Platelets modulate formation of osteoclasts and osteoblasts, but research with different preparations of platelets remains inconclusive. Here, we assessed whether serum compon- ents modulate the effect of platelet preparations. In murine bone marrow cultures, osteo- clastogenesis was investigated in the presence of platelet-released supernatant (PRS), serum containing PRS (SC-PRS), and serum. Osteoclastogenesis was quantified by the num- bers of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells, TRAP activity and resorption assays. Viability and proliferation were tested by MTT and 3[H]thymidine incorporation assays, respectively. We found PRS to increase the number of TRAP+ multinucleated cells in the early phase and TRAP activity in the later phase of osteoclastogenesis. SC-PRS and serum decreased the number and activity of TRAP+ multinucleated cells. Both serum containing preparations reduced viability and proliferation of hematopo- ietic progenitors. These results show that activated platelets support osteoclastogenesis, while platelet preparations that contain serum components decrease osteoclastogenesis in vitro, suggesting that serum components modulate the effects of platelets on osteoclastogenesis.