METABOLIC BONE

DISEASES IN
CHILDREN
G Parthasarathy

Metabolic bone diseases

Disorders caused by abnormalities of

minerals such as calcium, phosphorus,
magnesium or vitamin D.
Disturbed metabolism of bone tissue.
Commonly reversible once the
underlying defect has been treated.

Bone metabolism

Lifelong process where mature

bone tissue is removed from
skeleton (bone resorption) and new
bone tissue is formed (ossification).

Composition of bone.
- Matrix : 60% inorganic - Calcium Hydroxyapatite
40% organic Type I collagen (tensile strength)
- Proteoglycans (compressive strength)
- Osteocalcin, osteonectin
- Growth factors
- Cells : Osteoblasts, osteoclasts, osteocytes, progenitors

Growth Plate Anatomy

Resting cell zone germinal layer

that supplies developing cartilage
cells.
Zone of Proliferating cartilage
active mitotic activity of chondrocytes.
Hypertrophic cell zone maturation
zone, chondrocytes terminally
differentiate.
Zone of Provisional calcification
with death of chondrocytes, cartilage
matrix becomes calcified.
Invasion by blood vessels from
metaphysis, formation of bone along
walls of calcified cartilage matrix.

Classification

Defective mineralisation:
Rickets / Osteomalacia
Hypophosphatasia
Defective Organic matrix production:
Scurvy
Osteogenesis imperfecta
Copper deficiency
Disorders of bone resorption:
Hyperparathyroidism
Osteopetrosis

RICKETS

Loss of orderly maturation and mineralisation

of cartilage cells at the growth plate resulting
from vitamin D deficiency.
Skeletal effects are due to lack of
calcification of osteoid (osteoid seams).
Equivalent of Osteomalacia in adults.
Most important changes are at growth plates.
The cartilage cells at the physis grow
normally but fail to calcify and degenerate.
Growth plate is occupied by enlarged
masses of overgrown cartilage widens the
region radiographically.

Causes

Inadequate dietary intake of vitamin D.

Inadequate exposure to ultraviolet
radiation.
Intestinal malabsorption.
Vitamin D metabolism defects.
Chronic acidosis.
Renal tubular defects.
Aluminium intoxication.
Chronic administration of anticonvulsants.

Role of Vitamin D

Nutritional Rickets

Dietary deficiencies vitamin D,

calcium, phosphorus.
Inadequate sunlight exposure,
malabsorption syndromes.
Skeletal findings, hypocalcemic tetany,
seizures, developmental delay, failure to
thrive.
Treated with oral supplements, im
vitamin D.

Vitamin D dependent
Rickets

TYPE I
Deficiency of renal 1alpha Hydroxylase
Autosomal recessive
Younger than 2 years
Severe bony changes,
tetany, seizures, dental
enamel hypoplasia
Treated with Calcitriol

TYPE II
Mutation in vitamin D
receptor.
Autosomal recessive
Younger than 1 year
Severe bony
changes, alopecia
Treated with massive
doses of Calcitriol
and Calcium

Vitamin D resistant
Rickets
X- linked
Hypophosphatemic
Rickets
Mutation in PHEX gene
which inactivates
phosphatonins- excess
phosphate excretion
Low calcitriol levels
X-linked dominant
Short stature, leg bowing,
dental abnormalities
Treated with oral
phosphate, calcitriol

Hereditary
Hypophosphatemic
Rickets with
Hypercalciuria
Mutation in SodiumPhosphate Cotransporter
gene- impaired renal
tubular reabsorption
Increased calcitriol levels
AR, AD
Bone pain, muscular
weakness
Treated with oral
phosphate

Miscellaneous

Renal Rickets / Renal Osteodystrophy:

Loss of functional renal parenchyma leads to
mineral derangements and decreased calcitriol.
Bone pain, fractures, muscle weakness.
Treated with vitamin D and phosphate binding
compounds.
Metaphyseal changes are less severe.
If growth failure is severe, radiological features
of hyperparathyroidism predominate.

Rickets of prematurity :
Multifactorial.
Osteopenia, fractures.
Oncogenic Rickets :
Tumour induced inhibition of renal 1- alpha
Hydroxylase.
Production of phosphatonin by mesenchymal
tumours.
Fractures, muscle weakness.
Underlying malignancy should be treated.

Clinical features

Irritability
Tetany
Weakness
Delayed maturity
Deformities
Growth plate swellings

Radiologic features

In infants, typical changes are seen in distal radius

and ulna.
In weight bearing children, radiographs of knees
will depict changes.
First change Defective mineralisation and
absence of a calcified zone of provisional
calcification.
Indistinctness of metaphyseal margin
progressing to frayed appearance with widening
of growth plate.
Hypertrophic zone loss of orderly columnar
arrangement and transformation into thick, grossly
disorganised mass of cartilaginous cells.

Weight bearing and stress on

uncalcified bone leads to
splaying and cupping of
metaphysis.
Cupping due to inward
protusion of the cartilaginous
cell mass at the centre of
growth plate.
Generalised osteopenia,
coarse trabecular changes.
In hypophosphatemic rickets,
leg bowing more prominent.
Enthesopathy and ectopic
calcifications occur. Bones are
more sclerotic.

Bending of bones bow legs, knock

knees.
Deformity of hips coxa valga, coxa vara.
Bulbous enlargement of costochondral
junctions rachitic rosary.
Indrawing of ribs Harrisons sulcus.
Fractures, decreased bony length,
pseudofractures.
Craniotabes.
Spine changes scoliosis, biconcave
vertebral bodies.

Bow legs and

knock knees

Rachitic rosary

Healing Rickets

The absent white line

reappears on healing
indicator of therapeutic
response.
Extensive periosteal new bone
formation occurs along
diaphysis.
Remodeling of bone
deformities occurs.
In skull, characteristic bossing
of frontal and parietal bones
becomes apparent with
premature closure of sutures.

Sequelae Post Rickets

Complete healing and restoration of

normal structure is rule.
Distortion/ sclerosis of spongiosa in
affected segment may occur after
healing.
Cortical thickening of involved bone
segments may persist.
Angulation deformities secondary to
pathological fractures can occur.

Differential diagnosis
Metaphyseal Chondrodysplasia

Congenital dysplastic bone disorders involving

metaphysis.
Schmid, Jansen, McKusick, Rosenberg are few.
Present in 3rd or 4th yr with short stature,
waddling gait.
Widening and cupping of metaphysis seen with
normal mineralisation.
Irregular sclerotic bands with radiolucent
streaks seen in metaphysis.
Epiphysis and diaphysis are normal.

Schmid disease
Defective type X
collagen.
Mild short stature, leg
pains, bowed legs,
increased lordosis.
Flexion contractures of
elbow.
Lower limbs more
severely involved with
varus of knees and
ankles.

Jansen disease
Autoactivation of
PTHR1- undetectable
PTH.
Hypercalcemia,
hypophosphatemia.
Short stature,
exophthalmos, high
arched palate.
Micrognathia,
nephrocalcinosis.

Hypophosphatasia

TNSALP- Tissue Nonspecific Serum Alkaline

Phosphatase deficiency in osteoblasts and
chondrocytes impair bone mineralisation.
Range from rapidly fatal perinatal variant
(AR) to milder osteomalacia in adults (AD).
Prenatal long bone bowing, pathological
fractures (metaphyseal).
Premature loss of deciduous teeth.
In adults, metatarsal stress fractures, femoral
pseudofractures common.

Imaging findings

Hypomineralisation, rachitic changes.

Incomplete vertebral ossification.
Lateral bony spurs from mid-shaft of ulna and
fibula.
Large areas of hypomineralised calvaria illusion of open fontanelles.
Tongues of radiolucency protuding from
metaphysis into bone shaft.
Alveolar bone loss involving anterior
mandible.

A) Alveolar bone loss

B) Tongues of radiolucency
C) Pseudofracture

DD for Bow legs

Physiological bowing:
Metaphyseal diaphyseal
angle of Drennan < 11 degrees,
resolves by 2 years.
Gradual curving involving both
tibia and femur.
Blounts disease:
MD angle > 16 degrees, persist
beyond 2 years.
Proximal tibial angulation acute,
occuring immediately below the
medial metaphyseal beak.

The metaphyseal-diaphyseal
angle is defined as the angle
between a line perpendicular to
the axis of the tibia and a line
through the most distal ossified
beak of the medial and lateral
beak of the tibial metaphysis

Rickets:
Affects skeleton in a generalised and
symmetric fashion.
Typical biochemical abnormalities.
Post traumatic:
Growth plate injury of proximal tibia.
Metaphyseal chondrodysplasia:
Persistent bowing with multiple metaphyseal
deformities.
Short stature.
Normal bone density, normal serum
biochemistry.

DD for Growth plate

widening

Rickets osteopenia, hazy metaphyseal

outline.
Metaphyseal chondrodysplasia widened
GP on concave side due to altered distribution
of stress.
Epiphyseal fracture separated and
displaced from metaphysis.
Endocrine disturbances like hypothyroidism.
Chronic illness leading to delayed
maturation.

Scurvy

Disorder due to deficiency of vitamin C.

Mainly affects infants aged 8-14 months fed solely
on boiled milk preparations.
Elderly affected when diet is compromised.
Latent period 4 months.
Spontaneous hemorrhages cutaneous
petechiae, bleeding gums.
Joint swelling, irritability, pain, lying motionlessfrog-legged (pseudoparalysis).
Scorbutic rosary tender, sharp nodular beading
at costochondral junctions due to subluxation.

Perifollicular hemorrhages

Bleeding gums

Subperiosteal hemorrhage

Vitamin C is important for collagen

synthesis (hydroxylation of proline) and
chondroitin sulphate.
Deficiency leads to depressed
intercellular substance formation in
connective tissue, cartilage, and bone.
At growth plate, though cartilage
proliferation is decreased, mineralisation
is unimpaired.
Resorption continues and generalised
osteopenia results.

Radiological findings

Ground glass appearance of shaft and

epiphysis loss of trabecular pattern and
osteopenia.
Penciling of cortex with sharply outlined
epiphyseal ends.
White line of Frankel dense zone of calcified
cartilage at metaphyseal edge just beneath
physis.
Wimbergers ring sign radiolucent epiphyseal
centres with white ring of compressed collagen.

Corner (Angle) sign irregularity of

metaphyseal margins- subphyseal
infarctions.
Pelkans spurs bony protuberances at
metaphyseal margins.
Trummerfelds scorbutic zone
radiolucent band due to disordered
osteoid formation beneath Frankels line.
Lifting of periosteum from cortex due to
subperiosteal hemorrhage.

Scurvy findings

Healing Scurvy

All changes are reversible

on vitamin C therapy.
A single growth arrest line
may remain in metaphysis
residual of Frankels line.
Subperiosteal hematomas
rapidly calcify and
demarcate.

Differential diagnosis

Congenital syphilis:
Periosteal reaction is more
generalised, usually thick or
multilaminated.
Produces radiolucent metaphyseal
bands.
Causes beak like metaphyseal lesions,
metaphyseal serrations (sawtooth
metaphyses)
Wimberger sign: Localised bony
destruction of medial portion of
proximal tibial metaphysis.
Parrots pseudoparalysis: due to
syphilitic osteochondritis of epiphysis.

Battered child syndrome:

Multiple asymmetric fractures in
different stages of healing.
Marked irregularity and
fragmentation of metaphysis with
separation of distal epiphysis.
Corner fracture, Bucket-handle
fracture, posterior rib fractures,
spiral fractures of diaphysis.
Extensive periosteal reaction
from large subperiosteal
hematoma.

DD for Dense Metaphyseal Lines

Growth lines symmetric distribution, very

fine lines.
After severe systemic diseases
(leukemia,chemotherapy) prominent
growth recovery lines.
Neuroblastoma/ Bone metastases
metaphyseal involvement may entail
osteolysis with irregular sclerotic rim.
Lead lines dense metaphyseal bands
evident in proximal fibula and other slow
growing bones.
Healing Rickets.

Summary
Rickets

Osteopenia with coarse trabecular changes

Absent Zone of Provisional calcification.
Cupping, splaying, fraying of MP.

Metaphyseal
Chondrodysplasia

Widening, cupping of MP with normal bone

density
Epiphysis and diaphysis are normal.

Hypophosphatasia

Hypomineralisation with rachitic changes.

Lateral bony spurs from ulna/ fibula.
Tongues of radiolucency from MP into bone
shaft.

Scurvy
Congenital
Syphilis
Battered
child
syndrome

Ground glass appearance of shaft.

Periosteal elevation.
White line of Frankel.

Generalised and thick periosteal reaction.

Radiolucent metaphyseal bands,
metaphyseal serrations.

Asymmetric fractures in different stages

of healing.
Corner fracture, bucket handle fracture.
Posterior rib fractures.

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