Osteoporosis and Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD): Back to Basics.

Osteoporosis is defined as "a skeletal disorder of compromised bone strength predisposing to an increased risk of fracture". However, based on bone histology, the term osteoporosis is only part of a spectrum of skeletal complications that includes osteomalacia and the various forms of renal osteodystrophy of chronic kidney disease-mineral and bone disorder (CKD-MBD). In addition, a label, "kidney-induced osteoporosis", has been proposed, despite the fact that CKD does not cause osteoporosis, as is diagnosed histologically. It is clear, therefore, that such terminology may not be helpful diagnostically or in making treatment decisions. A new label, CKD-MBD/Osteoporosis could be a more appropriate term as it brings osteoporosis under the official label of CKD-MBD.. Neither laboratory nor non-invasive diagnostic investigations can discriminate osteoporosis from the several forms of renal osteodystrophy. Transiliac crest bone biopsy can make the diagnosis of osteoporosis by exclusion of other kidney-associated bone diseases but its availability is limited. Recently, classification of metabolic bone diseases based on bone turnover, from low to high, together with mineralization, and bone volume, has been proposed. Therapeutically, no antifracture treatments have been FDA approved for patients with kidney-associated bone disease. Agents that suppress PTH (vitamin D analogues and calcimimetics) are used to treat hyperparathyroid bone disease. Antiresorptive and osteoanabolic agents approved for osteoporosis are being used off label in stage 3B-5 CKD in high risk patients. It has now been suggested that intermittent administration of PTH, as early as stage 2 CKD, could be an effective management. If confirmed in clinical trials, it could mitigate the retention of phosphorus and subsequently the rise in FGF-23 and, it may be beneficial for co-existing osteoporosis.

[1]  P. Miller,et al.  The CKD‐MBD Syndrome: Hysteresis in PTH Involvement and PTH Administration for Its Management , 2020, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[2]  J. Compston,et al.  Defining Very High Fracture Risk: Is FRAX Fit for Purpose? , 2020, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[3]  W. Leslie,et al.  Trabecular bone score in patients with chronic kidney disease , 2020, Osteoporosis International.

[4]  P. Miller,et al.  Current Understanding of Mineral and Bone Disorders of Chronic Kidney Disease and the Scientific Grounds on the Use of Exogenous Parathyroid Hormone in Its Management , 2020, Journal of bone metabolism.

[5]  M. Allen,et al.  Elevations in Cortical Porosity Occur Prior to Significant Rise in Serum Parathyroid Hormone in Young Female Mice with Adenine-Induced CKD , 2019, Calcified Tissue International.

[6]  M. Fusaro,et al.  How and when to assess bone mineral density and bone quality in chronic kidney disease patients? , 2019, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[7]  M. Pazianas Bones, heart and the new anabolic agent romosozumab , 2019, Postgraduate Medical Journal.

[8]  Nadine Kaesler,et al.  Sclerostin in chronic kidney disease-mineral bone disorder think first before you block it! , 2019, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[9]  N. Lane Glucocorticoid-Induced Osteoporosis: New Insights into the Pathophysiology and Treatments , 2019, Current Osteoporosis Reports.

[10]  T. Nickolas,et al.  Rethinking Bone Disease in Kidney Disease , 2018, JBMR plus.

[11]  P. Kerr,et al.  Gonadal Hormones in the Pathogenesis and Treatment of Bone Health in Patients with Chronic Kidney Disease: a Systematic Review and Meta-Analysis , 2018, Current Osteoporosis Reports.

[12]  T. Nickolas,et al.  Management of Osteoporosis in CKD. , 2018, Clinical journal of the American Society of Nephrology : CJASN.

[13]  P. Ebeling,et al.  Deterioration of Cortical Bone Microarchitecture: Critical Component of Renal Osteodystrophy Evaluation , 2018, American Journal of Nephrology.

[14]  T. Nickolas The Quest for Better Biomarkers of Bone Turnover in CKD. , 2018, Journal of the American Society of Nephrology : JASN.

[15]  G. Elder,et al.  The trabecular bone score is associated with bone mineral density, markers of bone turnover and prevalent fracture in patients with end stage kidney disease , 2018, Osteoporosis International.

[16]  J. Carrero,et al.  Cinacalcet use and the risk of cardiovascular events, fractures and mortality in chronic kidney disease patients with secondary hyperparathyroidism , 2018, Scientific Reports.

[17]  James M. Eales,et al.  Tick-Tock Chimes the Kidney Clock – from Biology of Renal Ageing to Clinical Applications , 2018, Kidney and Blood Pressure Research.

[18]  J. Craig,et al.  Phosphate binders for preventing and treating chronic kidney disease-mineral and bone disorder (CKD-MBD). , 2018, The Cochrane database of systematic reviews.

[19]  R. Eastell,et al.  Use of bone turnover markers in postmenopausal osteoporosis. , 2017, The lancet. Diabetes & endocrinology.

[20]  S. Sprague,et al.  Extended-release calcifediol for secondary hyperparathyroidism in stage 3-4 chronic kidney disease , 2017, Expert review of endocrinology & metabolism.

[21]  Mary B Leonard,et al.  Executive summary of the 2017 KDIGO Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD) Guideline Update: what's changed and why it matters. , 2017, Kidney international.

[22]  Andreja Marn Pernat,et al.  Bone mineral disturbances in patients with chronic kidney disease stage 5 not yet on dialysis. , 2017, Clinical Nephrology.

[23]  S. Moe Renal Osteodystrophy or Kidney-Induced Osteoporosis? , 2017, Current Osteoporosis Reports.

[24]  J. Kanis,et al.  FRAX Update. , 2017, Journal of clinical densitometry : the official journal of the International Society for Clinical Densitometry.

[25]  A. Rule,et al.  The Substantial Loss of Nephrons in Healthy Human Kidneys with Aging. , 2017, Journal of the American Society of Nephrology : JASN.

[26]  D. Davenport,et al.  Two-year cortical and trabecular bone loss in CKD-5D: biochemical and clinical predictors , 2017, Osteoporosis International.

[27]  H. Kimura-Suda,et al.  Efficacy and safety of osteoporosis medications in a rat model of late-stage chronic kidney disease accompanied by secondary hyperparathyroidism and hyperphosphatemia , 2017, Osteoporosis International.

[28]  C. Christiansen,et al.  Effect of Abaloparatide vs Placebo on New Vertebral Fractures in Postmenopausal Women With Osteoporosis: A Randomized Clinical Trial. , 2016, JAMA.

[29]  S. Moe,et al.  Diagnostic Accuracy of Bone Turnover Markers and Bone Histology in Patients With CKD Treated by Dialysis. , 2016, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[30]  C C Glüer,et al.  Trabecular bone score (TBS) as a new complementary approach for osteoporosis evaluation in clinical practice. , 2015, Bone.

[31]  S. Jamal,et al.  Teriparatide and bone turnover and formation in a hemodialysis patient with low-turnover bone disease: a case report. , 2015, American Journal of Kidney Diseases.

[32]  A. Cheung,et al.  Rationale and Approaches to Phosphate and Fibroblast Growth Factor 23 Reduction in CKD. , 2015, Journal of the American Society of Nephrology : JASN.

[33]  C. Chiang,et al.  Hypocalcemia Post Denosumab in Patients with Chronic Kidney Disease Stage 4-5 , 2015, American Journal of Nephrology.

[34]  S. Boonen,et al.  Renal safety in patients treated with bisphosphonates for osteoporosis: A review , 2013, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[35]  K. Hruska,et al.  Pathophysiology of Chronic Kidney Disease Mineral Bone Disorder (CKD‐MBD) , 2013 .

[36]  P. Miller,et al.  Skeletal effects of primary hyperparathyroidism: bone mineral density and fracture risk. , 2013, Journal of clinical densitometry : the official journal of the International Society for Clinical Densitometry.

[37]  J. Bacchetta,et al.  Bone microarchitecture is more severely affected in patients on hemodialysis than in those receiving peritoneal dialysis. , 2012, Kidney international.

[38]  S. Cummings,et al.  Effects of denosumab on fracture and bone mineral density by level of kidney function , 2011, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[39]  Jacques P. Brown,et al.  Effects of denosumab on bone histomorphometry: The FREEDOM and STAND studies , 2010, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[40]  C. Cooper,et al.  Long-term treatment with bisphosphonates and their safety in postmenopausal osteoporosis , 2010, Therapeutics and clinical risk management.

[41]  H. Macdonald,et al.  Changes in trabecular and cortical bone microarchitecture at peripheral sites associated with 18 months of teriparatide therapy in postmenopausal women with osteoporosis , 2010, Osteoporosis International.

[42]  P. Miller Fragility fractures in chronic kidney disease: An opinion-based approach , 2009, Cleveland Clinic Journal of Medicine.

[43]  M. Almeida,et al.  Increased Lipid Oxidation Causes Oxidative Stress, Increased Peroxisome Proliferator-activated Receptor-γ Expression, and Diminished Pro-osteogenic Wnt Signaling in the Skeleton* , 2009, The Journal of Biological Chemistry.

[44]  P. Miller The role of bone biopsy in patients with chronic renal failure. , 2008, Clinical journal of the American Society of Nephrology : CJASN.

[45]  A. Levin,et al.  Prevalence of abnormal serum vitamin D, PTH, calcium, and phosphorus in patients with chronic kidney disease: results of the study to evaluate early kidney disease. , 2007, Kidney international.

[46]  G. Eknoyan,et al.  Definition, evaluation, and classification of renal osteodystrophy: a position statement from Kidney Disease: Improving Global Outcomes (KDIGO). , 2006, Kidney international.

[47]  E. Schwartz,et al.  Teriparatide in postmenopausal women with osteoporosis and mild or moderate renal impairment , 2006, Osteoporosis International.

[48]  G. Eknoyan,et al.  Definition and classification of chronic kidney disease: a position statement from Kidney Disease: Improving Global Outcomes (KDIGO). , 2005, Kidney international.

[49]  G. Eknoyan,et al.  Prevalence of chronic kidney disease and decreased kidney function in the adult US population: Third National Health and Nutrition Examination Survey. , 2003, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[50]  R. Turner,et al.  Printed in U.S.A. Copyright © 1997 by The Endocrine Society The Effects of Programmed Administration of Human Parathyroid Hormone Fragment (1–34) on Bone Histomorphometry and Serum Chemistry in Rats* , 2022 .

[51]  Claus Christiansen,et al.  Assessment of fracture risk and its application to screening for postmenopausal osteoporosis. Report of a WHO Study Group. , 1994, World Health Organization technical report series.

[52]  E. Ritz,et al.  Calcium metabolism in early chronic renal failure: implications for the pathogenesis of hyperparathyroidism. , 1991, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[53]  E. Ritz,et al.  Bone histology in incipient and advanced renal failure. , 1976, Kidney international.