Bone

Question 1

Only protein in bone that is unique to it and function

Answer 1

Osteopotin (osteocalcin)→produced by Osteoblast role in formation and mineralization and Can homeostasis

Question 2

A sensitive and specific marker for osteoblastic activity

Answer 2

Serum level of osteopotin

Question 3

Age of gestation when analgen is invaded by chondroblast

Answer 3

8weeks

Question 4

Pathways involved in inc osteoclast activity

Answer 4

1. Stimulated RANKL on Osteoblast activate RANK on osteoclast→activate osteoclast
2. M-CSF produced by Osteoblast→ activates it’s receptor on osteoclast→ generate osteoclast
3. Sclerostin→ inhibits WNT/ß catenin pathway→ inc osteoclast
4. PTH
5. IL 1
6. Glucocorticoids

Question 5

Pathway that inhibit osteoclast

Answer 5

1. WNT/ẞ catenin pathway: wnt produced by osteoprogentor cells bind to LRP5 and LRP6 receptors on osteoblast→inc production of Osteoprotegrin (OPG)
2. Bone morphologic protein
3. Sex hormones (estrogen) inhibit osteoclast proliferation

Question 6

Dysostosis and examples

Answer 6

Developmental anomalies caused by problems in migration and condensation of mesenchyme due to genetic alterations in transcription factors
→ complete absence of bone→Aplasia
→extra→supernumerary digits
→ abnormal fusion→syndactyly, craniosynostosis

Question 7

Dysplasia and examples

Answer 7

Disorganised bone and/ or cartilage due mutation in genes that control development and remodeling of skeleton

Question 8

Shortening of terminal phalanges of thumb and big toe and what mutation

Answer 8

Bradydactyly type D and E

Mutation in home box HOXD13 gene

Question 9

Patient has 
1. Patent fontanelles
2. Delayed closure of cranial sutures
3. Wormian bones
4. Delayed eruption of secondary teeth
5. Primitive clavicle
4. Short height 
What mutation

Answer 9

cleidocranial dysplasia →autosomal dominant→LOF mutation of RUNX2 gene(responsible for osteoclast and osteoblast differentiation)

Question 10

Patient has short upper and lower proximal extremities, normal sized trunk, larger head with bulging forehead, saddle nose and midface hypoplasia.
No deficits in intelligences or reproductive status

Answer 10

Achondroplasia (dwarfism) →autosomal dominant GOF mutation of tyrosine kinase receptor gene FGFR3 on chromosome 4→ defect in endochondral bone formation

Question 11

Newborn died 1 days after birth due to respiratory insufficiency, she had micromelic shortening of limbs, frontal bossing, macrocephaly, small chest cavity, bellshaped abdomen. Growth plate showed diminished proliferation of chondrocyte and disorganised zone of proliferation what diagnosis and cause

Answer 11

Thanatophoric dysplasia→lethal form of dwarfism→GOF mutation in FGFR3 differ from achondroplasia

Question 12

15yr patient present with skeletal fragility leading to frequent fractures postnatally, joint laxity, has blue sclera, small opalescent teeth, conductive hearing impairment, and normal stature. Vital signs normal. What’s the diagnosis and cause

Answer 12

Type 1 OI→AD mutation in type 1 collagen→dec synthesis of COL1A1 or Abnormal COL1A1/2 chains

Question 13

15yr patient present with skeletal fragility leading to frequent fractures postnatally, joint laxity, has blue sclera, small opalescent teeth, conductive hearing impairment, and normal stature. Vital signs normal. What’s the diagnosis and cause

Answer 13

Type 1 OI→AD mutation in type 1 collagen→dec synthesis of COL1A1 or Abnormal COL1A1/2 chains

Question 14

In utero death of fetus at 26 weeks, showed excessive skeletal fragility and multiple in utero fractures.

Answer 14

Type 2 OI→ mostly AR→ mutation COL1→abnormally short COL1A1/ unstable triple helix/ abnormal or insufficient COL1A2→ defect in assembling triple helix

Question 15

25 year old male present with short growth retardation, multiple fractures, worsening kyphoscoliosis, his stated that his eyes were previously blue but now have turned white, hearing impairment and small teeth. What’s the diagnosis and cause

Answer 15

Type 3 OI→ mostly AD→ altered structure of COL1A2 peptide/ impaired formation of triple helix→progressive and deforming disease

Question 16

16yr old patient present with postnatally fractures, moderate skeletal fragility, short stature (sometimes dentinogenesis imperfecta). Diagnosis and cause

Answer 16

Type 4 OI→AD→Mutation causes short COL1A1/unstable triple helix (compatible with survival)

Question 17

Newborn present with in utero fractures, severe anemia, PE shows hepatosplenomegaly, cranial nerve deficits of CNVII (or CNIII, CNVIII) x-rays show Erlenmeyer flask deformity. 4 days later patients patient died due to Inc infections. What’s diagnosis and cause

Answer 17

Infantile malignant Osteopetrosis→ AR mutation of carbonic anhydrase 2 enzyme found in kidney and osteoclast required to form protons from CO2 and water→ineffective acidification of resorption pits May also Dec acidity of urine

Question 18

15 yr old patient came in for X ray for frequent fractures, showed bulbous thicken of end of long bones (Erlenmeyer flask deformity), patient is anemic and lab also show leukopenia, PE noted slight hepatosplenomegaly and deficit in hearing (CNVIII). what the diagnosis and cause

Answer 18

Osteopetrosis→ AD Mutation in CLCN7 gene which encodes a proton pump on osteoclast→dec resorption

Question 19

Albers Schöneburg Disease and tx

Answer 19

Osteopetrosis/marble bone disease

Tx with hemopoietic stem cell transplant→since osteoclast derived from mononuclear cells

Question 20

20 yr old Patient presents with abnormalities in costochondral cartilage, anlage, articular surfaces, chest wall deformity and deformed bone, mucopolysaccharidosis symptoms (search)

Answer 20

Mucopolysaccharidosis ( lysosomal storage Disorder)→deficient lysosomal enzyme→accumilation of mucopolysaccharides in osteoclast→cell apoptosis

Question 21

55 yr old woman presents to your clinic with a fractured femoral neck when she fell at standing. She has a short stature due to kyphoscoliosis, she complains of back pain. What is the next step in diagnosis and it’s mostly likely finding

Answer 21

Most likely Post menopausal osteoporosis→diagnosised based on pathologic fracture
→DEXA can be done find T score: -2.5 with pathologic fractures→osteoporosis

Question 22

60yr old male presents to clinic with acute dyspnea, peripheral edema and cyanosis. He Had recently had a femur fracture after tripping/falling while standing, presents with kyphoscoliosis what’s diagnosis

Answer 22

Fat emboli from fracture→causing Pulmonary embolism secondary to senile osteoporosis

Question 23

Diagnostic test for patients suspected of osteoporosis

Answer 23

1. Biopsy(rare)
2. DEXA
3. Quantitative CT

Question 24

80yr old male patient present with fractured femur and complains of pain in back and femur over the fracture over which the skin is also warm to touch. He complains that his hats don’t fit anymore. Presents bowed legs which he confirmed he didn’t have while younger. Biopsy of bone shows “Mosiac pattern. X ray shows area of radiolucency along with sclerotic bright areas. Labs show high ALP, normal P and Ca. Diagnosis and tx

Answer 24

Based on imaging and labs→ Pagets disease

Symptoms suppressed with calcitonin and bisphosphonates

Question 25

Patient presents with progressive dyspnea and basilar crackles, S4 sound and holosystolic murmur on auscultation. X ray shows pul edema. Patient has a present history of paget disease. Diagnosis

Answer 25

LHF secondary to inc shunting of blood to hypervascular bones seen in Pagets disease

Question 26

3 yr old girl presents with bone pain, bowed legs, soft skull with frontal bossing and delayed closure of fontanelles, radiographs shows lateral widening of the epiphyseal plate with fraying at metaphysis. Anterior chest wall present with palpable nodules at the end of ribs. Diagnosis

Answer 26

Rickets disease cause defect in type 2 hyaline cartilage due to Dec mineralization

Question 27

28 yr old male with CKD present with joint pain and fractures. Radiographs show pseudo fractures "loser lines". Labs show ↑ALP, PTH, and P but low to normal Ca

Answer 27

Osteomalacia second to vit D deficiency caused by CKD. Loser lines are radiolucent areas of Dec mineralization

Question 28

60yr old woman presents to your clinic with bone pain, constipation, lab: ↑ PTH, ALP, Ca ↓P, imaging showed enlargement of all 4 PT glands what is the diagnosis and likely histologic finding

Answer 28

1° hyperparathyroidism→diffuse parathyroid hyperplasia (no involvement of kidney since P is low) Constipation probably cause by Inc Ca→↓sm tone histologic: 1. osteoporosis 2. dissecging osteitis→osteolocast tunnel along length of trabeculae 3. brown tumors→dec bone density Inc risk of microfractures and 2° hemorrhage→influx of macrophages→fibrous tissue deposition and brown due to vascularity, hemorrhage and hemosiderin. 4. osteitis fibrosa cystica (Von Ricklinghausen disease of bone) →the combination of the 2

Question 29

60yr old woman presents to your clinic with bone pain and fractures in the last 2 visits, lab: ↑ PTH, ALP, low to normal Ca and ↑P, imaging showed enlargement of all 4 PT glands, subperiosteal thining of bone with tapering of digital bones

Answer 29

2° hyperparathyroidism due to CKD due to high P levels

Question 30

Renal osteodystrophy and it's mechanisms of action

Answer 30

Skeletal changes that occur due to chronic renal disease including those associated with dialysis 1. Tubular dysfunction→ RTA→dec pH →osteomalacia 2. Generalized renal failure→↑ P and ↓Ca 3. Dec productive of vit D3→dec Ca Dec in BMP7 produces by tubular cells→dec osteoblast differentiation Dec Klotho production by kidney→dec FGF23 secreted by osteocyte→dec P homeostasis and vit D production

Question 31

20 yr old male presents with pain which explain use to occur only while doing something but recently become constant. He takes Prednisone daily for asthma. What are the microscopic finding

Answer 31

Osteonecrosis due to vascular insufficiency cause by the corticosteroid use. Mostly like caused subchondral infarct→causes pain ( medullary infarcts are smaller and clinically silent) Microscopic: 1. Wedged shaped seg of necrosis 2. Empty lacunae surrounded with necrotic adipocytes 3. Released FFA bind calcium→insoluble calcium soaps persist for life 4. Area of healing→creeping substitution→osteoclast remove necrotic tissue and new bone is deposited (not always effective)

Question 32

Most common cause of pyogenic osteomyelitis 80-90%

Answer 32

Staphylococcus aureus

Question 33

Pyogenic osteomyelitis most likely caused by which pathogen in ff settings: 1. Patients with GU infections and IV drug abusers 2. Neonates 3. Patients with sickle cell anemia

Answer 33

1. E.coli, pseudomona and Klebsiella 2. Haemophilia influenza and group B strep 3. Salmonella

Question 34

Most likely areas affected by pyogenic osteomyelitis in these individuals: 1. Neonates 2. Children 3. Adults

Answer 34

Based on osseous vascular circulation: 1. metaphyseal vessels penetrate plate→affect metaphysis, epiphysis or both 2. Metaphysis 3. Metaphyseal vessels reunite with epiphyseal ves→affect epiphysis and subchondral regions

Question 35

Patient presents with malaise, fever, chills leukocytosis and throbbing pain over the femur. Radiologic finding show an radiolucent lytic focus surrounded by zone of sclerosis. Diagnosis? What further test? And treatment

Answer 35

Pyogenic osteomyelitis. Blood cultures to identify pathogen for appropriate antibiotic Tx→antibiotics and survival drainage if abscess is present

Question 36

Complications seen in pyogenic osteomyelitis

Answer 36

1. In infants abscess can enter the joint →suppurative arthritis 2. Pathologic fractures 3. Secondary amyloidosis 4. Endocarditis 5. Sepsis 6. Development of scc in the draining sinus tract 7. Sarcoma of infected bone

Question 37

Patient presents with localised bone pain in the spine, fever chills and weight loss. Present with mild kyphosis. Patient has a history of TB that was treated 2 months ago. What diagnosis and histologic finding

Answer 37

``` Tuberculosis spondylitis (Pott disease)→type of mycobacterial osteomyelitis (40% affect the spine) Histo→caseous necrosis and granuloma ```

Question 38

Complications of mycobacterial osteomyelitis

Answer 38

1. Nerve cord compression 2. Tuberculosis arthritis 3. Sinus tract formation 4. Psoas abscess 5. Amyloidosis

Question 39

Feotus of 6months show bone lesions with areas of inflammation containing edematous granulation tissue in tibia. Massive reactive periosteal bone deposition of anterior and medial surface of tibia. Soft tumor like growth seen on imaging.diagnosis

Answer 39

Congenital syphilis Lesion usually develop in 5month of gestation Reactive bone development→saber shin Tumor like outgrowth→ gumma which are characteristic Spirochetes can be demonstrated in the area of endochondral ossification

Question 40

Diagnostic tools for bone tumors

Answer 40

Radiographic imaging | Biopsy for definitive diagnosis

Question 41

Mutations involved in osteosarcoma

Answer 41

1. RB gene LOF →more common in sporadic form 2. TP53 gene LOF→mostly sporadic →Li fraumeni syndrome→germline mutation Inc risk 3. INK4a→ encode TS p16(neg regulator CDK) and p14 ( Inc TP53 function)→ LOF 4. MDM2→inhibits p53→ GOF 5. CDK4→inhibits RB → gof

Question 42

Histologic features of osteosarcoma

Answer 42

1. Grey white tumors 2. Area of hemorrhage and cystic degeneration 3. Infiltrate medullary canal, epiphysis 4. Tumor cells have large hyperchromatic nuclei, so present are giant cells 5. May cause chondroblastic osteosarcoma

Question 43

Multiple osteochondroma detected during childhood causing bowing and shortening of underlying bone is characteristic of. And what is its solitary counter part

Answer 43

Multiple Hereditary exostosis syndrome→autodominant hereditary disease Counter part→ solitary exostosis→more common and present in late adolescences and early adulthood

Question 44

Mutations involved in Hereditary exostosis

Answer 44

Germline/sporadic LOF mutation in either EXT1 or EXT2 gene→encode enzyme which synthesize heparan sulfate glycosaminoglycans→dec in this GAG→prevents normal diffusion of Factor Indian hedgehog →disrupts chondrocyte differentiation and skeletal development.