Osteopetrosis is a rare bone disease characterized by abnormally dense and brittle bones. It is caused by a failure of bone remodeling due to osteoclast dysfunction. There are several forms that vary in severity from benign to lethal. The most severe, malignant infantile form is often fatal in the first years of life without treatment due to bone marrow failure and neurological complications. Radiographs show generalized osteosclerosis and other findings help differentiate it from other bone diseases. Management depends on the form but may include bone marrow transplant, medications, or surgery.

1. OSTEOPETROSIS
PRESENTED BY
DR. ORJI MICHAEL

2. Outline
Definition
Epidemiology
Pathophysiology
Clinical features
Role of the Radiologist
Imaging Modalities
Radiological Features
Management/Prognosis
Differential Diagnosis

3. INTRODUCTION
Osteopetrosis is also referred to as {
Marble
bones, Albers-Schonberg disease, ivory
bone,
osteosclerosis fragilis}
It is a clinical syndrome characterized by :-
Osteoclast failure
Impaired modeling and remodeling
Defective bone turnover result:-
-skeletal fragility despite increase
density/bone mass

4. Epidemiology
Incidence—1:20-50,000 {dominant
form}
1: 200,000 {recessive}
1:100,000-500,000
{overall}
Sex
Race

5. Pathophysiology
Understanding of the bone remodeling
cycle
and cell biology of osteoclasts:-
-Osteoblast—bone matrix(type1 col)
+extracellular
matrix>osteocytes; role.
-Osteoclast->monocyte/macrophages+intergrin receptor->sealling
zone(sequestered compartment) + acidification->solubilization; by protease cathepsin-k -
>degradation of the matrix prote
-Bone modeling{change –shape,marrow cavity expands as bone grows,failure->
hematopeiotic features in osteopetrosis }
Remodeling{degradation and replacement; failure->persistence prim spongiosaand woven
bone}
Osteoclast intrinsic fxn defect-> osteopetrosis

6. Forms
In the human, based on the age & clinical
features
Malignant/ infantile autosomal recessive
Bening adult autosomal dominant
Intermediate autosomal recessive
A syndrome of CA II deficiency associated
with RTA.
Others(e.g lethal, transient, post infectious, acquired).

7. Malignant/ Infantile autosomal
recessive
= congenital more severe form
- Defect on chromosome 11q13
- Premature senile appearance of facies
- Severe dental caries
- Pancytopenia (= anemia,leukocytopenia,thrombocytopenia) due to severe
marrow
depression.
- Cranial nerve compression ( optic atrophy, deafness)
- Hepatosplenomegaly, lymphadenopathy
- SAH,dense skeleton, fractures

8. Benign adult autosomal
dominant
- Defect on chromosome Ip21
- 50% asymptomatic
- Recurrent fractures, mild anemia
- Occasional cranial nerve palsy
- Erlenmeyer's flask deformity
Phenotype I: diffuse osteosclerosis=generalized dense amorphous structureless bones with
obliteration of normal trabecular pattern, cortical thickening with medullary encroachment( skull vault more
affected,almost normal spine)
Phenotype I: bone within bone(endobone), sandwich vert/rugger- jersey spine;
alternating sclerotic + radiolucent transverse metaphyseal lines(phalanges, Ilium); longitudinal
metaphyseal striations; sclerosis involve base of skull more than the calvaria

9. Characteristics Type 1 Type 2
Skull sclerosis Marked sclerosis mainly
on the vault
Sclerosis mainly of the
base
Spine Does not show much
sclerosis
Shows the rugger-jerssey
appearance
Pelvis No endobones Show endobones in the
pelvis
Transverse banding of
metaphysis
Absent May or may not be
present
Risk of fracture Low High
Serum acid phosphatase Normal Very high

10. Intermediate
-recessive , no family history
- In childhood b/4 age 10
- Has some of the symptom of infantile
type but less
severe(blindness,deafness
hematological symptoms)

11. Carbonic Anhydrase II Deficiency
- Chromosome 8q22
- Associated with renal tubular acidosis
- Affect bones, kidneys and brain
- Causes blood chemistry to change
- Commoner in the Mediterranean and Arab
children
- Causes calcium deposit in the brain,60% =
blindness and deafness
- CA II -> carbonic acid 4m H2O+CO2, -HCO
dissociate to release protons needed for
acidic environment in d sealing zone/
resorption lacunae

12. Characteristics Adult onset Infantile Intermediate
Inheritance Autosomal
dominant
Autosomal
recessive
Autosomal
recessive
Bone marrow
failure
None Severe None
Prognosis Good Poor Poor
Diagnosis Often diagnose
incidentaly
Usually diagnose
b/4 1yr
Not applicable

13. Clinical features
 Pain
 Frequent fractures esp. of long bones
 Nerve compression ->blindness, deafness, headache
 Hematological->anemia, thrombocytopenia, luekopenia
 Enlarged spleen
 Osteomylitis
 Frontal bossing
 Unusual dentition(malformed +unerupted
teeth)
 Infection, bleeding stroke

14. Diagnosis
 Made through skeletal x-ray
 Bone density test
 Biopsy for histology

15. Role Of The Radiologist
 To make or confirm diagnosis
 To monitor response to treatment or
progression

16. Imaging Modalities
 Plain film
 Ultrasound
 CT-Scan
 MRI

17. RADIOLOGICAL FAETURES
-Generalized osteosclerosis, increased
density and thickness may be seen in
utero.
-Bone in bone
-Sinuses are small
-vertebrae are very radiodense and may
show alternating bands(rugger-jersey
sign),spondylolisthesis
-Evidence of fracture or osteomylitis
-Erlenmeyer's flask deformity
-uss

18. Differential Diagnosis
 Myelofibrosis
 Renal osteodystrophy
 Melorheostosis
 Inherited hypophosphataemia
 Fluorosis
 Hypoparathyroidism
 Psuedohypoparathyroidism
 Lead toxicity

19. Treatment
 Bone marrow transplant
 1,25-dihydroxy vitamin D
 Recombinant human interferon
gamma
 Surgical management of fractures and
cranial nerve compression

20. Prognosis
 If untreated infantile type will result in
death due to anemia, infection or
bleeding
 Adults with osteopetrosis are usually
asymptomatic and have good long-
term survival rates

36. This is a terribly
serious congenital
condition(not a
disease) with often
tragic
consequences.
Thanks