Bone Histology and Childhood Disorders

Question 1

Answer 1

Question 2

Differentiate these two types of bone on the basis of:
• Abundance
• Function

Answer 2

Abundance:
• Cortical bone (top) makes up about 80% of bone mass

Function:
• Cortical bone houses mature osteocytes that help to maintain bone, but it consists mostly of calcified matrix

• Spongy bone is covered in osteoblasts and provides housing for hematopoesis

Question 3

What two types of bone are seen on the right and left?
• which is often pathologic?

Answer 3

Left:
• Lamellar bone - this is the same as cortical bone and is arranged into osteons (Havarsian systems) that communicate with the marrow space via volksmann’s canals. This bone is STRONG and RIGID

Right:
• Woven bone - this bone has a RANDOM orientation an is often pathologic. Woven bone is weaker and more flexible with a GREATER AMOUNT OF OSTEOBLASTS AND MORE TURNOVER.

Question 4

What are the 2 components of bone?
• what are they composed of?

Answer 4

Bone is composed of an osteoid and mineral component. The osteoid component consists of TYPE I COLLAGEN and GAGs. The mineral component is made of HYDROXYAPATITE (calcium and phosphate).

Question 5

What is the function of the osteoblast, osteocyte, and osteoclast?

Answer 5

Osteoblasts: Located on the bone surface and Synthesize bone

Osteocytes: Found inside lacunae and work on MECHANODETECTION and detection of mineral levels in bone.

Osteoclasts: are derived from monocytes and secrete MMPs to breakdown bone. Dig pits called HOWSHIP LACUNAE

Question 6

Explain the interaction between osteoblasts and osteoclast precursors that leads to osteoclast formation.

Answer 6

Osteoblasts (stromal cells) recieve signals from Vitamin D3 and PTH via receptors that tell it to upregulate synthesis of M-CSF (macrophage colony stimulating factor) and RANKL (receptor activator of NFkB ligand). M-CSF in combination with RANKL binds to M-CSF receptors and RANK on osteoclast precursors that then lead to formation of multinucleate osteoclasts. This effect can be toned down by secretion of osteoprotegrin (OPG) that bind to RANK and prevents osteoclast activation.

Question 7

Where does new bone created at the epiphyseal plate deposit?

Answer 7

On the side of the diaphysis

Question 8

Differentiate enchondral ossification and membranous ossification.

Answer 8

Endochondral Ossification leads to the formation of bone through an intermediate cartilage step. In intramembranous ossification there is no cartilage intermediate instead cells from periosteum differentiate into osteoblasts to make bone.

Question 9

Osteogenesis Imperfecta
• Pathogenesis
• What are some of the tissue OTHER THAN BONE that are heavily affected in this disorder?

Answer 9

Osteogenesis imperfecta arises due to mutations in type I collagen (either the alpha 1 or 2 subunits) most often this is due to a replacement of glycine with another amino acid. The either prevents collagen from folding (type I OI) or causes defective folding (type II OI).

Teeth are affected and may appear blue/yellow due to a loss in dentin

Eyes may appear to have blue sclera from choroid plexus showing through

Ears may have hearing loss due to defective bone formation in the middle ear

Skin and Joints may also be affected

Question 10

Achrondroplasia
• what casues this disease?
• how is it inherited?

Answer 10

Achondroplasia is an autosomal dominant disorder that is PATERNALLY inherited, but MOST OFTEN ARISES SPORATICALLY. It is caused by an activating point mutation in the FGF-3 receptor. FGF-3 is a receptor that typically leads to inhibtion of chondrocyte growth so inhibition leads to achondroplasia.

Question 11

Thanatophoric Dwarfism
• how does this differ from achondroplasia.

Answer 11

This disease is fatal due to failure of the thorax to enlarge

Question 12

Osteopetrosis
• What cells are defective in this disease?
• What’s the pathogenesis?

Answer 12

Osteopetrosis results from a defect in OSTEOCLASTS. These people lack Carbonic Anhydrase II (CAD II) in their osteoclasts which is required to acidify the environment of the bone so that remodeling can take place. This leads to loss of the marrow space and bone that easily fractures.

Question 13

Differentiate the two most common types of Osteogenesis imperfecta.

Answer 13

Type I:
• Collagen type I may still may have some function in these patients. These people will experience multiple fractures througout childhood but are much less symptomatic after puberty.

Type II:
• This disease results from inability of collagen to form a triple helix. These patients typically die in utero or very shortly after birth.

Question 14

T or F: achondroplasia is the most common form of dwarfism.

Answer 14

True

Question 15

Why do you suspect people with achondroplasia have normal sized heads and thorax?

Answer 15

This is a defect in cartilage synthesis. Long bones form by enchondral growth. Bones of the skull, sternum, and the vertebrae are created by intramembranous ossification, a process not requiring cartilage, so the structures are normal sized.

Question 16

T or F: inheriting 2 FGF-3 mutations as a result of having to achondroplastic parents is a fatal mutation.

Answer 16

True, 2 parents with achondroplasia have a 1/4 chance of this happening

Question 17

Differentiate the Autosomal Dominant and Autosomal Recessive forms of osteopetrosis.

Answer 17

Autosomal Recessive:
• Is sever and may result in hydroencephaly from occlusion of foramen magnum, closure of other formana leading to cranial nerve dysfunction. Loss of marrow space may lead to pancytopenia.

Autosomal Dominant:
• is the less severe version of osteopetrosis and mainly just manifests as an increased incidence of bone fractures and renal tubular acidosis.

Question 18

What is the treatment for osteopetrosis?

Answer 18

Bone Marrow Transplant

Question 19

What disease is seen in this histology?
• what are the key features?

Answer 19

Seen here is Ostopetrosis. Key things to notice are the irregular bony trabeculae without increased numbers of osteoclasts. There is also marked reduction in the marrow space.

Below you can see blue present in this stain of a patient with osteopetrosis indicating the presence of a lot of immature bone due to a lack of remodeling by osteoclasts.

Question 20

What radiologic changes do you expect to see in a kid with rickets?

Answer 20

• Flaring of the ends of the long bones with fraying and cupping
• Additionally there will be increased distance between metacarpals because osteoid is filling the space where there should be ossified bone

Question 21

T or F: kids with vit. D deficiency will have a failure of the epiphyseal plate to form.

Answer 21

False, these kids have an epiphyseal plate but there is lack of calcification of osteoid that forms here

Question 22

What drugs may cause increased Vit. D excretion?

Answer 22

Thiazides are known to cause increased Excretion of Vit. D.

***Note: Vit. D deficiency also has an effect on immune function because it is required for synthesis of immune enzymes

Question 23

Question 24

What is shown in these images?

Answer 24