Name: METABOLIC BONE DISEASE Lecture clinical Biochemistry
Uploaded: 2022-07-13
Duration: 7 min 19 s
Description: METABOLIC BONE DISEASE Lecture clinical Biochemistry.

METABOLIC BONE DISEASE Lecture clinical Biochemistry. 

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METABOLIC  BONE   DISEASE Lecture clinical Biochemistry

Composition of Bone. The extracellular matrix 40% organic Type 1 collagen Proteoglycan Osteocalcin/osteonectin Growth factors/cytokines 60% inorganic Calcium hydroxyapatite Ca 10 (PO 4 ) 6 (OH) 2 The cells Osteo-clast/blast/cytes/progenitors. 

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The  extracellular   matrix 40%   organic Type  1   collagen Proteoglycan Osteocalcin/osteonectin Growth   factors/cytokines 60%   inorganic Calcium  hydroxyapatite   Ca 10 (PO 4 ) 6 (OH) 2 The   cells Osteo-clast/blast/cytes/progenitors

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Calcium metabolism. What is recommended daily intake? Adult: 1000 mg/day Pregnancy,lactation,postmenopausal: 1.3 g/day Children (1-18 yrs): 0.5-1.3 g/day Infant (<1 yr): 300-500 mg/day What is plasma concentration? Total (mg/dL): 8.6-10.3 (mmol/L): 2.15-2.57 Ionized (mg/dL):	4.5-5.6 (mmol/L): 1.1-1.4. 

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What is  recommended  daily   intake? Adult: 1000   mg/day Pregnancy,lactation,postmenopausal: 1.3 g/day Children (1-18 yrs): 0.5-1.3   g/day Infant (<1 yr): 300-500   mg/day What is plasma   concentration? Total  (mg/dL): 8.6-10.3 (mmol/L):  2.15-2.57 Ionized   (mg/dL):	4.5-5.6 (mmol/L):  1.1-1.4

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Phosphate Metabolism. What is recommended daily intake? Infants (< 1yrs): 100-275 mg/day Children (1-18 yrs): 460-1250 mg/day Adults:700-1250 mg/day Pregnancy/lactation: 700-1250 mg/day What is plasma concentration? Adult:2.5-4.5 mg/dL Children:4-7 mg/ dL. 

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What is  recommended  daily   intake? Infants  (<  1yrs):  100-275   mg/day Children  (1-18  yrs):  460-1250   mg/day Adults:700-1250   mg/day Pregnancy/lactation:  700-1250   mg/day What is plasma   concentration? Adult:2.5-4.5   mg/dL Children:4-7   mg/ dL

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Parathyroid hormone (PTH). Synthesizes and secreted by chief cells of parathyroid gland Synthesized as pre-pro-PTH, cleaved enzymatically to intact PTH Plasma calcium : primary physiological regulator of PTH synthesis and secretion Normal Reference Range: 10 -65 ng/L. 

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Synthesizes and secreted by chief cells   of parathyroid   gland Synthesized as pre-pro-PTH,   cleaved  enzymatically to intact   PTH Plasma  calcium : primary physiological  regulator of PTH synthesis and   secretion Normal  Reference  Range: 10 -65   ng/L

Effect on serum levels: increase Ca, decrease P. Target organ Action Kidney Increase reabsorption of Ca Increase excretion of P Bone Increase Ca/P mobilization from bone GIT Increase in Ca absorption by stimulating activation of Vitamin D. 

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Effect  on  serum levels: increase  Ca,  decrease   P

Target   organ Action Kidney Increase  reabsorption  of   Ca  Increase excretion of   P Bone Increase  Ca/P   mobilization   from   bone GIT Increase in Ca absorption  by  stimulating activation   of   Vitamin   D

Vitamin D. Sources of vitamin D? Diet UV light exposure on precursor in skin Daily requirement? 400 International units. 

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Sources of vitamin   D? Diet UV  light  exposure on precursor in   skin Daily   requirement? 400 International   units

Target organ Action Bone Increase Ca mobilisation from bone GIT Increase in Ca absorption. 

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Target   organ Action Bone Increase Ca mobilisation from   bone GIT Increase in  Ca   absorption

Effect  on serum  levels: increase Ca, decrease   P

Calcitonin. Secreted by parafollicular or C cells distributed throughout thyroid	gland Normal serum concentration Men :<8.8 pg/mL Women :<5.8 pg/mL Level Increases when serum Ca concentration > 2.25mmol/L. 

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Secreted by  parafollicular or C   cells distributed   throughout   thyroid	gland Normal serum   concentration Men :<8.8   pg/mL Women :<5.8   pg/mL Level Increases when serum Ca   concentration > 2.25mmol/L

Effect on serum levels: decrease Ca, increase P. Target organ Action Bone Supresses resorption Kidney Increase excretion of Ca. 

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Effect  on serum levels: decrease Ca, increase   P

Target   organ Action Bone Supresses   resorption Kidney Increase excretion of   Ca

Alkaline Phosphate. Present in all tissue, concentrated in liver, intestins, kidney, bone and placenta Normal range: 20 – 140 IU/L. 

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Present  in all  tissue, concentrated  in  liver,   intestins,  kidney,  bone and   placenta Normal range:  20 – 140   IU/L

Recent Markers. Osteoblasts. Osteoid. Os t eoc y t e Bone matrix. 

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Markers  of bone  resorption   (Urine) Hydroxyproline Collagen   cross-links Pyridinolines (pyridinoline,   deoxypyridinoline) Cross-linked  telopeptides  (NTx, CTx)  Tartrate-Resistant  Acid   Posphate

Markers  of bone  formation  (serum) Bone  alkaline phosphatase  Osteocalcin Procollagen  type I  propeptides  (PINP,   PICP)

Disease with markers. Disease S. Ca S. PO 4 S.PTH S. ALP Recent biomarker Osteoporosis N N N N/high Cathepsin K C- telopeptide Rickets/Osetmalacia Low low high high Osteocalcin Paget’s disease N N N high --. 

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Disease S.   Ca S.   PO 4 S.PTH S.   ALP Recent   biomarker Osteoporosis N N N N/high Cathepsin   K C-   telopeptide Rickets/Osetmalacia Low low high high Osteocalcin Paget’s  disease N N N high --

Metabolic bone diseases. heterogeneous group of disorders characterized by abnormalities in calciummetabolism and/or bone cell physiology. They lead to analtered serum calcium concentration and/or skeletal failure. The most common type of metabolic bone disease in developed countries is osteoporosis Osteoporosis Osteomalacia & Rickets Renal Osteodystrophy. 

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heterogeneous group  of  disorders characterized by abnormalities   in calciummetabolism and/or  bone  cell  physiology.  They  lead  to  analtered serum  calcium concentration  and/or  skeletal  failure.  The most common  type  of metabolic  bone disease  in  developed countries  is   osteoporosis Osteoporosis Osteomalacia  &   Rickets Renal   Osteodystrophy

Rickets & Osteomalacia. Rickets is defective mineralization of bones before epiphysial closure in immature mammals due to deficiency or impaired metabolism of vitamin D, phosphorus or calcium ,potentially leading to fractures and deformity. Osteomalacia is a similar condition occurring in adults, generally due to a deficiency of vitamin D but occurs after epiphyseal closure.. 

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Rickets  is  defective mineralization  of  bones   before  epiphysial closure  in  immature  mammals   due  to  deficiency  or  impaired   metabolism of  vitamin  D,  phosphorus  or  calcium ,potentially  leading  to  fractures and   deformity. Osteomalacia  is a similar  condition occurring in   adults,  generally due  to  a deficiency  of  vitamin   D but  occurs after epiphyseal   closure.

Rickets & Osteomalacia. Vit D deficiency low intake plus inadequate sunlight exposure malabsorption Abnormal vit D metabolism Liver disease Renal disease Drugs(anticonvulsants) Hypophosphatemia Low intake Hypophosphatemic Vitamin D resistant rickets(X-linked ). 

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Vit  D  deficiency low  intake  plus inadequate sunlight   exposure malabsorption Abnormal vit D   metabolism Liver disease Renal   disease Drugs(anticonvulsants) Hypophosphatemia Low   intake Hypophosphatemic Vitamin  D  resistant   rickets(X-linked )

Skeletal deformity Toddlers: Bowed legs ( genu varum ) Older children: Knock-knees ( genu valgum ) or "windswept knees" Cranial deformity (such as skull bossing or delayed fontanelle closure) Pelvic deformity Spinal deformity (such as kyphoscoliosis or lumbar lordosis ). 

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Skeletal   deformity Toddlers:  Bowed legs ( genu   varum ) Older children:  Knock-knees  ( genu  valgum )  or  "windswept  knees" Cranial  deformity  (such as   skull  bossing   or  delayed   fontanelle  closure) Pelvic   deformity Spinal deformity  (such as   kyphoscoliosis   or   lumbar   lordosis )

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Rickets & Osteomalacia. Lab investigations include : S. ALP ↑ Ca low in Vitamin D deficiency Phosphate may be normal or low PTH may ↑. 

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Lab  investigations  include   : S.  ALP   ↑ Ca  low  in  Vitamin  D   deficiency Phosphate  may  be normal or   low PTH  may   ↑

OSTEOPOROSIS. Common in developed countries Associated with advanced age Associated with increased risk of fractures (hip, vertebrae, forearm) Exercise & nutrition play an important role in attaining adequate skeletal mass During early adult life bone formation = bone resorption Aging increases bone resorption. 

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Common  in  developed   countries Associated  with  advanced   age Associated  with increased risk  of fractures   (hip,   vertebrae,  forearm) Exercise  &  nutrition play an  important  role   in   attaining  adequate  skeletal   mass During  early  adult  life  bone  formation  =  bone  resorption Aging increases  bone   resorption

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OSTEOPOROSIS. Pathophysiology Inadequate bone formation during growth Pathophysiological process impairing osteoblastic bone formation Increase in bone resorption. 

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Pathophysiology Inadequate  bone  formation during  growth Pathophysiological  process  impairing osteoblastic  bone   formation Increase in bone   resorption

Factors involved in causation of osteoporosis. Hormones Poor diet Genetic factors Cytokines Prostaglandins Growth factors Low physical activity and low exposure to sunlight. 

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Factors  involved  in  causation of   osteoporosis

Hormones Poor   diet Genetic  factors Cytokines Prostaglandins Growth  factors Low  physical  activity and low  exposure  to   sunlight

O s t eoporosis. Risk Factors Early menopause family history Sedentary life Low calcium intake Cigarette smoking Excessive alcohol Excessive caffeine steroid therapy. 

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Risk   Factors Early   menopause family   history Sedentary   life Low calcium   intake Cigarette   smoking Excessive   alcohol Excessive   caffeine steroid   therapy

-	 Most commonly  encountered  in  post   menopausal   females

Clinical presentations. Back pain Fractures Investigations Routine X-rays Bone scan Investigations for secondary causes. 

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Back  pain Fractures Investigations Routine   X-rays Bone   scan Investigations  for  secondary   causes

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Osteoporosis (management). Exercise Calcium Vit D Bisphosponates Oestrogen replacement Androgens. 

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Exercise Calcium Vit   D Bisphosponates Oestrogen   replacement Androgens

Pagets Disease. Disease of bone remodelling osteoclast mediated bone resorption followed by new bone formation Cause unknown ?virus (paramyxovirus) More common in caucasian. 

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Disease  of bone   remodelling osteoclast  mediated  bone resorption  followed  by  new  bone   formation Cause unknown ?virus   (paramyxovirus) More  common  in   caucasian

Pagets Disease (clinical manifestation ). Bone pain Joint pain Deformity Spontaneous fractures. 

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Pagets  Disease  (clinical   manifestation )

Bone   pain Joint   pain Deformity Spontaneous   fractures

Pagets Disease (complications). Fractures Deafness Nerve entrapment Spinal stenosis Cardiac failure Osteogenic sarcoma Hypercalcemia. 

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Fractures Deafness Nerve  entrapment Spinal   stenosis Cardiac   failure Osteogenic   sarcoma Hypercalcemia

Pagets Disease (investigations). ↑ markers of bone formation ↑ ↑ Serum alk phosphatase Urinary hydroxy proline and pyridinoline cross links X-rays cortical thikening osteolytic, & osteiosclerotic bone scan. 

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↑   markers	 of bone   formation ↑ ↑  Serum alk   phosphatase Urinary  hydroxy  proline  and pyridinoline  cross   links X-rays cortical   thikening osteolytic,  &   osteiosclerotic bone   scan

RENAL OSTEODYSTROPHY. Associated with CRF ↓excretion of PO4 > ↑ PO4 Inability of kidney to synthesise 1,25 (OH) 2 D (↓ renal mass & ↑ PO 4 ) ↓ intestinal absorption of Ca > hypocalcemia Results in hyper parathyroidism. 

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Associated with   CRF ↓excretion  of PO4  >  ↑   PO4 Inability of kidney to synthesise 1,25  (OH) 2 D (↓  renal   mass & ↑   PO 4 ) ↓ intestinal absorption of Ca  >   hypocalcemia Results in hyper parathyroidism

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RENAL OSTEODYSTROPHY : CLINICAL MENIFESTATIONS. BONE PAINS (WT BEARING) SKELETAL DEFORMITIES IN CHILD EXTRACELLULAR CALCIFICATION. 

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RENAL  OSTEODYSTROPHY  : CLINICAL   MENIFESTATIONS

BONE  PAINS  (WT   BEARING) SKELETAL  DEFORMITIES  IN   CHILD EXTRACELLULAR   CALCIFICATION

LAB INVESTIGATIONS: ↑ PO4 HYPOCALCEMIA ↑ PTH ↓ 1,25 (OH)2 D ↑ ALP Mg ↑. 

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LAB   INVESTIGATIONS: ↑  PO4 HYPOCALCEMIA ↑   PTH ↓ 1,25 (OH)2   D ↑   ALP Mg   ↑

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METABOLIC BONE DISEASE
Lecture clinical Biochemistry  

 Skeletal   deformity Toddlers:  Bowed legs ( genu   varum ) Older children:  Knock-knees  ( genu  valgum )  or  "windswept  knees" Cranial  deformity  (such as   skull  bossing   or  delayed   fontanelle  closure) Pelvic   deformity Spinal deformity  (such as   kyphoscoliosis   or   lumbar   lordosis )