Formation and Remodeling of the Bone Study Guide

Question 1

What is ossification/osteogenesis? When does it begin?

Answer 1

• Process of bone formation
• Begins in month 2 of development

Question 2

When does bone remodeling occur?

Answer 2

Lifelong

Question 3

Why is the embryonic skeleton made of connective tissue membranes and cartilage?

Answer 3

So that it can be a flexible structure that can accommodate mitosis

Question 4

Write out the steps of intramembranous ossification.

Answer 4

• Ossification centers are formed when mesenchymal cells cluster and differentiate into osteoblasts
• Osteoid is secreted by osteoblasts, then calcified
• Accumulating osteoid is laid down around blood vessels - forms trabeculae. Vascularized mesenchyme condenses on the external face - becomes periosteum
• Just deep to the periosteum, compact bone replaces spongy bone. Red marrow develops

Question 4

Define endochondral ossification. Define intramembranous ossification. Know which bones are created by each method.

Answer 4

• Endochondral ossification: bone forms by replacing hyaline cartilage (endochondral bones- all bones inferior to skull except clavicles)
• Intramembranous ossification: bones forms by replacing fibrous connective tissue (membrane bones- the skull and clavicles)

Question 5

Write out the steps of endochondral ossification.

Answer 5

• Bone collar forms around the diaphysis of a cartilage model
• Central cartilage in the diaphysis calcifies, develops cavities
• Periosteal bud invades cavities, starts formation of spongy bone
  
  • Bud is made of blood vessels, nerves, red marrow, osteogenic cells, and osteoclasts
• Diaphysis elongates, medullary cavity forms
  
  • Secondary ossification centers appear in the epiphyses
• Epiphyses ossify - hyaline cartilage remains only in the epiphyseal plates and articular cartilages

Question 6

In endochondral ossification, the perichondrium is converted to:

Answer 6

periosteum

Question 7

How is the periosteum formed in intramembranous ossification?

Answer 7

Vascularized mesenchyme condenses and becomes periosteum

Question 8

What does interstitial growth look like in bones? Where does it occur?

Answer 8

• Occurs at the epiphyseal plate
• Long bones grow in length

Question 9

How does appositional growth occur in bones?

Answer 9

• Bones thicken in response to increased stress - via muscle activity or added weight
• Osteoblasts in the periosteum secrete bone matrix on the external bone surface
• Osteoclasts on the endosteal surface remove bone (inside)
• Typically, osteoblasts slightly outperform the osteoclasts and controlled bone growth occurs
• Growth in width / thickness

Question 10

List the 5 zones of the epiphyseal plate. Come up with a method of remembering them in order from either the epiphysis side to diaphysis side or vice versa.

Answer 10

From closest to epiphysis Evil Rita Pets Houla in Colorado
- Resting (quiescent) zone
- Proliferation (growth) zone
- Hypertrophic zone
- Calcification zone
- Ossification (osteogenic) zone

Question 11

What things can stimulate appositional growth of bones? During appositional growth, where is bone built up? And where is bone broken down? What is the functional importance of bone breakdown during appositional growth?

Answer 11

• Appositional bone growth can be stimulated by increase stress on the bones by muscle activity or added weight
• The bone is built up externally (and broken down internally)
• The bone breaks down internally so that the growth isn’t overdone, but typically the osteoblasts still outperform the osteoclasts, which is how bone growth occurs

Question 12

How + when does interstitial long bone growth stop?

Answer 12

• Near the end of adolescence, chondroblasts divide less often
• Epiphyseal plate things, is replaced by bone
• Eventually, the epiphyseal plate closes - the epiphysis and diaphysis fuse - bone lengthening ceases at age 18 in females and 21 in males

Question 13

What is the role of each of the following in bone growth: testosterone, estrogen, growth hormone, thyroid hormone.

Answer 13

• Testosterone and estrogen: promote adolescent growth spurts at puberty; induce closure of epiphyseal plates
• Growth hormone: the most important hormone in stimulating epiphyseal plate activity in infancy and childhood - secreted by the anterior pituitary gland
• Thyroid hormone: modulates activity of growth hormone - ensures proper proportions

Question 14

Write out the negative feedback loop that stimulates bone breakdown including the appropriate hormone. How do osteoclasts break down bone? BONE RESORPTION

Answer 14

• Osteoclasts are activated by Parathyroid hormone PTH and the immune system
• Osteoclasts break down bone by secreting lysosomal enzymes and h+ protons. Acidity converts calcium salts to soluble forms. Depressions and grooves are created.
• Osteocytes phagocytize demineralized matrix and dead osteocytes - ingested products are moved into interstitial fluid and then blood via transcytosis
• Osteoclasts undergo apoptosis after resorption is complete

Question 15

Write out the negative feedback loop that stimulates bone building including the appropriate hormone. What’s the osteoid seam? The calcification front? The concentrations of calcium and phosphate must be adequately high for mineralized bone to form.

Answer 15

• Osteoid seam: unmineralized band of gauzy-looking bone matrix secreted by osteoblasts
• Calcification front: abrupt transition between osteoid seam and older mineralized bone
• Proteins of newly deposited osteoid bind calcium ions and the coal concentration of calcium rises
• Osteoblasts release vesicles studded with alkaline phosphatase - the enzyme removes phosphate ions form the osteoid and rises the local concentration of phosphate ions
• When the concentrations of calcium and phosphate are high enough, tiny calcium phosphate ions form
• Thyroid hormone causes growth/deposition

Question 16

Why is maintaining appropriate levels of calcium in the blood so important?

Answer 16

Maintaining appropriate calcium levels in the extracellular fluid is critical for maintaining the resting membrane potential of all cells. It’s also required for neuronal transmission, muscle contraction, blood coagulation, glandular secretion, and cell division.

Question 17

What is required to absorb calcium from the intestines?

Answer 17

Vitamin D

Question 18

What are some signs of hypercalcemia? Hypocalcemia?

Answer 18

• Hypercalcemia signs: high levels of calcium that cause bone pain, nausea, vomiting, and kidney stones
• Hypocalcemia: low levels of calcium in the blood that causes tingling, muscle aches, seizures etc.

Question 19

What roles can glucocorticoids, sex hormones, and serotonin play in bone remodeling?

Answer 19

• Glucocorticoids: hormones from the adrenal cortex may indirectly stimulate osteoclasts and bone resorption
• Sex hormones: indirectly stimulate osteoblasts and bone deposition
• Serotonin: neurotransmitter that regulates mood and sleep - potentially interferes with oestoblast activity to slow bone formation when new dietary calcium is introduced

Question 20

Define Wolf’s Law.

Answer 20

Bones grown and remodel in response to the demands placed on them
- Bones tend to bend as stresses are typically uneven
- Diaphysis is thickest where bending stress is greatest

Question 21

In the context of Wolf’s Law, explain why bones can be hollow.

Answer 21

Bones can be hollow because compression and tension stresses cancel in the center of the bone

Question 22

Deformation of bones under stress, creates an ———– that is perceived by the ———- in the canaliculi.

Answer 22

• electrical current
• osteocytes

Question 23

Hormonal controls regulate —– and —– bones are remodeled. Mechanical stresses determine —— bones are remodeled.

Answer 23

• whether and when
• where