Homocysteine (Hcy) and C-reactive protein (CRP) are novel risk factors for osteoporosis. The purpose of this analysis was to determine the relationship of Hcy and CRP to volumetric trabecular bone, but also to assess their relationship to areal composite bone in healthy postmenopausal women (N=184). We used peripheral quantitative computed tomography to assess volumetric bone at the distal tibia and dual-energy X-ray absorptiometry to assess areal composite bone at the proximal femur and lumbar spine. Multiple regression revealed that 22% of the variability in trabecular bone mineral content (F=9.59, p<or=0.0001) was accounted for by weight (12.4%; p<or=0.0001), hemoglobin (5.5%; p=0.0006), uric acid (4.2%; p=0.003), and blood glucose (1.5%; p=0.07). Multiple regression revealed that 5.4% of the variability in trabecular bone mineral density (F=3.36; p=0.020) was accounted for by hemoglobin (4.2%; p=0.006) and Hcy (1.5%; not significant, p=0.10). Total Hcy and CRP were not significantly related to trabecular bone, perhaps because these were nonosteoporotic women. However, our results suggested a weak but negative relationship between Hcy and trabecular bone. Further investigation is needed to examine the relationship of Hcy as an endogenous bioactive molecule to trabecular bone loss in early postmenopausal women and the response of trabecular bone to dietary intervention.