To explore the molecular mechanism(s) driving the osteopenia and the increase in osteoclast numbers and activity in middle-aged male Dmp1-PPRKO mice, we treated bone marrow mononuclear cells (BMMCs) isolated from wild type mice (3–4 months old) with serum obtained from 13-month-old male mice (Dmp1-PPRKO and littermate controls) and analyzed osteoclastogenesis by TRAP staining and activity. The gene discussed is TRAF2; the disease is Osteopenia.