METABOLIC BONE

DISEASES
Physiology
Serum calcium = 2.25 – 2.60 mmo/l
47% ionized, 46% protein bound and the rest is complexed.
Parathyroid hormone
- secretion is stimulated by low s-calcium
- increases calcium absorption in the gut (Vitamin D : increased hydroxylation)
- directly increases calcium absortion in the kidney
- stimulates osteoclasts to increase bone resorption via activation of osteoclasts
Vitamin D

Calcitonin
- inhibition of osteoclasts
Other hormones
- corticosteroids
- sex hormones
- thyroxine
- growth hormone
 Osteoporosis
Defined as a condition in which there is a reduction in the amount of bone, without a
change in its composition, associated with microarchitectural failure and bone fragility,
predisposing to fracture = qualitative definition.
Defined as a condition which is present when the bone mineral density(BMD) is 2.5
standard deviations(SD) or more below the peak bone mass = quantitative definition.
Neither definition is complete in itself.
Densitometry:
- measurement of bone density
- DXA = dual X-ray absorptiometry
- accurate, reproducible and radiation dose is low
- hip most reliable decrease in BMD with age
- WHO: osteopenia = 1 to 2.5 SD < peak bone mass
osteoporosis = >2.5 SD below peak bone mass (confirmed with fragility #)
- T score (SD value) / Z score (BMD in relation to the age-matched mean)
- IMPORTANCE: RELATION TO FRACTURE RISK. RISK OF FRACTURE
COMPARED TO AGE-MATCHED CONTROLS DOUBLES WITH EACH STANDARD
DEVIATION BELOW THE MEAN.
Causes/Classification: Considerations:
Osteoporosis in men: testosterone
deficiency / myeloma
Endocrine causes: pituatary insuff. /
thyrotoxicicosis / hyperparathyroidism
Corticosteroid osteoporosis: cushing
syndrome / iatrogenic
Hyperprolactinemia: pituatary tumours /
stress / hyperthyroidism / renal failure
Osteoporosis and malabsorption
Idiopathic osteoporosis
- idiopathic juvenile osteoporosis
- osteoporosis in pregnancy
Inherited osteoporosis: type 1 OI /
osteoporosis pseudoglima syndrome
Mastocytosis
Multiple myeloma
Osteoporosis and malignant disease
Investigations:
Indications for DXA:
- presence of risk factors for bone loss
- radiologic evidence of osteopenia or
vertebal deformity or both
- previous fragility fracture
- monitoring therapy
- research
Densitometry should not be done if it will not
alter the clinical care.
Major radiographic features:
- generalized osteopenia
- cortical bone thinning
- in vertebrae there is initailly thinning and
eventually disappearance of the transverse
trabeculae, with prominence of the vertical
trabeculae
- thoracic vertebrae exhibit wedge fractures
- lumbar vertebrae exhibit crush fractures
- intervertebral discs may show widening
Major pathologic features:
Trabecular bone volume is decreased
Osteoid volume is decreased
Management:

1. Maximise peak bone mass

- Activity
- calcium
- avoid risk factors i.e. excessive
alcohol and smoking

2. Prevent bone loss

Increase formation
- exercise
- sodium fluoride
- PTH fragments
Decrease resorption
- HRT
- biphosphonates
- calcium
- vitamin D
Hyperparathyroidism
Common endocrine condition, but overt
hyperthyroidism is rare.
Malignancy and hyperparathyroidism
are the most common causes of
hypercalcemia (90%).

Causes:
- primary hyperparathyroidism
(adenoma)
- hyperparathyroidism in MEN I / IIA
- parathyroid carcinoma
- secondary hyperparathyroidism
(present to a variable degree in all
forms of rickets and osteomalacia)
- tertiary (autonomic)
hyperparathyroidism
Clinical features:
Most asymptomatic, discovered on
biochemical screening.
Bone disease: bone and joint pain,
fractures and deformities, osteoporosis
Proximal myopathy, and myalgia
Renal stones, polyuria
Constipation, PUD and N+V
Hypertension
Psychological disorders: depression,
psychosis, neurosis
Pancreatitis

Radiographic features:
Diffuse osteopenia
‘Pepperpot’ skull – diffuse areas of
resorption
Subperiosteal resorption evident in the
region of the =
- symphysis pubis
- ischial tuberosities
- proximal and distal clavicle
- scapula
- plates of vertabral bodies
- tufts of the phalanges
- cortical resorption on the radial side of
the phalangeal shafts
Periarticular erosions in the hand,
wrists and feet
‘Brown tumour’: lytic bony lesion
Renal stones
Soft tissue calcifications
Diagnosis:
Clincal picture
Radiography
Hypercalcemia
Low serum phosphate
Alkaline phosphatase only elevated in
clinically evident bone disease
Serum circulating PTH elevated
Densitometry reveals osteoporosis

Pathologic features:
- osteoclasts increased on bone surface
- ‘tunneling’ resorption of trabeculae
- with secondary hyperparathyroidism
due to renal failure, marrow fibrosis and
increased woven bone are present
- ‘brown’ tumour is a giant cell reparative
granuloma, consisting of numerous
multinucleated giant cells lying in
spindle cell, mononuclear cell stroma
Management:
Treating persistant hypercalcemia
Treating complications of bone disease
i.e. fracture. Peristant large ‘brown’
tumours may require curretage and
grafting.
Urological intervention for renal stones
Parathyroidectomy is curative
Osteomalacia and Rickets
 Causes:
Osteomalacia in adults and rickets in
children are due to a deficiency in
vitamin D = disturbance of bone
metabolism = DEFECTIVE
MINERALIZATION OF BONE.

Pathophysiology:
Viatimin D deficiency causes defective
mineralization, with excessive amount
and thickness of osteoid. This causes a
loss of strength of the bone with
subsequent deformity of the
weightbearing bones.
There is no change in the amount of the
organic matrix.
Clinical picture:
Bone pain: oftem sufficient to wake the patient at night, worse with weightbearing
Tenderness: marked, especially over Looser zones
Proximal muscle weakness
Deformity: most marked if deformities develop in childhood
- bossing of the frontal and parietal bones
- beading of the costochondral junctions (‘rachitic rosary’)
- ‘Harrison’s sulcus’: depression along the line of diaphragm attachment
- wrists and ankles are enlarged due to the flare and enlargement of the epiphysis
- bowing or curvature of the long bones
- pigeon chest especially in osteomalacia
- spinal deformities include = thoracic kyphosis, lumbar lordosis and scoliosis
Abnormal gait ; especially in younger children
Growth failure in children
Clues to an underlying disorder
Biochemistry:
Most common:
- low to normal serum calcium
- low inorganic phosphate
- raised alkaline phosphatase
Changes seen depend partly on the stage of the disease, and partly on the degree of
parathyroid overactivity.
Low plasma 25(OH) Vit. D may be confirmatory in the work-up.
Radiography:
A) Rickets
- cortical thinning
- metaphyseal flaring and osteopenia
- wide irregular / jagged growth plate
- ‘cupping’ of the growth plate
- pseudofractures (Looser zone)
- intervertebral disc expansion with bi-concavity of the vertebrae
- squared configuration of the frontal and parietal bones of the skull
- scoliosis and long bone bowing
B) Osteomalacia
- generalised osteopenia
- multiple, bilaterally symmetrical cortical lucencies/pseudofractures (Looser zones)
- axial skeleton is more affected than the apendicular skeleton: ‘codfish’ vertebrae
- radiographic changes of secondary hyperparathyroidism may be present
- severe bone resorption in renal osteodystrophy : ‘rotting stump’ with severe deformity
- tri-radiate pelvis
Histology:
Treatment:
Vitamin D in physiological doses at about 1000 IU / day
- muscle weakness improves within a few days
- radiologic improvement occurs in about a month
Look for and treat any possible cause!!

NB: must differentiate from :

- other metabolic bone diseases
- other causes of proximal weakness
- other causes of bone pain
- other psychological illnesses
NB:
Some histological studies have proven up to a 30% incidence of osteomalacia in elderly
patients with hip fractures, i.e. can be combined with osteoporosis. Therefore consider
vitamin D therapy if in doubt.
The end.