Oral diabetes drugs linked to lower levels of bone formation marker

Patients with type 2 diabetes had lower levels of a bone formation marker after treatment with metformin in a Danish clinical trial.

Procollagen type 1 N-terminal peptide (P1NP) plasma concentrations were lower in patients who received either metformin or metformin plus rosiglitazone, Tore Bjerregaard Stage, PhD, a specialist in clinical pharmacology and pharmacy at the University of Southern Denmark, Odense, and his coauthors wrote in Bone.

By contrast, insulin did not appear to influence markers of bone turnover.

Improving glycemic control was associated with increased plasma concentrations of C-terminal telopeptide of collagen (CTx), a marker of bone resorption. However, this finding might reflect “normalization, rather than an abnormal increase in bone resorption,” Dr. Stage and his colleagues wrote.

These findings come from an analysis of the South Danish Diabetes Study, a 2-year, multicenter, randomized, controlled trial including 371 patients with type 2 diabetes. Patients were first randomized to receive short- or long-acting human insulin, then further randomized to metformin plus rosiglitazone, metformin plus placebo, rosiglitazone plus placebo, or two placebos.

Bone turnover markers were assessed at baseline and at 3-, 12-, and 24-month follow-ups.

Dr. Stage and his coinvestigators hoped the analysis would provide insights into how antidiabetic medication might influence bone turnover, potentially helping explain the increased risk of fracture found in patients with type 2 diabetes. “Alterations in bone metabolism due to antidiabetic medication may influence bone metabolism both directly, e.g., by insulin promoting bone formation, and indirectly by improvement of glycemic control,” they wrote.

Overall, levels of both bone turnover markers increased over time in the study. However, investigators found that concentrations of the bone formation marker P1NP were 13% lower in patients randomized to metformin alone, and 21% lower in patients randomized to metformin and rosiglitazone; no such association was found between P1NP concentrations and treatment with rosiglitazone alone. By contrast, the type of oral antidiabetic drug treatment had no effect on concentrations of CTx concentrations, the investigators said.

Type of insulin treatment received in the trial did not appear to have an impact on concentrations of either bone turnover marker, they added.

HbA_1c had no influence on concentrations of P1NP; but it was inversely correlated with levels of CTx, a finding that the investigators said merits more study.

“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,” Dr. Stage and his coauthors wrote.

This study was funded with grants from the Danish Council for Independent Research and the Region of Southern Denmark. Dr. Stage and coauthors reported no conflicts of interest related to the report.

SOURCE: Stage TB et al. Bone. 2018 Apr 12;112:35-41.

Patients with type 2 diabetes had lower levels of a bone formation marker after treatment with metformin in a Danish clinical trial.

Procollagen type 1 N-terminal peptide (P1NP) plasma concentrations were lower in patients who received either metformin or metformin plus rosiglitazone, Tore Bjerregaard Stage, PhD, a specialist in clinical pharmacology and pharmacy at the University of Southern Denmark, Odense, and his coauthors wrote in Bone.

By contrast, insulin did not appear to influence markers of bone turnover.

Improving glycemic control was associated with increased plasma concentrations of C-terminal telopeptide of collagen (CTx), a marker of bone resorption. However, this finding might reflect “normalization, rather than an abnormal increase in bone resorption,” Dr. Stage and his colleagues wrote.

These findings come from an analysis of the South Danish Diabetes Study, a 2-year, multicenter, randomized, controlled trial including 371 patients with type 2 diabetes. Patients were first randomized to receive short- or long-acting human insulin, then further randomized to metformin plus rosiglitazone, metformin plus placebo, rosiglitazone plus placebo, or two placebos.

Bone turnover markers were assessed at baseline and at 3-, 12-, and 24-month follow-ups.

Dr. Stage and his coinvestigators hoped the analysis would provide insights into how antidiabetic medication might influence bone turnover, potentially helping explain the increased risk of fracture found in patients with type 2 diabetes. “Alterations in bone metabolism due to antidiabetic medication may influence bone metabolism both directly, e.g., by insulin promoting bone formation, and indirectly by improvement of glycemic control,” they wrote.

Overall, levels of both bone turnover markers increased over time in the study. However, investigators found that concentrations of the bone formation marker P1NP were 13% lower in patients randomized to metformin alone, and 21% lower in patients randomized to metformin and rosiglitazone; no such association was found between P1NP concentrations and treatment with rosiglitazone alone. By contrast, the type of oral antidiabetic drug treatment had no effect on concentrations of CTx concentrations, the investigators said.

Type of insulin treatment received in the trial did not appear to have an impact on concentrations of either bone turnover marker, they added.

HbA_1c had no influence on concentrations of P1NP; but it was inversely correlated with levels of CTx, a finding that the investigators said merits more study.

“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,” Dr. Stage and his coauthors wrote.

This study was funded with grants from the Danish Council for Independent Research and the Region of Southern Denmark. Dr. Stage and coauthors reported no conflicts of interest related to the report.

SOURCE: Stage TB et al. Bone. 2018 Apr 12;112:35-41.

Patients with type 2 diabetes had lower levels of a bone formation marker after treatment with metformin in a Danish clinical trial.

Procollagen type 1 N-terminal peptide (P1NP) plasma concentrations were lower in patients who received either metformin or metformin plus rosiglitazone, Tore Bjerregaard Stage, PhD, a specialist in clinical pharmacology and pharmacy at the University of Southern Denmark, Odense, and his coauthors wrote in Bone.

By contrast, insulin did not appear to influence markers of bone turnover.

Improving glycemic control was associated with increased plasma concentrations of C-terminal telopeptide of collagen (CTx), a marker of bone resorption. However, this finding might reflect “normalization, rather than an abnormal increase in bone resorption,” Dr. Stage and his colleagues wrote.

These findings come from an analysis of the South Danish Diabetes Study, a 2-year, multicenter, randomized, controlled trial including 371 patients with type 2 diabetes. Patients were first randomized to receive short- or long-acting human insulin, then further randomized to metformin plus rosiglitazone, metformin plus placebo, rosiglitazone plus placebo, or two placebos.

Bone turnover markers were assessed at baseline and at 3-, 12-, and 24-month follow-ups.

Dr. Stage and his coinvestigators hoped the analysis would provide insights into how antidiabetic medication might influence bone turnover, potentially helping explain the increased risk of fracture found in patients with type 2 diabetes. “Alterations in bone metabolism due to antidiabetic medication may influence bone metabolism both directly, e.g., by insulin promoting bone formation, and indirectly by improvement of glycemic control,” they wrote.

Overall, levels of both bone turnover markers increased over time in the study. However, investigators found that concentrations of the bone formation marker P1NP were 13% lower in patients randomized to metformin alone, and 21% lower in patients randomized to metformin and rosiglitazone; no such association was found between P1NP concentrations and treatment with rosiglitazone alone. By contrast, the type of oral antidiabetic drug treatment had no effect on concentrations of CTx concentrations, the investigators said.

Type of insulin treatment received in the trial did not appear to have an impact on concentrations of either bone turnover marker, they added.

HbA_1c had no influence on concentrations of P1NP; but it was inversely correlated with levels of CTx, a finding that the investigators said merits more study.

“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,” Dr. Stage and his coauthors wrote.

This study was funded with grants from the Danish Council for Independent Research and the Region of Southern Denmark. Dr. Stage and coauthors reported no conflicts of interest related to the report.

SOURCE: Stage TB et al. Bone. 2018 Apr 12;112:35-41.