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pathology
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Acquired diseases of bone
growth
OsteoporosisOsteomalacia and Rickets Hyperparathyroidism Renal osteodystrophyPaget disease
Osteoporosis
Definition Disease characterized by increased porosity of
bone resulting from reduced bone mass where structural weakness of the bone leads to bone fracture and deformity
Classification
Primary- no underlying disease
Secondary- known causal factors present
Classification
Primary Postmenopausal (type I)
Age related- senile (type II)
Secondary
Endocrine disorders Hyperparathyroidism Hypo/hyperthyroidism
Neoplasia Multiple myeloma Carcinomatosis
Gastrointestinal Malnutrition Malabsorption Vitamin C, D deficiency
Rheumatologic disease
Drugs Heparin Corticosteroids
Miscellaneous Osteogenesis imperfecta Immobilization Vitamin A intoxication
Primary osteoporosis
Bone loss occurs more rapidly after menopause
Peak bone mass is determined genetically and is higher in males than females
Also depends on body size, nutritional, endocrine, and mechanical factors
Failure to obtain maximal peak bone mass- risk factor
Pathogenesis
Accelerated bone loss that occurs in women after menopause indicates that estrogen and other sex hormones are likely to play
Estrogen deficiency causes increased level of cytiokines (IL-1) which leads to increased osteoclast formation and activity
Clinical features
Accelerated trabecular bone loss- affects mainly those bone which contain large volume of trabecular bone- vertebra, distal radius, neck of femur
Vertebral crush fractures, back pain, kyphosis, loss of height, Colles fracture
Senile osteoporosis occurs in patients over 70, both in male and females- fractures- femur, tibia, and pelvis
Osteomalacia and Rickets
Metabolism of vitamin D Two sources
Endogenous- skin Exogenous- diet
Skin- 7- dehydrocholesterol- vitamin D3- 80% needed synthesized by this manner
Diet- plants, fish and grains
Plants- precursor- ergosterol- converted to vitamin D2
D2 and D3 identical metabolic transformation and function= vitamin D
Metabolism of vitamin D
Absorption of vitamin D from gut or from skin Binding to plasma alpha- globulin (vitamin D
binding protein) and transfer to liver
Conversion to 25-hydroxyvitamin D by 25 hydroxylase in liver
Conversion into 1, 25 (OH)2D by alpha1 hydroxylase in kidney – most active
Metabolism of vitamin D
1, 25 (OH)2D production is mediated by Negative feed back- increased 1, 25 (OH)2D
causes decreased formation of alpha1 hydroxylase
Hypocalcemia stimulates secretion of PTH, activates alpha1 hydroxylase
Hypophosphatemia directly activates alpha1 hydroxylase
1α-hydroxylase (PCT)
25-hydroxylase
Functions of vitamin D
Maintenance of normal plasma level of calcium and phosphorus- involving intestine, bones and kidneys
Stimulates intestinal absorption of calcium and phosphorus
Mobilization of calcium from bone (act together with PTH)
Stimulates PTH dependent reabsorption of calcium from distal renal tubules
Osteomalacia and Rickets Disease characterized by defect in
bone matrix mineralization
Most often related to lack of Vitamin D or its metabolic disturbances
Rickets Disorder in children Deranged bone growth- skeletal deformities
Osteomalacia Adults Undermineralized bone Osteopenia
Morphology
Excess of unmineralized matrix in both conditions
Rickets- derangement of enchondral ossification
Overgrowth of epiphyseal cartilage due to inadequate calcification and failure of cartilage to mature and disintegrate
Deposition of osteoid matrix on inadequately mineralized cartilage
Morphology
Disturbance of the orderly replacement of cartilage by osteoid matrix results in enlargement and lateral expansion of osteochondral junction
Deformation of skeleton
Morphology
Nonambulatory infancy Greatest stress on head and chest with soft and
flat occipital bone
Parietal bones can be buckled inward by pressure, with release of pressure, back into original position by elastic recoil- craniotabes
Due to excess of osteiod- Frontal bossing and squared appearance of head
Morphology
Nonambulatory infancy Deformation of chest due to overgrowth of cartilage
or osteoid at costochondral junction- “rachitic rosary”
Pigeon chest deformity- inward pulling of ribs by respiratory muscles at weakened metaphyseal areas
Harrison’s groove - inward pulling at margin of diaphragm
Morphology
Ambulating child Spine, pelvis and long
bone deformity- lumbar lordosis, bowing of legs
Inadequate mineralization of osteoid
Weak bone, vulnerable to fracture- vertebral bodies and femoral neck
Histologically thickened layer of matrix- pink on H&E (normal basophilic)
Osteomalacia
Hyperparathyroidism
Increased parathyroid hormone activates osteoclasts
Increased bone resorption and mobilize calcium
Severe cases- due to thin and weak bone- fractures, hemorrhage, fibrosis and formation of cyst- osteitis fibrosa cystica
Aggregates of osteoclasts, reactive giant cells, hemorrhage- may mistaken for neoplasm- brown tumor of hyperparathyroidism
Renal osteodystrophy Skeletal changes of chronic renal disease
Increased osteoclastic bone resorption mimicking osteitis fibrosa cystica
Delayed matrix mineralization (osteomalacia)
Osteoporosis
Pathogenesis Renal failure causes phosphate retention
Phosphates directly stimulates parathyroid to produce PTH (hyperparathyroidism)
Hypocalcemia due to decreased formation of active vitamin D in kidney