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