Acquired

diseases of bone
growth
Osteoporosis
Osteomalacia and Rickets
Hyperparathyroidism
Renal osteodystrophy
Paget 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

Rheumatologic disease

Drugs

Neoplasia
Multiple myeloma
Carcinomatosis

Miscellaneous

Gastrointestinal

Malnutrition
Malabsorption
Vitamin C, D deficiency

Heparin
Corticosteroids

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 massrisk 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

se
yla
x
ro
yd
h
25

1-hydroxylase (PCT)

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

Harrisons groove - inward pulling at margin of

diaphragm

Morphology

Ambulating child

Spine, pelvis and long

bone deformity- lumbar
lordosis, bowing of legs

Osteomalacia

Inadequate mineralization of osteoid

Weak bone, vulnerable to fracturevertebral bodies and femoral neck

Histologically thickened layer of matrixpink on H&E (normal basophilic)

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