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Metabolic bone disorders-I

Dr. Mehzabin Ahmed


Bone is a mineralized connective tissue consisting
of organic matrix and inorganic elements.
Calcium salt is the mineral.
Unmineralised bone is known as osteoid. Organic
matrix of the bone consists of: -
 Bone forming cells including osteoprogenator cells,
osteoblasts and osteocytes.
 Osteoclasts are responsible for bone resorption, which
are derived from monocytes macrophage precursors.
 Proteins in the bone is mainly type I collagen.
Bone is constantly being refashioned or
remodeled by osteoblastic new bone formation
and osteoclastic removal of old bone.
Combined activity of osteoblasts and osteoclasts
can produce re-shaping of bone in order to meet
new directional stresses.
Several factors are involved in bone formation
and destruction: -
 Parathyroid hormone (PTH)
 ↓ Plasma Ca+ → ↑ PTH → bone resorption
 Vitamin D → promotes mineralisation of the bone
 Calcitonin → opposite effects of PTH
 Other factors are – GH, corticosteroids, androgens,
estrogens, and insulin.
Common Metabolic Disorders of Bone
Disorder of chondrocytes = abnormal cartilage
 Achondroplasia

 Mucopolyssacharidoses

Disorder of osteoblasts = abnormal bone matrix


 Osteogenesis Imperfecta

 Osteoporosis

Disorder of Osteoclast function = abnormal remodeling


 Osteopetrosis

 Paget Disease

 Osteitis fibrosa cystica (Hyperparathyroidism)

Disorders of mineralisation = inadequate calcification


 Rickets/ Osteomalacia

 Renal Osteodystrophy
Disorders of bone mineralization
Osteomalacia
Occurs due to failure of mineralisation of osteoid,
due to vitamin D deficiency in adults.
It results in bone pain, micro factures of cortical plate
and trabecular bone.
The cortical microfractures are seen radiologically
and are known as ‘Looser’s zone’ and are most
common in the bones of the lower limbs.
Severe long-standing untreated osteomalacia results
in bowing of legs.
Causes: - Because of vitamin D deficiency, which is
required for mineralisation of the bones.
Vitamin D deficiency is due to
 Inadequate dietary intake
 Inadequate body synthesis of vitamin
 Malabsorption due to intestinal diseases
 Renal diseases
Disorders of bone mineralization
Renal osteodystrophy
Refers to metabolic and structural abnormalities of bone
caused by presence of chronic renal failure.
There are two main components to renal ostrodystrophy:
a) Osteomalacia of renal origin → due to failure of
conversion of 25 hydroxy vitamin D3 to the active
principle 1,25 dihydroxy vitamin D3 in the kidney because
of tubular damage.
b) Secondary hyperparathyroid effects – secondary to low
calcium because of a combination of vitamin D deficiency,
excess calcium loss in urine and phosphate retention.
The bone in renal ostrodystrophy therefore shows
combination of secondary hyperparathyroid changes,
excessive bone erosion by osteoclasts and failure of
mineralisation of osteoid collagen
Chronic renal failure

Deficiency of active Hyperparathyroidism due


to form of Vitamin D calcium loss, Vitamin D def
& Phosphate retention

Deficient mineralization  osteoclastic activity

Osteomalacia Erosion of the bone


Disorders of chondrocytes/ chondroid matrix
Achondroplasia Mucopolysaccharidoses
Mutation in FGFR3 (fibroblast Lysosomal storage
growth factor receptor 3) gene disorders - Deficiency in
the acid hydrolases
required to degrade
cartilage matrix

Hurler and Hunter disease


- Abnormality in hyaline
cartilage
Disorders of osteoblasts/ osteoid matrix
Osteogenesis imperfecta

Congenital defect in the collagen


synthesis resulting in abnormally
fragile bones and teeth and blue
sclera
Disorders of osteoblasts/ osteoid matrix
Osteoporosis
is characterized by generalized reduction in the mass of bone.
It is the most common metabolic disease of the bone.
The bone is composed of abnormally thin trabeculae.
The condition is common in elderly
Causes:
 Senile osteoporosis encountered in the menopausal
women. Estrogen is required for the maintenance of the
bone mass
 Prolonged corticosteroid therapy
 Cushing syndrome
Senile osteoporosis
KYPHOSIS

Compression # Wedge #
Clinical features
Bone pain – back pain
Compression fracture of one of more
vertebral bodies
Overall loss of height because of
compressions of vertebrae
Kyphosis (bending of the spine
anterioposteriorly)
Fractures of neck of femur and wrists are
common complication following trivial injury
Metabolic bone disorders-II
Disorders of osteoclasts/ bone remodelling
Osteopetrosis

Genetic disorders due to reduction in osteoclastic


bone resorption due to Osteoclast dysfunction
Also known as ‘Marble Bone disease’
Disorders of osteoclasts/ bone remodelling
Osteopetrosis
Bones are brittle like chalk and
fracture easily
Bones are bulbous and misshapen
Bones do not develop a medullary
cavity
No place for Hemopoietic tissue to
develop
Extramedullary hemopoiesis
continues with
hepatosplenomegaly
Patient develops anemia, infections
and tendency to bleed
Narrow neural foramina may
compress exiting nerves
Disorders of osteoclasts/ bone remodelling
Paget’s diseases
In Paget’s disease there is excessive uncontrolled
resorption of bone by abnormal osteoclasts.
Excessive osteoclastic activity results in localized
destruction of bones
followed by an uncoordinated osteoblastic
response, producing new osteoid in an attempt to
fill the defects.
Both osteoclastic and osteoblastic responses are
random, haphazard and unrelated to the
functional stresses on the bone.
There is increase bone bulk but it is weaker than
normal
Paget’s disease may be

widespread, affecting

many bones, or may be

confined to one area in a

single bone.

Etiology is not known.


Clinical effects
•Bone pain
•Bone deformity –
•Enlargement of the
skull,
• Thickening, and
enlargement and
bowing of the tibia.
•Nerve compression
symptoms are usually
seen in association with
Paget’s disease of the
skull.
•Pathological fractures
•Malignant tumor –
Mosaic of cement lines Osteosarcoma
Disorders of osteoclasts/ bone remodelling
Hyperparathyroidism
Produces bone erosion by stimulation
of osteoclastic activity.
Normally PTH stimulates osteoclastic
resorption of bone, with the release of
calcium from the bone into the
plasma.
Its activity is normally finely
controlled by a feed back mechanism.
Failure of the feed back mechanisms
leads to excessive Parathormone
secretion with continuing PTH output
and excessive osteoclastic destruction
of bone.
Two patterns of hyperparathyroidism:
Primary hyperparathyroidism is because of an autonomous
parathyroid tumor, usually a parathyroid adenoma, secrets
excess PTH continuously outside of the control of the feed
back mechanism.
In secondary hyperparathyroidism a persistently low
serum calcium level (due to excess Ca+ loss in the urine in
chronic renal disease) leads to continuous stimulation of the
parathyroids by the feedback mechanism this results in
hyperplasia of all the parathyroid glands and a constant
excessive secretion of PTH.
Effects of bone of constant PTH stimulation are
 uncontrolled absorption of bone
 followed by compensatory attempts by osteoblasts to
deposit new bone,
 in addition to affecting all bones single or multiple focal
osteolytic lesions are also present in bone.
 These osteolytic lesions appear as soft, semi fluid brown
material because of old and recent hemorrhages called as
‘brown tumors’.
 Multiple brown tumors produce numerous osteolytic
lesions in many bones know as ‘Von Recklinghousin’s
disease’ of bone or osteitis fibrosa cystica’
At the end of the lesson on Metabolic Bone Diseases , the
student should be able to:
Describe briefly the composition of bone
Explain the terms bone modeling, remodeling, woven bone,
lamellar bone, osteoid.
List the factors involved in bone metabolism
Enumerate metabolic bone disease
Briefly explain the pathologenesis, pathological features and
clinical manifestations of’
 Osteopetrosis
 Osteomalacia, rickets
 Paget’s disease
 Hyper parathyroidism
 Renal osteodystrophy
 Osteoporosis
 Osteogenesis imperfecta and achondroplasia
Discuss the role of physical therapy in the management of
metabolic bone disease