Osteoporosis, bone mineral density and CKD–MBD: treatment considerations
- 1.8k Downloads
Osteoporosis and chronic kidney disease (CKD) have both independently important potential impact on bone health. A significant number of patients with CKD stages 3a–5D have been shown to have low bone mineral density (BMD), leading to a strikingly elevated risk of fractures (mainly hip fractures) and higher associated morbidity and mortality. Mechanical properties of bone beyond age and menopausal status are additionally affected by intrinsic uremic factors. Therefore, we review in this article not only general concepts of osteoporosis and related consequences, but also the diagnostic and therapeutic implications of low BMD and bone fractures in CKD, beyond increased vascular calcification. Antiresorptive agents (mainly bisphosphonates) were not previously recommended when the estimated glomerular filtration rate (GFR) was lower than 30 ml/min/1.73 m2. However, post-hoc analysis of large randomized clinical trials found that these drugs (i.e. alendronate, ribandronate, denosumab) had comparable efficacy in improving BMD and reducing fracture risk in individuals (mainly women) with moderate reductions of GFR (mostly CKD stages 3–4). Therefore, at least in the absence of clear abnormalities of CKD-related mineral metabolism disturbances, bone antiresorptive agents (and maybe anabolic agents) that are or will be approved for general osteoporosis may be appropriate for CKD. Nephrologists should probably not ignore any longer fracture risk assessment, especially in patients with additional risk factors for osteoporosis if results will impact treatment decisions. However, although different therapeutic agents have been shown to reduce the risk of fracture in CKD patients with low BMD, specific prospective studies, with or without bone biopsies, in CKD are urgently needed.
KeywordsOsteoporosis Secondary hyperparathyroidism CKD–MBD Bone mineral density Fractures CKD Bisphosphonates Denosumab Teriparatide
Dr Jordi Bover belongs to the Spanish National Network of Kidney Research RedinRen (RD06/0016/0001 and RD12/0021/0033) and the Spanish National Biobank network RD09/0076/00064. Dr Jordi Bover also belongs to the Catalan Nephrology Research Group AGAUR 2009 SGR-1116. We thank Mr. Ricardo Pellejero for his invaluable bibliographic assistance.
Compliance with ethical standards
Financial support for this work
Conflict of interest
The authors declare that they have no competing interests.
This article does not contain any studies with human participants or animals performed by any of the authors.
- 5.Llach F, Bover J, Brenner BM (eds) (2000) The kidney, 6th edn. WB Sanders Company, ed., PhiladelphiaGoogle Scholar
- 16.Genant HK, Li J, Wu CY, Shepherd JA (2000) Vertebral fractures in osteoporosis 3(3):281–290Google Scholar
- 24.Kidney Disease: Improving Global Outcomes (KDIGO) (2009) KDIGO Clinical Practice Guideline for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD–MBD). Off J Int Soc Nephrol Kidney Int 76Google Scholar
- 28.KDIGO (2009) KDIGO clinical practice guideline for the diagnosis, evaluation, prevention, and treatment of chronic kidney disease-mineral and bone disorder (CKD–MBD). Kidney Int Suppl. 113:S1–130. doi: 10.1038/ki.2009.188
- 43.Agarwal R, Georgianos PI (2016) Con: nutritional vitamin D replacement in chronic kidney disease and end-stage renal disease. Polar views in nephrology. JAMA 706–713. doi: 10.1093/ndt/gfw080
- 51.Drake MT, Clarke BL, Khosla S (2008) Bisphosphonates: mechanism of action and role in clinical practice. Mayo Clin Proc 83(9):1032–1045. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2667901/
- 66.Ma S, Goh EL, Jin A et al (2017) Long-term effects of bisphosphonate therapy: perforations, microcracks and mechanical properties. Nat Publ Gr (November 2016) 1–10. doi: 10.1038/srep43399
- 68.Black DM, Kelly MP, Genant HK, Palermo L, Eastell R, Bucci-Rechtweg C, Cauley J, Leung PC, Boonen S, Santora A, de Papp A, Bauer DC, For the FIT, Committees and HPFTS (2010) Bisphosphonates and fractures of the subtrochanteric or diaphyseal femur. N Engl J Med 309:1761–1771. doi: 10.1056/NEJMoa0904327 CrossRefGoogle Scholar
- 71.Whitaker M, Guo J, Ph D, Kehoe T, Benson G (2012) Bisphosphonates for osteoporosis—where do we go. N Engl J MedGoogle Scholar
- 76.Ketteler M, Elder GJ, Evenepoel P et al (2015) Revisiting KDIGO clinical practice guideline on chronic kidney disease-mineral and bone disorder: a commentary from a Kidney Disease: improving global outcomes controversies conference. Kidney Int 87(3):502–528. doi: 10.1038/ki.2014.425 CrossRefPubMedGoogle Scholar
- 78.Miller PD, Roux C, Boonen S et al (2005) Safety and efficacy of risedronate in patients with age-related reduced renal function as estimated by the cockcroft and gault method: a pooled analysis of nine. Clin Trials 20(12). doi: 10.1359/JBMR.050817
- 81.Beaudoin C, Jean S, Bessette L, Ste-Marie L-G, Moore L, Brown JP (2016) Denosumab compared to other treatments to prevent or treat osteoporosis in individuals at risk of fracture: a systematic review and meta-analysis. Osteoporos Int 27(9):2835–2844. doi: 10.1007/s00198-016-3607-6 CrossRefPubMedGoogle Scholar
- 82.Samelson EJ, Miller PD, Christiansen C et al (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(2):450–457. doi: 10.1002/jbmr.2043 CrossRefPubMedPubMedCentralGoogle Scholar
- 84.Aapro M, De Castro G, Cohen E, Deray G, Dooley M (2015) Renal effects of molecular targeted therapies in oncology: a review by the cancer and the kidney. 252–255. doi: 10.1093/annonc/mdv136
- 85.Block GA, Bone HG, Fang L, Lee E, Padhi D (2012) A single-dose study of denosumab in patients with various degrees of renal impairment. J Bone Miner Res 27(7):1471–1479. doi: 10.1002/jbmr.1613
- 87.Dave V, Chiang CY, Booth J, Mount PF (2015) Hypocalcemia post denosumab in patients with chronic kidney disease stage 4–5. Am J Nephrol 41(2):129–137. http://www.karger.com/DOI/10.1159/000380960
- 94.Nishikawa A, Yoshiki F, Taketsuna M, Kajimoto K, Enomoto H (2016) Safety and effectiveness of daily teriparatide for osteoporosis in patients with severe stages of chronic kidney disease: post hoc analysis of a postmarketing observational study. Clin Interv Aging 11:1653–1659. doi: 10.2147/CIA.S120175 CrossRefPubMedPubMedCentralGoogle Scholar
- 102.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. doi: 10.1002/jbmr.2372