Investigation of factors associated with osteoporosis using metabolome analysis.

Osteoporosis is associated with low bone mineral density and poor bone quality in patients with type 2 diabetes mellitus (T2DM). Reports on the association between serum metabolome and osteoporosis in diabetes mellitus are rare. We aimed to identify osteoporosis-related factors in patients with T2DM. This prospective observational study included 67 patients with T2DM without osteoporosis and 24 patients with T2DM with osteoporosis who were treated with teriparatide. The association between the serum metabolome at baseline and changes in bone mineral density and the bone quality of the lumbar spine and proximal femur over 1 year was evaluated. In the teriparatide-treated group, bone mineral density, young adult mean values, and trabecular bone scores (T-scores) of the lumbar spine significantly increased 1 year after baseline compared with those at baseline. Improvements in these bone assessment indices were significantly higher in the teriparatide-treated group than in the non-treated group. Baseline alkaline phosphatase, bone-specific alkaline phosphatase, and malonic acid levels were significantly negatively correlated with bone mineral density, young adult mean values, and T-scores. Changes in bone mineral density, young adult mean values, and T-score 1 year after baseline were significantly positively correlated with baseline alkaline phosphatase, bone-specific alkaline phosphatase, oxalic acid, and aspartic acid levels in the teriparatide-treated group. Serum oxalic acid and malonic acid levels may be novel markers of osteoporosis. Teriparatide may be more effective in patients with higher baseline serum oxalic acid and aspartic acid levels than in those with lower levels.