Effects of calcitriol on type 5b tartrate-resistant acid phosphatase and interleukin-6 in secondary hyperparathyroidism.
OBJECTIVE
Secondary hyperparathyroidism (SHP) is characterized by high bone turnover and elevated serum bone remodeling markers. Elevation of serum interleukin-6 (IL-6) levels is also characteristic of end-stage renal disease. This study investigates the effects of intravenous calcitriol on serum bone resorptive markers, namely, type 5b tartrate-resistant acid phosphatase (TRACP5b) and IL-6 in patients with SHP.


METHODS
Intravenous calcitriol therapy was given for 16 weeks to 24 patients on maintenance hemodialysis with plasma intact parathyroid hormone (iPTH) levels >300 pg/ml. Blood was drawn at baseline and every 4 weeks for 16 weeks for determination of the levels of biochemical parameters, iPTH, IL-6 and bone remodeling markers, including bone-specific alkaline phosphatase (bAP) and TRACP5b.


RESULTS
Only 21 patients responded to the calcitriol therapy, with significant decrements in serum iPTH after 4 weeks of therapy and thereafter. After 16 weeks of calcitriol therapy, 21 patients had significant decrements in serum iPTH (707.9 +/- 317.8 vs. 205.0 +/- 63.1 pg/ml, p < 0.01). Prior to treatment, a significant correlation was found between increased levels of serum iPTH and IL-6 levels (r = 0.45, p < 0.05). After treatment, there was also a significant and parallel lowering of levels of serum iPTH, IL-6 (8.52 +/- 3.59 vs. 7.24 +/- 2.81 pg/ml, p < 0.01), bAP (54.68 +/- 36.17 vs. 24.55 +/- 13.84 U/l, p < 0.01) and TRACP5b (3.41 +/- 1.89 vs. 1.80 +/- 0.55 U/l, p < 0.01). Our results additionally showed significant positive correlationsbetween baseline levels of serum IL-6 and those of iPTH, bAP and TRACP5b. After 16 weeks of calcitriol treatment, the correlation between IL-6 and iPTH levels lost significance but levels of serum IL-6, bAP and TRACP5b remained significantly correlated.


CONCLUSIONS
Elevated levels of serum IL-6 and bone remodeling markers, namely, bAP and TRACP5b which are common features of SHP, are effectively suppressed by calcitriol therapy. This indicates that hyperparathyroidism not only accelerates bone remodeling but may also aggravate inflammation in patients on maintenance hemodialysis.
Lu
Kuo-Cheng
KC
Division of Nephrology, Department of Medicine, Cardinal Tien Hospital, School of Medicine, Fu-Jen Catholic University, Taipei, Taiwan.
Tseng
Chin-Feng
CF
Wu
Chia-Chao
CC
Yeung
Lai-King
LK
Chen
Jin-Shuen
JS
Chao
Tsu-Yi
TY
Janckila
Anthony J
AJ
Yam
Lung T
LT
Chu
Pauling
P
D000135:Acid Phosphatase / Q000097:blood*; D000368:Aged; D015415:Biomarkers / Q000097:blood; D050071:Bone Density Conservation Agents / Q000008:administration & dosage*; D001862:Bone Resorption / Q000097:blood*; D002117:Calcitriol / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000097:blood / Q000628:therapy*; D007249:Inflammation / Q000097:blood / Q000628:therapy; D015850:Interleukin-6 / Q000097:blood*; D007527:Isoenzymes / Q000097:blood*; D008297:Male; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000097:blood; D006435:Renal Dialysis; D000071681:Tartrate-Resistant Acid Phosphatase; D013997:Time Factors
D015415:Biomarkers; D050071:Bone Density Conservation Agents; D015850:Interleukin-6; D007527:Isoenzymes; D010281:Parathyroid Hormone; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase; D002117:Calcitriol