CPC 17 th April 2008

Female, 48 years old 2 years prior to admission: Proximal muscle weakness left lower extremity 1.5 years prior to admission:Weakness, on wheel chair Muscle atrophy 1 year prior to admission :Upper extremities weakness 1 week prior to admission : Quadriparesis

MRI: At 1.5 years prior to admission (lower extremities weakness with muscle atrophy) Cervical spondylosis, cervical canal stenosis C5-T1 Herniated disc C 3-7 Physical therapy/ Orthropaedic surgery: C3-4 with instrument

Asymptomatic Degenerative Disk Disease and Spondylosis of the Cervical Spine: MR Imaging’ Radiology 1987; 164:83-88

40Yrs. Old (N= 97) Major Minor Abnormality Abnormality Abnormality Abnormality Herniated disc 5 (3%) 7 (4%) 1 (1%) 4 (4%) Bulging disc 0 8 (5%) 1 (1%) 5 (5%) Foraminal stenosis 5 (3%) 7 (4%) 9 (9%) 14 (14%) Disc-space narrowing 3 (2%) 18 (1 1%) 15 (16%) 21 (22%) Degenerated disc 13 (8%) NA36 (37%) NA Spurs (spondylosis) 5 (3%) 23 (14%) 6 (6%) 33 (34%) Abnormal cords 15 (9%) 15 (9%) 1 (1%) 17 (18%) Abnormal magnetic-resonance scans of the cervical spine in asymptomatic subjects. A prospective investigation J Bone Joint Surg Am. 1990;72:

Muscle weakness/motor predominate No cranial nerves involvement No paresthesia No bowel/urinary bladder/autonomic dysfunction Asymmetry to symmetry by clinical course Chronic progressive course Muscle atrophy

Corticospinal tract Anterior horn cell: Amyotrophic lateral sclerosis, Radiculoneuropathy: Demyelination disease Mononeuritis multiplex Neuromuscular junction:Myasthenia gravis Lambert-Eaton myasthenic syndrome Myopathy:Polymyositis, Metabolic disorder

Cervical spondylosis Compressed fracture C6 HNP C 3-7, Kyphoscoliosis Osteopenia

Metabolic Bone Disease Bone turnover: Primary hyperparathyroidism Secondary hyperparathyroidism Adynamic bone disease Low Bone content:Osteoporosis High bone content:Osteopetrosis Bisphosphonate Abnormal mineralization: Osteomalacia/rickets

Causes of Osteomalacia Abnormal matrix Abnormal matrix Abnormal vitamin D metabolism Abnormal vitamin D metabolism Gastrointestinal disease Chronic liver disease Chronic kidney disease Hypoparathyroidism Mineralization inhibitor Mineralization inhibitor Aluninum toxicity Fluoride Chronic metabolic acidosis Hypophosphatasia (AR) Hypophosphatasia (AR) Hypophosphatemia Hypophosphatemia

Labs: BUN 9 mg %, Cr 0.4 mg %, Calculated creatinine clearance 151 mL/min Measured creatinine clearance 68.2 mL/min Na mEq/L, K mEq/L, Cl mEq/L, HCO mEq/L Ca mg%, PO mg% iPTH 72 pg/mL

Daily requirement = 800 mg Foods Meat, poultry & fish Dairy products Processed foods Soda

Etiology of Hypophosphatemia Internal redistribution Re-feeding Acute respiratory alkalosis Hungry bone syndrome Decreased intestinal absorption Inadequate intake (< 100 mg/day) Chronic diarrhea, malabsorption Vitamin D deficiency or resistance Aluminum or magnesium ingestion Increased urinary excretion Primary hyperparathyroidism Secondary hyperparathyroidism Proximal tubule dysfunction Hereditary hypophosphatemic rickets Onchogenic osteomalacia

Filtered Phosphate Excreted Phosphate

Renal phosphate wasting 24 hours urine phosphate = mg/day ( < 100 mg/day) Fractional PO 4 2+ excretion = U PO 4 2+ xPcr P PO 4 2+ xUcr = 26.73% (5 -10 %) Renal phosphate clearance = U PO 4 2+ x V P PO 4 2+ x 1440 = mL/min (5 -15 % mL/min)

Renal threshold phosphate conc (Tm PO 4 2+ /GFR) Normal 2.0 – 3.5 mg% = 0.9 mg% Lancet1975;309-10

. Glucosuria Glucosuria Hypophosphatemia Hypophosphatemia Hypouricemia Hypouricemia Hypokalemia Hypokalemia Aminoaciduira Aminoaciduira Autosomal dominant, recessive, or X-linked Autosomal dominant, recessive, or X-linked Wilson’s disease, Wilson’s disease, Galactosemia, tyrosinemia, cystinosis Galactosemia, tyrosinemia, cystinosis Multiple myeloma, amyloid, Multiple myeloma, amyloid, Heavy metal toxicity, chemotherapeutic drugs (ifosfamide), imatinib mesylate Heavy metal toxicity, chemotherapeutic drugs (ifosfamide), imatinib mesylate

Disorder Serum phosphate Serum calcium ALP Vit D deficiencyLow Elevated Renal phosphate wastingLowNormal Chronic metabolic acidosisNormal Proximal RTALowNormal HypophosphatasiaNormal Low Bone matrix abnormalityNormal

Hypophosphatemia with renal phosphate wasting Proximal RTA Hyperparathyroidism Mutation of type 2a sodium-phosphate co-transport: Absorptive hypercalciuria type III, nephrolithiasis Hereditary hypophosphatemic rickets with hypercalciuria Hereditary hypophosphatemic ricket Tertiary hyperparathyroidism post-kidney transplantation Onchogenic osteomalacia: High phosphatonin: FGF 23, matrix extracellular phosphaglycoprotein (MEPE), frizzled growth factor 4 (FRP-4)

iPTH stimulate FGF 23

Kidney Int 2003, 64 : 2272–2279 Log FGF-23

CKD, Renal bone disease, Aging

New Engl J Med 2003;348:1656

Fibrous dysplasia Hemangiopericytoma Osteosarcoma Chrondroblastoma Chondromyxoid fibroma Malignant fibrous histiocytoma Giant cell tumor hemangioma Mayo clinic 1994 Mesenchymal tumor cause TIO

Progressive muscle weakness Severe metabolic bone disease/Osteomalacia Hypophosphatemia/Severe renal phosphate wasting Groin mass Onchogenic osteomalacia/immobilization osteoporosis Investigation: Groin mass excision/immunohistochem staining Serum FGF-23 concentration (Octreotide labeled indium-111 scan)

Mesenchymal tumor mass Acquired high phosphatonin (FGF-23) Severe renal phosphate wasting Severe osteomalacia, immobilization osteopenia Muscle weakness