Pathoma - MSK - Bones

Question 1

What is the basic premise of achondroplasia

Answer 1

Impaired cartilage proliferation in the growth plate –> failure of longitudinal growth –> common cause of dwarfism

Question 2

What is the mutation in achondroplasia

Answer 2

Activating mutation in fibroblast growth factor receptor 3 (FGFR3)

Overexpression of FGFR3 inhibits growth

Question 3

What is a risk factor for mutation of FGFR3 (achondroplasia)

Answer 3

Paternal age

Question 4

What is endochondral ossification?

Answer 4

Bones of axial skeletal, appendicular skeleton, and base of skull

Chondrocytes lay down a cartilagenous model of bone which is then replaced by osteoclasts and osteoblasts into first woven bone and then lamellar bone

Question 5

What is membranous ossification?

Answer 5

Bones of skull, face, and chest

Woven bone is formed directly without cartilage and then later remodelled to lamellar bone

Question 6

What type of bone formation is abnormal in achondroplasia? Endochondral or membranous ossification?

Answer 6

Poor endochondrol bone formation (long bones) - which is why patients have short limb

Normal membranous bone formation (skull and chest) - so patients have normal sized head and chest

Question 7

What is the defect in osteogenesis imperfecta

Answer 7

Defect in collagen type I synthesis

Question 8

What is the triad of clinical features of osteogenesis imperfecta?

Answer 8

Multiple bone fractures, blue sclera, hearing loss

Question 9

Why is there blue sclera in osteogenesis imperfecta?

Answer 9

Thinning of scleral collagen reveals underlying choroidal veins

Question 10

Why is there hearing loss in osteogenesis imperfecta?

Answer 10

Bones of the middle ear are easily fractured

Question 11

What is the basic premise behind osteopetrosis?

Answer 11

Inherited defect of bone resorption (defective osteoclasts) resulting in abnormally thick, heavy bone that fractures easily

Question 12

What is a common mutation leading to osteopetrosis?

Answer 12

Carbonic anhydrase II mutation

Leads to loss of acidic environment required for bone resorption

Question 13

Why do you get pancytopenia in osteopetrosis?

Answer 13

Bone fills the marrow space leading to myelophthisic process (marrow can no longer carry out hematopoiesis - extramedullary hematopoiesis)

Question 14

What are common complications of osteopetrosis?

Answer 14

Cranial nerve impingements due to narrowing of foramina

Hydrocephalus due to narrowing of foramen magnum

Question 15

What is the metabolic/respiratory acidosis/alkalosis commonly found in osteopetrosis?

Answer 15

Metabolic acidosis

Carbonic anhydrase deficiency leads to lack of HCO3- reabsorption

Question 16

What is the treatment for osteopetrosis?

Answer 16

Bone marrow transplant (osteoclasts are derived from monocytes)

Question 17

What is the defective process in osteomalacia/rickets?

Answer 17

Defective mineralization of osteoid (osteid is still produced by osteoblasts, but is unable to be mineralized with calcium and phosphate to form bone)

Due to low levels of Vitamin D, leading to low serum calcium and phosphate

Question 18

Describe the activation of Vitamin D

Answer 18

25-hydroxylation via liver

1-alpha-hydroxylation via kidney

Question 19

Common clinical findings of rickets

Answer 19

Pigeon-breast deformity

Frontal bossing (enlarged forehead) - due to osteoid deposition on the skull

Rachitic rosary - osteoid deposition at the costochondral junction

Bowing of the legs

Question 20

Is alkaline phosphatase increased or decreased in osteomalacia and why

Answer 20

Increased - in order to try to create an alkaline environment, wich is necessary to lay down calcium into osteoid

Question 21

What is the basic premise behind osteoporosis

Answer 21

Loss of mass of trabelular (spongy) and cortical bone

Question 22

What is the most common cause of osteoporosis?

Answer 22

Increased bone resorption due to decreased estrogen (post-menopausal) or old age

Question 23

Describe lab values in osteoporosis (calcium, phosphate, PTH, alkaline phosphatase)

Answer 23

Normal lab values

Can be used to help exclude osteomalacia (which will have low calcium, high PTH, low phosphate, and high alkaline phosphatase)

Question 24

Treatment options for osteoporosis

Answer 24

Weight-bearing exercise, vitamin D, calcuium

Bisphosphonates, SERMs

Question 25

Describe the basic premise behind paget disease of the bone

Answer 25

Imbalance between osteoclast and osteoblast function that leads to thick, sclerotic bone that fractures easily

Question 26

What are the stages of paget disease of the bone?

Answer 26

(1) Lytic - Osteoclastic
(2) Mixed - Osteoclasts + osteoblasts
(3) Sclerotic - Osteoblastic
(4) Quiescent - minimal osteoclast/osteoblast activity

Question 27

At what stage of life do patients usually develop paget’s disease of the bone?

Answer 27

Late adulthood (usually > 60 y/o)

Question 28

Describe histology of paget disease of the bone

Answer 28

Mosaic pattern of woven and lamellar bone (osteocytes with lacunae in chaotic juxtapositions)

Question 29

Common clinical findings of paget disease of the bone

Answer 29

Bone pain - due to microfractures

Increasing hat size - skull thickening

Hearing loss - auditory foramen narrowing

Lion-like facies

Question 30

Describe lab findings in paget disease (calcium, phosphate, PTH, alkaline phosphatase)

Answer 30

Will see isolated elevated alkaline phosphatase (due to end stage where osteoblasts are trying to lay down bone)

All other levels will be normal

Question 31

Complications of paget diseas

Answer 31

High-output cardiac failure - due to increased blood flow from increased arteriovenous shunts in bone

Osteosarcoma - end-stage osteoblasts at risk for mutation

Question 32

Describe most common location of osteomyelitis in children and adults

Answer 32

Children - metaphysis

Adults - epiphysis

Question 33

What is the most common bacterial cause of osteomyelitis

Answer 33

Staph aureus

Question 34

Common causes of avascular (aseptic) necrosis

Answer 34

Trauma or fracture, steroids, sickle cell anemia, caisson disease (“the bends” - gas emboli precipitate out of the blood and deposit in bone)

Question 35

Most common site of avascular necrosis

Answer 35

Femoral head (due to insufficiency of medial circumflex femoral artery)