bone 1: non neoplastic
TRANSCRIPT
NON NEOPLASTIC CONDITIONS OF
THE BONE
NON NEOPLASTIC CONDITIONS OF
THE BONE
Dr. V. P. Sumathi
The Royal Orthopaedic Hospital
Woodlands, Birmingham
Dr. V. P. Sumathi
The Royal Orthopaedic Hospital
Woodlands, Birmingham
NORMAL BONE
FUNCTION
MECHANICAL
CHEMICAL
HAEMATOLOGICAL
TYPES OF
BONE
Trabecular
Compact
COMPOSITION OF BONE
Inorganic elements (65%) � Calcium hydroxyapotite
Organic matrix (35%) � Cells and Proteins. Type 1 collagen
Osteocalcin
BONE FORMING CELLS
OSTEOPROGENATOR CELLS
OSTEOBLASTS
OSTEOCLASTS
OSTEOCYTES
BASIC MULTICELLULAR UNIT
BMP
FGF
PDGF
TGF
CORTICAL BONE TRABECULAR BONE
LAMELLAR BONE WOVEN BONE
REGULATION OF OSTEOCLAST FORMATION
ABNORMALITIES IN BONE
DEVELOPMENTAL
(Genetic)ACQUIRED
• DEFECTS IN NUCLEAR PROTEIN
-Transcription factor (homeobox gene)–
dyostoses
localised abnormality
Craniorachischisis-failure of closure of spinal canal
and skull
• Defects in hormones and signal-dysplasia
-Transduction mechanism – Achondroplasia
ACHONDROPLASIA
� FGF3 inhibits cartilage proliferation in normal
� Mutation of FGFR3 gene on chromosome 4
� Substitution of arginine for glycine
� Symptoms such as bowlegs, large head, and limited
elbow extension
� Abnormal body proportions, short arms and legs,
normal torso size, reduced height, upper arms/thighs
more shortened than forearms/lower legs
� Homozygous infants have shorter life expectancy than
heterozygous infants
OSTEOGENESIS IMPERFECTA (OI)
BRITTLE BONE DISEASE
• Genetic disorder of type I collagen
• Four types Type I-IV
• Most are autosomal dominant mutation of
genes7&17
• 25% have spontaneous mutation
OSTEOGENESIS IMPERFECTA (OI)
• Affects all connective tissue
• Decreased osteoblasts
• Sparse cancellous bone
• Osteoporosis - prone for fracture
OI
Type I
60-80% of cases
Normal stature
Hyper-extendibility
Hearing loss
Average life expectency
OI
• Subtype B –dentinogenesis imperfecta
• abnormal dentin collagen –
• Affects primary and permanent teeth
• translucent discoloured teeth
• Enamel fracture
• Short roots
• Periapical lucencies
OI
Type II
Fatal perinatal or intrauterine
Abnormal extremities and skull
Blue black sclera
Defects in Metabolic Pathways
� Osteopetrosis (Marble bone disease/Albers-Schonberg disease)
Carbonic anhydrase II deficiency, enzyme required for
acidification and excretion of hydrogen ions.
Reduced osteoclast bone resorption
Characterised by systemic sclerosis
Diseases associated with decreased bone mass
OSTEOPOROSIS
PRIMARY
� Post menopausal
� Senile
�disuse
SECONDARY
� Hyperparathyroidism
� Hypothyroidism
� Multiple Myeloma
� Drugs
� Corticosteroids
� Anticoagulants
� Chemotherapy
PATHOGENESIS OF OSTEOPEROSIS
1. Reduced osteoblastic activity-low turnover
2. Reduced physical activity
3. Genetic factors-polymorphism of vit D receptor
4. Nutritional status
5. Hormonal influence
DISEASES CAUSED BY OSTEOCLAST
DYSFUNCTION
1. PAGET’S DISEASE
2. Pathogenesis – Paramyxovirus infection (IL6, M-CSF
Osteoclast activation)
Complications of Paget’s Disease
• Sarcoma (osteosarcoma, chondrosarcoma,
fibrosarcoma)
• Metastatic carcinoma
• Hematologic malignancies
• Giant-cell tumor
Diseases associated with abnormal mineral
homeostasis
� Vitamin D deficiency
Osteomalacia – poor calcification causing a delay
or failure of bone matrix mineralization usually
caused by Vitamin D deficiency or a disturbance in
its metabolism
Rickets – osteomalacia happening before the
epiphyses have fused
RICKETSTender /swollen joints, classically wrists
Deformed bones
Bone pain or tenderness
Fits or irritability
Breathing difficulties
Occurs during rapid growth
Bow legs or knock knees
Delayed walking or waddling gait
Rickety rosary
Tetany or convulsions
Apnoea or stridor
Impaired growth or delayed fontanelle closure
Delayed eruption of teeth or enamel hypoplasia
HYPERPARATHYROIDISM
PRIMARY: (increased parathormone production)
� ADENOMA (MEN 1,2)
� HYPERPLASIA
�Parathyroid carcinoma
SECONDARY: (compensatory overactivity of parathyroid glands)
� Chronic renal failure
OSTEOMYELITIS
• Infectious process of the bone(s)
• Classification based on Route of Entry
– Contiguous spread of adjoining soft tissue infection
– Direct inoculation secondary to trauma or surgery
– Hematogenous bacterial emboli lodging in the bone
• Children - primarily in the long bones (femur, tibia,
fibula, humerus)
• Adults (50-60s) - primarily vertebrae
• Neonates - have multiple bone infectious sites
Pain - predominant factor
– Fever
– Increased WBC (< 15,000)
– Edema, erythema, and
tenderness at the site of infection in 50%
of cases
