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Association between primary biliary cholangitis and fracture: A meta-analysis
+Model CLINRE-1028; No. of Pages 2
ARTICLE IN PRESS
Clinics and Research in Hepatology and Gastroenterology (2017) xxx, xxx—xxx
Available online at
ScienceDirect www.sciencedirect.com
RESEARCH LETTER
Association between primary biliary cholangitis and fracture: A meta-analysis Primary biliary cholangitis (PBC), previously called primary biliary cirrhosis, is a cholestatic autoimmune liver disease characterized by the progressive lymphocytic destruction of the smallest bile ducts, leading to fibrosis and potential cirrhosis. Many observational studies have shown that bone loss such as osteoporosis is a common complication of PBC. One important reason for that is chronic cholestasis can result in vitamin D deficiency and interrupt bone metabolism [1]. Osteoporosis can lead to bone fragility and increased risk of fracture, which may bring severe consequences for both patients and the health system. Although PBC is closely associated with osteopenic bone disorder, it has been discussed whether PBC itself represents a risk factor for bone fracture and what the prevalence of fracture is among PBC patients. Several studies have been conducted in this field, but the findings from these studies were inconsistent. Therefore, we conducted a meta-analysis to evaluate the prevalence of fracture among patients with PBC and the association between PBC and fracture. We reviewed published studies in MEDLINE and EMBASE from their inception to February 2017 with search strategy that included the terms for ‘‘PBC’’ and ‘‘fracture’’. A manual search for additional studies using references of selected retrieved articles was also performed to identify other possible studies. The major inclusion criteria was observational studies that reported prevalence, relative risks, odd ratios, hazard ratios or standardized incidence ratio of bone fracture among PBC patients. Of 1460 potentially relevant articles, 1422 articles were excluded due to the title and abstract not meeting inclusion criteria. Subsequently, 30 articles were excluded because they did not describe the outcomes of interest. Finally, 8 observational studies (4 cross-sectional, 3 case-control and 1 cohort studies) met all inclusion criteria. Four cross-sectional [2—5] studies with 515 patients were included in the analysis to assess the prevalence of fracture in PBC population. The estimated prevalence of fracture among PBC patients was 15.2% (95%CI: 10.5—19.9%). Four studies[6—9] (3 case-control and 1 cohort) with 1002 PBC
Figure 1 Forest plots. A: Forest plot of overall prevalence of fracture among PBC patients. B: forest plot of the association between PBC and fracture.
patients and 8805 controls were included in the analysis to assess the risk of fracture among PBC patients. We found a significantly increased risk of fracture in PBC patients with the pooled OR of 1.93 (95%CI: 1.35—2.74, P = 0.000). Forest plots are presented in Fig. 1. So far, this is the first meta-analysis conducted to summarize all presently available data on the prevalence of fracture among PBC patients and the association between PBC and fracture. Our study demonstrated an estimated prevalence of fracture in PBC patients of 15.2%. Besides, we found a 1.93 fold increased risk of fracture among PBC patients. The results of our study validate that PBC may increase the risk of developing bone fracture.
http://dx.doi.org/10.1016/j.clinre.2017.05.008 2210-7401/© 2017 Elsevier Masson SAS. All rights reserved.
Please cite this article in press as: Zhao J, et al. Association between primary biliary cholangitis and fracture: A metaanalysis. Clin Res Hepatol Gastroenterol (2017), http://dx.doi.org/10.1016/j.clinre.2017.05.008
+Model CLINRE-1028; No. of Pages 2
ARTICLE IN PRESS
2
Research letter
It is recognized multiple factors underlie the osteopenic bone disease in PBC. In addition to cholestasis, risk factors include female sex, low body-mass index, advanced age, history of fragility fracture [10,11]. Steroids use may also contributes to bone loss in PBC [12], especially in autoimmune hepatitis-primary biliary cirrhosis overlap syndrome. We conclude that the prevalence of bone fracture among PBC patients is relatively high and PBC increases the risk of fracture. Calcium and vitamin D supplementation or even bisphosphonate therapy should be recommended for PBC patients with bone loss to decrease the risk of fracture.
Disclosure of interest The authors declare that they have no competing interest.
References [1] Agmon-Levin N, Kopilov R, Selmi C, et al. Vitamin D in primary biliary cirrhosis, a plausible marker of advanced disease. Immunol Res 2015;61(1—2):141—6. [2] Corless L, Majeed F, Abouda G. Bone disease in primary biliary cirrhosis-is the risk higher than previously thought? Gut 2015;64:A259. [3] Krishnamoorthy R, Grant A, Sheldon P, Delahooke T. Fracture prevalence and vitamin D status in primary biliary cirrhosis: the Leicestershire experience. Gut 2012;61:A410—1. [4] Taniai M, Hashimoto E, Mizuno A, et al. Clinicopathological features of patients with primary biliary cirrhosis whose age were over 80 years. Hepatology 2011;54:1210A. [5] Guanabens N, Cerda D, Monegal A, et al. Low bone mass and severity of cholestasis affect fracture risk in patients with primary biliary cirrhosis. Gastroenterology 2010;138(7):2348—56.
[6] Gao X, Zhang Y, Liu T, et al. Clinical study of hepatic osteoporosis in primary biliary cirrhosis. Hepatol Int 2017;11(1):S591. [7] Mounach A, Ouzzif Z, Wariaghli G, et al. Primary biliary cirrhosis and osteoporosis: a case-control study. J Bone Miner Metab 2008;26(4):379—84. [8] Solaymani-Dodaran M, Card TR, Aithal GP, West J. Fracture risk in people with primary biliary cirrhosis: a population-based cohort study. Gastroenterology 2006;131(6):1752—7. [9] Boulton-Jones JR, Fenn R, West J, Logan RFA, Ryder SD. Fracture risk of women with primary biliary cirrhosis: no increase compared with general population controls. Aliment Pharmacol Ther 2004;20(5):551—7. [10] Ormarsdottir S, Ljunggren O, Mallmin H, Brahm H, Loof L. Low body mass index and use of corticosteroids, but not cholestasis, are risk factors for osteoporosis in patients with chronic liver disease. J Hepatol 1999;31(1):84—90. [11] Le Gars L, Grandpierre C, Chazouilleres O, Berenbaum F, Poupon R. Bone loss in primary biliary cirrhosis: absence of association with severity of liver disease. Joint Bone Spine 2002;69(2):195—200. [12] Wariaghli G, Allali F, El MA, Hajjaj-Hassouni N. Osteoporosis in patients with primary biliary cirrhosis. Eur J Gastroenterol Hepatol 2010;22(12):1397—401.
Jian Zhao Wei Li Jia Cao Caiquan Liang Ding-Kang Yao ∗ Department of Internal Medicine, Changzheng Hospital, Second Military Medical University, 200003 Shanghai, China ∗
Corresponding author. E-mail address: [email protected] (D.-K. Yao)
Please cite this article in press as: Zhao J, et al. Association between primary biliary cholangitis and fracture: A metaanalysis. Clin Res Hepatol Gastroenterol (2017), http://dx.doi.org/10.1016/j.clinre.2017.05.008
ARTICLE IN PRESS
Clinics and Research in Hepatology and Gastroenterology (2017) xxx, xxx—xxx
Available online at
ScienceDirect www.sciencedirect.com
RESEARCH LETTER
Association between primary biliary cholangitis and fracture: A meta-analysis Primary biliary cholangitis (PBC), previously called primary biliary cirrhosis, is a cholestatic autoimmune liver disease characterized by the progressive lymphocytic destruction of the smallest bile ducts, leading to fibrosis and potential cirrhosis. Many observational studies have shown that bone loss such as osteoporosis is a common complication of PBC. One important reason for that is chronic cholestasis can result in vitamin D deficiency and interrupt bone metabolism [1]. Osteoporosis can lead to bone fragility and increased risk of fracture, which may bring severe consequences for both patients and the health system. Although PBC is closely associated with osteopenic bone disorder, it has been discussed whether PBC itself represents a risk factor for bone fracture and what the prevalence of fracture is among PBC patients. Several studies have been conducted in this field, but the findings from these studies were inconsistent. Therefore, we conducted a meta-analysis to evaluate the prevalence of fracture among patients with PBC and the association between PBC and fracture. We reviewed published studies in MEDLINE and EMBASE from their inception to February 2017 with search strategy that included the terms for ‘‘PBC’’ and ‘‘fracture’’. A manual search for additional studies using references of selected retrieved articles was also performed to identify other possible studies. The major inclusion criteria was observational studies that reported prevalence, relative risks, odd ratios, hazard ratios or standardized incidence ratio of bone fracture among PBC patients. Of 1460 potentially relevant articles, 1422 articles were excluded due to the title and abstract not meeting inclusion criteria. Subsequently, 30 articles were excluded because they did not describe the outcomes of interest. Finally, 8 observational studies (4 cross-sectional, 3 case-control and 1 cohort studies) met all inclusion criteria. Four cross-sectional [2—5] studies with 515 patients were included in the analysis to assess the prevalence of fracture in PBC population. The estimated prevalence of fracture among PBC patients was 15.2% (95%CI: 10.5—19.9%). Four studies[6—9] (3 case-control and 1 cohort) with 1002 PBC
Figure 1 Forest plots. A: Forest plot of overall prevalence of fracture among PBC patients. B: forest plot of the association between PBC and fracture.
patients and 8805 controls were included in the analysis to assess the risk of fracture among PBC patients. We found a significantly increased risk of fracture in PBC patients with the pooled OR of 1.93 (95%CI: 1.35—2.74, P = 0.000). Forest plots are presented in Fig. 1. So far, this is the first meta-analysis conducted to summarize all presently available data on the prevalence of fracture among PBC patients and the association between PBC and fracture. Our study demonstrated an estimated prevalence of fracture in PBC patients of 15.2%. Besides, we found a 1.93 fold increased risk of fracture among PBC patients. The results of our study validate that PBC may increase the risk of developing bone fracture.
http://dx.doi.org/10.1016/j.clinre.2017.05.008 2210-7401/© 2017 Elsevier Masson SAS. All rights reserved.
Please cite this article in press as: Zhao J, et al. Association between primary biliary cholangitis and fracture: A metaanalysis. Clin Res Hepatol Gastroenterol (2017), http://dx.doi.org/10.1016/j.clinre.2017.05.008
+Model CLINRE-1028; No. of Pages 2
ARTICLE IN PRESS
2
Research letter
It is recognized multiple factors underlie the osteopenic bone disease in PBC. In addition to cholestasis, risk factors include female sex, low body-mass index, advanced age, history of fragility fracture [10,11]. Steroids use may also contributes to bone loss in PBC [12], especially in autoimmune hepatitis-primary biliary cirrhosis overlap syndrome. We conclude that the prevalence of bone fracture among PBC patients is relatively high and PBC increases the risk of fracture. Calcium and vitamin D supplementation or even bisphosphonate therapy should be recommended for PBC patients with bone loss to decrease the risk of fracture.
Disclosure of interest The authors declare that they have no competing interest.
References [1] Agmon-Levin N, Kopilov R, Selmi C, et al. Vitamin D in primary biliary cirrhosis, a plausible marker of advanced disease. Immunol Res 2015;61(1—2):141—6. [2] Corless L, Majeed F, Abouda G. Bone disease in primary biliary cirrhosis-is the risk higher than previously thought? Gut 2015;64:A259. [3] Krishnamoorthy R, Grant A, Sheldon P, Delahooke T. Fracture prevalence and vitamin D status in primary biliary cirrhosis: the Leicestershire experience. Gut 2012;61:A410—1. [4] Taniai M, Hashimoto E, Mizuno A, et al. Clinicopathological features of patients with primary biliary cirrhosis whose age were over 80 years. Hepatology 2011;54:1210A. [5] Guanabens N, Cerda D, Monegal A, et al. Low bone mass and severity of cholestasis affect fracture risk in patients with primary biliary cirrhosis. Gastroenterology 2010;138(7):2348—56.
[6] Gao X, Zhang Y, Liu T, et al. Clinical study of hepatic osteoporosis in primary biliary cirrhosis. Hepatol Int 2017;11(1):S591. [7] Mounach A, Ouzzif Z, Wariaghli G, et al. Primary biliary cirrhosis and osteoporosis: a case-control study. J Bone Miner Metab 2008;26(4):379—84. [8] Solaymani-Dodaran M, Card TR, Aithal GP, West J. Fracture risk in people with primary biliary cirrhosis: a population-based cohort study. Gastroenterology 2006;131(6):1752—7. [9] Boulton-Jones JR, Fenn R, West J, Logan RFA, Ryder SD. Fracture risk of women with primary biliary cirrhosis: no increase compared with general population controls. Aliment Pharmacol Ther 2004;20(5):551—7. [10] Ormarsdottir S, Ljunggren O, Mallmin H, Brahm H, Loof L. Low body mass index and use of corticosteroids, but not cholestasis, are risk factors for osteoporosis in patients with chronic liver disease. J Hepatol 1999;31(1):84—90. [11] Le Gars L, Grandpierre C, Chazouilleres O, Berenbaum F, Poupon R. Bone loss in primary biliary cirrhosis: absence of association with severity of liver disease. Joint Bone Spine 2002;69(2):195—200. [12] Wariaghli G, Allali F, El MA, Hajjaj-Hassouni N. Osteoporosis in patients with primary biliary cirrhosis. Eur J Gastroenterol Hepatol 2010;22(12):1397—401.
Jian Zhao Wei Li Jia Cao Caiquan Liang Ding-Kang Yao ∗ Department of Internal Medicine, Changzheng Hospital, Second Military Medical University, 200003 Shanghai, China ∗
Corresponding author. E-mail address: [email protected] (D.-K. Yao)
Please cite this article in press as: Zhao J, et al. Association between primary biliary cholangitis and fracture: A metaanalysis. Clin Res Hepatol Gastroenterol (2017), http://dx.doi.org/10.1016/j.clinre.2017.05.008