X RAYS OF METABOLIC BONE DISEASES. CONTENTS XRAY OF METABOLIC DISEASE OF BONE SUMMARY.
Metabolic Bone Disease
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Transcript of Metabolic Bone Disease
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Metabolic Bone DiseaseMetabolic Bone Disease
Douglas Stahura DO
19 March 2002
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OverviewOverview
Normal bone undergoes constant remodeling:– Production of organic matrix (osteoblasts)– Matrix maturation– Mineralization of mature matrix– Osteoclastic resorption of mineralized bone
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OverviewOverview
Metabolic bone disease refers to :– Diffuse decrease in bone density
(osteopenia) and strength– Due to:
– Increased bone resorption– Decreased bone formation
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OverviewOverviewExamples
– Osteoporosis - decreased bone mass in combination with disruption of normal architecture
– Osteomalacia – disorder of mineralization of newly formed matrix
– Hyperparathyroidism – chronic excess of PTH leads to marrow fibrosis, woven osteoid, expansion of osteoid surface, increased collection of osteoclasts
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Renal OsteodystrophyRenal Osteodystrophy
Spectrum of disorders that include:– Osteitis fibrosa – increased bone turnover– Adynamic bone disease – low turnover– Osteomalacia – defective mineralization
All related to disorders of:– Mineral ions Ca++, PO4
--, Mg++
– Parathyroid hormone (PTH)– Vitamin D metabolism
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Sherrard,Hercz Kid Int 1993;43:436-42
EpidemiologyEpidemiology
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Clinical FeaturesClinical Features
Musculoskeletal– Bone Pain - in advanced renal/severe bone
Low back, hips, legs aggravated by weight bearing
Acute localized pain Periarthritis with deposition of calcium
phosphate crystals Gradual onset muscle weakness Axial bone fractures – small increase in
axial/hip fractures
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Clinical FeaturesClinical Features
Pruritus – common in hemodialysisMetastatic calcification
– Extraskeletal – aggravated by persistently elevated Ca x P product
Most commonly found in the arteries
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CalciphylaxisCalciphylaxisSyndrome characterized by skin necrosis that is attributed to medial calcification of small and medium sized arteries
Possible depression of Protein C activity causes vessel thrombosis
Manifests as painful violaceous lesions with peu d’orange changes, often symmetrical with involvement of the trunk and extremities
Commonly progress to superficial ulceration, necrosis, and infection
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CalciphylaxisCalciphylaxis
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Calciphylaxis Calciphylaxis HistologyHistology
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Pathogenesis of Renal Pathogenesis of Renal OsteodystrophyOsteodystrophy
Role of Phosphorous retentionRole of Calcitriol replacementRole of parathyroidectomy
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Phosphorous and CalciumPhosphorous and Calcium
Phosphate – found as a mineral and as a ester
Widely found in milk products, meat, eggs and cereal
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Phosphorous and CalciumPhosphorous and Calcium
Na+/Phosphate co-transport major route of absorption
Calcitriol stimulates Na+/Phosphate function
Hyperphosphatemia directly suppresses calcitriol production
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Phosphorous and CalciumPhosphorous and Calcium
Kidney eliminates phosphate in amount equal to GI absorption
5-20% of filtered load is excreted In renal failure (loss of nephron mass),
ultrafiltered load goes up, Tubular reabsorption goes down, and fractional excretion of phosphate can reach 60-90% until GFR falls to <25 ml/min
Phos excretion in kidney is stimulated by PTH, but limited by total GFR.
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Vitamin D MetabolismVitamin D Metabolism
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Phosphorous and CalciumPhosphorous and Calcium
Ionized Ca++ level is regulated closely
Regulators are:– PTH– Calcitriol ( 1,25-
dihydroxycholecalciferol)
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Phosphorous and CalciumPhosphorous and Calcium
Calcitriol binds to VDR and increases the activity of calbindin D9k and CA++ ATPase
Paracellular transport is greatly increased in the presence of CITRATE
Paracellular transport not affected by ACETATE.
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In renal failure Hyperphosphatemia due to reduced nephron
mass– Reduces Ca concentration– Suppresses calcitriol production directly– Reduces the sensitivity of parathyroid to inhibition by
calcitriol Hypocalcemia stimulates PTH
– Maintenance of Ca level with exogenous Ca does not prevent hyperparathyroidism
Decreased responsiveness to Calcitriol– Normal levels of calcitriol cannot suppress PTH
possibly due to downregulation of VDR receptors– Monoclonal expansion of parathyroid cells/nodular
adenoma = tertiary hyperparathyroidism Skeletal resistance to PTH Chronic metabolic acidosis
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Phosphorous and CalciumPhosphorous and Calcium
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Slatopolsky, Bricker Kid Int 1973;4:14
Phosphorous and CalciumPhosphorous and Calcium
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Martinez, Llach Neprol Dial Transplant 1996,11:22-28
Recent InvestigationRecent Investigation
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Recent InvestigationRecent Investigation
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Calcitriol ReplacementCalcitriol Replacement
Calcitriol therapy for advanced and end-stage renal disease and iPTH> 200 pg/ml– Calcitriol superior to Ca alone in
suppressing PTH– Prevention of hyperparathyroidism is key to
minimizing metabolic bone disease– Calcijex(IV), Rocaltrol(po)
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Phosphate BindersPhosphate Binders
Target Ca++ level 7.5-9.5, Phos 3.0-5.0minimize hyperphosphatemia by use of phosphate binders
CaCO3 – Tums CaAcetate – Phoslo Sevelemar – Renagel, Renvela Lanthanum Carbonate - Fosrenol Aluminum hydroxide - alternagel only for severe cases
for short term control only! Magnesium Oxide - Magox (watch Mag level!)
– Up to 2.5 gms elemental Ca/day tolerated
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Calcitriol ReplacementCalcitriol Replacement
– Must control serum phosphate levels <6 mg/dl to prevent metastatic calcification
– Therapeutic endpoint is iPTH between 130-195 pg/ml
– Adverse side effects are hypercalcemia, hyperphosphatemia, possibly metastatic calcification
– PTH <100 could set pt up for adynamic bone disease which can also cause hypercalcemia (not a typo- hypercalcemia).
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Calcitriol ReplacementCalcitriol Replacement
Vitamin D Analogs– Hectorol (doxercalciferol) PO or IV– Zemplar (paracalcitol) PO or IV– Paracalcitol produces less hypercalcemia
or hyperphosphatemia, much more effective than Calcitriol.
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CalcimimeticsCalcimimetics
New treatment for secondary hyperparathyroidism:– Sensipar (30-60-90 mg pills)– Binds to receptors for calcium in the
parathyroid cytoplasm.– Potent suppression of PTH– Rare hypercalcemia (but it still happens)
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ParathyroidectomyParathyroidectomy
Severe Hyperparathyroidism– Tertiary (iPTH > 700) – Or refractory hypercalcemia…– Or refractory hyperphosphatemia…– Despite adequate therapy
Secondary Hyperparathyroid– With refractory symptoms (pruritis), or– In transplant candidate
PTX is Rare since the introduction of Zemplar and Sensipar.
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TreatmentTreatment
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ReferencesReferences
Comprehensive Clinical Nephrology, Johson 2000. Atlas of Physiology, Despopoulos 1991. Llach et al, Secondary Hyperparathyroidism in
Chronic Renal Failure: Pathogenic and Clinical Aspects, AJKD;38;5,Suppl 5, s20-s33.
Clinical Physiology of Acid-Base and Electrolyte Disorders, Rose, 2001
Harrison’s Priniples of Internal Medicine, 14th Ed Martin et al, Vitamin D Analogs for the Management
of Secondary Hyperparathyroidism, AJKD;38:5, Suppl 5, s34-s40.