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

doi:10.1053/j.ajkd.2020.12.024

American Journal of Kidney Diseases

Volume 78, Issue 4, October 2021, Pages 582-589

https://doi.org/10.1053/j.ajkd.2020.12.024 Get rights and content

Osteoporosis is defined as a skeletal disorder of compromised bone strength predisposing those affected to an elevated risk of fracture. However, based on bone histology, 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, the label “kidney-induced osteoporosis” has been proposed, even though the changes caused by CKD do not qualify as osteoporosis by the histological diagnosis. 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 because it brings osteoporosis under the official label of CKD-MBD. Neither laboratory nor noninvasive 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, a 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 approved by the US Food and Drug Administration for patients with kidney-associated bone disease. Agents that suppress parathyroid hormone (vitamin D analogues and calcimimetics) are used to treat hyperparathyroid bone disease. Antiresorptive and osteoanabolic agents approved for osteoporosis are being used off-label to treat CKD stages 3b-5 in high-risk patients. It has now been suggested that intermittent administration of parathyroid hormone as early as CKD stage 2 could be an effective management strategy. If confirmed in clinical trials, it could mitigate the retention of phosphorus and subsequently the rise in fibroblast growth factor 23 and may be beneficial for coexisting osteoporosis.

Section snippets

Differential Diagnosis: Osteoporosis Versus Renal Osteodystrophy

Osteoporosis has no obvious symptoms until there is a fracture. In CKD, patients with mild to moderate decreases in kidney function and skeletal involvement are rarely symptomatic. Patients with adynamic bone disease (a low bone turnover form of renal osteodystrophy) are asymptomatic. Patients with severely decreased kidney function with secondary/tertiary hyperparathyroidism (a high bone turnover form) may report bone pain and tenderness. In osteomalacia, diffuse bone pain is common in the

Renal Osteodystrophy: Treatment

The clinical management of CKD-MBD is an uphill battle because the currently available treatment options do not completely correct the abnormalities leading to its development and progression. The effect of phosphate binders on reducing hyperphosphatemia, the stimulus for FGF-23 production, is minimal.³¹ Additionally, the effect of phosphate binders on important clinical outcomes such as fractures and vascular calcification is uncertain.³²

The current treatment paradigm for renal osteodystrophy

Conclusion

Osteoporosis can coexist with CKD-MBD. The existing definitions of osteoporosis by the NIH and WHO, together with the proposed labels of kidney-induced osteoporosis and CKD-associated osteoporosis, project a dominant role for osteoporosis rather than renal osteodystrophy in CKD-MBD. Therefore, to prevent CKD-MBD from being marginalized, we would suggest a new diagnostic label, CKD-MBD/osteoporosis. This term captures both the CKD-MBD component of renal osteodystrophy and the osteoporosis

Article Information

Authors’ Full Names and Academic Degrees

Michael Pazianas, MD, and Paul D. Miller, MD.

Support

None.

Financial Disclosure

The authors declare that they have no relevant financial interests.

Peer Review

Received August 23, 2020. Evaluated by 3 external peer reviewers, with direct editorial input from an Associate Editor and a Deputy Editor. Accepted in revised form December 29, 2020.

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

Section snippets

Differential Diagnosis: Osteoporosis Versus Renal Osteodystrophy

Renal Osteodystrophy: Treatment

Conclusion

Article Information

Authors’ Full Names and Academic Degrees

Support

Financial Disclosure

Peer Review

Kidney Int

J Biol Chem

Lancet Diabetes Endocrinol

Kidney Int

Am J Kidney Dis

J Clin Densitom

J Clin Densitom

Kidney Int

Bone

Kidney Int

Am J Kidney Dis

Am J Kidney Dis

Kidney Int

Kidney Int

Glucocorticoid-induced osteoporosis: new insights into the pathophysiology and treatments

Curr Osteoporos Rep

Two-year cortical and trabecular bone loss in CKD-5D: biochemical and clinical predictors

Osteoporos Int

39. Die Entwicklung der renalen Osteopathie unter Chronischer Hämodialysebehandlung bei bilateral nephrektomierten, skelettgesunden Patienten [The renal osteodystrophy of bilateral nephrectomised patients with preoperative normal skeletal histology during chronic hemodialysis]

Verh Dtsch Ges Pathol

Tick-tock chimes the kidney clock—from biology of renal ageing to clinical applications

Kidney Blood Press Res

The substantial loss of nephrons in healthy human kidneys with aging

J Am Soc Nephrol

Assessment of fracture risk and its application to screening for postmenopausal osteoporosis. Report of a WHO Study Group

World Heath Organ Tech Rep Ser

Renal osteodystrophy or kidney-induced osteoporosis?

Curr Osteoporos Rep

Rethinking bone disease in kidney disease

JBMR Plus

Pathophysiology of chronic kidney disease mineral bone disorder (CKD-MBD)

Gonadal hormones in the pathogenesis and treatment of bone health in patients with chronic kidney disease: a systematic review and meta-analysis

Curr Osteoporos Rep

Defining very high fracture risk: is FRAX fit for purpose?

J Bone Miner Res

How and when to assess bone mineral density and bone quality in chronic kidney disease patients?

Nephrol Dial Transplant

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

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