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Diagnosis and management of osteoporosis in chronic kidney disease stages 4 to 5D: a call for a shift from nihilism to pragmatism

Abstract

The European Renal Association–European Dialysis and Transplant Association (ERA-EDTA) CKD-MBD working group, in collaboration with the Committee of Scientific Advisors of the International Osteoporosis Foundation, published a position paper for the diagnosis and management of osteoporosis in patients with CKD stages 4–5D (eGFR < 30 ml/min 1.73 m2). The present article reports and summarizes the main recommendations included in this 2021 document. The following areas are reviewed: diagnosis of osteoporosis; risk factors for fragility fractures; fracture risk assessment; intervention thresholds for pharmacological intervention; general and pharmacological management of osteoporosis; monitoring of treatment, and systems of care, all in patients with CKD stages 4–5D. Guidance is provided for clinicians caring for CKD stages 4–5D patients with osteoporosis, allowing for a pragmatic individualized diagnostic and therapeutic approach as an alternative to current variations in care and treatment nihilism.

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References

  1. 1.

    Moe S, Drueke T, Cunningham J, Goodman W, Martin K, Olgaard K, Ott S, Sprague S, Lameire N, Eknoyan G (2006) Definition, evaluation, and classification of renal osteodystrophy: a position statement from Kidney Disease: Improving Global Outcomes (KDIGO). kidney int 69:1945–1953

    PubMed  CAS  Google Scholar 

  2. 2.

    (2001) Osteoporosis prevention, diagnosis, and therapy. JAMA 285:785–795

  3. 3.

    KANIS JA (1994) Assessment of fracture risk and its application to screening for postmenopausal osteoporosis: synopsis of a WHO report. WHO Study Group. Osteoporos Int 4:368–381

    CAS  Google Scholar 

  4. 4.

    KANIS JA, Cooper C, Rizzoli R, Reginster JY (2019) European guidance for the diagnosis and management of osteoporosis in postmenopausal women. Osteoporos Int. 30:3–44

    PubMed  CAS  Google Scholar 

  5. 5.

    Hernlund E, Svedbom A, Ivergard M, Compston J, Cooper C, Stenmark J, McCloskey EV, Jonsson B, JA KANIS (2013) Osteoporosis in the European Union: medical management, epidemiology and economic burden. A report prepared in collaboration with the International Osteoporosis Foundation (IOF) and the European Federation of Pharmaceutical Industry Associations (EFPIA). Arch Osteoporos 8:136

    PubMed  PubMed Central  CAS  Google Scholar 

  6. 6.

    Moe SM, Nickolas TL (2016) Fractures in patients with CKD: time for action. Clin J Am Soc Nephrol 11:1929–1931

    PubMed  PubMed Central  Google Scholar 

  7. 7.

    Wilson LM, Rebholz CM, Jirru E, Liu MC, Zhang A, Gayleard J, Chu Y, Robinson KA (2017) Benefits and harms of osteoporosis medications in patients with chronic kidney disease: a systematic review and meta-analysis. Ann Intern Med 2;166:649–658

    Google Scholar 

  8. 8.

    Evenepoel P, Cunningham J, Ferrari S, Haarhaus M, Javaid MK, Lafage-Proust MH, Prieto-Alhambra D, Torres PU, Cannata-Andia J (2021) European Consensus Statement on the diagnosis and management of osteoporosis in chronic kidney disease stages G4-G5D. Nephrol Dial Transplant 36:42–59

    PubMed  CAS  Google Scholar 

  9. 9.

    Miller PD (2014) Chronic kidney disease and osteoporosis: evaluation and management. Bonekey Rep 3:542

    PubMed  PubMed Central  CAS  Google Scholar 

  10. 10.

    Iimori S, Mori Y, Akita W, Kuyama T, Takada S, Asai T, Kuwahara M, Sasaki S, Tsukamoto Y (2012) Diagnostic usefulness of bone mineral density and biochemical markers of bone turnover in predicting fracture in CKD stage 5D patients—a single-center cohort study. Nephrol Dial Transplant 27:345–351

    PubMed  CAS  Google Scholar 

  11. 11.

    Yenchek RH, Ix JH, Shlipak MG, Bauer DC, Rianon NJ, Kritchevsky SB, Harris TB, Newman AB, Cauley JA, Fried LF (2012) Bone mineral density and fracture risk in older individuals with CKD. Clin J Am Soc Nephrol 7:1130–1136

    PubMed  PubMed Central  CAS  Google Scholar 

  12. 12.

    Naylor KL, Garg AX, Zou G, Langsetmo L, Leslie WD, Fraser LA, Adachi JD, Morin S, Goltzman D, Lentle B, Jackson SA, Josse RG, Jamal SA (2015) Comparison of fracture risk prediction among individuals with reduced and normal kidney function. Clin J Am Soc Nephrol 10:646–653

    PubMed  PubMed Central  Google Scholar 

  13. 13.

    West SL, Lok CE, Langsetmo L, Cheung AM, Szabo E, Pearce D, Fusaro M, Wald R, Weinstein J, Jamal SA (2015) Bone mineral density predicts fractures in chronic kidney disease. J Bone Miner Res 30:913–919

    PubMed  Google Scholar 

  14. 14.

    Evenepoel P, Claes K (2019) Meijers B. Laurent MR, Bammens B, Naesens M, Sprangers B, Pottel H, Cavalier E, Kuypers D. Bone mineral density, bone turnover markers, and incident fractures in de novo kidney transplant recipients. kidney int

    Google Scholar 

  15. 15.

    Ketteler M, Block GA, Evenepoel P, Fukagawa M, Herzog CA, McCann L, Moe SM, Shroff R, Tonelli MA, Toussaint ND, Vervloet MG, Leonard MB (2017) Executive summary of the 2017 KDIGO Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD) Guideline Update: what’s changed and why it matters. kidney int 92:26–36

    PubMed  Google Scholar 

  16. 16.

    Maruyama Y, Taniguchi M, Kazama JJ, Yokoyama K, Hosoya T, Yokoo T, Shigematsu T, Iseki K, Tsubakihara Y (2014) A higher serum alkaline phosphatase is associated with the incidence of hip fracture and mortality among patients receiving hemodialysis in Japan. Nephrol Dial Transplant 29:1532–1538

    PubMed  CAS  Google Scholar 

  17. 17.

    Coco M, Rush H (2000) Increased incidence of hip fractures in dialysis patients with low serum parathyroid hormone. Am J Kidney Dis 36:1115–1121

    PubMed  CAS  Google Scholar 

  18. 18.

    Jadoul M, Albert JM, Akiba T, Akizawa T, Arab L, Bragg-Gresham JL, Mason N, Prutz KG, Young EW, Pisoni RL (2006) Incidence and risk factors for hip or other bone fractures among hemodialysis patients in the Dialysis Outcomes and Practice Patterns Study. kidney int 70:1358–1366

    PubMed  CAS  Google Scholar 

  19. 19.

    Danese MD, Kim J, Doan OV, Dylan M, Griffiths R, Chertow GM (2006) PTH and the risks for hip, vertebral, and pelvic fractures among patients on dialysis. Am J Kidney Dis 47:149–156

    PubMed  Google Scholar 

  20. 20.

    Malluche HH, Monier-Faugere MC, Blomquist G, Davenport DL (2018) Two-year cortical and trabecular bone loss in CKD-5D: biochemical and clinical predictors. Osteoporos Int 29:125–134

    PubMed  CAS  Google Scholar 

  21. 21.

    Aleksova J, Kurniawan S, Elder GJ (2018) The trabecular bone score is associated with bone mineral density, markers of bone turnover and prevalent fracture in patients with end stage kidney disease. Osteoporos Int 29:1447–1455

    PubMed  CAS  Google Scholar 

  22. 22.

    Naylor KL, Prior J, Garg AX, Berger C, Langsetmo L, Adachi JD, Goltzman D, Kovacs CS, Josse RG, Leslie WD (2016) Trabecular bone score and incident fragility fracture risk in adults with reduced kidney function. Clin J Am Soc Nephrol 11:2032–2040

    PubMed  PubMed Central  CAS  Google Scholar 

  23. 23.

    Jamal SA, Gilbert J, Gordon C, Bauer DC (2006) Cortical pQCT measures are associated with fractures in dialysis patients. J Bone Miner Res 21:543–548

    PubMed  Google Scholar 

  24. 24.

    Bielesz B, Patsch JM, Fischer L, Bojic M, Winnicki W, Weber M, Cejka D (2017) Cortical porosity not superior to conventional densitometry in identifying hemodialysis patients with fragility fracture. PLoS One 12:e0171873

    PubMed  PubMed Central  Google Scholar 

  25. 25.

    Samelson EJ, Broe KE, Xu H, Yang L, Boyd S, Biver E, Szulc P, Adachi J, Amin S, Atkinson E, Berger C, Burt L, Chapurlat R, Chevalley T, Ferrari S, Goltzman D, Hanley DA, Hannan MT, Khosla S, Liu CT, Lorentzon M, Mellstrom D, Merle B, Nethander M, Rizzoli R, Sornay-Rendu E, Van RB SD, AKO W, Ohlsson C, Demissie S, Kiel DP, Bouxsein ML (2019) Cortical and trabecular bone microarchitecture as an independent predictor of incident fracture risk in older women and men in the Bone Microarchitecture International Consortium (BoMIC): a prospective study. Lancet Diabetes Endocrinol 7:34–43

    PubMed  Google Scholar 

  26. 26.

    Cejka D, Patsch JM, Weber M, Diarra D, Riegersperger M, Kikic Z, Krestan C, Schueller-Weidekamm C, Kainberger F, Haas M (2011) Bone microarchitecture in hemodialysis patients assessed by HR-pQCT. Clin J Am Soc Nephrol 6:2264–2271

    PubMed  PubMed Central  Google Scholar 

  27. 27.

    Nickolas TL, Stein EM, Dworakowski E, Nishiyama KK, Komandah-Kosseh M, Zhang CA, McMahon DJ, Liu XS, Boutroy S, Cremers S, Shane E (2013) Rapid cortical bone loss in patients with chronic kidney disease. J Bone Miner Res 28:1811–1820

    PubMed  CAS  Google Scholar 

  28. 28.

    Lentle B, Koromani F, Brown JP, Oei L, Ward L, Goltzman D, Rivadeneira F, Leslie WD, Probyn L, Prior J, Hammond I, Cheung AM, Oei EH (2019) The radiology of osteoporotic vertebral fractures revisited. J Bone Miner Res 34:409–418

    PubMed  Google Scholar 

  29. 29.

    Toussaint ND, Lau KK, Strauss BJ, Polkinghorne KR, Kerr PG (2009) Determination and validation of aortic calcification measurement from lateral bone densitometry in dialysis patients. Clin J Am Soc Nephrol 4:119–127

    PubMed  PubMed Central  Google Scholar 

  30. 30.

    Jamal SA, West SL, Nickolas TL (2014) The clinical utility of FRAX to discriminate fracture status in men and women with chronic kidney disease. Osteoporos Int 25:71–76

    PubMed  CAS  Google Scholar 

  31. 31.

    Przedlacki J, Buczynska-Chyl J, Kozminski P, Niemczyk E, Wojtaszek E, Gieglis E, Zebrowski P, Podgorzak A, Wscislak J, Wieliczko M, Matuszkiewicz-Rowinska J (2018) The utility of FRAX(R) in predicting bone fractures in patients with chronic kidney disease on hemodialysis: a two-year prospective multicenter cohort study. Osteoporos Int 29:1105–1115

    PubMed  CAS  Google Scholar 

  32. 32.

    Whitlock RH, Leslie WD, Shaw J, Rigatto C, Thorlacius L, Komenda P, Collister D, KANIS JA, Tangri N (2018) The Fracture Risk Assessment Tool (FRAX(R)) predicts fracture risk in patients with chronic kidney disease. kidney int

  33. 33.

    Ferrari SL, Abrahamsen B, Napoli N, Akesson K, Chandran M, Eastell R, El-Hajj FG, Josse R, Kendler DL, Kraenzlin M, Suzuki A, Pierroz DD, Schwartz AV, Leslie WD (2018) Diagnosis and management of bone fragility in diabetes: an emerging challenge. Osteoporos Int 29:2585–2596

    PubMed  PubMed Central  CAS  Google Scholar 

  34. 34.

    Johansson H, Siggeirsdottir K, Harvey NC, Oden A, Gudnason V, McCloskey E, Sigurdsson G, KANIS JA (2017) Imminent risk of fracture after fracture. Osteoporos Int 28:775–780

    PubMed  CAS  Google Scholar 

  35. 35.

    Kidney Disease: Improving Global Outcomes (KDIGO) CKD-MBD Work Group. KDIGO clinical practice guideline for the diagnosis, evaluation, prevention, and treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD) (2009) Kidney Int Suppl 113:S1–S130

    Google Scholar 

  36. 36.

    Kistler BM, Khubchandani J, Jakubowicz G, Wilund K, Sosnoff J (2018) Falls and fall-related injuries among US adults aged 65 or older with chronic kidney disease. Prev Chronic Dis 15:E82

    PubMed  PubMed Central  Google Scholar 

  37. 37.

    Desmet C, Beguin C, Swine C, Jadoul M (2005) Falls in hemodialysis patients: prospective study of incidence, risk factors, and complications. Am J Kidney Dis 45:148–153

    PubMed  Google Scholar 

  38. 38.

    Kutner NG, Zhang R, Huang Y, Wasse H (2014) Falls among hemodialysis patients: potential opportunities for prevention? Clin Kidney J 7:257–263

    PubMed  PubMed Central  Google Scholar 

  39. 39.

    Mitsopoulos E, Ginikopoulou E, Economidou D, Zanos S, Pateinakis P, Minasidis E, Memmos D, Thodis E, Vargemezis V, Tsakiris D (2012) Impact of long-term cinacalcet, ibandronate or teriparatide therapy on bone mineral density of hemodialysis patients: a pilot study. Am J Nephrol 36:238–244

    PubMed  CAS  Google Scholar 

  40. 40.

    Toussaint ND, Lau KK, Strauss BJ, Polkinghorne KR, Kerr PG (2010) Effect of alendronate on vascular calcification in CKD stages 3 and 4: a pilot randomized controlled trial. Am J Kidney Dis 56:57–68

    PubMed  CAS  Google Scholar 

  41. 41.

    Bergner R, Henrich D, Hoffmann M, Schmidt-Gayk H, Lenz T, Upperkamp M (2008) Treatment of reduced bone density with ibandronate in dialysis patients. J Nephrol 21:510–516

    PubMed  CAS  Google Scholar 

  42. 42.

    Iseri K, Watanabe M, Yoshikawa H, Mitsui H, Endo T, Yamamoto Y, Iyoda M, Ryu K, Inaba T, Shibata T (2019) Effects of denosumab and alendronate on bone health and vascular function in hemodialysis patients: a randomized, controlled trial. J Bone Miner Res 34:1014–1024

    PubMed  CAS  Google Scholar 

  43. 43.

    Wetmore JB, Benet LZ, Kleinstuck D, Frassetto L (2005) Effects of short-term alendronate on bone mineral density in haemodialysis patients. Nephrology (Carlton ) 10:393–399

    CAS  Google Scholar 

  44. 44.

    Thongprayoon C, Acharya P, Acharya C, Chenbhanich J, Bathini T, Boonpheng B, Sharma K, Wijarnpreecha K, Ungprasert P, Gonzalez Suarez ML, Cheungpasitporn W (2018) Hypocalcemia and bone mineral density changes following denosumab treatment in end-stage renal disease patients: a meta-analysis of observational studies. Osteoporos Int 29:1737–1745

    PubMed  CAS  Google Scholar 

  45. 45.

    Chen CL, Chen NC, Hsu CY, Chou KJ, Lee PT, Fang HC, Renn JH (2014) An open-label, prospective pilot clinical study of denosumab for severe hyperparathyroidism in patients with low bone mass undergoing dialysis. J Clin Endocrinol Metab 99:2426–2432

    PubMed  CAS  Google Scholar 

  46. 46.

    Allen MR, Aref MW (2017) What animal models have taught us about the safety and efficacy of bisphosphonates in chronic kidney disease. Curr Osteoporos Rep 15:171–177

    PubMed  Google Scholar 

  47. 47.

    Dempster DW, Brown JP, Fahrleitner-Pammer A, Kendler D, Rizzo S, Valter I, Wagman RB, Yin X, Yue SV, Boivin G (2018) Effects of long-term denosumab on bone histomorphometry and mineralization in women with postmenopausal osteoporosis. J Clin Endocrinol Metab 103:2498–2509

    PubMed  PubMed Central  Google Scholar 

  48. 48.

    Samelson EJ, Miller PD, Christiansen C, Daizadeh NS, Grazette L, Anthony MS, Egbuna O, Wang A, Siddhanti SR, Cheung AM, Franchimont N, Kiel DP (2014) 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 29:450–457

    PubMed  CAS  Google Scholar 

  49. 49.

    Tanko LB, Qin G, Alexandersen P, Bagger YZ, Christiansen C (2005) Effective doses of ibandronate do not influence the 3-year progression of aortic calcification in elderly osteoporotic women. Osteoporos Int 16:184–190

    PubMed  CAS  Google Scholar 

  50. 50.

    Cummings SR, Ferrari S, Eastell R, Gilchrist N, Jensen JB, McClung M, Roux C, Torring O, Valter I, Wang AT, Brown JP (2018) Vertebral fractures after discontinuation of denosumab: a post hoc analysis of the randomized placebo-controlled FREEDOM trial and its extension. J Bone Miner Res 33:190–198

    PubMed  CAS  Google Scholar 

  51. 51.

    Saag KG, Petersen J, Brandi ML, Karaplis AC, Lorentzon M, Thomas T, Maddox J, Fan M, Meisner PD, Grauer A (2017) Romosozumab or alendronate for fracture prevention in women with osteoporosis. N Engl J Med 377:1417–1427

    PubMed  CAS  Google Scholar 

  52. 52.

    Delmas PD, Vrijens B, Eastell R, Roux C, Pols HA, Ringe JD, Grauer A, Cahall D, Watts NB (2007) Effect of monitoring bone turnover markers on persistence with risedronate treatment of postmenopausal osteoporosis. J Clin Endocrinol Metab 92:1296–1304

    PubMed  CAS  Google Scholar 

  53. 53.

    Naylor KE, McCloskey EV, Jacques RM, Peel NFA, Paggiosi MA, Gossiel F, Walsh JS, Eastell R (2019) Clinical utility of bone turnover markers in monitoring the withdrawal of treatment with oral bisphosphonates in postmenopausal osteoporosis. Osteoporos Int 30:917–922

    PubMed  CAS  Google Scholar 

  54. 54.

    Ingle BM, Hay SM, Bottjer HM, Eastell R (1999) Changes in bone mass and bone turnover following ankle fracture. Osteoporos Int 10:408–415

    PubMed  CAS  Google Scholar 

  55. 55.

    Bell KJ, Hayen A, Macaskill P, Irwig L, Craig JC, Ensrud K, Bauer DC (2009) Value of routine monitoring of bone mineral density after starting bisphosphonate treatment: secondary analysis of trial data. BMJ 338:b2266

    PubMed  PubMed Central  Google Scholar 

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Acknowledgements

EUROD is supported by an unrestricted grant from Amgen.

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Correspondence to P. Evenepoel.

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PE has received lecture and consultancy fees from Amgen, Vifor FMC, and Medice, unrelated to this work.

JC has received lecture and consultancy fees from Amgen, Vifor FMC, and Opko, unrelated to this work.

MKJ has received advisory and lecture fees from Amgen, Lilly UK, Internis, Consilient Health, Zebra Medical Vision, Kyowa Kirin Hakin, UCB, and Abbvie.

MHLP has received lecture fees from AMGEN.

DPA’s institution has received research grants from UCB Biopharma, Amgen, and Les Laboratories Servier; speaker fees from Amgen, and consultancy fees from UCB Biopharma.

Janssen, on behalf of IMI-funded EHDEN and EMIF consortium, and synapse Management partners have supported training programs organized by DPA’s department and open for external participants.

PUT declares advisory and/or lecture fees from Amgen, Astellas, GSK, Hémotech, Medici, Sanofi, and Vifor-Pharma FMC.

SF has received research grants from AMGEN, UCB, Alexion, and Agnovos and has received advisory and/or lecture fees from Amgen, UCB, E Lilly, and Agnovos.

JCA declares has received lecture and advisory fees from Vifor, Amgen, Kyowa-Kirin, and ASOFARMA.

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Reprinted from: Evenepoel P, Cunningham J, Ferrari S, et al, European Renal Osteodystrophy (EUROD) workgroup, an initiative of the CKD-MBD working group of the ERA-EDTA, and the committee of Scientific Advisors and National Societies of the IOF, European Consensus Statement on the diagnosis and management of osteoporosis in chronic kidney disease stages G4–G5D, Nephrology Dialysis Transplantation 2021; 36 (1): 42–59. By permission of Oxford University Press on behalf of the ERA-EDTA from the full-text Consensus Statement published in Nephrology Dialysis Transplantation at https://doi.org/10.1093/ndt/gfaa192.

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Evenepoel, P., Cunningham, J., Ferrari, S. et al. Diagnosis and management of osteoporosis in chronic kidney disease stages 4 to 5D: a call for a shift from nihilism to pragmatism. Osteoporos Int 32, 2397–2405 (2021). https://doi.org/10.1007/s00198-021-05975-7

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Keywords

  • Chronic kidney disease
  • Osteoporosis