Remodeling and Aging of Bones; Pathology of Metabolic Bone Disease

Question 1

Why does bone loss occur during aging and why are vertebrae most susceptible?

Answer 1

Occurs because bone formation does not match bone resorption following a bone remodelling cycle as you get older -> incomplete refilling of the bone pits made by osteoclasts.

Vertebrae are most susceptible because cancellous bone has the highest turnover rate.

Question 2

Why does decreased estrogen predispose to osteoporosis?

Answer 2

Estrogen serves to decrease osteoclast activity and inhibit apoptosis of osteoblasts.

Loss of this hormone leads to -> increased cycles of remodeling and bone resorption -> progressive loss of bone

Question 3

How does physical activity influence the rate of bone loss in osteoporosis?

Answer 3

It decreases it -> increasing resistance will keep bone strong.

Infact, immobility will increase osteoporosis.

Question 4

With what symptoms does osteoporosis typically present?

Answer 4

Typically presents with acute back pain and loss of height as the osteopenia will lead to increased fracture risk -> formation of microfractures within vertebral bodies.

Also commonly cause kyphosis, loss of height, and fractures of femoral head and distal radius

Question 5

How does vitamin D work differently when there is low serum Ca+2 vs normal serum Ca+2?

Answer 5

Low - helps mobilize calcium and phosphorous, resorbing bone (keeping plasma levels is most important)

Normal - helps promote mineralization of osteoid

Question 6

How do GI and renal disease predispose to vitamin D deficiency?

Answer 6

GI - fat malabsorption, or liver disease (liver needed to convert vitamin D to active form, also need to produce vitamin D binding protein for plasma)

Renal disease - obviously cannot make 1a-hydroxylase

Question 7

Why does decreased vitamin D cause osteoporosis even if PTH can recover blood calcium levels?

Answer 7

Increased PTH will lead to phosphate wasting -> impaired bone mineralization with low plasma phosphate levels. Thus, if PTH needs to maintain serum calcium levels, bone formation will suffer.

Question 8

What will happen to osteoid seams in rickets vs scurvy?

Answer 8

Rickets - osteoid seams are very large -> osteoid laid down fine but cannot mineralize

Scurvy - osteoid seams are very narrow. Deficiency of osteoid -> mineralize occurs rapidly.

Question 9

Why is rickets different than osteomalacia? What process is occurring in endochondral ossification?

Answer 9

In children, the epiphyseal cartilage which is forming the physis has not closed up.

Lack of calcification of cartilage -> overgrowth of chondrocytes / wild cartilage formation, contributing to pathology of rickets

Question 10

What are the findings of rickets typically seen in infancy? define: craniotabes, rachitic rosary, pigeon breast deformity, harrison groove

Answer 10

Typically they are head / rib cage abnormalities since they aren’t walking around (no weightbearing)

Craniotabes - head is soft and compressible
Frontal bossing - head is overgrown and protruding
Rachitic rosary - overgrowth of costal cartilage
Pigeon-breast deformity - sternum protrudes (pectus carinatum)
Harrison groove -> groove can be seen below costal margin because ribs are so weak they get pulled in

Question 11

What are the later findings of rickets as kids start walking?

Answer 11

Bowing of the legs -> more weight and stress places on femurs with cartilage overgrowth

Lumbar lordosis

Question 12

How does vitamin D deficiency present in adulthood?

Answer 12

Osteomalacia, which his osteopenia with loss of bone density and cortical thickness, with increased susceptibility to fractures, weakness, and bone pain.

Looser zones - pseudofractures which are linear areas of unmineralized osteoid seen in bone.

Question 13

What is osteitis deformans and what is thought to underlie it?

Answer 13

Paget Disease of bone

-> accelerated bone turnover, thought to be started by possibly measles virus slowly infecting osteoclasts

Question 14

What bones are typically affected in Paget disease? Are they all the same stage of the disease?

Answer 14

Typically the axial skeleton and large bones of the extremities

Lesions are seen at various stages of the disease in different bones and even within the same bone

Question 15

What is the first stage of Paget disease and how do the cells look?

Answer 15

Osteolytic stage -> osteoclasts have increased size and number of nuclei. They are going crazy.

Can see sharply defined lytic areas within cortical bone on radiography

Question 16

How does the second stage of Paget disease appear on radiography and microscopically?

Answer 16

Mixed stage -> Heterogenous areas of increased bone lucency (osteoclast activity) intermixed with areas of sclerosis / bone thickening (osteoblast recovery)

Increased osteoclast and blast activity, producing new woven bone. Bone marrow gets replaced by granulation and fibrous tissue due to increased remodelling

Question 17

How does the third stage of Paget disease appear radiographically?

Answer 17

Sclerotic stage -> osteoblasts only. Bone enlargement with abnormally increased density and course bone thickening

Question 18

What is pathognomonic of the third stage of Paget disease histologically?

Answer 18

Mosaic, tile-like arrangement of lamellar bone separated by prominent cement lines
-> cement lines were formed by crazy osteoclasts

Question 19

What labs will be elevated in serum and urine in Paget disease?

Answer 19

1. Increased collagen breakdown products (i.e. hydroxyproline) in urine / serum -> due to increased osteoclast activity
2. Increased serum ALP -> very high osteoblast activity

Question 20

What will result form the bone deformities of paget disease, acutely?

Answer 20

1. Increased risk of chalk-stick fractures since the bone is woven and not lamellar bone
2. Bone pain
3. Facial and skull bone overgrowth -> increased hat size.
4. Hearing loss -> skull overgrowth impinges on cranial nerves as they exist through small foramina.

Question 21

What are you at increased risk for due to chronic Paget disease?

Answer 21

1. High-output cardiac failure due to increased vascularity and AV malformations in the affected bones - LOL ehab
2. Osteosarcoma -> increased osteoblast activity makes this a possibility in adults