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A. Introduction navigator

  1. Renal osteodystrophy describes skeletal complications of end-stage renal disease
  2. Types of Renal Osteodystrophy
    1. Osteitis Fibrosa
    2. Osteomalacia
    3. Adynamic Bone Disease (ABD)
  3. Contributing Factors
    1. 1alpha,25 dihydroxyvitamin D3 (DHVD3) deficiency
    2. Hyperphosphatemia may be major contributor
    3. These deficiencies lead to secondary hyperparathyroidism (HPT)
    4. Increased levels of circulating cytokines
    5. Aluminum accumulation in bone (dialysates now contain calcium, not aluminum)
  4. Hyperparathyroidism [2]
    1. Secondary Hyperparathyroidism occurs in renal disease due to chronic hypocalcemia and probably more due to hyperphosphatemia [3]
    2. Refractory secondary HTP occurs in patients with nonsuppressible parathyroid hormone
    3. Tertiary hyperparathyroidism - secondary HPT leading to hypercalcemia
    4. In secondary and tertiary HPT, the parathyroid gland has lost normal responses

B. Osteitis Fibrosa navigator

  1. Classic histologic form of renal osteodystrophy
    1. Marrow fibrosis - fibroblast-like cells in marrow
    2. Increased bone remodelling - both osteoclasts and osteoblasts
    3. Increased amount of osteoid and nonlamellar bone (high bone turnover markers)
  2. Secondary Hyperparathyroidism (HPT)
    1. Parathyroid hormone (PTH) release is stimulated by low calcium levels
    2. Low calcium levels due primarily to deficiency of DHVD3
    3. Kidney is responsible for conversion of 25-OH-D3 to DHVD3
    4. High phosphate levels may be primary driver for increased PTH release
    5. High phosphate due to reduced clearance and increased bone release (buffering effects)
    6. Replacement of vitamin D with calcitriol only partially reverses hyperparathyroidism
    7. Reduced DHVD3 receptor levels in parathyroid and reset-calcium sensor may play roles
  3. Laboratory Parameters
    1. Significantly elevated (heat labile) alkaline phosphatase
    2. High PTH levels
    3. Hypocalcemia and hyperphosphatemia

C. Osteomalacianavigator

  1. Characteristics
    1. Low rates of bone turnover
    2. Mineralization defect with accumulation of unmineralized osteoid (bone matrix)
  2. Pathophysiology
    1. Distinct from pure Vitamin D deficiency
    2. May be related to accumulation of aluminum and other heavy metals in bone
    3. These cause defective mineralization and longterm inhibition of osteoblast formation
    4. Iron overload may also cause osteomalacia

D. Adynamic Bone Disease navigator

  1. Poorly understood pathogenesis, but this is a failure of bone to remodel
  2. Occurs mainly in end-stage renal disease (ESRD) patients without hyperparathyroidism
  3. May be related to increase in suppressors of bone formation
    1. Interleukin 11: inhibits osteobastic bone formation
    2. IL-4
    3. Increased levels of IL-1 receptor antagonist and soluble TNF receptor
    4. High doses of vitamin D analogs may suppress PTH and bone modelling
    5. Previously, this disease was seen with aluminum intoxication
  4. Deficiency in activators of bone formation (such as osteogenic protein 1) may also play a role
  5. Associated with increased fracture rate, bone pain, possible osteopenia
  6. Laboratory Parameters
    1. Normal or slightly elevated alkaline phosphatase
    2. Near normal PTH levels
    3. Hypercalcemia

E. Diagnosisnavigator

  1. Laboratory parameters are rarely useful for determining type of disease in single patient
  2. Bone biopsy is not usually performed but is best method for determining disease type

F. Treatmentnavigator

  1. Low phosphate diet and phosphate binder [5]
    1. Maintain calcium in normal range and reduce phosphate levels
    2. Goal is to keep calcium - phosphate (Ca-P) product in optimal range, <70 mg2/dL2
    3. Target PTH in dialysis patients is <300pg/mL
    4. Calcium carbonate or acetate to raise calcium and reduce phosphate and PTH levels
    5. Calcium acetate (PhosLo®) preferred over calcium carbonate (OsCal®, Caltrate®)
    6. Dose of calcium acetate is 667mg tabs, 3-4 tabs tid with meals
    7. Sevelamer (RenaGel®) is a non-adsorbed phosphate binder with good tolerability approved for hyperphosphatemia [3]
    8. Dose of sevelamer is 800-1600mg tid with meals (400 and 800mg tabs)
    9. Calcium acetate reduces phosphate to <5.5mg/dL better than sevelamer
    10. Lanthanum carbonate (Fosrenol®) has minor absorption, good phosphate reductions
    11. Vitamin D replacement must also be given, and increases both calcium and phosphate
    12. Cinacalcet (Sensipar®) is a calcium-sensor receptor agonist which reduces Ca-P product [6]
  2. Calcium Levels
    1. Maintain high-normal levels of serum calcium to suppress PTH oversecretion
    2. Alter dialysate calcium to maintain such levels
    3. Additional dietary calcium may be given if needed
    4. However, caution with high serum calcium and high serum phosphate together
    5. This can lead to "metastatic calcificiation" and calcium phosphate deposition in tissues
  3. Vitamin D Analogs
    1. Calcitriol is usually preferred because it does not require activation for activity
    2. In addition, calcitriol levels do not build up in renal failure
    3. Alfacalcidol, dihydrotachysterol and calcifediol are also used
    4. Lessen bone pain, improve bone histology, and increase serum calcium (and phosphate)
    5. Use with caution in patients with high phosphate levels
    6. Moderate doses reduce phosphate concentrations, alkaline phosphatase, PTH
    7. Overuse may predispose to adynamic bone disease
  4. Calcium Senor Agonist [4]
    1. Calcium sensor is a G-protein coupled receptor glycoprotein mainly found in parathyroid
    2. Senses calcium levels and negatively affects PTH levels
    3. Secondary hyperPTH can now be treated with calcium sensor agonist cinacalcet
    4. Once daily doses initially 30mg up to 180mg titrated to reduce PTH to <250pg/dL
    5. Approved for use in renal osteodystrophy, hemodialysis

References navigator

  1. Hruska KA and Teitelbaum SL. 1995. NEJM. 333(3):166 abstract
  2. Mark SJ. 2000. NEJM. 343(25):1863 abstract
  3. Chertow GM, Burke SK, Lazarus JM, et al. 1997. Am J Kid Dis. 29(1):66 abstract
  4. Block GA, Martin KJ, de Rancisco ALM, et al. 2004. NEJM. 350(15):1516 abstract
  5. Phosphate Binders. 2006. Med Let. 48(1228):15 abstract
  6. Cinacalcet. 2004. Med Let. 46(1192):80 abstract