Metabolic bone diseases

There is a clinical problem?

Osteopertrosis

• Hereditary decreased osteoclastic function. Decreased resoprtion leads to thick sclerotic bones.

• Pathology– Problems with the osteoclast resorption pit– Increased bone density -> thick brittle bones -> fracture– Marrow decreased by bone growth, may cause

pancytopenia.– Extramedullarly haematopoeisis– Cranial nerve compression -> blindness, deafness,

vision loss

Osteopetrosis

• X ray– Osteosclerosis, long bones -> Erlenmeyer flask shaped deformity

• Clinical features– Autosomal recessive (malignant)

• Infants and children, multiple fractures, early death

– Autosomal dominant (benign type)• Adults, fractures, mild anaemia, cranial nerve impingement

– Carbonic anhydrase II deficiency• Renal tubular acidosis, cerebral calcificaiton

• Treatment– Bone marrow transplant

Paget’s disease (osteitis deformas)• Localised disorder of bone remodelling caused by excessive resorption and disorganised

replacement leading to thickened but weaker bone.• Epidemiology – begins after age 40, european ancestry• Etiology – possible genetic predisposition, possibly paramyxovirus• Forms of involvement

– Monostotic (15%), polystotic (85%)– Commonly – skull, pelvis, femur, vertebrae

• Pathology– Three stages

• Osteolytic – otseoclastic activity predominates• Mixed osteoclastic and osteoblastic• Osteosclerotic – osteoblastic activity predominates -> burnout stage

– Micro haphazard arrangement leads to mosiac pattern of lamellar bone– Bone is weak, fractures easily– Skull involvement

• Increase in head size• Foraminal narrowing leading impingement of the cranial nerves• Facial bones can be involved leading to a lion like face

Paget’s disease (osteitis deformas)

• X-ray – Bone enlargement with lytic and sclerotic areas.

• Complications– AV shunts within marrow can cause high output

cardiac failure.– Osteosarcoma or other sarcomas.

Osteoporosis

• Osteopenia• Epidemiology

– Most common bone disease– Elderly, post menopausal

• Pathogenesis– Primary……………………….– Secondary…………………..

• Clinical features– Bone pain and fractures– Weight bearing bone predisposed to fracture– Loss of height and kyphosis

Osteoporosis

• X-ray– General translucency of bone

• Treatment– Oestrogen replacement therapy – controversial– Weight bearing exercise– Calcium and vitamin D– Biphosphonate– Calcitonin

Osteomalacia and Rickets

• Decreased mineralisation of newly formed bones, usually caused by deficiency or abnormal metabolism of vitamin D.

• Etiology – deficiency of vit D, intestinal malabsorption, lack of sunlight, renal or liver disease.

• Epidemiology– Osteomalacia – adults– Rickets - children

Osteomalacia and Rickets

• Pathogenesis– Osteomalacia -> poor mineralisation of newly formed bone -

> thin fragile bones -> fracture– Rickets

• Remodelled bone and bone at growth plates are undermineralised• Endochondral bone formation also affected -> deformity• Fractures also occur

• Clinical presentation– Osteomalacia -> bone pain, fracture (vertebrae, hips, wrist)– Rickets -> bow legs, craniotabes, lumbar lordosis,

Hyperparathyroidism

• Primary – Adenoma or autonomous hyperplasia (Robbins)

• Secondary – Caused by prolonged states of hypocalcemia leading to hyperplasia

• Tertiary?– Autonomous hyperplasia

• Severe cases lead to osteitis cystic fibrosa (no longer though…)• Presentation

– Asymptomatic hypercalcamia• Treatment

– Curvative parathyroidectomy

Renal Osteodystrophy• Describes clinically all of the skeletal changes of chronic renal

disease.– Increased osteoclastic bone resorption mimicking osteoitis fibrosa

cystica.– Delayed matrix mineralisation.– Osteosclerosis.– Growth retardation.– Osteoporosis.

• Main types– High turnover -> increased resorption and bone formation (dominates)– Low turnover (aplastic) -> adynamic bone, less commonly osteomalacia

Renal Osteodystrophy

• Pathogenesis (long..)– Chronic renal failure results in phosphate retention and

hyperphosphatemia– Hyperphospatemia induces secondary hyperparathyroidism (via

regulating PTH secretion)– Hypocalcaemia develops due vitamin D problems (kidneys)– PTH secretion markedly increases at all levels of serum calcium

• In renal failure decrease in the binding of 1,25-(OH)2D3 to parathyroid cells• Decreased degradation and excretion of PTH (kidneys)

– Secondary hyperparathyroidism produces increased osteoclastic activity

– Metabolic acidosis associated with renal failure leads to bone resorption