Osteoporosis is caused by bone mineral density (BMD) reduction. Haemophilia patients are at increased risk of osteoporosis because of decreased physical activity and blood-borne virus infections. This systematic review of the literature aims at evaluating BMD reduction in severe haemophilia patients and its correlation with patients' characteristics. Seven case-control studies evaluating lumbar BMD values [g/cm2] (all studies), BMI (5/7 studies), and hepatitis C virus (HCV) seropositivity (6/7 studies) in severe haemophilia patients and controls were meta-analysed. Standardised mean difference (SMD) of BMD was used to compare cases and controls. The effect of body mass index (BMI) and HCV infection was investigated by meta-regression. One hundred one adult cases (age 33 +/- 8.9) with 101 controls and 111 paediatric cases (age 8 +/- 3.6) with 307 controls were available for analysis. Lumbar BMD was significantly lower in severe haemophilia patients than in controls, both in adult (pooled SMD -1.379, 95% confidence interval [CI] -2.355 to -0.403, p=0.006) and children (pooled SMD -0.438, 95% CI -0.686 to -0.189, p=0.001). The reduction in BMD in patients versus controls was not significantly correlated with the reduction in BMI or with the percentage of HCV-infected patients. This meta-analysis confirms the association between severe haemophilia and low BMD. Future studies should investigate fracture rates and interventions to prevent bone loss in persons with haemophilia.