PTH-01-Disease of Bone Flashcards
Bone forming
- Osteoblasts
- Osteoclasts
Bone Digesting
- Osteoclast precursors
- Functioning osteoclasts
Regulated by
-RANK-RANKL pathway
Inherited Syndromes Affecting Bones(Generalized Situation)
Hurler’s syndrome (Mucopolysaccharidosis)
Marfan’s syndrome
Hurler’s syndrome (Mucopolysaccharidosis)
Lysosomal storage disease
Marfan’s syndrome
Mutation in fibrillin gene required for structural integrity of connective tissue
Congenital for Bone(Specifically)
- Dysostosis
- Skeletal Dysplasia
Dysotosis-Definition
Localized developmental abnormalities of migration of mesenchymal cells
Dysostosis-Type
- Aplasia(missing part)
- Supernumerary digits(+ or - original no)
- Abnormal fusion of digits
Skeletal Dysplasia-Definition
- Abnormalities in bone or cartilage growth or maintenance
- Due to mutations in signal transduction or in components of extracellular matrix
Skeletal Dysplasia-Type
1- Achondroplasia
2- Osteogenesis Imperfecta
3- Osteopetrosis
Achondroplasia
- AD, dwarfism,
- Point mutation in the fibroblast growth factor receptor 3 → inhibits cartilage proliferation → suppression of growth
- Shortened proximal extremities, trunk of relatively normal length, enlarged head
- Normal life span, intellect & reproduction.
Osteogenesis Imperfecta
Brittle Bone Disease
- Defective synthesis of type 1 collagen present in bones, joints, eyes, ears, skin and teeth.
- Usually AD.
- It has several subtypes with different outcomes.
- Bone fragility & bone fractures, blue sclera, hearing defects, thin skull and dental abnormalities.
- Can be diagnosed in utero
Osteopetrosis
Marble bone disease
- Genetic, AD or RD → reduced bone resorption.
- Impaired osteoclast function or formation.
- Dense stone like bone, liable to fracture.
Osteopetrosis-Result
- Cranial nerve problems (compression).
- Decreased hematopoiesis
- May benefit from bone marrow transplant
Acquired Diseases of Bone Development
1- Osteoporosis
2- Rickets / Osteomalacia
3- Hyperparathyroidism
4- Paget’s Disease Of Bone
Osteoporosis
- Progressive Loss Of Bone Mass
- Up to 30years. Later,osteoclast activity exceeds osteoblast activity
- Result :Bone loss of 0.7%/year is normal
- Governed by several factors e.g. vit.D, parathyroid hormone , level of estrogen….etc.
- Commonest Disorder of bone;Localized, Generalized
- Primary or Secondary
- Mostly affect spine & femoral neck
Primary Osteoporosis
Post menapausal in women
Senile in both sexes as an aging process
Secondary Osteoporosis
Endocrine disorders
Carcinomatosis , multiple myeloma
GIT disorders: malnutrition, malabsorption, obesity…etc
Drugs : corticosteroids, chemotherapy..
Others : immoblization, pulmonary disease…etc
Factors Affecting Bone Resorption
Age related changes Hormonal factors Physical activity Genetic factors Nutritional factors
Pathophysiology : Osteoclast Activation
Osteoclast precursor→Active Osteoclast in present of RANK-RANKl, M-CSF, inhibited by Osteoprotegerin. (Estrogen prevent this activation by activating OPG)
Primary Post Menapausal
- cytokines and hormones(TNF,IL-1,IL-6), stimulate the expression of RANKL
- Estrogen deficiency
- Increase osteoclast activity
Osteoporosis-Morphology
- Thin bone trabeculae
- Widely separated
- Notable osteoclast activity
- Normal mineral bone content
- Most changes in weight bearing areas in vertebral bodies & femoral neck
Osteoporosis-Clinical Picture
- Post menapausalor senile
- Often missed until fractures occur
- Lumbar & Thoracic fractures, Head of femur
- Diminished height
- Kyphoscoliosis→Respiratory function
Osteoporosis-Diagnosis
- Plain X-ray only after 30-40% bone loss
- Radiographic measurement bone density
- Laboratory biochemical markers of bone:
- Formation (alkaline phosphatase)
- Resorption (urinary calcium)
- Rarely , bone biopsy
Osteoporosis-Treatment
- Estrogenreplacementtherapy
- Excercise
- Calciumand Vitamin D dietary intake& supplements
- Biphosphonate
Rickets / Osteomalacia:
•Decrease in vitamin D intake or metabolism
→excess of unmineralized matrix
•Normally almost 100% of bone is mineralized, whereas in these conditions , mineralization may be < 20%
•Histology : thick unmineralized osteoid around more mineralized bone trabeculae
•Weak bones →Bone deformities & Fractures
Sign of Rickets
- Soft spot on baby, slow to close
- Bony necklace
- Curved bones
- Big, lumpy joint
- Bowed leg
Hyperparathyroidism
- Primary or Secondary
* ↑parathormone→osteoclast activation →bone resorption→↑calcium
Hyperparathyroidism-Result
- Bone cyst in any site
- BROWN tumor/OSTEITIS FIBROSA CYSTICA in which there are osteoclasts, giant cells, hemosiderin & fibrovascular background
- Fractures & Deformities
Paget’s Disease Of Bone
- Paget disease is a localized disorder of bone remodeling , in middle age
- Disordered osteoclast hyperactivity with osteoblast activity →increased bone mass
- Disorganized mosaic of bone weaker bone , larger, less compact, more vascular,
- Cause : Viral, genetic, inflammatory disorder ???
PDB-Phase
- Primary phase of osteoclasticactivity, bone loss & hypervascularity.
- Phase of mixed osteoclastic& osteoblastic activity.
- Late osteosclerotic phase with formation of dense mineralized bone.
PDB-Pathology
- Focal replacement of the bone marrow by loose vascular connective tissue
- Bone trabeculae are lined by huge osteoclasts.
- Osteoblastic proliferation with concomitant bone resorption & new bone formation.
- Irregular woven bone deposition with bone thickening (mosaic pattern).
PDB-Clinical Picture
•Often asymptomatic & discovered incidentally.
•↑Alkaline phosphatase , serum calcium & phosphate normal
•Deformities:
-Lower limbs→Bowing of the legs.
-Skull deformed & enlarged→headache
PDB-Complication
- Nerve compression →deafness, visual disturbances
- Increased vascularity in bone marrow leads to arteriovenousshunting →may leads to high output heart failure.
- Osteosarcoma may develop (1 % )
- Prognosis good unless complications occur
Inflammatory Conditions
- Osteomyelitis
- Arthritis(Joint)(RA,IA)
- Osteoarthritis(Degenerative)
- Gout
- Pseudogout
- Tenosynovitis, GCT
Osteomyelitis
- Inflammation of the bone and the marrow cavity.
* Usually blood -borne infection
Osteomyelitis
- Pyogenic osteomyelitis.
- Tuberculousosteomyelitis.
- Syphilitic osteomyelitis.
- Pott’s disease*
Pyogenic Osteomyelitis
•Caused by pyogenic bacteria: -Staph. Aureus, E. coli, Salmonella -mixed infection •Sources: 1-Hematogenous* 2-Direct extension 3-Direct trauma. 4-Iatrogenic •Mainly affects in metaphysis. •Infants:Epiphyseal infection→joint
PO-Clinical Picture
- Acute : Fever, bone pain, leukocytosis, ↑BMR
* Chronic : Low grade fever, pain, abscess, discharging sinuses
PO-Diagnosis
- X-ray : Destructive lytic lesion with new bone formation
* Blood & sinus discharge culture
PO-Treatment
•Appropriate antibiotic & surgical debridement
PO-Pathology
- Acute,subacute,chronic stages
- Neutrophil infiltration,early bone necrosis (Sequestrum)
- Spread to periosteum→subperiosteal abscess → rupture into soft tissue →draining sinus
- Chronic:plasma cells & lymphocytes, reactive new bone ( involucrum), abscess (Brodie’s Abscess)
PO-Complication
- Pathological fracture.
- Septic arthritis.
- Bacteremia & septicemia.
- Endocarditis.
- Amyloidosis.
- Chronic skin sinus
- Squamous cell carcinoma of the skin.
Tuberculous Osteomyelitis
- May follow pulmonary or GIT tuberculosis.
- Most common in immunosuppressed
- Hematogenousor direct from nearby focus
- May be solitary or multicentric.
- Long bones & vertebrae most affected
- Pathology is a caseating granulomatous reaction destroying bone
Pott’s Disease
- Tuberculousosteomyelitis affecting the vertebrae → KYPOSIS,SCOLIOSIS ( Hunchback)
- May drain into soft tissue & adjacent psoas muscle →PSOAS ABSCESS
- Therapy: Antituberculous therapy, but difficult to treat.
Infectious arthritis
•Septic-Acute :Staph.,Strep.,Gonococci…..etc
Any joint, inflammation with suppuration .
Heals with antibiotics, or fibrosis & calcification
•Tuberculous: Complication of pulmonary or miliary
Granulomatous inflammation with caseation
destruction of cartilage & deformity.
More in children & spine
Rheumatoid Arthritis
•F>M, middle age, ? Etiology
•Autoimmune process →T-cell & macrophage reactions in genetically predisposed →TNF→tissue damage & synovial proliferation
•Systemic disease with involvement of small joints of hands & feet, mainly proximal interphalyngeal joints.
Later any joint
•Stiff swollen red joints, later deformity, & fusion of joints(ANKYLOSIS)
RA-Pathology
- Acute & chronic inflammatory cells, lymphoid follicles in hypertrophied synovium, extends into joint
- Later, synovium+ inflammatory cells →‘PANNUS’ →fibrosis →Joint destruction
- ‘Rheumatoid nodules’ in joints & soft tissue
RA-Diagnosis
- Serological tests : Hypergammaglbulinemia
- Rheumatoid Factor Positive (IgM or IgG autoAB that bind to Fc portion of IgG →immune complexes deposited throughout the body
Osteoarthritis
•Commonest type. Both sexes.
•Primary degenerative dis.ofcartilage: > 65yrs.
•Secondary in younger patients:
-trauma, obesity, bone deformity
•Genetic causes
•Hips, Knees , Hands & Intervertebral joints →Swelling & decreased mobility
OA-Pathology
- Proliferation& disorganization of chondrocytes, ↑water,↓proteoglycans →Cracking of cartilage superficially
- Loss of cartilage →Exposed smooth subchondral hard bone ( Bone eburnation )
- Minor fractures→Loose cartilage bodies ’Joint mice’ in joint space
- Gaps filled by synovial cysts & bony outgrowths ‘osteophytes’. Occasional fibrous Pannus.
OA-Clinical Picture
- Morning stiffness
- Pain & swelling in joints
- Progressive deformity in joints, but no ankylosis
- Spinal root compression due to involvement of vertebra by osteophytes
OA-Treatment
- Analgesics
* Joint replacement
Gout
•Accumulation of Uric Acid in soft tissue & joints→acute arthritis→chronic arthritis & renal complications
•Primary is unknown
-Middle aged men with high uric acid level
•Secondary :
-High nucleic acid turnover
-Renal failure
-Inborn error of metabolism
Gout-Pathology
Repeated attacks of ACUTE ARTHRITIS in small joints, with deposition of MONOSODIUM URATE crystals → severe inflammation
Repeated attacks → ” Tophi”
Tophi are foci of urate crystals surrounded by inflammation with foreign body giant cell reaction.
Chronic Tophaceous arthritis with joint destruction & deformity.
Gouty nephropathy : calculi, pyelonephritis
Pseudogout (chondrocalcinosis)
Deposition of calcium pyrophosphate with similar pathology to gout
Over the age of 50, often less severe
Acute, subacute, or chronic arthritis of knees, wrists, elbows, shoulders, and ankles.
Cause ?
Some cases are inherited
Tumor –Like Lesions in Joints
Ganglion :
- Small cyst near tendon or joint,
- most around wrist, symptomless
Synovial cyst :
-Herniation of synovium through joint capsule at popliteal fossa ( Baker’s cyst)
Pigmented Villo-nodular Tenosynovitis & Giant Cell Tumor of Tendon Sheath
PVNS mainly around knee, benign but may be large & aggressive
GCT smaller , painless nodule & around tendon
Cause ? Neoplasm ?
Both have similar morphology :
spindle cells, histiocytes , pigment
