Bone Basics

Question 1

bone development - overview

Answer 1

*initial skeleton that begins forming in utero is comprised of mesenchymal cells (like all connective tissue)
*2 processes by which bone forms:
1. endochondral ossification
2. intramembranous ossification

Question 2

endochondral ossification - overview

Answer 2

*endochondral: within cartilage; a cartilage framework occurs prior to formation of bone
most bones form in this way, particularly the **LONG bones
*mechanism: mesenchymal cells → hyaline CARTILAGE model → bone

Question 3

endochondral ossification - detailed mechanism

Answer 3

1. formation of bone collar around hyaline cartilage model
2. calcification of cartilage: cavitation of the hyaline cartilage within the cartilage model
3. invasion of internal cavities by the periosteal bud and spongy bone formation
4. formation of the medullary cavity as ossification continues; appearance of secondary ossification centers in the epiphyses in preparation for stage 5
5. ossification of the epiphyses; when completed, hyaline cartilage remains only in the epiphyseal plates (growth plates) and articular cartilages

Question 4

failure of endochondral ossification: ACHONDROPLASIA

Answer 4

*achondroplasia: failure of chondroblast activity, can’t deposit cartilage scaffold
*caused by constitutive activity of FGFR3 (paradoxically suppresses chondroblasts)
*most common cause of dwarfism
*characterized by normal head and torso, SHORT LIMBS

Question 5

intramembranous ossification - overview

Answer 5

*intramembranous = within membrane
*bone DIRECTLY replaces mesenchymal skeleton; there is NO collagen framework
*used to form: FLAT bones of the skull, scapula, ileum, and clavicle

Question 6

osteoblasts

Answer 6

*derived from mesenchymal progenitor cells
*B = build bones

Question 7

osteoclasts

Answer 7

*derived from hematopoietic progenitor cells
*C = CRUSH (destroy) bones

Question 8

osteocytes

Answer 8

*osteoblasts that become trapped within the bony matrix
*serve to maintain the bone

Question 9

trabecular bone

Answer 9

*aka cancellous bone or spongy bone
*found in the epiphyses of long bones, flat bones, and vertebrae
*allows for shock absorption

Question 10

cortical bone

Answer 10

*solid, outer layer of long bones
*important for weight bearing

Question 11

bone remodeling - general principles

Answer 11

*bones are not static; 10% of the skeleton is replaced every year
*important process for maintaining bone health
*involves a complex process driven by HORMONES and MECHANICAL STRESS
*significant cross-talk (paracrine communication) between osteoblasts, osteoclasts, and osteocytes

Question 12

osteoclast activation - overview

Answer 12

1. osteoBLASTS experience a biochemical or mechanical trigger that causes them to express/secrete RANK-Ligand (RANK-L)
2. RANK-L binds to RANK receptor on osteoCLAST precursors, which then form into multinucleated giant cells, becoming OSTEOCLASTS
3. osteoclasts begin the process of bone resorption (destruction of bone)

note: RANK = Receptor Activator of Nuclear Factor Kappa B

Question 13

bone resorption by osteoclasts

Answer 13

*once activated, osteoclasts latch on to an area of bone, forming “sealing zones,” and begin acidifying and breaking down the bone matrix with matrix metalloproteinase and hydrochloric acid
*the “ruffled border” of the osteoclast is where the action happens, and the resulting pit or groove within the bone is termed Howship’s Lacunae

Question 14

what signals bone resorption to stop?

Answer 14

*osteoblasts dictate when bone resorption should stop by secreting osteoprotegerin
*osteoprotegerin = a decoy receptor for RANK ligand

Question 15

bone ossification by osteoblasts

Answer 15

1. matrix deposition: osteoblasts secrete Type 1 collagen
2. mineralization:
   a. osteoblasts secrete calcium- and phosphorous-containing vesicles
   b. alkaline phosphatase enzyme causes the calcium and phosphorous to combine, forming Hydroxyapatite crystals

Question 16

communication between cells in the bones

Answer 16

*bone resorption takes ~10 days to complete
*bone formation takes 1-3 months to complete
*therefore, the paracrine effects and cross-talk between osteoblasts, osteoclasts, and osteocytes is necessary to avoid abnormal bone resorption/development
*a mismatch in bone resorption and formation can result in decreased bone density

Question 17

hormonal regulation of bone remodeling: ESTROGENS & ANDROGENS

Answer 17

*most important hormone for maintenance of bone density = ESTROGEN
*lack of estrogen after menopause is the primary cause of osteoporosis
*do not fully understand mechanism, but estrogen induces apoptosis of osteoclasts

Question 18

hormonal regulation of bone remodeling: GROWTH HORMONE / IGF-1

Answer 18

*promote bone growth and turnover
*important during puberty
*in acromegaly, even though there is increase in bone mass, bone is weaker and more prone to fractures

Question 19

hormonal regulation of bone remodeling: CORTICOSTEROIDS

Answer 19

*excess corticosteroids result in bone resorption and decreased bone density

Question 20

hormonal regulation of bone remodeling: PTH

Answer 20

*pulsatile parathyroid hormone is helpful in strengthening bones (activates osteoblasts)
*excess PTH for prolonged time results in bone resorption

Question 21

mechanical regulation of bone remodeling

Answer 21

*microtrauma or microfractures from stress on the bones are detected by osteocytes
*osteocytes signal the osteoblasts to begin the process of repairing the area of fracture
*this is why weight-bearing exercise (walking, running, weight training) is helpful to prevent bone loss because it causes microfractures