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Increased bone resorption in HD patients: is it caused by elevated RANKL synthesis?
Nephrol Dial Transplant. 2005 Mar; 20(3):566-70.ND

Abstract

BACKGROUND

The receptor activator of nuclear factor kappaB ligand (RANKL), produced by osteoblasts/stromal cells, is a member of the RANK/RANKL/OPG system, which regulates bone resorption by osteoclasts. Since RANKL and osteoprotegerin (OPG) production in bone is influenced by parathyroid hormone (PTH), we measured serum RANKL and OPG concentrations in haemodialysis (HD) patients, who commonly hypersecrete PTH. We aimed to determine if clinically demonstrated PTH-enhanced bone resorption is a consequence of increased RANKL synthesis.

METHODS

RANKL, OPG, osteocalcin, intact PTH, bone-specific alkaline phosphatase, tartrate-resistant acid phosphatase 5b and beta-CrossLaps (CTx) were measured in blood samples from 80 HD patients and 50 age-matched controls. HD patients were stratified to tertiles according to their serum PTH levels: 29.3-103.0, 109.7-263.0 and 262.0-1700.0 pg/ml in the first, second and third tertiles, respectively.

RESULTS

Mean serum RANKL levels were 1.6 times higher in HD patients than in age-matched controls (1.36+/-0.39 vs 0.83+/-0.70 pmol/l; P<0.001). All the measured bone markers significantly differed between patients and controls (P<0.001). Spearman's tests of correlation showed a statistically significant association of RANKL with PTH, osteocalcin and CTx (r=0.322, P=0.004; r=0.231, P=0.039; and r=0.230, P=0.040, respectively). Mean serum RANKL levels were significantly different between PTH tertiles (P = 0.003), but serum OPG levels were not (P=0.144). The highest RANKL levels were measured in the upper PTH tertile (1.54+/-0.39 pmol/l) and were significantly higher than in the middle or lower tertiles (1.27+/-0.42 and 1.23+/-0.26 pmol/l, respectively; P=0.003). Both of the measured bone-resorption markers, tartarate-resistant acid phosphatase 5b and CTx, as well as both bone formation markers, osteocalcin and bone-specific alkaline phosphatase were also significantly higher in the upper tertile, indicating that whole-bone remodelling is activated at high PTH and RANKL levels.

CONCLUSIONS

Serum RANKL levels were significantly higher in HD patients than in healthy age-matched controls. Moreover, RANKL levels were significantly higher in the upper PTH tertile, indicating enhanced RANKL synthesis in a PTH-dependent fashion. Thus, our clinical findings clearly support published in vitro studies that demonstrated a stimulating effect of PTH on RANKL synthesis. Therefore, the hypothesis that PTH increases bone resorption in HD patients through RANKL appears valid.

Authors+Show Affiliations

Department of Clinical Biochemistry, General Hospital Jesenice, Jesenice, Slovenia.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15665031

Citation

Avbersek-Luznik, Ivica, et al. "Increased Bone Resorption in HD Patients: Is It Caused By Elevated RANKL Synthesis?" Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association, vol. 20, no. 3, 2005, pp. 566-70.
Avbersek-Luznik I, Balon BP, Rus I, et al. Increased bone resorption in HD patients: is it caused by elevated RANKL synthesis? Nephrol Dial Transplant. 2005;20(3):566-70.
Avbersek-Luznik, I., Balon, B. P., Rus, I., & Marc, J. (2005). Increased bone resorption in HD patients: is it caused by elevated RANKL synthesis? Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association, 20(3), 566-70.
Avbersek-Luznik I, et al. Increased Bone Resorption in HD Patients: Is It Caused By Elevated RANKL Synthesis. Nephrol Dial Transplant. 2005;20(3):566-70. PubMed PMID: 15665031.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Increased bone resorption in HD patients: is it caused by elevated RANKL synthesis? AU - Avbersek-Luznik,Ivica, AU - Balon,Breda Pecovnik, AU - Rus,Igor, AU - Marc,Janja, Y1 - 2005/01/21/ PY - 2005/1/25/pubmed PY - 2005/5/17/medline PY - 2005/1/25/entrez SP - 566 EP - 70 JF - Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association JO - Nephrol Dial Transplant VL - 20 IS - 3 N2 - BACKGROUND: The receptor activator of nuclear factor kappaB ligand (RANKL), produced by osteoblasts/stromal cells, is a member of the RANK/RANKL/OPG system, which regulates bone resorption by osteoclasts. Since RANKL and osteoprotegerin (OPG) production in bone is influenced by parathyroid hormone (PTH), we measured serum RANKL and OPG concentrations in haemodialysis (HD) patients, who commonly hypersecrete PTH. We aimed to determine if clinically demonstrated PTH-enhanced bone resorption is a consequence of increased RANKL synthesis. METHODS: RANKL, OPG, osteocalcin, intact PTH, bone-specific alkaline phosphatase, tartrate-resistant acid phosphatase 5b and beta-CrossLaps (CTx) were measured in blood samples from 80 HD patients and 50 age-matched controls. HD patients were stratified to tertiles according to their serum PTH levels: 29.3-103.0, 109.7-263.0 and 262.0-1700.0 pg/ml in the first, second and third tertiles, respectively. RESULTS: Mean serum RANKL levels were 1.6 times higher in HD patients than in age-matched controls (1.36+/-0.39 vs 0.83+/-0.70 pmol/l; P<0.001). All the measured bone markers significantly differed between patients and controls (P<0.001). Spearman's tests of correlation showed a statistically significant association of RANKL with PTH, osteocalcin and CTx (r=0.322, P=0.004; r=0.231, P=0.039; and r=0.230, P=0.040, respectively). Mean serum RANKL levels were significantly different between PTH tertiles (P = 0.003), but serum OPG levels were not (P=0.144). The highest RANKL levels were measured in the upper PTH tertile (1.54+/-0.39 pmol/l) and were significantly higher than in the middle or lower tertiles (1.27+/-0.42 and 1.23+/-0.26 pmol/l, respectively; P=0.003). Both of the measured bone-resorption markers, tartarate-resistant acid phosphatase 5b and CTx, as well as both bone formation markers, osteocalcin and bone-specific alkaline phosphatase were also significantly higher in the upper tertile, indicating that whole-bone remodelling is activated at high PTH and RANKL levels. CONCLUSIONS: Serum RANKL levels were significantly higher in HD patients than in healthy age-matched controls. Moreover, RANKL levels were significantly higher in the upper PTH tertile, indicating enhanced RANKL synthesis in a PTH-dependent fashion. Thus, our clinical findings clearly support published in vitro studies that demonstrated a stimulating effect of PTH on RANKL synthesis. Therefore, the hypothesis that PTH increases bone resorption in HD patients through RANKL appears valid. SN - 0931-0509 UR - https://www.unboundmedicine.com/medline/citation/15665031/Increased_bone_resorption_in_HD_patients:_is_it_caused_by_elevated_RANKL_synthesis L2 - https://academic.oup.com/ndt/article-lookup/doi/10.1093/ndt/gfh672 DB - PRIME DP - Unbound Medicine ER -