Renal Osteodystrophy

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Renal Osteodystrophy
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• Skeletal disorders that primarily occur in
  patients with renal failure
• Osteitis fibrosa
• Osteomalacia
• Adynamic bone lesions
• Mixed lesions
• Dialysis related amyloidosis

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Osteitis fibrosa and secondary hyperparathyrodism

• High level of PTH, increase number and activity
  of osteoblasts and osteoclasts
• High bone turnover
• Increased quantity of unmineralized bone matrix(
  osteoid)

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Pathogenesis of secondary hyperparathyrodism(1)

• Phosphate retention and Calcitriol deficiency
• GFR less than 20 of normal ,hyperphosphatemia
  develops
• Limited amount of residual renal mass available
  for Calcitriol synthesis
• Calcium malabsorption
• Calcitriol deficiency leads to impaired GI
  absorption of calcium, as GFR falls below 50 ml
  /min

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Pathogenesis of secondary hyperparathyrodism(2)

• Skeletal resistance to Calcemic action of PTH
• Decreased number of Calcitriol receptors in the
  uremic parathyroid gland
• Calcitriol reduces prepro-PTH messenger RNA
  levels by decreasing the rate of gene
  transcription
• Parathyroid hyperplasia
• Little is known about the factors that lead to
  cellular proliferation
• Once established ,not reversed by short term
  calcitriol treatment

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Diagnosis of uremic hyperparathyrodism

• High level of I-PTH. Without liver disease, serum
  Alk-P level often correlate with PTH
• Radiographic changes of osteitis fibrosa
• Subperiosteal erosions of phalanges
• Erosions at proximal end of the tibia ,neck of
  femur or humerus and inferior surface of distal
  end of clavicle
• In the skull, salt and pepper appearance
• Bone biopsy necessary when diagnosis uncertain

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Prevention and treatment of uremic
hyperparathyrodism

• Phosphorus control
• In early renal failure, phosphorus accumulation
  may be avoided by restriction of dietary
  phosphorus intake to 600-800mg/d
• Limiting meats and dairy products
• More strict dietary phosphorus restriction is
  usually impractical

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• Phosphorus control
• Phosphorus binder
• Containing aluminum
• Calcium carbonate
• Calcium acetate
• not containing calcium or aluminum ,
  sevelamer hydrochloride
• As patients begin dialysis therapy, increase
  dietary phosphorus to 800-1200 mg/d
• Hemodialysis removes approximately 1000mg
  /treatment
• CAPD removes 300 mg/d

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Prevention and treatment of uremic
hyperparathyrodism

• Control of calcium
• Use of vitamin D sterols
• Metabolite of vitamin D directly suppressing PTH
  secretion, marked suppression of PTH
• administering 1-2 ug of calcitriol intravenously
  after each hemodialysis three times a week
• Pulse oral calcitriol 2-4 ug twice a week
• If PTH levels do not fall into an acceptable
  range after 1 year of treatment ,surgical
  parathyroidectomy or parathyroid gland ablation
  by ethanol should be considered

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• Use of vitamin D sterols
• Calcitriol should not be used
• when hyperphosphatemia is present
• Calcium-phosphorus product of greater than 75 may
  lead to soft tissue calcifications
• Paricalcitol and doxercalciferol , analogs of
  calcitriol ,less active in raising calcium and
  phosphorus level were approved in United States
• If PTH less than 250 pg/ml( or less than four
  times the upper limits of normal)
• Inducing adynamic bone lesions

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• Use of vitamin D sterols
• Vitamin D induced hypercalcemia is particularly
  prolonged and may require weeks for resolution

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Osteomalacia

• Pathogenesis
• Metabolic acidosis
• Aluminum intoxication ,directly suppresses PTH
  secretion
• Contamination of dialysate
• phosphorus binders containing aluminum
• Citrate increases absorption of aluminum from the
  gut

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Osteomalacia

• Diagnosis
• Low PTH level
• Exposure to aluminum
• Bone and muscle pain ,spontaneous fractures occur
  in approximately 15
• Radiographic findings are not distinctive
• DFO test
• Gold standard is bone biopsy

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• Diagnosis
• DFO test
• 5-20 mg/kg administered intravenously at the end
  of dialysis
• Serum aluminum measured 24 to 48 hrs later
• Basal serum aluminum level of gt100 ug/L and an
  increment in aluminum level of gt150 ug/L
  following chelation with DFO

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• Prevention and treatment of osteomalacia caused
  by aluminum
• Dialysate purified
• Avoidance of phosphorus binders containing
  aluminum
• Chronic chelation therapy with DFO
• Risk of mucormycosis infections occurs in up to
  5 of treated patients
• Acute encephalopathy has been described with DFO
• Binds iron
• DFO should be restricted to those who have severe
  symptoms of aluminum intoxication and
  histological evidence of aluminum accumulation in
  the bone

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Adynamic bone lesions

• Decreased bone mineralization ,with normal
  amounts of osteoid
• 50 of cases ,cause if aluminum deposition
  .Little is known about the etiology in the
  remaining
• Common in patients treated with PD ,in the
  elderly and patients with DM
• Fewer symptoms of bone pain, myopathy and
  fractures than osteomalacia and osteitis fibrosa
  

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Mixed lesions

• Histological evidence of both osteitis fibrosa
  and osteomalacia
• High PTH level
• Previously established osteodystrophy who
  developing a aluminum-related bone disease
• Treatment is withdrawal of aluminum exposure and
  aggressive treatment of the hyperparathyrodism

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Dialysis-related Amyloidosis

• Bone cysts ,pathological fracture ,arthritis ,and
  carpal tunnel syndrome treated with long term
  dialysis
• Deposition of ß 2-microglobulin
• No proven treatment for the amyloidosis
  arthropathy
• Use of high flux hemodialysis or
  hemodiafiltration removes some ß 2-microglobulin
• Early renal transplantation completely prevents
  the disease

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Renal osteodystrophy following renal
transplantation

• Mild to moderately severe osteitis fibrosa
  resolve within a year
• Severe hyperparathyrodism may not completely
  resolved ,and elevated PTH levels may persisted
  for 5-10 years
• Symptoms of amyloid deposition often improve, but
  radiographic findings do not change .This
  suggests that amyloid may be irreversibly bound
  to soft tissue

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Overall approach to the management of renal
osteodystrophy

• Target calcium and phosphorus levels are 9.5-10.5
  and 4.5-5.5 mg/dL
• At time of surgery ,all four glands should be
  identified
• Some surgeons will do a three and one half gland
  parathroidectomy others will remove all glands
  and implant small pieces of one gland into the
  forearm
• recurrence rates are the same for the two
  techniques 5-15