SUMMARY: Although haemophilia is not considered among the classic causes of secondary osteoporosis, the present meta-analysis provides strong evidence that men with haemophilia have a significant reduction in both lumbar spine and femoral bone mineral density, which appears to begin in childhood.INTRODUCTION: Haemophilia is not considered among the classic causes of secondary osteoporosis. The aim of this study was to systematically review the literature for case-control trials that have studied bone mass in males with haemophilia and to meta-analyze the best evidence available.METHODS: Electronic databases MEDLINE, EMBASE and CENTRAL were systematically searched for case-control trials that have studied bone mass in men or boys with haemophilia. Standardized mean difference (SMD) for bone mineral density (BMD) in the lumbar spine was the main study outcome and SMD in femoral neck and total hip BMD the secondary ones. Patient and control characteristics, such as age, body mass index (BMI), level of physical activity and blood-borne infections were recorded as possible predictors of the main outcome.RESULTS: Thirteen studies were included in the systematic review and ten in the main outcome meta-analysis. Men with haemophilia demonstrated reduced lumbar spine [random effects SMD [95 % confidence interval (CI)] = -0.56 (-0.84, -0.28), between-study heterogeneity (I (2)) = 51 %] and femoral neck BMD [random effects SMD (95 % CI) = -0.82 (-1.21, -0.44), I (2) = 63 %] compared with controls, which indicated a large and clinically significant association. Similar results were obtained for children [random effects SMD (95 % CI) = -0.92 (-1.77, -0.07), I (2) = 92 %]. No evidence of publication bias was detected. There was no evidence that age, BMI, level of physical activity or presence of blood-borne infections predicted lumbar spine BMD.CONCLUSIONS: This meta-analysis shows that men with haemophilia present a significant reduction in both lumbar spine and hip BMD, which appears to begin in childhood.