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Osteoporosis has been recently recognized as a comorbidity factor, which affects significantly the quality of life in hemophilia patients. Prolonged immobilization and severity of arthropaphy have been considered as the major factors contributing to the pathogenesis of osteoporosis in hemophilia. However, the exact mechanisms of bone loss have not been fully clarified in this disorder. The aim of this study was to evaluate the incidence of osteoporosis in hemophilia patients, and investigate the possible correlations with clinical and laboratory data in an attempt to better understand the pathogenetic mechanisms that are involved in its development. Ninety-three hemophilia patients were evaluated. Their median age was 36 years (range: 24–46 years). Eighty patients (86%) had severe and 13 patients (13%) moderate haemophilia. Fifty-seven patients (61%) were HIV negative and 36 (38%) HIV positive. The severity of hemophilic arthropahty was assessed using WFH clinical score and Petterson radiological score in all patients. Bone mineral density of the lumbar spine(LS) and the femoral neck(FN) was measured using DEXA technique in 78 out of 93 patients. Bone turnover was studied by the measurement of a series of serum indices: bone resorption markers [N- and C-telopeptide of type-I collagen (NTX and CTX, respectively), and tartrate-resistant acid phosphatase isoform-5b (TRACP-5b)], bone formation markers [bone-alkaline phosphatase (bALP), and osteocalcin], and osteoclast stimulating factors [receptor activator of nuclear factor-kB ligand (RANKL), osteoprotegerin (OPG), and tumor necrosis factor-alpha]. Osteopenia(−2,5