Skip to main content

Tipp

Weitere Artikel dieser Ausgabe durch Wischen aufrufen

Erschienen in: Journal für Mineralstoffwechsel & Muskuloskelettale Erkrankungen 3/2021

11.08.2021 | Originalien

Anti-Sklerostin-Therapie aus nephrologischer Sicht – mit einem Fokus auf kardiovaskuläre Sicherheit

verfasst von: Prim. PD Dr. Daniel Cejka

Erschienen in: Journal für Mineralstoffwechsel & Muskuloskelettale Erkrankungen | Ausgabe 3/2021

Einloggen, um Zugang zu erhalten

Zusammenfassung

Die Zusammenhänge zwischen Sklerostin und Knochendichte, Gefäßverkalkung, kardiovaskulärer Morbidität und Mortalität bei chronischer Niereninsuffizienz („chronic kidney disease“, CKD) sind komplex und unvollständig verstanden. Es gibt experimentelle Hinweise, dass eine Anti-Sklerostin-Therapie bei CKD eine verminderte Wirkung auf den Knochen hat. Da Sklerostin auch sehr prominent in urämischen Gefäßen exprimiert wird, sind die möglichen kardiovaskulären Folgen einer Sklerostin-Hemmung bei CKD unklar. Der vorliegende Review gibt einen Überblick über die Physiologie und Pathophysiologie von Sklerostin in Knochen und Gefäßen bei CKD, den aktuellen Kenntnisstand zur Wirksamkeit und kardiovaskulären Sicherheit der Hemmung von Sklerostin bei Nierengesunden und CKD sowie die daraus resultierenden therapeutischen Implikationen.
Literatur
1.
Zurück zum Zitat Moe S, Drueke T, Cunningham J et al (2006) Definition, evaluation, and classification of renal osteodystrophy: a position statement from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int 69:1945–1953 PubMedCrossRef Moe S, Drueke T, Cunningham J et al (2006) Definition, evaluation, and classification of renal osteodystrophy: a position statement from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int 69:1945–1953 PubMedCrossRef
2.
Zurück zum Zitat Sprague SM, Bellorin-Font E, Jorgetti V et al (2016) Diagnostic accuracy of bone turnover markers and bone histology in patients with CKD treated by dialysis. Am J Kidney Dis 67(4):559–566 PubMedCrossRef Sprague SM, Bellorin-Font E, Jorgetti V et al (2016) Diagnostic accuracy of bone turnover markers and bone histology in patients with CKD treated by dialysis. Am J Kidney Dis 67(4):559–566 PubMedCrossRef
3.
Zurück zum Zitat Maré A, Verhulst A, Cavalier E et al (2019) Clinical inference of serum and bone sclerostin levels in patients with end-stage kidney disease. J Clin Med 8(12):2027 PubMedCentralCrossRef Maré A, Verhulst A, Cavalier E et al (2019) Clinical inference of serum and bone sclerostin levels in patients with end-stage kidney disease. J Clin Med 8(12):2027 PubMedCentralCrossRef
4.
Zurück zum Zitat Mause SF, Deck A, Hennies M et al (2016) Validation of commercially available ELISAs for the detection of circulating sclerostin in hemodialysis patients. Discoveries (Craiova) 4:e55 CrossRef Mause SF, Deck A, Hennies M et al (2016) Validation of commercially available ELISAs for the detection of circulating sclerostin in hemodialysis patients. Discoveries (Craiova) 4:e55 CrossRef
5.
Zurück zum Zitat Moyses RM, Jamal SA, Graciolli FG et al (2015) Can we compare serum sclerostin results obtained with different assays in hemodialysis patients? Int Urol Nephrol 47:847–850 PubMedCrossRef Moyses RM, Jamal SA, Graciolli FG et al (2015) Can we compare serum sclerostin results obtained with different assays in hemodialysis patients? Int Urol Nephrol 47:847–850 PubMedCrossRef
6.
7.
Zurück zum Zitat de Oliveira RA, Barreto FC, Mendes M et al (2015) Peritoneal dialysis per se is a risk factor for sclerostin-associated adynamic bone disease. Kidney Int 87:1039–1045 PubMedCrossRef de Oliveira RA, Barreto FC, Mendes M et al (2015) Peritoneal dialysis per se is a risk factor for sclerostin-associated adynamic bone disease. Kidney Int 87:1039–1045 PubMedCrossRef
8.
Zurück zum Zitat Boltenstal H, Qureshi AR, Behets GJ et al (2019) Association of serum sclerostin with bone sclerostin in chronic kidney disease is lost in glucocorticoid treated patients. Calcif Tissue Int 104:214–223 PubMedCrossRef Boltenstal H, Qureshi AR, Behets GJ et al (2019) Association of serum sclerostin with bone sclerostin in chronic kidney disease is lost in glucocorticoid treated patients. Calcif Tissue Int 104:214–223 PubMedCrossRef
9.
Zurück zum Zitat Pelletier S, Dubourg L, Carlier MC, Hadj-Aissa A, Fouque D (2013) The relation between renal function and serum sclerostin in adult patients with CKD. Clin J Am Soc Nephrol 8(5):819–823 PubMedPubMedCentralCrossRef Pelletier S, Dubourg L, Carlier MC, Hadj-Aissa A, Fouque D (2013) The relation between renal function and serum sclerostin in adult patients with CKD. Clin J Am Soc Nephrol 8(5):819–823 PubMedPubMedCentralCrossRef
10.
Zurück zum Zitat Cejka D, Jäger-Lansky A, Kieweg H et al (2012) Sclerostin serum levels correlate positively with bone mineral density and microarchitecture in haemodialysis patients. Nephrol Dial Transplant 27(1):226–230 PubMedCrossRef Cejka D, Jäger-Lansky A, Kieweg H et al (2012) Sclerostin serum levels correlate positively with bone mineral density and microarchitecture in haemodialysis patients. Nephrol Dial Transplant 27(1):226–230 PubMedCrossRef
11.
Zurück zum Zitat Lima F, Mawad H, El-Husseini AA et al (2019) Serum bone markers in ROD patients across the spectrum of decreases in GFR: activin A increases before all other markers. Clin Nephrol 91:222–230 PubMedPubMedCentralCrossRef Lima F, Mawad H, El-Husseini AA et al (2019) Serum bone markers in ROD patients across the spectrum of decreases in GFR: activin A increases before all other markers. Clin Nephrol 91:222–230 PubMedPubMedCentralCrossRef
12.
Zurück zum Zitat Cejka D, Marculescu R, Kozakowski N et al (2014) Renal elimination of sclerostin increases with declining kidney function. J Clin Endocrinol Metab 99(1):248–255 PubMedCrossRef Cejka D, Marculescu R, Kozakowski N et al (2014) Renal elimination of sclerostin increases with declining kidney function. J Clin Endocrinol Metab 99(1):248–255 PubMedCrossRef
13.
Zurück zum Zitat Graciolli FG, Neves KR, Barreto F et al (2017) The complexity of chronic kidney disease-mineral and bone disorder across stages of chronic kidney disease. Kidney Int 91:1436–1446 PubMedCrossRef Graciolli FG, Neves KR, Barreto F et al (2017) The complexity of chronic kidney disease-mineral and bone disorder across stages of chronic kidney disease. Kidney Int 91:1436–1446 PubMedCrossRef
14.
Zurück zum Zitat Sabbagh Y, Graciolli FG, O’Brien S et al (2012) Repression of osteocyte Wnt/beta-catenin signaling is an early event in the progression of renal osteodystrophy. J Bone Miner Res 27:1757–1772 PubMedCrossRef Sabbagh Y, Graciolli FG, O’Brien S et al (2012) Repression of osteocyte Wnt/beta-catenin signaling is an early event in the progression of renal osteodystrophy. J Bone Miner Res 27:1757–1772 PubMedCrossRef
15.
Zurück zum Zitat Araújo MJCLN, Bacelar Marques ID, Graciolli FG et al (2019) Comparison of serum levels with bone content and gene expression indicate a contradictory effect of kidney transplantation on sclerostin. Kidney Int 96:1100–1104 PubMedCrossRef Araújo MJCLN, Bacelar Marques ID, Graciolli FG et al (2019) Comparison of serum levels with bone content and gene expression indicate a contradictory effect of kidney transplantation on sclerostin. Kidney Int 96:1100–1104 PubMedCrossRef
16.
Zurück zum Zitat Nordholm A, Mace ML, Gravesen E et al (2018) Klotho and activin A in kidney injury: plasma Klotho is maintained in unilateral obstruction despite no upregulation of Klotho biosynthesis in the contralateral kidney. Am J Physiol Renal Physiol 314:F753–F762 PubMedCrossRef Nordholm A, Mace ML, Gravesen E et al (2018) Klotho and activin A in kidney injury: plasma Klotho is maintained in unilateral obstruction despite no upregulation of Klotho biosynthesis in the contralateral kidney. Am J Physiol Renal Physiol 314:F753–F762 PubMedCrossRef
18.
Zurück zum Zitat Moustafa A, Sugiyama T, Prasad J et al (2012) Mechanical loading-related changes in osteocyte sclerostin expression in mice are more closely associated with the subsequent osteogenic response than the peak strains engendered. Osteoporos Int 23:1225–1234 PubMedCrossRef Moustafa A, Sugiyama T, Prasad J et al (2012) Mechanical loading-related changes in osteocyte sclerostin expression in mice are more closely associated with the subsequent osteogenic response than the peak strains engendered. Osteoporos Int 23:1225–1234 PubMedCrossRef
19.
Zurück zum Zitat Gaudio A, Pennisi P, Bratengeier C et al (2010) Increased sclerostin serum levels associated with bone formation and resorption markers in patients with immobilization-induced bone loss. J Clin Endocrinol Metab 95:2248–2253 PubMedCrossRef Gaudio A, Pennisi P, Bratengeier C et al (2010) Increased sclerostin serum levels associated with bone formation and resorption markers in patients with immobilization-induced bone loss. J Clin Endocrinol Metab 95:2248–2253 PubMedCrossRef
20.
Zurück zum Zitat Zhu D, Mackenzie NC, Millan JL et al (2011) The appearance and modulation of osteocyte marker expression during calcification of vascular smooth muscle cells. PLoS ONE 6:e19595 PubMedPubMedCentralCrossRef Zhu D, Mackenzie NC, Millan JL et al (2011) The appearance and modulation of osteocyte marker expression during calcification of vascular smooth muscle cells. PLoS ONE 6:e19595 PubMedPubMedCentralCrossRef
21.
Zurück zum Zitat Bisson SK, Ung RV, Picard S et al (2019) High calcium, phosphate and calcitriol supplementation leads to an osteocyte-like phenotype in calcified vessels and bone mineralisation defect in uremic rats. J Bone Miner Metab 37:212–223 PubMedCrossRef Bisson SK, Ung RV, Picard S et al (2019) High calcium, phosphate and calcitriol supplementation leads to an osteocyte-like phenotype in calcified vessels and bone mineralisation defect in uremic rats. J Bone Miner Metab 37:212–223 PubMedCrossRef
22.
Zurück zum Zitat Rukov JL, Gravesen E, Mace ML et al (2016) Effect of chronic uremia on the transcriptional profile of the calcified aorta analyzed by RNA sequencing. Am J Physiol Renal Physiol 310:F477–F491 PubMedPubMedCentralCrossRef Rukov JL, Gravesen E, Mace ML et al (2016) Effect of chronic uremia on the transcriptional profile of the calcified aorta analyzed by RNA sequencing. Am J Physiol Renal Physiol 310:F477–F491 PubMedPubMedCentralCrossRef
23.
Zurück zum Zitat Zhou H, Yang M, Li M et al (2017) Radial artery sclerostin expression in chronic kidney disease stage 5 predialysis patients: a cross-sectional observational study. Int Urol Nephrol 49:1433–1437 PubMedCrossRef Zhou H, Yang M, Li M et al (2017) Radial artery sclerostin expression in chronic kidney disease stage 5 predialysis patients: a cross-sectional observational study. Int Urol Nephrol 49:1433–1437 PubMedCrossRef
24.
Zurück zum Zitat Li M, Zhou H, Yang M et al (2019) Relationship between serum sclerostin, vascular sclerostin expression and vascular calcification assessed by different methods in ESRD patients eligible for renal transplantation: a cross-sectional study. Int Urol Nephrol 51:311–323 PubMedCrossRef Li M, Zhou H, Yang M et al (2019) Relationship between serum sclerostin, vascular sclerostin expression and vascular calcification assessed by different methods in ESRD patients eligible for renal transplantation: a cross-sectional study. Int Urol Nephrol 51:311–323 PubMedCrossRef
25.
Zurück zum Zitat Qureshi AR, Olauson H, Witasp A et al (2015) Increased circulating sclerostin levels in end-stage renal disease predict biopsy-verified vascular medial calcification and coronary artery calcification. Kidney Int 88:1356–1364 PubMedCrossRef Qureshi AR, Olauson H, Witasp A et al (2015) Increased circulating sclerostin levels in end-stage renal disease predict biopsy-verified vascular medial calcification and coronary artery calcification. Kidney Int 88:1356–1364 PubMedCrossRef
26.
Zurück zum Zitat Brandenburg VM, Verhulst A, Babler A et al (2019) Sclerostin in chronic kidney disease-mineral bone disorder think first before you block it! Nephrol Dial Transplant 34:408–414 PubMedCrossRef Brandenburg VM, Verhulst A, Babler A et al (2019) Sclerostin in chronic kidney disease-mineral bone disorder think first before you block it! Nephrol Dial Transplant 34:408–414 PubMedCrossRef
27.
Zurück zum Zitat Mace ML, Gravesen E, Nordholm A et al (2021) Chronic kidney disease-induced vascular calcification impairs bone metabolism. J Bone Miner Res 36:510–522 PubMedCrossRef Mace ML, Gravesen E, Nordholm A et al (2021) Chronic kidney disease-induced vascular calcification impairs bone metabolism. J Bone Miner Res 36:510–522 PubMedCrossRef
28.
Zurück zum Zitat Brunkow ME, Gardner JC, Van NJ et al (2001) Bone dysplasia sclerosteosis results from loss of the SOST gene product, a novel cystine knot-containing protein. Am J Hum Genet 68:577–589 PubMedPubMedCentralCrossRef Brunkow ME, Gardner JC, Van NJ et al (2001) Bone dysplasia sclerosteosis results from loss of the SOST gene product, a novel cystine knot-containing protein. Am J Hum Genet 68:577–589 PubMedPubMedCentralCrossRef
29.
Zurück zum Zitat Balemans W, Ebeling M, Patel N et al (2001) Increased bone density in sclerosteosis is due to the deficiency of a novel secreted protein (SOST). Hum Mol Genet 10:537–543 PubMedCrossRef Balemans W, Ebeling M, Patel N et al (2001) Increased bone density in sclerosteosis is due to the deficiency of a novel secreted protein (SOST). Hum Mol Genet 10:537–543 PubMedCrossRef
30.
Zurück zum Zitat Balemans W, Patel N, Ebeling M et al (2002) Identification of a 52 kb deletion downstream of the SOST gene in patients with van Buchem disease. J Med Genet 39:91–97 PubMedPubMedCentralCrossRef Balemans W, Patel N, Ebeling M et al (2002) Identification of a 52 kb deletion downstream of the SOST gene in patients with van Buchem disease. J Med Genet 39:91–97 PubMedPubMedCentralCrossRef
31.
Zurück zum Zitat Hamersma H, Gardner J, Beighton P (2003) The natural history of sclerosteosis. Clin Genet 63:192–197 PubMedCrossRef Hamersma H, Gardner J, Beighton P (2003) The natural history of sclerosteosis. Clin Genet 63:192–197 PubMedCrossRef
32.
Zurück zum Zitat Li X, Ominsky MS, Warmington KS et al (2009) Sclerostin antibody treatment increases bone formation, bone mass, and bone strength in a rat model of postmenopausal osteoporosis. J Bone Miner Res 24:578–588 PubMedCrossRef Li X, Ominsky MS, Warmington KS et al (2009) Sclerostin antibody treatment increases bone formation, bone mass, and bone strength in a rat model of postmenopausal osteoporosis. J Bone Miner Res 24:578–588 PubMedCrossRef
33.
Zurück zum Zitat Ominsky MS, Vlasseros F, Jolette J et al (2010) Two doses of sclerostin antibody in cynomolgus monkeys increases bone formation, bone mineral density, and bone strength. J Bone Miner Res 25:948–959 PubMedCrossRef Ominsky MS, Vlasseros F, Jolette J et al (2010) Two doses of sclerostin antibody in cynomolgus monkeys increases bone formation, bone mineral density, and bone strength. J Bone Miner Res 25:948–959 PubMedCrossRef
34.
Zurück zum Zitat Li X, Ominsky MS, Niu QT et al (2008) Targeted deletion of the sclerostin gene in mice results in increased bone formation and bone strength. J Bone Miner Res 23:860–869 PubMedCrossRef Li X, Ominsky MS, Niu QT et al (2008) Targeted deletion of the sclerostin gene in mice results in increased bone formation and bone strength. J Bone Miner Res 23:860–869 PubMedCrossRef
35.
Zurück zum Zitat Turk JR, Deaton AM, Yin J et al (2020) Nonclinical cardiovascular safety evaluation of romosozumab, an inhibitor of sclerostin for the treatment of osteoporosis in postmenopausal women at high risk of fracture. Regul Toxicol Pharmacol 115:104697 PubMedCrossRef Turk JR, Deaton AM, Yin J et al (2020) Nonclinical cardiovascular safety evaluation of romosozumab, an inhibitor of sclerostin for the treatment of osteoporosis in postmenopausal women at high risk of fracture. Regul Toxicol Pharmacol 115:104697 PubMedCrossRef
36.
Zurück zum Zitat Kaesler N, Verhulst A, De Mare A et al (2018) Sclerostin deficiency modifies the development of CKD-MBD in mice. Bone 107:115–123 PubMedCrossRef Kaesler N, Verhulst A, De Mare A et al (2018) Sclerostin deficiency modifies the development of CKD-MBD in mice. Bone 107:115–123 PubMedCrossRef
37.
Zurück zum Zitat Bovijn J, Krebs K, Chen CY et al (2020) Evaluating the cardiovascular safety of sclerostin inhibition using evidence from meta-analysis of clinical trials and human genetics. Sci Transl Med 12(549):eaay6570 PubMedPubMedCentralCrossRef Bovijn J, Krebs K, Chen CY et al (2020) Evaluating the cardiovascular safety of sclerostin inhibition using evidence from meta-analysis of clinical trials and human genetics. Sci Transl Med 12(549):eaay6570 PubMedPubMedCentralCrossRef
39.
Zurück zum Zitat Desjardins L, Liabeuf S, Oliveira RB et al (2014) Uremic toxicity and sclerostin in chronic kidney disease patients. Nephrol Ther 10:463–470 PubMedCrossRef Desjardins L, Liabeuf S, Oliveira RB et al (2014) Uremic toxicity and sclerostin in chronic kidney disease patients. Nephrol Ther 10:463–470 PubMedCrossRef
40.
Zurück zum Zitat Hsu BG, Liou HH, Lee CJ et al (2016) Serum sclerostin as an independent marker of peripheral arterial stiffness in renal transplantation recipients: a cross-sectional study. Medicine 95:e3300 PubMedPubMedCentralCrossRef Hsu BG, Liou HH, Lee CJ et al (2016) Serum sclerostin as an independent marker of peripheral arterial stiffness in renal transplantation recipients: a cross-sectional study. Medicine 95:e3300 PubMedPubMedCentralCrossRef
41.
Zurück zum Zitat Jin S, Zhu M, Yan J et al (2016) Serum sclerostin level might be a potential biomarker for arterial stiffness in prevalent hemodialysis patients. Biomark Med 10:689–699 PubMedCrossRef Jin S, Zhu M, Yan J et al (2016) Serum sclerostin level might be a potential biomarker for arterial stiffness in prevalent hemodialysis patients. Biomark Med 10:689–699 PubMedCrossRef
42.
Zurück zum Zitat Stavrinou E, Sarafidis PA, Koumaras C et al (2019) Increased sclerostin, but not Dickkopf‑1 protein, is associated with elevated pulse wave velocity in hemodialysis subjects. Kidney Blood Press Res 44:679–689 PubMedCrossRef Stavrinou E, Sarafidis PA, Koumaras C et al (2019) Increased sclerostin, but not Dickkopf‑1 protein, is associated with elevated pulse wave velocity in hemodialysis subjects. Kidney Blood Press Res 44:679–689 PubMedCrossRef
43.
Zurück zum Zitat Wu CF, Hou JS, Wang CH et al (2020) Serum sclerostin but not DKK‑1 correlated with central arterial stiffness in end stage renal disease patients. Int J Environ Res Public Health 17(4):1230 PubMedCentralCrossRef Wu CF, Hou JS, Wang CH et al (2020) Serum sclerostin but not DKK‑1 correlated with central arterial stiffness in end stage renal disease patients. Int J Environ Res Public Health 17(4):1230 PubMedCentralCrossRef
44.
Zurück zum Zitat Kundakci Gelir G, Sengul S, Nergizoglu G et al (2018) Is sclerostin level associated with cardiovascular diseases in hemodialysis patients? Blood Purif 46:118–125 PubMedCrossRef Kundakci Gelir G, Sengul S, Nergizoglu G et al (2018) Is sclerostin level associated with cardiovascular diseases in hemodialysis patients? Blood Purif 46:118–125 PubMedCrossRef
45.
Zurück zum Zitat Petrovic M, Baralic M, Brkovic V et al (2020) Significance of acPWV for survival of hemodialysis patients. Medicina (Kaunas) 56(9):435 CrossRef Petrovic M, Baralic M, Brkovic V et al (2020) Significance of acPWV for survival of hemodialysis patients. Medicina (Kaunas) 56(9):435 CrossRef
46.
Zurück zum Zitat Thambiah S, Roplekar R, Manghat P et al (2012) Circulating sclerostin and Dickkopf‑1 (DKK1) in predialysis chronic kidney disease (CKD): relationship with bone density and arterial stiffness. Calcif Tissue Int 90:473–480 PubMedCrossRef Thambiah S, Roplekar R, Manghat P et al (2012) Circulating sclerostin and Dickkopf‑1 (DKK1) in predialysis chronic kidney disease (CKD): relationship with bone density and arterial stiffness. Calcif Tissue Int 90:473–480 PubMedCrossRef
47.
Zurück zum Zitat Viaene L, Behets GJ, Claes K et al (2013) Sclerostin: another bone-related protein related to all-cause mortality in haemodialysis? Nephrol Dial Transplant 28(12):3024–3030 PubMedCrossRef Viaene L, Behets GJ, Claes K et al (2013) Sclerostin: another bone-related protein related to all-cause mortality in haemodialysis? Nephrol Dial Transplant 28(12):3024–3030 PubMedCrossRef
48.
Zurück zum Zitat Kanbay M, Siriopol D, Saglam M et al (2014) Serum sclerostin and adverse outcomes in nondialyzed chronic kidney disease patients. J Clin Endocrinol Metab 99:E1854–E1861 PubMedCrossRef Kanbay M, Siriopol D, Saglam M et al (2014) Serum sclerostin and adverse outcomes in nondialyzed chronic kidney disease patients. J Clin Endocrinol Metab 99:E1854–E1861 PubMedCrossRef
49.
Zurück zum Zitat Drechsler C, Evenepoel P, Vervloet MG et al (2015) High levels of circulating sclerostin are associated with better cardiovascular survival in incident dialysis patients: results from the NECOSAD study. Nephrol Dial Transplant 30:288–293 PubMedCrossRef Drechsler C, Evenepoel P, Vervloet MG et al (2015) High levels of circulating sclerostin are associated with better cardiovascular survival in incident dialysis patients: results from the NECOSAD study. Nephrol Dial Transplant 30:288–293 PubMedCrossRef
50.
Zurück zum Zitat Jean G, Chazot C, Bresson E et al (2016) High serum sclerostin levels are associated with a better outcome in haemodialysis patients. Nephron 132:181–190 PubMedCrossRef Jean G, Chazot C, Bresson E et al (2016) High serum sclerostin levels are associated with a better outcome in haemodialysis patients. Nephron 132:181–190 PubMedCrossRef
51.
Zurück zum Zitat Lips L, de Roij van Zuijdewijn CLM, Ter Wee PM et al (2017) Serum sclerostin: relation with mortality and impact of hemodiafiltration. Nephrol Dial Transplant 32:1217–1223 PubMed Lips L, de Roij van Zuijdewijn CLM, Ter Wee PM et al (2017) Serum sclerostin: relation with mortality and impact of hemodiafiltration. Nephrol Dial Transplant 32:1217–1223 PubMed
52.
Zurück zum Zitat Chen A, Sun Y, Cui J et al (2018) Associations of sclerostin with carotid artery atherosclerosis and all-cause mortality in Chinese patients undergoing maintenance hemodialysis. BMC Nephrol 19:264 PubMedPubMedCentralCrossRef Chen A, Sun Y, Cui J et al (2018) Associations of sclerostin with carotid artery atherosclerosis and all-cause mortality in Chinese patients undergoing maintenance hemodialysis. BMC Nephrol 19:264 PubMedPubMedCentralCrossRef
53.
Zurück zum Zitat Kalousová M, Dusilová-Sulková S, Kuběna AA et al (2019) Sclerostin levels predict cardiovascular mortality in long-term hemodialysis patients: a prospective observational cohort study. Physiol Res 68:547–558 PubMedCrossRef Kalousová M, Dusilová-Sulková S, Kuběna AA et al (2019) Sclerostin levels predict cardiovascular mortality in long-term hemodialysis patients: a prospective observational cohort study. Physiol Res 68:547–558 PubMedCrossRef
54.
Zurück zum Zitat Zou Y, Yang M, Wang J et al (2020) Association of sclerostin with cardiovascular events and mortality in dialysis patients. Ren Fail 42:282–288 PubMedPubMedCentralCrossRef Zou Y, Yang M, Wang J et al (2020) Association of sclerostin with cardiovascular events and mortality in dialysis patients. Ren Fail 42:282–288 PubMedPubMedCentralCrossRef
55.
Zurück zum Zitat Zeng S, Slowinski T, Pommer W et al (2020) Sclerostin is an independent risk factor for all-cause mortality in kidney transplant recipients. Clin Exp Nephrol 24:1177–1183 PubMedPubMedCentralCrossRef Zeng S, Slowinski T, Pommer W et al (2020) Sclerostin is an independent risk factor for all-cause mortality in kidney transplant recipients. Clin Exp Nephrol 24:1177–1183 PubMedPubMedCentralCrossRef
56.
Zurück zum Zitat Stavrinou E, Sarafidis PA, Loutradis C et al (2021) Associations of serum sclerostin and Dickkopf-related protein‑1 proteins with future cardiovascular events and mortality in haemodialysis patients: a prospective cohort study. Clin Kidney J 14:1165–1172 PubMedCrossRef Stavrinou E, Sarafidis PA, Loutradis C et al (2021) Associations of serum sclerostin and Dickkopf-related protein‑1 proteins with future cardiovascular events and mortality in haemodialysis patients: a prospective cohort study. Clin Kidney J 14:1165–1172 PubMedCrossRef
57.
Zurück zum Zitat Goncalves FL, Elias RM, dos Reis LM et al (2014) Serum sclerostin is an independent predictor of mortality in hemodialysis patients. BMC Nephrol 15:190 PubMedPubMedCentralCrossRef Goncalves FL, Elias RM, dos Reis LM et al (2014) Serum sclerostin is an independent predictor of mortality in hemodialysis patients. BMC Nephrol 15:190 PubMedPubMedCentralCrossRef
58.
Zurück zum Zitat Gong L, Zheng D, Yuan J et al (2018) Elevated levels of serum sclerostin are linked to adverse cardiovascular outcomes in peritoneal dialysis patients. Int Urol Nephrol 50:955–961 PubMedCrossRef Gong L, Zheng D, Yuan J et al (2018) Elevated levels of serum sclerostin are linked to adverse cardiovascular outcomes in peritoneal dialysis patients. Int Urol Nephrol 50:955–961 PubMedCrossRef
59.
Zurück zum Zitat Sato M, Hanafusa N, Kawaguchi H et al (2018) A prospective cohort study showing no association between serum sclerostin level and mortality in maintenance hemodialysis patients. Kidney Blood Press Res 43:1023–1033 PubMedCrossRef Sato M, Hanafusa N, Kawaguchi H et al (2018) A prospective cohort study showing no association between serum sclerostin level and mortality in maintenance hemodialysis patients. Kidney Blood Press Res 43:1023–1033 PubMedCrossRef
61.
Zurück zum Zitat Jørgensen HS, Winther S, Dupont L et al (2018) Sclerostin is not associated with cardiovascular event or fracture in kidney transplantation candidates. Clin Nephrol 90:18–26 PubMedCrossRef Jørgensen HS, Winther S, Dupont L et al (2018) Sclerostin is not associated with cardiovascular event or fracture in kidney transplantation candidates. Clin Nephrol 90:18–26 PubMedCrossRef
62.
Zurück zum Zitat Kirkpantur A, Balci M, Turkvatan A et al (2016) Serum sclerostin levels, arteriovenous fistula calcification and 2‑years all-cause mortality in prevalent hemodialysis patients. Nefrologia 36:24–32 PubMedCrossRef Kirkpantur A, Balci M, Turkvatan A et al (2016) Serum sclerostin levels, arteriovenous fistula calcification and 2‑years all-cause mortality in prevalent hemodialysis patients. Nefrologia 36:24–32 PubMedCrossRef
63.
Zurück zum Zitat Ishimura E, Okuno S, Ichii M et al (2014) Relationship between serum sclerostin, bone metabolism markers, and bone mineral density in maintenance hemodialysis patients. J Clin Endocrinol Metab 99:4315–4320 PubMedCrossRef Ishimura E, Okuno S, Ichii M et al (2014) Relationship between serum sclerostin, bone metabolism markers, and bone mineral density in maintenance hemodialysis patients. J Clin Endocrinol Metab 99:4315–4320 PubMedCrossRef
64.
Zurück zum Zitat Kuo TH, Lin WH, Chao JY et al (2019) Serum sclerostin levels are positively related to bone mineral density in peritoneal dialysis patients: a cross-sectional study. BMC Nephrol 20:266 PubMedPubMedCentralCrossRef Kuo TH, Lin WH, Chao JY et al (2019) Serum sclerostin levels are positively related to bone mineral density in peritoneal dialysis patients: a cross-sectional study. BMC Nephrol 20:266 PubMedPubMedCentralCrossRef
65.
Zurück zum Zitat Ho TY, Chen NC, Hsu CY et al (2019) Evaluation of the association of Wnt signaling with coronary artery calcification in patients on dialysis with severe secondary hyperparathyroidism. BMC Nephrol 20:345 PubMedPubMedCentralCrossRef Ho TY, Chen NC, Hsu CY et al (2019) Evaluation of the association of Wnt signaling with coronary artery calcification in patients on dialysis with severe secondary hyperparathyroidism. BMC Nephrol 20:345 PubMedPubMedCentralCrossRef
66.
Zurück zum Zitat Elsalam MA, El-Abden MZ, Mahmoud E et al (2019) Correlation between serum sclerostin level and bone density status in children on regular hemodialysis. Saudi J Kidney Dis Transpl 30:1022–1031 PubMedCrossRef Elsalam MA, El-Abden MZ, Mahmoud E et al (2019) Correlation between serum sclerostin level and bone density status in children on regular hemodialysis. Saudi J Kidney Dis Transpl 30:1022–1031 PubMedCrossRef
67.
Zurück zum Zitat Szulc P, Boutroy S, Vilayphiou N et al (2013) Correlates of bone microarchitectural parameters and serum sclerostin levels in men—the STRAMBO study. J Bone Miner Res 28(8):1760–1770 PubMedCrossRef Szulc P, Boutroy S, Vilayphiou N et al (2013) Correlates of bone microarchitectural parameters and serum sclerostin levels in men—the STRAMBO study. J Bone Miner Res 28(8):1760–1770 PubMedCrossRef
68.
Zurück zum Zitat Atteritano M, Di Mauro E, Canale V et al (2017) Higher serum sclerostin levels and insufficiency of vitamin D are strongly associated with vertebral fractures in hemodialysis patients: a case control study. Osteoporos Int 28:577–584 PubMedCrossRef Atteritano M, Di Mauro E, Canale V et al (2017) Higher serum sclerostin levels and insufficiency of vitamin D are strongly associated with vertebral fractures in hemodialysis patients: a case control study. Osteoporos Int 28:577–584 PubMedCrossRef
69.
Zurück zum Zitat Malluche HH, Davenport DL, Cantor T et al (2014) Bone mineral density and serum biochemical predictors of bone loss in patients with CKD on dialysis. Clin J Am Soc Nephrol 9:1254–1262 PubMedPubMedCentralCrossRef Malluche HH, Davenport DL, Cantor T et al (2014) Bone mineral density and serum biochemical predictors of bone loss in patients with CKD on dialysis. Clin J Am Soc Nephrol 9:1254–1262 PubMedPubMedCentralCrossRef
70.
Zurück zum Zitat Malluche HH, Monier-Faugere MC, Blomquist G et al (2018) Two-year cortical and trabecular bone loss in CKD-5D: biochemical and clinical predictors. Osteoporos Int 29:125–134 PubMedCrossRef Malluche HH, Monier-Faugere MC, Blomquist G et al (2018) Two-year cortical and trabecular bone loss in CKD-5D: biochemical and clinical predictors. Osteoporos Int 29:125–134 PubMedCrossRef
71.
Zurück zum Zitat Ferrari SL (2018) Romosozumab to rebuild the foundations of bone strength. Nat Rev Rheumatol 14:128–128 PubMedCrossRef Ferrari SL (2018) Romosozumab to rebuild the foundations of bone strength. Nat Rev Rheumatol 14:128–128 PubMedCrossRef
72.
Zurück zum Zitat Cosman F, Crittenden DB, Adachi JD et al (2016) Romosozumab treatment in postmenopausal women with osteoporosis. N Engl J Med 375(16):1532–1543 PubMedCrossRef Cosman F, Crittenden DB, Adachi JD et al (2016) Romosozumab treatment in postmenopausal women with osteoporosis. N Engl J Med 375(16):1532–1543 PubMedCrossRef
73.
Zurück zum Zitat Saag KG, Petersen J, Brandi ML et al (2017) Romosozumab or alendronate for fracture prevention in women with osteoporosis. N Engl J Med 377:1417–1427 PubMedCrossRef Saag KG, Petersen J, Brandi ML et al (2017) Romosozumab or alendronate for fracture prevention in women with osteoporosis. N Engl J Med 377:1417–1427 PubMedCrossRef
74.
Zurück zum Zitat Lewiecki EM, Blicharski T, Goemaere S et al (2018) A phase III randomized placebo-controlled trial to evaluate efficacy and safety of romosozumab in men with osteoporosis. J Clin Endocrinol Metab 103:3183–3193 PubMedCrossRef Lewiecki EM, Blicharski T, Goemaere S et al (2018) A phase III randomized placebo-controlled trial to evaluate efficacy and safety of romosozumab in men with osteoporosis. J Clin Endocrinol Metab 103:3183–3193 PubMedCrossRef
75.
Zurück zum Zitat Lv F, Cai X, Yang W et al (2020) Denosumab or romosozumab therapy and risk of cardiovascular events in patients with primary osteoporosis: systematic review and meta-analysis. Bone 130:115121 PubMedCrossRef Lv F, Cai X, Yang W et al (2020) Denosumab or romosozumab therapy and risk of cardiovascular events in patients with primary osteoporosis: systematic review and meta-analysis. Bone 130:115121 PubMedCrossRef
76.
Zurück zum Zitat Li L, Gong M, Bao D et al (2020) Denosumab and romosozumab do not increase the risk of cardiovascular events in patients with primary osteoporosis: a reanalysis of the meta-analysis. Bone 134:115270 PubMedCrossRef Li L, Gong M, Bao D et al (2020) Denosumab and romosozumab do not increase the risk of cardiovascular events in patients with primary osteoporosis: a reanalysis of the meta-analysis. Bone 134:115270 PubMedCrossRef
77.
Zurück zum Zitat Cummings SR, McCulloch C (2020) Explanations for the difference in rates of cardiovascular events in a trial of alendronate and romosozumab. Osteoporos Int 31:1019–1021 PubMedCrossRef Cummings SR, McCulloch C (2020) Explanations for the difference in rates of cardiovascular events in a trial of alendronate and romosozumab. Osteoporos Int 31:1019–1021 PubMedCrossRef
78.
Zurück zum Zitat Langdahl BL, Hofbauer LC, Forfar JC (2021) Cardiovascular safety and sclerostin inhibition. J Clin Endocrinol Metab 106:1845–1853 PubMedCrossRef Langdahl BL, Hofbauer LC, Forfar JC (2021) Cardiovascular safety and sclerostin inhibition. J Clin Endocrinol Metab 106:1845–1853 PubMedCrossRef
79.
Zurück zum Zitat Kang JH, Keller JJ, Lin HC (2013) Bisphosphonates reduced the risk of acute myocardial infarction: a 2-year follow-up study. Osteoporos Int 24:271–277 PubMedCrossRef Kang JH, Keller JJ, Lin HC (2013) Bisphosphonates reduced the risk of acute myocardial infarction: a 2-year follow-up study. Osteoporos Int 24:271–277 PubMedCrossRef
80.
81.
Zurück zum Zitat Kranenburg G, Bartstra JW, Weijmans M et al (2016) Bisphosphonates for cardiovascular risk reduction: a systematic review and meta-analysis. Atherosclerosis 252:106–115 PubMedCrossRef Kranenburg G, Bartstra JW, Weijmans M et al (2016) Bisphosphonates for cardiovascular risk reduction: a systematic review and meta-analysis. Atherosclerosis 252:106–115 PubMedCrossRef
82.
Zurück zum Zitat Cummings SR, Lui LY, Eastell R et al (2019) Association between drug treatments for patients with osteoporosis and overall mortality rates: a meta-analysis. JAMA Intern Med 179:1491–1500 PubMedPubMedCentralCrossRef Cummings SR, Lui LY, Eastell R et al (2019) Association between drug treatments for patients with osteoporosis and overall mortality rates: a meta-analysis. JAMA Intern Med 179:1491–1500 PubMedPubMedCentralCrossRef
83.
Zurück zum Zitat Vestergaard Kvist A, Faruque J, Vallejo-Yague E et al (2021) Cardiovascular safety profile of romosozumab: a pharmacovigilance analysis of the US Food and Drug Administration Adverse Event Reporting System (FAERS). J Clin Med 10(8):1660 PubMedPubMedCentralCrossRef Vestergaard Kvist A, Faruque J, Vallejo-Yague E et al (2021) Cardiovascular safety profile of romosozumab: a pharmacovigilance analysis of the US Food and Drug Administration Adverse Event Reporting System (FAERS). J Clin Med 10(8):1660 PubMedPubMedCentralCrossRef
84.
Zurück zum Zitat FDA (2019) Meeting of the Bone, Reproductive and Urologic Drugs Advisory Committee. 16. Jan. 2019. Meeting announcement FDA (2019) Meeting of the Bone, Reproductive and Urologic Drugs Advisory Committee. 16. Jan. 2019. Meeting announcement
85.
Zurück zum Zitat Cejka D, Parada-Rodriguez D, Pichler S et al (2016) Only minor differences in renal osteodystrophy features between wild-type and sclerostin knockout mice with chronic kidney disease. Kidney Int 90(4):828–834 PubMedPubMedCentralCrossRef Cejka D, Parada-Rodriguez D, Pichler S et al (2016) Only minor differences in renal osteodystrophy features between wild-type and sclerostin knockout mice with chronic kidney disease. Kidney Int 90(4):828–834 PubMedPubMedCentralCrossRef
86.
Zurück zum Zitat Moe SM, Chen NX, Newman CL et al (2015) Anti-sclerostin antibody treatment in a rat model of progressive renal osteodystrophy. J Bone Miner Res 30(3):499–509 PubMedCrossRef Moe SM, Chen NX, Newman CL et al (2015) Anti-sclerostin antibody treatment in a rat model of progressive renal osteodystrophy. J Bone Miner Res 30(3):499–509 PubMedCrossRef
87.
Zurück zum Zitat Miller PAJ, Albergari B, Cheung AM, Chines A, Gielen E, Langdahl B, Miyauchi A, Oates M, Reid I, Ruiz Santiago N, Vanderkelen M, Yang W, Yu Z (2020) Efficacy and safety of romosozumab among postmenopausal women with osteoporosis and mild-to-moderate chronic kidney disease. Ann Rheum Dis 79:185 CrossRef Miller PAJ, Albergari B, Cheung AM, Chines A, Gielen E, Langdahl B, Miyauchi A, Oates M, Reid I, Ruiz Santiago N, Vanderkelen M, Yang W, Yu Z (2020) Efficacy and safety of romosozumab among postmenopausal women with osteoporosis and mild-to-moderate chronic kidney disease. Ann Rheum Dis 79:185 CrossRef
88.
Zurück zum Zitat ClinicalTrials.gov (2021) Study of romosozumab (AMG 785) administered to healthy participants and patients with stage 4 renal impairment or stage 5 renal impairment requiring hemodialysis ClinicalTrials.gov (2021) Study of romosozumab (AMG 785) administered to healthy participants and patients with stage 4 renal impairment or stage 5 renal impairment requiring hemodialysis
89.
Zurück zum Zitat Amgentrials.com (2015) A phase 1, open-label, single-dose study of romosozumab (AMG 785). Administered subcutaneously to healthy subjects and subjects with stage 4 renal impairment or stage 5 renal impairment requiring hemodialysis Amgentrials.com (2015) A phase 1, open-label, single-dose study of romosozumab (AMG 785). Administered subcutaneously to healthy subjects and subjects with stage 4 renal impairment or stage 5 renal impairment requiring hemodialysis
Metadaten
Titel
Anti-Sklerostin-Therapie aus nephrologischer Sicht – mit einem Fokus auf kardiovaskuläre Sicherheit
verfasst von
Prim. PD Dr. Daniel Cejka
Publikationsdatum
11.08.2021
Verlag
Springer Vienna
Erschienen in
Journal für Mineralstoffwechsel & Muskuloskelettale Erkrankungen / Ausgabe 3/2021
Print ISSN: 2412-8260
Elektronische ISSN: 2412-8287
DOI
https://doi.org/10.1007/s41970-021-00162-w

Weitere Artikel der Ausgabe 3/2021

Journal für Mineralstoffwechsel & Muskuloskelettale Erkrankungen 3/2021 Zur Ausgabe

Editorial

Editorial

News-Screen Physikalische Medizin

News-Screen Physikalische Medizin

Mitteilungen des Magnesiumforum Bad Radkersburg

Mitteilungen des Magnesiumforum Bad Radkersburg