Loss of renal function perturbs bone metabolism because kidney is a vital organ maintaining homeostasis of calcium and phosphate. In hemodialysis patients, bone diseases are serious complications resulting in fractures and extraosseous calcification. The latest clinical practice guidelines by the National Kidney Foundation (New York, US) recommend a dialysate calcium concentration (D-Ca) of 2.5 mEq/L rather than 3.0 mEq/L to avoid excess calcium load and to prevent subsequent vascular calcification. However, there is no perfect agreement yet about which concentration should be chosen because lowering D-Ca might enhance uncoupled bone resorption. Here, we studied effects of lowering D-Ca from 3.0 to 2.5 mEq/L on bone metabolism in 67 patients. Doses of vitamin D and phosphate binders were kept constant for a 2-month period beginning 1 month before the change in D-Ca, and were adjusted thereafter. In group A [intact parathyroid hormone (iPTH) < 100 pg/ml before the study], serum cross-linked N-terminal telopeptide of type I collagen (NTx) increased immediately after lowering D-Ca and then remained stable. Intact osteocalcin (iOC) increased later along with iPTH, suggesting the improvement of adynamic bone disease which shows a marked decrease in bone turnover without osteoid accumulation. Vitamin D was not dosed up in this group. In group B (100 < or = iPTH < 300), serum NTx increased transiently, which is followed by an increase of iOC but not by a change of iPTH. In group C (300 < or = iPTH), lowering D-Ca allowed us to increase the dose of vitamin D without hypercalcemia, leading to a significant decrease in NTx and iPTH. Overall, serum phosphate increased from 5.4 +/- 1.6 to 6.1 +/- 1.6 mg/dL (P < 0.0001) and serum NTx increased by 1.5-fold (P < 0.0001) 1 month after lowering D-Ca. Over a 3-month period after that, serum phosphate and serum NTx decreased to their basal levels. These indicate that bone resorption predominated over formation for only a short period. In conclusion, a D-Ca of 2.5 mEq/L with adjustment of vitamin D ameliorates metabolic abnormalities of bone which develop under 3.0 mEq/L.