title: Effects of pioglitazone on renal calcium excretion.
abstract: BACKGROUND
  Glitazones increase fracture risk in long-term users and in postmenopausal women. Studies have demonstrated deleterious effects of glitazones on bone metabolism. Glitazones also have direct renal tubular effects increasing sodium reabsorption. We hypothesized that glitazones may also regulate renal calcium excretion.
  
  
  METHODS
  In this double-blind, randomized, placebo-controlled, four-way, crossover study, we examined the effects of pioglitazone (45 mg/d for 6 wk) or placebo on renal calcium and phosphate excretion and PTH levels during different sodium intakes in 16 individuals (eight with type 2 diabetes and eight with essential hypertension).
  
  
  RESULTS
  Pioglitazone had no effect on corrected plasma calcium and phosphate levels but decreased significantly the alkaline phosphatase and PTH levels. Pioglitazone induced on average a 45% increase in urinary calcium excretion. The fractional excretion of calcium rose to the same extent, suggesting a glomerular filtration rate-independent effect. Sodium intake did not influence the calciuric effect of pioglitazone. Changes in diurnal and nocturnal calciuria were similar. There was no effect of pioglitazone on phosphate excretion.
  
  
  CONCLUSIONS
  Pioglitazone decreases PTH levels and increases urinary calcium excretion, independently from changes in glomerular filtration rate and from the sodium load, suggesting an inhibitory effect of pioglitazone on the tubular reabsorption of calcium. These effects may contribute to the increased fracture risk with glitazone treatment.
authors.affiliation: Service of Nephrology, Department of Medicine, Lausanne University Hospital, Centre Hospitalier Universitaire Vaudois, 1011 Lausanne, Switzerland. Anne.Zanchi@chuv.ch
authors.forename: Anne
authors.initials: A
authors.lastname: Zanchi
authors.forename: Antoinette
authors.initials: A
authors.lastname: Pechère-Bertschi
authors.forename: Michel
authors.initials: M
authors.lastname: Burnier
authors.forename: Olivier
authors.initials: O
authors.lastname: Bonny
mesh_terms: D002118:Calcium / Q000652:urine*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000097:blood; D010710:Phosphates / Q000652:urine; D000077205:Pioglitazone; D012982:Sodium, Dietary / Q000378:metabolism; D045162:Thiazolidinediones / Q000494:pharmacology*
chemical_list: D007004:Hypoglycemic Agents; D010281:Parathyroid Hormone; D010710:Phosphates; D012982:Sodium, Dietary; D045162:Thiazolidinediones; D002118:Calcium; D000077205:Pioglitazone