Objectives Tenofovir disoproxil fumarate (TDF) and entecavir (ETV) are recommended as first-line treatments for chronic hepatitis B (CHB). However, the safety of these two drugs remains controversial. This study aimed to evaluate and compare renal function and bone mineral density in patients with CHB who took TDF or ETV. Methods The electronic databases of the Cochrane Library, PubMed, and Embase were searched. The keywords were: "CHB", "tenofovir", and "entecavir". Heterogeneity and subgroups were analyzed. Results A total of 16 studies met the inclusion criteria. There was no significant difference in serum creatinine levels between the TDF and the ETV group. There was a significant standardized mean difference (SMD) in the serum estimated glomerular filtration rate between months (12 months: SMD [95% confidence interval] = -0.07 [-0.12, -0.01]; 18-24 months: SMD [95% confidence interval] = -0.11 [-0.17, -0.05]), but no significant difference emerged in the long-term drug use for over 24 months. There was no significant difference in the incidence of osteopenia/osteoporosis (I 2 = 41%, risk ratio [95% confidence interval] = 1.29 [0.93, 1.77], P -value = 0.13 >0.05). Conclusion Compared with the ETV group, a greater reduction in estimated glomerular filtration rate and serum phosphorus levels was observed in the TDF group. There was no significant difference in the incidence of osteopenia/osteoporosis between the two groups.
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