Original Article Quercetin improves bone strength in experimental biliary cirrhosis Hoda Derakhshanian, 1 Sajad Ghadbeigi, 2 Maryam Rezaian, 4 Arash Bahremand, 3 Mohammad Hassan Javanbakht, 1 Atefeh Golpaie, 1 Payam Hosseinzadeh, 5 Narges Tajik 1 and Ahmad Reza Dehpour 3 1 Department of Nutrition and Biochemistry, School of Public Health, 2 Department of Medicinal Chemistry, School of Pharmacy, 3 Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, 4 Department of Histology, School of Veterinary Medicine, University of Tehran, Tehran, and 5 Department of Nutrition and Biochemistry, The International Campus, Tehran University of Medical Sciences, Kish, Iran Aim: Metabolic bone disorders and reduced bone mass are common complications in patients with biliary cirrhosis. As a result of there being no clear etiology, no specific therapy has been established yet. Previous studies have reported that quercetin, a plant-derived flavonoid, might improve bone quality. The present study was designed to investigate the effect of quercetin on bone strength of biliary cirrhotic rats. Methods: Twenty-four male Sprague–Dawley rats aged 6–7 months were randomized into three groups of eight. One group served as control (sham operated), while the other two groups underwent a complete bile duct ligation (BDL). Four weeks after the operation, serum bilirubin, alkaline phos- phatase, alanine aminotransferase and aspartate aminotrans- ferase were measured in animal blood samples to confirm the occurrence of cirrhosis in the BDL rats. Then, one of the BDL groups received placebo and the other one was injected once a day with 150 mmol/kg of quercetin for 4 weeks. At the end of the study, femora were removed and tested for bone strength and histomorphometric parameters. The serum levels of osteocalcin, C-terminal cross-linked telopeptide of type I collagen, calcium and phosphorus were determined as bone turnover markers. Results: Femur breaking strength was dramatically lower in the BDL group compared with control. However, receiving quercetin could reverse the deteriorating effect of cirrhosis on bone strength of BDL rats. Quercetin could noticeably elevate osteocalcin as a bone formation marker. Conclusion: These data suggest that quercetin can signifi- cantly improve bone strength particularly due to increasing bone formation in biliary cirrhosis. Key words: bone, cirrhosis, quercetin, rat INTRODUCTION M ETABOLIC BONE DISORDERS, reduced bone mass and increased fracture risk are common complications in patients with biliary cirrhosis. 1–4 Previ- ous studies have reported that a noticeable percentage of patients with chronic liver diseases suffer from osteoporosis, and the risk of fracture is approximately doubled among these patients compared with the general population. 5,6 The underlying mechanism of this phenomenon is not yet well recognized. However, both decreased bone formation and increased bone resorp- tion might be responsible. 7 As a result of there being no clear etiology, no specific therapy has been established yet. Different drugs such as bisphosphonates, calcitonin and hormone-replacement therapy have been adminis- trated in these cases with inconsistent outcomes. 8,9 One study reported that decreased bone mass in bile duct ligated (BDL) rats was compensated when 40 mg/kg per day human parathyroid hormone was injected s.c. for 4 weeks. 10 It was also shown that administration of 1 mg/kg per day 1,25(OH)2D3 could partially prevent bone disturbance in growing rats with liver cirrhosis. 11 More researches are needed to find an effective and safe treatment for this medical condition. Correspondence: Dr Ahmad Reza Dehpour, Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Poorsina Street, Enghelab Avenue, PO Box 13145-784, Tehran, Iran. Email: dehpour@yahoo.com Conflict of interest: none. Received 16 May 2012; revision 2 July 2012; accepted 4 July 2012. Hepatology Research 2013; 43: 394–400 doi: 10.1111/j.1872-034X.2012.01075.x © 2012 The Japan Society of Hepatology 394