metabolic bone disease
TRANSCRIPT
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METABOLIC BONE DISEASE
Dr. KAPIL DEV
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Composition of Bone
The extracellular matrix
40% organic
Type 1 collagen
Proteoglycan
Osteocalcin/osteonectin
Growth factors/cytokines
60% inorganic
Calcium hydroxyapatite Ca10(PO4)6(OH)2
The cells
Osteo-clast/blast/cytes/progenitors
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Bone Turn over
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Calcium metabolism What is recommended daily intake?
Adult:1000 mg/day
Pregnancy,lactation,postmenopausal:1.3g/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
Ref: Harrison’s 18th edition
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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
Ref: Harrison’s 18th edition
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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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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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Vitamin D
• Sources of vitamin D?
Diet
UV light exposure on precursor in skin
• Daily requirement?
400 International units
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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
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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
Ref: Harrison’s 18th edition
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Effect on serum levels: decrease Ca, increase P
Target organ Action
Bone Supresses resorption
Kidney Increase excretion of Ca
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Alkaline Phosphate
Present in all tissue, concentrated in liver,
intestins, kidney, bone and placenta
Normal range: 20 – 140 IU/L
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Recent Markers
OsteoblastsOsteoid
Osteocyte
Bone matrix
Osteoclast
Markers of bone resorption (Urine)HydroxyprolineCollagen cross-linksPyridinolines (pyridinoline, deoxypyridinoline)Cross-linked telopeptides (NTx, CTx)Tartrate-Resistant Acid Posphate
Markers of bone formation (serum)Bone alkaline phosphataseOsteocalcinProcollagen type I propeptides (PINP, PICP)
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Disease with markers
Disease S. Ca S. PO4 S.PTH S. ALP Recent biomarker
Osteoporosis N N N N/high Cathepsin KC- telopeptide
Rickets/Osetmalacia Low low high high Osteocalcin
Paget’s disease N N N high --------
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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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Rickets & OsteomalaciaRickets 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 & 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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• 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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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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OSTEOPOROSIS
• Pathophysiology
Inadequate bone formation during growth
Pathophysiological process impairing osteoblastic bone formation
Increase in bone resorption
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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
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Osteoporosis• 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
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Clinical presentations
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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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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Pagets Disease (clinical manifestation)
Bone pain
Joint pain
Deformity
Spontaneous fractures
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Pagets Disease (complications)Fractures
Deafness
Nerve entrapment
Spinal stenosis
Cardiac failure
Osteogenic sarcoma
Hypercalcemia
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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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RENAL OSTEODYSTROPHY
• Associated with CRFa) ↓excretion of PO4 ---> ↑ PO4
b) Inability of kidney to synthesise 1,25 (OH)2D (↓ renal
mass & ↑ PO4)
c) ↓ 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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• LAB INVESTIGATIONS: ↑ PO4
HYPOCALCEMIA
↑ PTH
↓1,25 (OH)2 D
↑ ALP
Mg ↑
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THANK YOU