Rosiglitazone decreases serum bone-specific alkaline phosphatase activity in postmenopausal diabetic women

J Clin Endocrinol Metab. 2007 Sep;92(9):3523-30. doi: 10.1210/jc.2007-0431. Epub 2007 Jun 26.


Objectives: Our objectives were to evaluate the effect of rosiglitazone on bone metabolism and to assess the association between changes in bone turnover parameters and plasma cytokine levels in postmenopausal diabetic women.

Design: This was a 12-wk open-label randomized-controlled trial.

Patients or other participants: A total of 56 obese postmenopausal women with newly diagnosed diabetes and 26 nondiabetic healthy controls matched for age and body mass index were included in the study.

Interventions: The subjects were instructed to follow a weight-maintenance diet. Half were randomly assigned to receive rosiglitazone 4 mg/d, and the other half remained on diet alone.

Main outcome measures: Before and after the interventions, metabolic bone markers and serum cytokine levels were assessed.

Results: Serum total alkaline phosphatase (ALP) and bone-specific ALP levels were statistically significantly lower 12 wk after initiation of rosiglitazone treatment. There were no statistically significant changes in osteocalcin levels among the three groups or in deoxypyridinoline levels in the rosiglitazone group. At the end of 12 wk, all patients had statistically significantly decreased IL-1beta and TNF-alpha levels compared with baseline. Changes in bone-specific ALP levels showed a moderate negative correlation with the changes in the TNF-alpha levels after rosiglitazone treatment and after diet in the diabetic control group.

Conclusions: Rosiglitazone use is associated with reduced bone formation at earlier stages in postmenopausal diabetic women. The cytokine-lowering effects of rosiglitazone and lifestyle changes could reverse the early inhibitory effect of rosiglitazone therapy on bone formation. Further studies will clarify the long-term effects of rosiglitazone therapy on bone loss and fracture.

Trial registration: NCT00440375.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Alkaline Phosphatase / blood*
  • Alkaline Phosphatase / metabolism
  • Body Composition / drug effects
  • Body Mass Index
  • Bone Remodeling / drug effects
  • Bone and Bones / drug effects
  • Bone and Bones / enzymology*
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Female
  • Haptoglobins / analysis
  • Humans
  • Hypoglycemic Agents / pharmacology
  • Hypoglycemic Agents / therapeutic use
  • Interleukin-1beta / blood
  • Interleukin-6 / blood
  • Middle Aged
  • Postmenopause / blood
  • Postmenopause / drug effects*
  • Rosiglitazone
  • Thiazolidinediones / pharmacology*
  • Thiazolidinediones / therapeutic use*
  • Tumor Necrosis Factor-alpha / blood


  • HP protein, human
  • Haptoglobins
  • Hypoglycemic Agents
  • Interleukin-1beta
  • Interleukin-6
  • Thiazolidinediones
  • Tumor Necrosis Factor-alpha
  • Rosiglitazone
  • Alkaline Phosphatase

Associated data