Long-term use of unfractioned heparin data has been associated with a 2.2-5% incidence of heparin-induced osteoporotic fracture, but for low-molecular-weight heparin (LMWH) data is scarce and there is lack of clarity of the risks of osteoporosis and osteoporotic fractures. In this paper we review the differential diagnosis of osteoporosis and osteoporotic fractures, and we conduct a systematic review of all related cases from case reports and trials. Two new cases of possible LMWH-induced osteoporosis are also presented and the difficulties in making the diagnosis are highlighted. The authors conclude that, until large clinical trials are designed to investigate pre- and post-treatment bone density and to compare different dosages of LMWH effect on the bone density in different patient groups, no safe conclusions can be made.