Renal osteodystrophy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Nazia Fuad M.D.

Synonyms and keywords:Chronic kidney disease- mineral bone disorder

Overview

Renal osteodystrophy is defined as the complex metabolic bone disorders which are present in chronic renal insufficiency. Secondary hyperparathyroidism and 1,25-dihydroxycholecalciferol (Vitamin D3) deficiency play a major role in renal osteodystrophy. Renal osteodystrophy is defined as an alteration of bone morphology in patients with chronic kidney disease and is considered to be a component of chronic kidney disease - mineral bone disorder (CKD-MBD). Renal osteodystrophy is an important cause of morbidity, decreased quality of life, and extravascular calcifications that have been associated with increased cardiovascular mortality. The classification of renal osteodystrophy describes a wider clinical syndrome based on bone turnover, bone mineralization, and bone volume. To investigate renal osteodystrophy, blood levels of parathyroid hormone (PTH), calcium, phosphorus, alkaline phosphatase, bicarbonate should initially be ordered. Imaging studies should focus on finding calcification in soft tissues. A bone biopsy is indicated if the results of biochemical markers are not consistent, there is unexplained bone pain, or presence of unexplained bone fractures. However, bone biopsies are infrequently used in clinical practice due to invasiveness and lower cost effectiveness. The major objective in the prevention and management of renal osteodystrophy is either prevention of hyperparathyroidism or treatment if present already.

Historical Perspective

  • Renal osteodystrophy was first defined by Kidney Disease: Improving Global Outcomes (KDIGO) in 2006.
  • It was discovered in the 1970s and 1980s, that aluminum in water that is used for dialysis and aluminum salts that are used as phosphate binders caused osteomalacia and an adynamic bone disease.
  • The identification of these disorders led to define renal osteodystrophy. [1]

Classification

  • Renal osteodystrophy can be classified according to histology into the following subtypes:[2][3]
Histologic Classification of Renal Osteodystrophy
Disorder Description Pathogenesis Frequency (%)
Osteitis fibrosa  Peritrabecular fibrosis, increased

remodeling — resorption and formation.

Secondary hyperparathyroidism, secondary

role of cytokines and growth factors

50
Osteomalacia  Increased osteoid, defective

mineralization

Aluminum deposition, plus

unknown factors

7
Mixed disease  Features of both osteitis fibrosa

and osteomalacia

Secondary hyperparathyroidism

and aluminum deposition,

plus unknown factors

13
Mild disease  Slightly increased remodeling Early or treated secondary

hyperparathyroidism

3
Adynamic renal

bone disease

Hypocellular bone surfaces,

no remodeling

Aluminum deposition, parathyroid hormone

suppression, and other factors

(deficiency of bone growth factors or

increased suppressors of bone remodeling)

27
  • After the bone pathology is assessed by histomorphometry,renal osteodystrophy can be subdivided according to TMV classification
  • TMV uses three descriptions- bone turnover(T), bone mineralization(M)

and bone volume(V).

Pathophysiology

The following factors in chronic kidney disease are considered to be the main contributors to renal osteodystrophy:[5][6][7]

 Factors in the pathogenesis of hyperparathyroidism in chronic renal disease
Phosphorus retention Hypocalcemia Low calcitriol Skeletal

resistance

Altered

parathyroid function

↓Renal mass + +
Phosphorus + + + ?
Calcium +
Calciterol + + +
Skeletal resistance +
Desensitization to PTH +
Vit D receptors +
Altered cell growth +
Acidosis +

Causes

Differentiating Renal Osteodystrophy from Other Diseases

  • Renal osteodystrophy must be differentiated from the diseases that cause abnormal bone mineralization, unexplained bone fractures and bone pain:[10]

Epidemiology and Demographics

  • The prevelence of renal osteodystrophy is 8,000 per 100,000 in the adult population in US. Incidence of renal osteodystrophy increases in patients with chronic kidney disease who have glomerular filtration rate (GFR) less than 60 mL/min.[11]
  • Prevalence in developing countries:
    • The prevalence of renal osteodystrophy in developing countries is 24.4% to 63%.
    • Aluminum, high strontium levels and iron overload play a major role in the development of renal osteodystrophy in patients who undergo dialysis in developing countries.

Risk Factors

Natural History, Complications, and Prognosis

Common complications of renal osteodystrophy include:[13]

Prognosis

Diagnosis

Diagnostic Study of Choice

Bone biopsy

  • A definitive tool for diagnosis of renal osteodystrophy is bone biopsy according to KIDGO 2017 guidelines.[14]
  • However, bone biopsies are infrequently performed because it is an invasive and expensive procedure.

Serum biomarkers

The following biomarkers are used in the diagnosis of renal osteodystrophy:

  • The following framework is used to describe the risk for different subtypes of renal osteodystrophy:[17]
    • PTH <100 pg/mL  means adynamic bone disease and a decreased risk of osteitis fibrosa cystica
    • PTH >450 pg/mL means osteitis fibrosa cystica and/or MUO(mixed uremic osteodystrophy)
    • Intermediate PTH levels between 100 and 450 pg/mL  Intermediate values may be due to normal or increased turnover or even reduced bone turnover[18]   

History and Symptoms

Physical Examination

Laboratory Findings

  •  Measurement of bone turnover on a bone biopsy is determined by labeling the bone with tetracycline. The procedure is done at two separate times approximately 2 weeks apart. The distance between the two areas of tetracycline deposition is measured and can be used to calculate bone growth.

PTH(parathyroid hrmone) levels are the best noninvasive option for assessment of bone turnover.[21]

  • The following parameters are used to define the risk for specific subtypes of renal osteodystrophy.[17]
    • PTH <100 pg/mL suggests adynamic bone disease and a decreased risk of osteitis fibrosa cystica and or MUO(mixed uremic osteodystrophy)
    • PTH >450 pg/mL suggests osteitis fibrosa cystica and/or MUO(mixed uremic osteodystrophy).
    • Intermediate PTH levels between 100 and 450 pg/mL.  Intermediate values may be associated with normal or increased bone turnover or even reduced turnover.[22] 

Electrocardiogram

X-ray

Echocardiography or Ultrasound

CT scan

  • CT scan findings associated with renal osteodystrophy are the same that are related to chronic kidney disease.

MRI

  • There are no MRI findings associated with renal osteodystrophy.

Other Imaging Findings

  • There are no other imaging findings associated with renal osteodystrophy.

Other Diagnostic Studies

Treatment

Medical Therapy:

Control of Serum Calcium

  • Calcium malabsorption is seen in end-stage renal disease because of deficient 1,25-dihydroxycholecalciferol.[27]
  • To prevent or suppress oversecretion of parathyroid hormone, calcium concentrations should be maintained at the high end of the normal range.
  • In patients with calcium intakes of 800–1000 mg/day, additional calcium supplements or calcium-containing medications should be avoided.
  • Patients with total calcium intakes (>approx. 1000 mg/day) should be advised to decrease calcium intake.
  • Patients with lower calcium intakes should be advised to increase calcium intake in foods,or take calcium supplements.
  • . Calcium-rich foods include dairy, dark green leafy vegetables, calcium-set tofu, and calcium-fortified orange juice.
  • The timing of taking oral calcium is crucial as calcium taken between meals is more like a calcium supplement than a phosphate binder.

Control of Serum Phosphate

Use of Vit D analogue[28]

Surgery

Primary Prevention

Secondary Prevention

References

  1. Hruska, Keith A.; Epstein, Franklin H.; Teitelbaum, Steven L. (1995). "Renal Osteodystrophy". New England Journal of Medicine. 333 (3): 166–175. doi:10.1056/NEJM199507203330307. ISSN 0028-4793.
  2. Hruska, Keith A.; Epstein, Franklin H.; Teitelbaum, Steven L. (1995). "Renal Osteodystrophy". New England Journal of Medicine. 333 (3): 166–175. doi:10.1056/NEJM199507203330307. ISSN 0028-4793.
  3. Moe, S.; Drüeke, 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 International. 69 (11): 1945–1953. doi:10.1038/sj.ki.5000414. ISSN 0085-2538.
  4. Moe, S.; Drüeke, 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 International. 69 (11): 1945–1953. doi:10.1038/sj.ki.5000414. ISSN 0085-2538.
  5. Gonzalez, E. A.; Martin, K. J. (1995). "Renal osteodystrophy: pathogenesis and management". Nephrology Dialysis Transplantation. 10 (supp3): 13–21. doi:10.1093/ndt/10.supp3.13. ISSN 0931-0509.
  6. Moe, S.; Drüeke, 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 International. 69 (11): 1945–1953. doi:10.1038/sj.ki.5000414. ISSN 0085-2538.
  7. Hruska, Keith A.; Epstein, Franklin H.; Teitelbaum, Steven L. (1995). "Renal Osteodystrophy". New England Journal of Medicine. 333 (3): 166–175. doi:10.1056/NEJM199507203330307. ISSN 0028-4793.
  8. https://www.orthopaedicsone.com/display/MSKMed/Renal+osteodystrophy
  9. Nissenson, Allen (2009). Current diagnosis & treatment. New York: McGraw-Hill Medical. ISBN 978-0-07-144787-4.
  10. https://www.orthopaedicsone.com/display/MSKMed/Renal+osteodystrophy
  11. https://www.orthopaedicsone.com/display/MSKMed/Renal+osteodystrophy
  12. 12.0 12.1 Malluche, Harmut H.; Faugere, Marie-Claude (1989). "Renal Osteodystrophy". New England Journal of Medicine. 321 (5): 317–319. doi:10.1056/NEJM198908033210509. ISSN 0028-4793.
  13. 13.0 13.1 13.2 Hruska, Keith A.; Epstein, Franklin H.; Teitelbaum, Steven L. (1995). "Renal Osteodystrophy". New England Journal of Medicine. 333 (3): 166–175. doi:10.1056/NEJM199507203330307. ISSN 0028-4793.
  14. Markus Ketteler, Geoffrey A. Block, Pieter Evenepoel, Masafumi Fukagawa, Charles A. Herzog, Linda McCann, Sharon M. Moe, Rukshana Shroff, Marcello A. Tonelli, Nigel D. Toussaint, Marc G. Vervloet & Mary B. Leonard. "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 international. 92 (1): 26–36. PMID 28646995. Unknown parameter |= ignored (help); Unknown parameter |month= ignored (help)
  15. Gonzalez, E. A.; Martin, K. J. (1995). "Renal osteodystrophy: pathogenesis and management". Nephrology Dialysis Transplantation. 10 (supp3): 13–21. doi:10.1093/ndt/10.supp3.13. ISSN 0931-0509.
  16. Hruska, Keith A.; Epstein, Franklin H.; Teitelbaum, Steven L. (1995). "Renal Osteodystrophy". New England Journal of Medicine. 333 (3): 166–175. doi:10.1056/NEJM199507203330307. ISSN 0028-4793.
  17. 17.0 17.1 Sharon M. Moe. "Management of renal osteodystrophy in peritoneal dialysis patients". Peritoneal dialysis international : journal of the International Society for Peritoneal Dialysis. 24 (3): 209–216. PMID 15185768. Unknown parameter |= ignored (help); Unknown parameter |month= ignored (help)
  18. Moe, S.; Drüeke, 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 International. 69 (11): 1945–1953. doi:10.1038/sj.ki.5000414. ISSN 0085-2538.
  19. https://www.orthopaedicsone.com/display/MSKMed/Renal+osteodystrophy
  20. https://www.orthopaedicsone.com/display/MSKMed/Renal+osteodystrophy
  21. Hruska, Keith A.; Epstein, Franklin H.; Teitelbaum, Steven L. (1995). "Renal Osteodystrophy". New England Journal of Medicine. 333 (3): 166–175. doi:10.1056/NEJM199507203330307. ISSN 0028-4793.
  22. Moe, S.; Drüeke, 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 International. 69 (11): 1945–1953. doi:10.1038/sj.ki.5000414. ISSN 0085-2538.
  23. https://radiopaedia.org/articles/renal-osteodystrophy
  24. Gonzalez, E. A.; Martin, K. J. (1995). "Renal osteodystrophy: pathogenesis and management". Nephrology Dialysis Transplantation. 10 (supp3): 13–21. doi:10.1093/ndt/10.supp3.13. ISSN 0931-0509.
  25. https://www.orthopaedicsone.com/display/MSKMed/Renal+osteodystrophy
  26. https://www.orthopaedicsone.com/display/MSKMed/Renal+osteodystrophy
  27. Hruska, Keith A.; Epstein, Franklin H.; Teitelbaum, Steven L. (1995). "Renal Osteodystrophy". New England Journal of Medicine. 333 (3): 166–175. doi:10.1056/NEJM199507203330307. ISSN 0028-4793.
  28. Hruska, Keith A.; Epstein, Franklin H.; Teitelbaum, Steven L. (1995). "Renal Osteodystrophy". New England Journal of Medicine. 333 (3): 166–175. doi:10.1056/NEJM199507203330307. ISSN 0028-4793.
  29. Gonzalez, E. A.; Martin, K. J. (1995). "Renal osteodystrophy: pathogenesis and management". Nephrology Dialysis Transplantation. 10 (supp3): 13–21. doi:10.1093/ndt/10.supp3.13. ISSN 0931-0509.
  30. 30.0 30.1 Malluche, Harmut H.; Faugere, Marie-Claude (1989). "Renal Osteodystrophy". New England Journal of Medicine. 321 (5): 317–319. doi:10.1056/NEJM198908033210509. ISSN 0028-4793.

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Renal Osteodystrophy

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