Bone as a tissue and organ

Question 1

Contrast cortical and trabecular bone

Answer 1

• Cortical
  
  • 80-90% calcified
  • fulfills mainly a mechanical and protective function
  • organized as osteons (also called Haversian systems), cylindrical structures in which concentric layers of bone matrix form lamellae around a central canal
  • lamellar organization of osteons is an important contributor to bone’s ability to resist fracture
• Trabecular
  
  • 15-25% calcified
  • fulfills mainly a metabolic function
  • accounts for most of the bone surface area and most of the remodeling activity

Question 2

Describe intramembranous bone

Answer 2

• formed (de novo) by formation of osteoblasts from mesenchymal stem cells present within what will become the periosteum
• type of bone formed in healing fractures and at the periosteal surface of long bones as they model to achieve greater diameters
• e.g. skull and ribs

Question 3

Describe Endochondral bone

Answer 3

• grow in length by proliferation of chondrocytes within the growth plate, a specialized structure present within growing endochondral bones
• e.g. long bones of the limbs
• In humans, the growth plates close in late adolescence in response to estrogen signaling… The epiphyses of different anatomical sites fuse at different ages

Question 4

Describe how bones grow in length

Answer 4

• Chondrocytes in the proliferative zone divide, replenishing the growth plate
• then they hypertrophy, undergo apoptosis, and are mineralized
• blood vessels invade the zone of calcified cartilage, which is resorbed by chondroclasts and the space is filled by osteoblasts and bone matrix
• **growth of the long bones depends on the relative speed with which cells in the hypertrophic zone undergo apoptosis and those in the proliferative zone divide

Question 5

At any given time, how much of the skeleton is being remodeled? How does this differ between cortical and trabecular bone?

Answer 5

• At any given time, about 10% of the skeleton is being remodeled
• Trabecular bone is much more actively remodeled than cortical bone. (This makes sense in light of its more prominent role in maintaining mineral homeostasis)
  
  • Remodeling of trabecular bone provides a mechanism by which extracellular fluid can buffer its calcium and phosphate content

Question 6

What are the 2 principles that are essential to understanding the bone remodeling cycle?

Answer 6

• First, bone resorption and bone formation are coupled processes
• Second, bone r_esorption is relatively rapid_, requiring ~2 weeks, while bone formation is slow, requiring 4-6 months for full mineralization to take place.

Question 7

What process is essential in moment-to-moment mineral homeostasis?

Answer 7

• bone resorption involves dissolution of the bone mineral, thus providing free Ca and PO4 that can enter the extracellular fluids and blood.
• Conversely, excess Ca and PO4 can be deposited into the bone.
• **This active exchange of minerals between the bone and the circulation is essential for moment-to-moment mineral homeostasis.

Question 8

Describe the concept of bone modeling… what is an example?

Answer 8

• bones not only grow in length, but grow in radial size and change shape as well (called modeling)
• mediated at least in part by physiological responses to mechanical loading
• WNT signaling pathway is a critical regulator of modeling
• e.g. elite racquet sport athletes, comparing the cross-sections of their dominant and non- dominant arms.

Question 9

Define strain

Answer 9

• the fractional change in the length of a structure as a result of a force being applied to it
• pure compression causes negative strain
• pure stretching causes positive strain

**mechanical loading results in a mixture of compression and tension, as occurs in the case of either bending or shear

Question 10

How is bone a “composite material”? (allowing it to withstand a variety of loads)

Answer 10

• compressive strength comes from the mineral phase (about 2/3 of the bone extracellular matrix by mass)
  
  • mineral phase of bone is intercalated into the collagen fibril structure
• tensile strength comes from the protein and water (about 1/3 of the bone extracellular matrix by mass)

**Together, these properties of the extracellular matrix lead to a tissue that is stiff but not brittle, capable of withstanding mixed loading, and highly resistant to fracture.

Question 11

What ions are found in bone mineral?

Answer 11

• Ca and PO4 are the most abundant ions in bone mineral
• also significant amounts of Mg, Na, OH, CO3, SO4, and Cl
• mineral in bone = apatite (a mineral that results from substitution of hydroxyapatite with other ions)
  
  • important in promoting bone’s function in mineral homeostasis

Question 12

What inhibits the mineralization of bone? What modulates it?

Answer 12

• sulfate and pyrophosphate are potent inhibitors of mineralization
• Proteins in the SIBLING (small integrin-binding ligand, N-linked glycoprotein) family are modulators of mineralization

Question 13

What is the benefit of the lamellar structure of bone?

Answer 13

• provides toughness, or the ability to resist the propagation of a fracture
• the interfaces between lamellae, and between osteons (called cement lines) can absorb and dissipate force while preventing a crack from passing from one lamella to its neighbor
• toughness is anisotropic: transverse cracks are less able to propagate than are longitudinal cracks

Question 14

Describe Osteogenesis imperfecta

Answer 14

• group of diseases that are caused by mutations in the genes encoding type 1 collagen or critical enzymes in the assembly and processing of type 1 collagen
  
  • causes deficient production or improper assembly of the extracellular matrix
• resultant susceptibility to fracture, as well as a number of other abnormalities in other tissues that contain large amounts of type 1 collagen
• severity can range from subclinical to lethal.

**thought of as a pure osteoblast disease

Question 15

Describe Osteomalacia

Answer 15

• results from inadequate mineralization of the bone matrix and can be a consequence of several different conditions (various malabsorptive disorders, vitamin D deficiency or resistance, phosphate wasting disorders, or low Ca diet)
• results in weak, undermineralized bones
• when it occurs in a growing individual, bone modeling is abnormal and the long bones assume a bowed shape **Ricketts

**thought of as a disorder in which the bone cells function normally, but lack of the appropriate mineral substrates leads to abnormal bone function

Question 16

What are two disorders in which the skeletal mass is abnormally high?

Answer 16

Sclerosteosis and Van Buchem’s disease

• due to mutations of the protein sclerostin (SOST)
• disturbs the mechanosensory system, resulting in bones perceiving that they are being loaded even when they are not.

**These can be thought of as osteocyte diseases

Question 17

Describe Osteopetrosis

Answer 17

• group of diseases in which osteoclast function or maturation is impaired so remodeling is deficient
• severe cases are lethal (marrow space is not formed and hematopoiesis is severely impaired as a result)
• inability to remodel bone results in bones that while dense and massive are nevertheless weak, because they are unable to assume the lamellar structure that remodeling produces.

**can be thought of as a pure osteoclast disease