In patients with hemophilia, osteoporosis is frequently observed for which the etiology remains unclear. The aim of this paper is to review the available experimental evidence indicating the presence of this disorder in patients with hemophilia, explore the potential mechanisms which may lead to reduced bone mineral density (BMD) and speculate on useful interventions to circumvent it. A narrative review of the English literature up to April 2018 was performed. The available evidence demonstrates an increased rate of bone resorption and an excess of osteoporosis among patients with hemophilia. FVIII and FIX may act through at least two pathways: promoting bone formation by a thrombin-mediated mitogenic effect on osteoblasts and by cytokine-mediated osteoclast activity. Another potential indirect mechanism mediated through the RANK-RANKL pathway has been suggested but remains controversial. The role of confounders such as lack of activity and immobility must be considered.