disease
Bone is a living tissue that undergoes constant remodeling by bone-forming cells (osteoblasts) and bone-resorbing cells (osteoclasts). Imbalances in bone formation and resorption lead to osteoporosis. Several gastrointestinal disorders have been associated with osteoporosis and osteopenia, including inflammatory bowel disease, celiac disease, and chronic liver disease.5, 6 The etiology of osteoporosis in inflammatory bowel disease is multifactorial, with risk factors including age,
Role of Corticosteroids
Because glucocorticoids are a treatment mainstay for chronic inflammatory diseases, it is important to recognize the effects they have on bone remodeling. They have been shown to impair osteoblast function, induce osteoblast apoptosis, reduce intestinal calcium absorption, and increase renal excretion of calcium.5, 7 Patients on glucocorticoids are at increased risk for fracture, with the greatest bone loss occurring in the initial months of treatment.8 Interestingly, studies show a decrease in
Role of Inflammation
There is a developing wealth of information about the role of inflammation in Crohn's disease and ulcerative colitis and the development of osteoporosis. In inflammatory bowel disease, the immune response, mediated by T lymphocytes and other inflammatory cells like macrophages, leads to production of various proinflammatory cytokines such as interleukin (IL)-2 and tumor necrosis factor (TNF). Within mononuclear cells, the key nuclear transcription factor is nuclear factor-kappa B (NFκB), which
Genetic Factors
The recent discoveries of signal transduction pathways and transcription factors critical for osteoblast differentiation and function have opened up new approaches to the understanding of the pathogenesis of osteoporosis.22 Identification of the critical role for the Wnt (wingless genes) signaling pathway in regulating osteoblast function is of particular interest, because it has been shown to play an important role in determining bone mass and strength.23 The precise mechanisms whereby Wnt
Nutritional Factors
Inflammatory bowel disease-related nutritional deficiencies have been implicated as other pathogenic mechanisms resulting in low bone mineral density. Calcium is required for normal growth and development of the skeleton. Adequate calcium intake is critical to achieving optimal peak bone mass and modifies the rate of bone loss associated with aging. Calcium deficiency (as a result of either low intake or poor intestinal absorption) has been reported in Crohn's disease.27 Vitamin D deficiency
Screening Guidelines
The World Health Organization (WHO) defines osteoporosis as bone mineral density at the hip or spine < 2.5 standard deviations below the mean for young healthy sex- and race-matched adults. Although bone mineral density assessment is the most common means of diagnosing osteoporosis, the WHO has developed a web-based interactive tool, FRAX™ (Fracture Risk Assessment Model), that includes 10 risk factors.33 This tool helps physicians calculate the 10-year probability of having major osteoporotic
Nonpharmacologic Therapies
Several nonpharmacologic therapies are recommended for all patients at risk for developing osteoporosis, including those suffering from inflammatory bowel disease (Table 2).6, 35, 36 These include regular weight-bearing exercise (resulting in improved bone mineral density and decreased risk of fall from increased agility, strength, and balance), avoidance of tobacco use and limiting alcohol intake (both risk factors on the WHO's Fracture Risk Assessment Tool),33 and fall prevention. It is
Conclusion
Osteoporosis imparts a significant burden on today's health care system, accounting for high costs, increased hospitalizations, disability, and time lost from work. Considerable information is known about osteoporosis and inflammatory bowel disease, but further work is needed. As more is understood about the pathophysiology linking these diseases, more treatment modalities will become available. For physicians, it is important to recognize the risk factors that are associated with inflammatory
References (48)
- et al.
AGA technical review on osteoporosis in gastrointestinal diseases
Gastroenterology
(2003) - et al.
Predominant role of NF-kappa B p65 in the pathogenesis of chronic intestinal inflammation
Immunobiology
(1997) - et al.
Genetic factors determine extent of bone loss in inflammatory bowel disease
Gastroenterology
(2000) - et al.
Interleukin-1 beta and tumor necrosis factor-alpha, but not interleukin-6, stimulate osteoprotegerin ligand gene expression in human osteoblastic cells
Bone
(1999) - et al.
Osf2/Cbfa1: a transcriptional activator of osteoblast differentiation
Cell
(1997) - et al.
LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development
Cell
(2001) - et al.
Glucocorticoid suppresses the canonical Wnt signal in cultured human osteoblasts
Biochem Biophys Res Commun
(2005) - et al.
Serum undercarboxylated osteocalcin is a marker of the risk of hip fracture: a three year follow-up study
Bone
(1996) - et al.
National Osteoporosis Foundation 2008 Clinician's Guide to Prevention and Treatment of Osteoporosis and the World Health Organization Fracture Risk Assessment Tool (FRAX): what they mean to the bone densitometrist and bone technologist
J Clin Densitom
(2008) - et al.
Bone mineral density in relation to efficacy and side effects of budesonide and prednisolone in Crohn's disease
Clin Gastroenterol Hepatol
(Feb 2005)
Assessment of fracture risk and its application to screening for postmenopausal osteoporosisReport of a WHO Study Group
World Health Organ Tech Rep Ser
Osteoporosis in patients with inflammatory bowel disease
Gut
Reduced bone density in patients with inflammatory bowel disease
Gut
Femoral neck osteopenia in patients with inflammatory bowel disease
Am J Gastroenterol
The pathophysiology of bone disease in gastrointestinal disease
Eur J Gastroenterol Hepatol
Recommendations for the prevention and treatment of glucocorticoid-induced osteoporosis
Arthritis Rheum
Oral corticosteroids and fracture risk: relationship to daily and cumulative doses
Rheumatology (Oxford)
The epidemiology of corticosteroid-induced osteoporosis: a meta-analysis
Osteoporos Int
Nuclear factor-kappaB: a pivotal transcription factor in chronic inflammatory diseases
N Engl J Med
Osteoclasts are essential for TNF-alpha-mediated joint destruction
J Clin Invest
The role of IL-6 type cytokines and their receptors in bone
Ann N Y Acad Sci
The RANKL/RANK/OPG pathway
Curr Osteoporos Rep
Serum osteoprotegerin is increased in Crohn's disease: a population-based case control study
Inflamm Bowel Dis
The RANKL/OPG system is activated in inflammatory bowel disease and relates to the state of bone loss
Gut
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Funding: Dr. Humphrey received funding from US Department of Veterans Affairs.
Conflict of Interest: None.
Authorship: All authors contributed to writing this manuscript.