The Korean journal of internal medicine

The Korean Association of Internal Medicine (대한내과학회)
권호 표지
DOI QR코드

DOI QR Code

Efficacy and safety of denosumab treatment for Korean patients with Stage 3b-4 chronic kidney disease and osteoporosis

  • Jin Taek Kim (Division of Endocrinology and Metabolism, Department of Internal Medicine, Nowon Eulji University Hospital, Eulji University School of Medicine) ;
  • You Mi Kim (Division of Nephrology, Department of Internal Medicine, Nowon Eulji University Hospital, Eulji University School of Medicine) ;
  • Kyong Yeun Jung (Division of Endocrinology and Metabolism, Department of Internal Medicine, Nowon Eulji University Hospital, Eulji University School of Medicine) ;
  • Hoonsung Choi (Department of Internal Medicine, Chung-Ang University College of Medicine) ;
  • So Young Lee (Division of Nephrology, Department of Internal Medicine, Nowon Eulji University Hospital, Eulji University School of Medicine) ;
  • Hyo-Jeong Kim (Division of Endocrinology and Metabolism, Department of Internal Medicine, Nowon Eulji University Hospital, Eulji University School of Medicine)
  • Received : 2023.07.11
  • Accepted : 2023.09.16
  • Published : 2024.01.01
Download PDF
⟨ Previous Next ⟩

Abstract

Background/Aims: We evaluated the efficacy and safety of denosumab treatment in severe chronic kidney disease (CKD) patients with osteoporosis. We also investigated whether the treatment affects the coronary artery calcifications. Methods: Twenty-seven postmenopausal women with Stage 3b-4 CKD and osteoporosis were enrolled. Twenty patients received denosumab plus calcium carbonate and vitamin D, and seven controls received calcium carbonate and vitamin D for 1 year. Dual-energy X-ray absorptiometry and coronary artery calcium (CAC) scoring computed tomography were performed before and after treatment. Hypocalcemic symptoms and serum calcium levels were evaluated. Results: After 1 year of treatment, the percent changes of femur neck (3.6 ± 3.2% vs. -0.7 ± 4.4%, p = 0.033) and total hip (3.4 ± 3.8% vs. -1.9 ± 2.1%, p = 0.001) bone mineral density (BMD) were significantly increased in the denosumab treated group compared to the control group. However, the percent change of lumbar spine BMD did not differ between two groups (5.6 ± 5.9% vs. 2.7 ± 3.9%, p = 0.273). The percent change of bone alkaline phosphatase was significantly different in the denosumab-treated group and control group (-31.1 ± 30.0% vs. 0.5 ± 32.0%, p = 0.027). CAC scores did not differ between groups. No hypocalcemic events occurred in both groups. Conclusions: If carefully monitored and supplemented with calcium and vitamin D, denosumab treatment for 1 year provides significant benefits in patients with Stage 3b-4 CKD and osteoporosis. However, denosumab treatment did not affect coronary artery calcifications in these patients.

Keywords

Acknowledgement

This study was funded by DALIM BIOTECH.

References

  1. Connelly K, Collister D, Tangri N. Fracture risk and treatment in chronic kidney disease. Curr Opin Nephrol Hypertens 2018;27:221-225. https://doi.org/10.1097/MNH.0000000000000411
  2. Damasiewicz MJ, Nickolas TL. Rethinking bone disease in kidney disease. JBMR Plus 2018;2:309-322. https://doi.org/10.1002/jbm4.10117
  3. Kidney Disease: Improving Global Outcomes (KDIGO) CKDMBD Update Work Group. KDIGO 2017 Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD). Kidney Int Suppl (2011) 2017;7:1-59. https://doi.org/10.1016/j.kisu.2017.04.001
  4. Cummings SR, San Martin J, McClung MR, et al.; FREEDOM Trial. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med 2009;361:756-765. https://doi.org/10.1056/NEJMoa0809493
  5. Block GA, Bone HG, Fang L, Lee E, Padhi D. A single-dose study of denosumab in patients with various degrees of renal impairment. J Bone Miner Res 2012;27:1471-1479. https://doi.org/10.1002/jbmr.1613
  6. Broadwell A, Chines A, Ebeling PR, et al. Denosumab safety and efficacy among participants in the FREEDOM extension study with mild to moderate chronic kidney disease. J Clin Endocrinol Metab 2021;106:397-409. https://doi.org/10.1210/clinem/dgaa851
  7. McCormick BB, Davis J, Burns KD. Severe hypocalcemia following denosumab injection in a hemodialysis patient. Am J Kidney Dis 2012;60:626-628. https://doi.org/10.1053/j.ajkd.2012.06.019
  8. Ungprasert P, Cheungpasitporn W, Srivali N, Kittanamongkolchai W, Bischof EF. Life-threatening hypocalcemia associated with denosumab in a patient with moderate renal insufficiency. Am J Emerg Med 2013;31:756.e1-e2. https://doi.org/10.1016/j.ajem.2012.11.011
  9. Krueger D. ISCD in 2015: state of the society. J Clin Densitom 2015;18:445-446. https://doi.org/10.1016/j.jocd.2015.06.004
  10. Carr JJ, Nelson JC, Wong ND, et al. Calcified coronary artery plaque measurement with cardiac CT in population-based studies: standardized protocol of Multi-Ethnic Study of Atherosclerosis (MESA) and Coronary Artery Risk Development in Young Adults (CARDIA) study. Radiology 2005;234:35-43. https://doi.org/10.1148/radiol.2341040439
  11. Agatston AS, Janowitz WR, Hildner FJ, Zusmer NR, Viamonte M Jr, Detrano R. Quantification of coronary artery calcium using ultrafast computed tomography. J Am Coll Cardiol 1990;15:827-832. https://doi.org/10.1016/0735-1097(90)90282-T
  12. Pletcher MJ, Tice JA, Pignone M, Browner WS. Using the coronary artery calcium score to predict coronary heart disease events: a systematic review and meta-analysis. Arch Intern Med 2004;164:1285-1292. https://doi.org/10.1001/archinte.164.12.1285
  13. Kunizawa K, Hiramatsu R, Hoshino J, et al. Denosumab for dialysis patients with osteoporosis: a cohort study. Sci Rep 2020;10:2496.
  14. Henriksen K, Byrjalsen I, Andersen JR, et al.; SMC021 investigators. A randomized, double-blind, multicenter, placebo-controlled study to evaluate the efficacy and safety of oral salmon calcitonin in the treatment of osteoporosis in postmenopausal women taking calcium and vitamin D. Bone 2016;91:122- 129. https://doi.org/10.1016/j.bone.2016.07.019
  15. Bezerra de Carvalho KS, Vasco RFV, Custodio MR, Jorgetti V, Moyses RMA, Elias RM. Chronic kidney disease is associated with low BMD at the hip but not at the spine. Osteoporos Int 2019;30:1015-1023. https://doi.org/10.1007/s00198-019-04864-4
  16. Inker LA, Eneanya ND, Coresh J, et al.; Chronic Kidney Disease Epidemiology Collaboration. New creatinine- and cystatin C-based equations to estimate GFR without race. N Engl J Med 2021;385:1737-1749. https://doi.org/10.1056/NEJMoa2102953
  17. Dave V, Chiang CY, Booth J, Mount PF. Hypocalcemia post denosumab in patients with chronic kidney disease stage 4-5. Am J Nephrol 2015;41:129-137. https://doi.org/10.1159/000380960
  18. Huynh AL, Baker ST, Stewardson AJ, Johnson DF. Denosumab-associated hypocalcaemia: incidence, severity and patient characteristics in a tertiary hospital setting. Pharmacoepidemiol Drug Saf 2016;25:1274-1278. https://doi.org/10.1002/pds.4045
  19. Hwang E, Choi BS, Oh KH, Kwon YJ, Kim GH. Management of chronic kidney disease-mineral and bone disorder: Korean working group recommendations. Kidney Res Clin Pract 2015;34:4-12. https://doi.org/10.1016/j.krcp.2015.02.002
  20. Chiang C. The use of bone turnover markers in chronic kidney disease-mineral and bone disorders. Nephrology (Carlton) 2017;22 Suppl 2:11-13. https://doi.org/10.1111/nep.13014
  21. Regidor DL, Kovesdy CP, Mehrotra R, et al. Serum alkaline phosphatase predicts mortality among maintenance hemodialysis patients. J Am Soc Nephrol 2008;19:2193-2203. https://doi.org/10.1681/ASN.2008010014
  22. Yamada S, Inaba M, Kurajoh M, et al. Utility of serum tartrate-resistant acid phosphatase (TRACP5b) as a bone resorption marker in patients with chronic kidney disease: independence from renal dysfunction. Clin Endocrinol (Oxf) 2008;69:189-196. https://doi.org/10.1111/j.1365-2265.2008.03187.x
  23. Wu M, Rementer C, Giachelli CM. Vascular calcification: an update on mechanisms and challenges in treatment. Calcif Tissue Int 2013;93:365-373. https://doi.org/10.1007/s00223-013-9712-z
  24. Tintut Y, Demer L. Role of osteoprotegerin and its ligands and competing receptors in atherosclerotic calcification. J Investig Med 2006;54:395-401. https://doi.org/10.2310/6650.2006.06019
  25. Suzuki S, Suzuki M, Hanafusa N, Tsuchiya K, Nitta K. Denosumab recovers aortic arch calcification during long-term hemodialysis. Kidney Int Rep 2020;6:605-612. https://doi.org/10.1016/j.ekir.2020.12.002
  26. Samelson EJ, Miller PD, Christiansen C, et al. RANKL inhibition with denosumab does not influence 3-year progression of aortic calcification or incidence of adverse cardiovascular events in postmenopausal women with osteoporosis and high cardiovascular risk. J Bone Miner Res 2014;29:450-457. https://doi.org/10.1002/jbmr.2043
  27. Menon V, Sarnak MJ, Greene T, et al. Relationship between homocysteine and mortality in chronic kidney disease. Circulation 2006;113:1572-1577. https://doi.org/10.1161/CIRCULATIONAHA.105.570127
  28. McLean RR, Jacques PF, Selhub J, et al. Homocysteine as a predictive factor for hip fracture in older persons. N Engl J Med 2004;350:2042-2049. https://doi.org/10.1056/NEJMoa032739
  29. Gjesdal CG, Vollset SE, Ueland PM, et al. Plasma total homocysteine level and bone mineral density: the Hordaland Homocysteine Study. Arch Intern Med 2006;166:88-94. https://doi.org/10.1001/archinte.166.1.88
  30. van Meurs JB, Dhonukshe-Rutten RA, Pluijm SM, et al. Homocysteine levels and the risk of osteoporotic fracture. N Engl J Med 2004;350:2033-2041. https://doi.org/10.1056/NEJMoa032546