Troglitazone treatment increases bone marrow adipose tissue volume but does not affect trabecular bone volume in mice

Aging is associated with decreased trabecular bone mass and increased adipo cyte formation in bone marrow,. As osteoblasts and adipocytes share common precursor cells present in the bone marrow stroma, it has been proposed tha t an inverse relationship exists between adipocyte and osteoblast different iation. In order to test this hypothesis, we studied mice treated with trog litazone (n = 9) given as a 0.2% of food admixture (2.0 a troglitazone per kg food) for 10 months and control mice (n = 9). Troglitazone is a potent s timulator of adipogenesis acting at the nuclear receptor: peroxisome prolif erator activated receptor-gamma (PPAR gamma). Histomorphometric analysis of proximal tibia was performed in order to quantitate the amount of trabecul ar bone volume per total volume(BV/TV %), adipose tissue volume per total v olume (AV/TV %), and hematopoietic marrow volume per total volume (HV/TV %) using the point-counting technique. Bone size did not differ between the t wo groups. In troglitazone-treated mice, AV/TV was significantly higher tha n in control mice (4.7 +/- 2.1% vs. 0.2 +/- 0.3%, respectively, mean SD, P < 0.001). BV/TV was similar in the two groups (16.9 +/- 5.6% for troglitazo ne-treated group vs. 14.9 +/- 4.7%, for control group) as well as ash weigh t of the vertebrae. HV/TV was reduced in troglitazone-treated mice compared with control mice (78.4 +/- 6.8%, vs. 84.9 +/- 4.7%, respectively, P < 0.0 5) and the presence of vascular sinusoids was reduced (7.3 +/- 1.7% vs. 16. 1 5.6%, respectively, P < 0.05). Our data demonstrate that adipogenesis and osteogenesis can be regulated independently. Troglitazone-induced adipogen esis in the bone marrow may be caused by changes in the bone marrow vascula rity.