Risk of Morbidity in Contemporary Celiac Disease

Nina R Lewis; Geoffrey KT Holmes


Expert Rev Gastroenterol Hepatol. 2010;4(6):767-780. 

In This Article

Metabolic Bone Disease & Fracture Risk

A meta-analysis of published studies suggests that there is a modest increase in the risk of fracture in celiac disease (any fracture relative risk: 1.38 [95% CI: 1.14–1.68]).[90] Although osteoporosis is just one of many factors predisposing to fracture, it is appreciated that the risk of sustaining an osteoporotic fracture doubles with each standard deviation decrease in bone mineral density (BMD).[91] For example, a 50-year-old woman with T-score -2 at the femoral neck has 9.2% 10-year probability of sustaining a hip, vertebral or wrist fracture in comparison with the 5.9% probability in a woman of the same age with T-score -1. Although osteoporosis can be reliably assessed by the measurement of BMD using noninvasive dual-energy x-ray absorptiometry (DEXA), the real issue is identifying which celiacs are at particular risk of reduced BMD, and thus rationalizing referrals for DEXA screening. Meta-analysis of published studies suggest there is a moderate reduction of BMD in untreated celiac disease, with weighted mean Z scores at the lumbar spine and hip of -1.3 (95% CI -1.4 to -1.2) and -1.1 (95% CI: -1.2 to -1.0).[90] Observational studies have suggested that a gluten-free diet improves BMD in people with symptomatic celiac disease. For example, Valdimarsson et al. observed a median 3% (interquartile range: 1–7) increase in BMD at the lumbar spine in 62 celiac patients following 12 months treatment with a gluten-free diet,[92] whereas McFarlane et al. observed a 6.6% (95% CI: 3.1–10.1) absolute increase in the lumbar spine over an identical time period of treatment in 21 celiacs.[93] A systematic review of those risk factors for fractures in the general population that are probably related to a low BMD identified high-risk factors (relative risk or OR of >2.0) such as age over 70 years, previous osteoporotic fracture, weight loss greater than 10% and low body weight as reflected by BMI (<20 kg/m2 or weight <40 kg).[94] DEXA screening for osteoporosis should therefore be offered to untreated celiacs with these features; to those celiacs with persisting symptoms despite adherence with at least a year's treatment with a gluten-free diet; and those celiacs with poor adherence to a gluten-free diet.[90]

Studies observing prevalence of osteomalacia in newly diagnosed celiac disease patients involved particular reasons for measuring different elements of bone profile, so are probably limited by such ascertainment bias. Elevated alkaline phosphatase is a useful biochemical test to screen for osteomalacia in celiacs, as it is in the general population.[39,95,96] Elevated alkaline phosphatase is also independently associated with clinical features of malabsorption in adults newly diagnosed with celiac disease.[39] The observed reduction in alkaline phosphatase with treatment of celiac disease[39,92,97,98] supports the importance of gluten withdrawal to help treat any underlying osteomalacia[92,97,98] Normalization of an isolated elevated alkaline phosphatase with treatment of celiac disease may also remove the need for further invasive investigations such as a bone biopsy.


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