Increased bone resorption in patients with Crohn's disease R. J. ROBINSON*, S. J. IQBAL  , K. ABRAMS à , F. AL-AZZAWI§ & J. F. MAYBERRY* *Gastrointestinal Research Unit, Leicester General Hospital;  Department of Clinical Chemistry, Leicester Royal In®rmary; àDepartment of Epidemiology and Public Health, University of Leicester; and §Department of Obstetrics & Gynaecology, Leicester Royal In®rmary, Leicester, UK Accepted for publication 7 April 1998 INTRODUCTION Osteoporosis is a common complication of in¯ammatory bowel disease, and people with Crohn's disease are at particular risk. 1, 2 Many factors contribute to low bone mineral density, 3 however the pathophysiology and mechanisms of bone loss have yet to be established. Histomorphometric analysis of iliac crest biopsy speci- mens in patients with in¯ammatory bowel disease suggests osteoporosis is the result of reduced bone formation and negative remodelling imbalance. 4, 5 However, the severity of osteoporosis and the rapid rates of bone loss suggest increased bone turnover is also likely to contribute to the development of osteopo- rosis. 3 Biochemical markers of osteoblast and osteoclast function re¯ect bone turnover 6 and can be used to investigate mechanisms of bone loss in in¯ammatory bowel disease. Osteoblast markers re¯ecting the rate of bone formation include osteocalcin (BGP), pro-collagen carboxy-terminal peptide (PICP) and bone speci®c alkaline phosphatase (BALP). Markers of bone resorp- tion include urinary deoxypyridinoline (DPD) and serum type 1 collagen carboxy-terminal telopeptide SUMMARY Background: Patients with Crohn's disease are at risk of osteoporosis and premature fracture. However, the pathophysiology underlying bone loss remains poorly understood and the optimum treatment has not been established. Aim: To investigate mechanisms of bone loss in Crohn's disease using biochemical markers of bone turnover. Methods: Bone mineral density was measured at the hip and spine using dual-energy X-ray absorptiometry in 117 patients (48 male) with Crohn's disease. Bone turnover was assessed by measuring serum osteocalcin (BGP), pro-collagen carboxy-terminal propeptide (PICP), bone speci®c alkaline phosphatase (BALP) and urinary deoxypyridinoline (DPD); and compared to age-matched healthy controls (n  28). Results: Bone mineral density was reduced (z-score < )1) in 48 (41%) patients with Crohn's disease. Mean values for bone formation markers in patients with Crohn's disease were all within the normal reference range (BGP 8.92 ( 3.23) ng/mL (normal range 3.4±10.0), BALP 17.6 ( 12.6) U/L (normal range 11.6±43.3), PICP 95.1 ( 46.5) ng/mL (normal range 69±163)) and were not signi®cantly different to the control population. However, mean urinary DPD was signi®cantly higher in patients with Crohn's disease compared to healthy controls (10.97 ( 9.22) nM DPD/mM creatinine vs. 5.02 ( 1.03) nM DPD/mM creatinine, difference in means  5.95, 95% CI: )9.6 to )2.3, P  0.00001) and compared to the UK reference range DPD levels were increased in 74 (63%) patients. Conclusions: Bone resorption as evidenced by urinary DPD was frequently increased in patients with Crohn's disease and was signi®cantly higher than in an age- matched control population. The high levels of urinary DPD suggest increased bone collagen degradation may contribute to osteoporosis in patients with Crohn's disease. These results suggest anti-resorptive agents such as the bisphosphonates may be effective treatment for osteoporosis in Crohn's disease. Correspondence to: Dr R. Robinson, Gastrointestinal Research Unit, Leicester General Hospital, Gwendolen Road, Leicester LE5 4PW, UK. Aliment Pharmacol Ther 1998; 12: 699±705. Ó 1998 Blackwell Science Ltd 699