Good Glycemic Control May Influence Bone Metabolism in Type 2 Diabetes

knee joint affected by Chondrocalcinosis
knee joint affected by Chondrocalcinosis
Researchers showed that improved glycemic control is associated with higher bone resorption, possibly reflecting normalization rather than an abnormal increase in bone resorption.

The type of insulin regimen does not appear to affect bone metabolism in patients with type 2 diabetes (TD2), but improvements in glycemic control might influence bone resorption activity, according to a study published in Bone.

Additional therapies were also evaluated, and the investigators found that metformin did not increase bone formation in patients with fairly well-controlled disease. The use of rosiglitazone was also not associated with increased bone resorption, which may be due to concurrent insulin treatment.

Fracture risk in T2D is associated with complex underlying pathophysiologic mechanisms that include factors such as hyperglycemia, insulinopenia, and antidiabetic drugs. This study evaluated the effect of different insulin regimens, metformin, and rosiglitazone on bone metabolism.

The cohort included 371 patients with T2D who were randomly assigned to receive short- or long-acting human insulin and then further randomly assigned to receive either metformin plus placebo, rosiglitazone plus placebo, metformin plus rosiglitazone, or placebo plus placebo (blinded). All participants were measured at baseline and after 3, 12, and 24 months for fasting bone turnover markers (BTM) representing bone resorption (CTX) and formation (PINP), including glycated hemoglobin (HbA1c).

The type of insulin regimen was not associated with BTM, although BTMs did increase from baseline to month 12 and remained higher at month 24. CTX and PINP also rose 28.5% and 23.0% (all: P <.001), respectively. In patients receiving metformin alone, PINP concentrations were 13% lower (CI 95%, 3%-22%) and patients randomly assigned to metformin and rosiglitazone had 21% (CI 95%, 12%-29%) reduced PINP concentrations. Treatment with rosiglitazone alone was not associated with lower bone formation, and neither metformin nor rosiglitazone plasma concentrations was associated with BTMs.

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The study results demonstrated that improved glycemic control was associated with higher bone resorption, “possibly portraying normalization rather than an abnormal increase in bone resorption,” the researchers concluded. “Further clinical trials investigating the effects of improved glycemic control on bone remodeling including other biochemical markers of bone turnover are needed to confirm if lowering of glucose levels solely changes bone resorption and not formation.”


Stage TB, Christensen MH, Jørgensen NR, et al. Effects of metformin, rosiglitazone and insulin on bone metabolism in patients with type 2 diabetes. Bone. 2018;112:35-41.