PTH-01-Disease of Bone

Question 1

Bone forming

Answer 1

• Osteoblasts

- Osteoclasts

Question 2

Bone Digesting

Answer 2

• Osteoclast precursors

- Functioning osteoclasts

Question 3

Regulated by

Answer 3

-RANK-RANKL pathway

Question 4

Inherited Syndromes Affecting Bones(Generalized Situation)

Answer 4

Hurler’s syndrome (Mucopolysaccharidosis)

Marfan’s syndrome

Question 5

Hurler’s syndrome (Mucopolysaccharidosis)

Answer 5

Lysosomal storage disease

Question 6

Marfan’s syndrome

Answer 6

Mutation in fibrillin gene required for structural integrity of connective tissue

Question 7

Congenital for Bone(Specifically)

Answer 7

• Dysostosis

- Skeletal Dysplasia

Question 8

Dysotosis-Definition

Answer 8

Localized developmental abnormalities of migration of mesenchymal cells

Question 9

Dysostosis-Type

Answer 9

• Aplasia(missing part)
• Supernumerary digits(+ or - original no)
• Abnormal fusion of digits

Question 10

Skeletal Dysplasia-Definition

Answer 10

• Abnormalities in bone or cartilage growth or maintenance

- Due to mutations in signal transduction or in components of extracellular matrix

Question 11

Skeletal Dysplasia-Type

Answer 11

1- Achondroplasia
2- Osteogenesis Imperfecta
3- Osteopetrosis

Question 12

Achondroplasia

Answer 12

• 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.

Question 13

Osteogenesis Imperfecta

Brittle Bone Disease

Answer 13

• 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

Question 14

Osteopetrosis

Marble bone disease

Answer 14

• Genetic, AD or RD → reduced bone resorption.
• Impaired osteoclast function or formation.
• Dense stone like bone, liable to fracture.

Question 15

Osteopetrosis-Result

Answer 15

• Cranial nerve problems (compression).
• Decreased hematopoiesis
• May benefit from bone marrow transplant

Question 16

Acquired Diseases of Bone Development

Answer 16

1- Osteoporosis
2- Rickets / Osteomalacia
3- Hyperparathyroidism
4- Paget’s Disease Of Bone

Question 17

Osteoporosis

Answer 17

• 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

Question 18

Primary Osteoporosis

Answer 18

Post menapausal in women

Senile in both sexes as an aging process

Question 19

Secondary Osteoporosis

Answer 19

Endocrine disorders
Carcinomatosis , multiple myeloma
GIT disorders: malnutrition, malabsorption, obesity…etc
Drugs : corticosteroids, chemotherapy..
Others : immoblization, pulmonary disease…etc

Question 20

Factors Affecting Bone Resorption

Answer 20

Age related changes
Hormonal factors
Physical activity
Genetic factors
Nutritional factors

Question 21

Pathophysiology : Osteoclast Activation

Answer 21

Osteoclast precursor→Active Osteoclast in present of RANK-RANKl, M-CSF, inhibited by Osteoprotegerin. (Estrogen prevent this activation by activating OPG)

Question 22

Primary Post Menapausal

Answer 22

• cytokines and hormones(TNF,IL-1,IL-6), stimulate the expression of RANKL
• Estrogen deficiency
• Increase osteoclast activity

Question 23

Osteoporosis-Morphology

Answer 23

• Thin bone trabeculae
• Widely separated
• Notable osteoclast activity
• Normal mineral bone content
• Most changes in weight bearing areas in vertebral bodies & femoral neck

Question 24

Osteoporosis-Clinical Picture

Answer 24

• Post menapausalor senile
• Often missed until fractures occur
• Lumbar & Thoracic fractures, Head of femur
• Diminished height
• Kyphoscoliosis→Respiratory function

Question 25

Osteoporosis-Diagnosis

Answer 25

* 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

Question 26

Osteoporosis-Treatment

Answer 26

* Estrogenreplacementtherapy * Excercise * Calciumand Vitamin D dietary intake& supplements * Biphosphonate

Question 27

Rickets / Osteomalacia:

Answer 27

•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

Question 28

Sign of Rickets

Answer 28

- Soft spot on baby, slow to close - Bony necklace - Curved bones - Big, lumpy joint - Bowed leg

Question 29

Hyperparathyroidism

Answer 29

* Primary or Secondary | * ↑parathormone→osteoclast activation →bone resorption→↑calcium

Question 30

Hyperparathyroidism-Result

Answer 30

* Bone cyst in any site * BROWN tumor/OSTEITIS FIBROSA CYSTICA in which there are osteoclasts, giant cells, hemosiderin & fibrovascular background * Fractures & Deformities

Question 31

Paget’s Disease Of Bone

Answer 31

* 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 ???

Question 32

PDB-Phase

Answer 32

* Primary phase of osteoclasticactivity, bone loss & hypervascularity. * Phase of mixed osteoclastic& osteoblastic activity. * Late osteosclerotic phase with formation of dense mineralized bone.

Question 33

PDB-Pathology

Answer 33

* 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).

Question 34

PDB-Clinical Picture

Answer 34

•Often asymptomatic & discovered incidentally. •↑Alkaline phosphatase , serum calcium & phosphate normal •Deformities: -Lower limbs→Bowing of the legs. -Skull deformed & enlarged→headache

Question 35

PDB-Complication

Answer 35

* 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

Question 36

Inflammatory Conditions

Answer 36

- Osteomyelitis - Arthritis(Joint)(RA,IA) - Osteoarthritis(Degenerative) - Gout - Pseudogout - Tenosynovitis, GCT

Question 37

Osteomyelitis

Answer 37

* Inflammation of the bone and the marrow cavity. | * Usually blood -borne infection

Question 38

Osteomyelitis

Answer 38

* Pyogenic osteomyelitis. * Tuberculousosteomyelitis. * Syphilitic osteomyelitis. * Pott's disease*

Question 39

Pyogenic Osteomyelitis

Answer 39

``` •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 ```

Question 40

PO-Clinical Picture

Answer 40

* Acute : Fever, bone pain, leukocytosis, ↑BMR | * Chronic : Low grade fever, pain, abscess, discharging sinuses

Question 41

PO-Diagnosis

Answer 41

* X-ray : Destructive lytic lesion with new bone formation | * Blood & sinus discharge culture

Question 42

PO-Treatment

Answer 42

•Appropriate antibiotic & surgical debridement

Question 43

PO-Pathology

Answer 43

* 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)

Question 44

PO-Complication

Answer 44

* Pathological fracture. * Septic arthritis. * Bacteremia & septicemia. * Endocarditis. * Amyloidosis. * Chronic skin sinus * Squamous cell carcinoma of the skin.

Question 45

Tuberculous Osteomyelitis

Answer 45

* 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

Question 46

Pott’s Disease

Answer 46

* Tuberculousosteomyelitis affecting the vertebrae → KYPOSIS,SCOLIOSIS ( Hunchback) * May drain into soft tissue & adjacent psoas muscle →PSOAS ABSCESS * Therapy: Antituberculous therapy, but difficult to treat.

Question 47

Infectious arthritis

Answer 47

•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

Question 48

Rheumatoid Arthritis

Answer 48

•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)

Question 49

RA-Pathology

Answer 49

* 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

Question 50

RA-Diagnosis

Answer 50

* Serological tests : Hypergammaglbulinemia * Rheumatoid Factor Positive (IgM or IgG autoAB that bind to Fc portion of IgG →immune complexes deposited throughout the body

Question 51

Osteoarthritis

Answer 51

•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

Question 52

OA-Pathology

Answer 52

* 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.

Question 53

OA-Clinical Picture

Answer 53

* Morning stiffness * Pain & swelling in joints * Progressive deformity in joints, but no ankylosis * Spinal root compression due to involvement of vertebra by osteophytes

Question 54

OA-Treatment

Answer 54

* Analgesics | * Joint replacement

Question 55

Gout

Answer 55

•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

Question 56

Gout-Pathology

Answer 56

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

Question 57

Pseudogout (chondrocalcinosis)

Answer 57

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

Question 58

Tumor –Like Lesions in Joints

Answer 58

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)

Question 59

Pigmented Villo-nodular Tenosynovitis & Giant Cell Tumor of Tendon Sheath

Answer 59

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