Formation and Remodeling of Bone

Question 1

Ossification / Osteogenesis

Answer 1

the process of bone formation
- begins in month 2 of development
- post natal bone growth occurs until early adulthood
- bone repair + remodeling are lifelong

Question 2

Endochondral Ossification

Answer 2

bone forms by replacing hyaline cartilage
- bone are called cartilage (endochondral) bones
- more common, begins late in month 2 of development
- requires breakdown of hyaline cartilage before ossificiation
- begins in a primary ossification center in the center of a bone shaft
- creates all bones inferior to the skull (except clavicle)

Question 3

Intramembranous Ossification

Answer 3

bone forms by replacing fibrous connective tissue
- bones are called membrane bones
- begins within fibrous connective tissue membranes formed by mesenchymal cells
- forms the parietal, occipital, temporal, and clavicle bones

Question 4

5 main steps of endochondral ossification

Answer 4

1. bone collar forms around the diaphysis of a cartilage model
2. central cartilage in the diaphysis calcifies, develops cavities
3. periosteal bud invades cavities, starts formation of spongy bone
   - bud is made of blood vessels, nerves, red marrow, osteogenic cells, osteoclasts
4. diaphysis elongates, medullary cavity forms
   - secondary ossification centers appear in the epiphysis
5. epiphyses ossify - hyaline cartilage remains only in the epiphyseal plates and articular cartilages

Question 5

4 main steps of intramembranous ossification

Answer 5

1. ossification centers are formed when mesenchymal cells cluster and differentiate into osteoblasts
2. osteoid is secreted by osteoblasts, then calcified
3. accumulating osteoid is laid down around blood vessels - forms trabeculae. vascularized mesenchyme condenses on the external face - becomes periosteum
4. just deep to the periosteum, compact bone replaces spongy bone. red marrow develops

Question 6

post natal bone growth

Answer 6

• long bones grow in length via interstitial bone growth at the epiphyseal plate
• bones increase in thickness via appositional growth
• largely, bones stop growing during adolescence - some facial bones continue to grow slowly throughout life

Question 7

Long bone growth

Answer 7

• interstitial growth of long bones requires the presence of epiphyseal cartilage in the epiphyseal plate
• epiphyseal plates maintain a constant thickness - rate of cartilage growth is balanced by rate of bone replacement
• there are five zones of the epiphyseal plate: resting (quiescent) zone, proliferation (growth zone), hypertonic zone, calcification zone, ossification (osteogenic) zone

Question 8

Resting (quiescent) zone

Answer 8

area of cartilage on the epiphyseal side that is relatively inactive

Question 9

Proliferation (growth) zone

Answer 9

area of cartilage on the epiphyseal side that is rapidly dividing; newly formed cells push the epiphysis away and lengthen the bone

Question 10

hypertonic zone

Answer 10

area closer to the diaphysis with older chondrocytes. chondrocytes hypertrophy (get bigger) and lacunae erode/enlarge producing large interconnecting spaces

Question 11

Calcification zone

Answer 11

surrounding cartilage matrix calcifies, and chondrocytes die. slender spicules of calcified cartilage are created. blood vessels invade

Question 12

Ossification zone

Answer 12

osteoclasts partially erode the cartilage spicules. osteoblasts cover them with new spongy bone. medullary cavity lengthens.

Question 13

End of long bone growth

Answer 13

• chondroblasts divide less near the end of adolescence
• epiphyseal plate thins, is replaced by bone
• eventually, the epiphyseal plate closes - the epiphysis and diaphysis fuse - bone lengthening ceases (age 18 in women + 21 in men)

Question 14

Growth in width / thickness

Answer 14

• appositional growth can occur throughout life
• bones thicken in response to increased stress
• osteoblasts secrete bone matrix on the external bone surface
• osteoclasts on the endosteal surface remove bone
• osteoblasts slightly outperform osteoclasts leading to controlled bone growth

Question 15

Growth hormone

Answer 15

the most important hormone in stimulating the epiphyseal plate activity in infancy and childhood - secreted by the anterior pituitary gland

Question 16

Thyroid hormone

Answer 16

modulates activity of growth hormone - ensures proper proportions

Question 17

Testosterone (males) and estrogen (females)

Answer 17

promote adolescent growth spurts at puberty; induce closure of epiphyseal plates

Question 18

Bone resorption

Answer 18

• function of osteoclasts
• osteoclasts are activated by parathyroid hormones and immune system
• clasts breakdown bone by secreting lysosomal enzymes and H+ protons, acidity turns calcium salts into soluble forms and depressions and grooves are created
• clasts phagocytize demineralized matrix and dead osteocytes - ingested products are moved into interstitial fluid and into blood via transcytosis
• when resorption is complete, clasts undergo apoptosis

Question 19

Deposition

Answer 19

• function of osteoblasts
• osteoid seam: unmineralized band of gauzy-looking bone matrix secreted by osteoblasts
• calcification front: abrupt transition zone between osteoid seam and older mineralized bone
• proteins of newly deposited osteoid bind calcium ions and local concentration of calcium ions rises
• blasts release vesicles studded with alkaline phosphotase - the enzyme the enzyme removes phosphate ions from the osteoid and rises the local concentration of phosphate ions
• tiny calcium phosphate crystals form when concentration of calcium and phosphate are high enough

Question 20

Maintaining Ca2+ homeostasis

Answer 20

a hormonal negative feedback loop involving parathyroid hormone maintains CA2+ homeostasis in blood
- maintaining calcium levels in extracellular fluid maintains the resting membrane of all cells and also is required for neuronal transmission, muscle contraction, blood coagulation, glandular secretion, and cell division
- 99% of calcium is stored in bones - deposits and withdrawals are regulated by hormones
- vitamin d is required to absorb calcium from instestines

Question 21

keeping bone strong

Answer 21

mechanical and gravitational forces act on bone and drive remodeling where strengthening is required

Question 22

hypocalcemia

Answer 22

hyperexcitability
- levels of calcium in blood are too low

Question 23

hypercalcemia

Answer 23

non-responsiveness, inability to function
- sustained hypercalcemia = kidney stones
- levels of calcium in blood are too high

Question 24

Parathyroid Hormone

Answer 24

produced by parathyroid gland. released in response to low blood calcium levels
- stimulates osteoclasts to resorb bone and release calcium into blood - cannot discriminate new vs old bone
- secretion of pth stops when homeostatic blooc calcium levels are reached

Question 25

calcitonin

Answer 25

produced by parafolliar cells of the thyroid gland. released in response to high blood calcium levels
- effects are typically fairly negligible, but does temporarily decrease blood calcium levels when administered in high doses

Question 26

Glucocorticoids

Answer 26

hormones from the adrenal cortex may indirectly stimulate osteoclasts and bone resporption

Question 27

sex hormones

Answer 27

indirectly stimulate osteoblasts and bone deposition

Question 28

serotonin

Answer 28

neurotransmitter that regulates mood and sleep - potentially interferes with osteoblast activity to slow bone formation when new dietary calcium is introduced

Question 29

wolfs law

Answer 29

bones grow 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
- bones can be hollow because compression and tension stresses cancel in the center of the bone

Question 30

mechanical control of bone remodeling

Answer 30

• deformation of bones under mechanical stress pushes fluid containing ions through canaliculi - creation of an electrical current
• electrical current is detected by osteocytes
• osteocytes release chemical messengers that promote the formation of additional bone