• Bone has two main types (Fig. 80.5):
  • Cortical (compact) bone
  • Trabecular (spongy) bone
• Cortical bone forms the hard outer layer and makes up about 80% of total bone mass.
• It is especially thick in the shafts of long bones, where it provides strong support for body weight.
• Trabecular bone forms about 20% of bone mass and lies mainly inside bones.
• It is more porous and is commonly found:
  • At the ends of long bones
  • Near joints
  • Inside vertebrae
• Trabecular bone consists of branching bony spicules called trabeculae, forming a meshwork.
• Spaces between trabeculae contain red bone marrow, where hematopoiesis (blood cell formation) occurs.
• Trabecular bone has a higher rate of synthesis, resorption, and turnover than cortical bone.
• Bone consists of a tough organic matrix strengthened by deposits of calcium salts.
• Average cortical bone contains about:
  • 30% organic matrix
  • 70% mineral salts
• Newly formed bone contains relatively more matrix and less mineral.

Organic Matrix of Bone Is Comprised of Collagen Fibers and Proteoglycans

• About 90%–95% of the organic matrix consists of collagen fibers.
• The remaining portion is a gelatinous ground substance.
• Collagen fibers mainly run along lines of tension and provide strong tensile strength.
• Ground substance consists of extracellular fluid and proteoglycans, especially:
  • Chondroitin sulfate
  • Hyaluronic acid
• These proteoglycans help control calcium salt deposition and participate in bone repair after injury.

Bone Crystalline Salts Are Mainly Calcium and Phosphate

• The main mineral salts in bone are calcium and phosphate.
• The major crystal is hydroxyapatite: Ca₁₀(PO₄)₆(OH)₂
• This means one hydroxyapatite unit contains:
  • 10 calcium ions
  • 6 phosphate groups
  • 2 hydroxyl groups
• Hydroxyapatite crystals are long, flat plates about:
  • 400 Å long
  • 10–30 Å thick
  • 100 Å wide
• The calcium-to-phosphorus ratio by weight can vary from about 1.3 to 2.0, depending on nutrition.
• Bone salts also contain magnesium, sodium, potassium, and carbonate.
• These ions are believed to attach to hydroxyapatite crystals rather than form separate crystals.
• Other ions and heavy metals can also become attached to bone crystals.
• Radioactive substances deposited in bone can produce prolonged irradiation and, in sufficient amounts, may eventually cause osteogenic sarcoma.

Tensile and Compressional Strength of Bone

• Cortical bone collagen fibers contain repeating segments about every 640 Å.
• Hydroxyapatite crystals lie closely beside these collagen segments and bind tightly to them.
• This close attachment prevents collagen and crystals from slipping past each other, strengthening the bone.
• Adjacent collagen fibers overlap, and the hydroxyapatite crystals also overlap like bricks in a wall.
• Collagen fibers provide tensile strength.
• Calcium salts provide compressional strength.
• Together, their strong bonding gives bone both very high tensile and compressional strength.

KEY CONCEPT

• Cortical bone = dense outer bone, ~80% of bone mass.
• Trabecular bone = porous inner bone, ~20%, with faster turnover.
• Bone structure:
  • Organic matrix → mainly collagen → tensile strength
  • Hydroxyapatite → calcium + phosphate → compressional strength
• Main bone crystal: Ca₁₀(PO₄)₆(OH)₂
• Strong bonding between collagen + hydroxyapatite gives bone its overall strength.

Conceptual Examples

• Long-bone shaft:
  Thick cortical bone → strong support for body weight.
• Inside vertebrae:
  Trabecular meshwork + red marrow → high bone turnover + blood cell formation.
• Bone pulled or stretched:
  Collagen fibers resist the force → tensile strength.
• Bone compressed by body weight:
  Calcium salts resist compression → compressional strength.
• Overall bone strength:
  Collagen + hydroxyapatite tightly linked → strong bone that resists both pulling and compression.

Figure 80.5 — Cortical (Compact) vs Trabecular (Spongy) Bone

Easiest Concept

Think of a long bone like a strong building:

• Cortical bone = hard outer wall
• Trabecular bone = light internal framework
• Marrow = material inside the spaces

Each part in the figure

• Cartilage
  • Smooth covering at the end of the bone.
  • Helps the joint move with less friction.
• Cortical (compact) bone
  • Dense, hard outer layer.
  • Gives bone strength and support.
  • Especially thick in the shaft of long bones.
• Trabecular (spongy) bone
  • Porous, lattice-like bone inside.
  • Makes bone lighter while still strong.
  • Common near the ends of long bones.
• Trabeculae
  • Thin bony plates/struts forming the spongy network.
  • The enlarged box shows these branching structures.
• Red marrow
  • Occupies spaces between trabeculae.
  • Main function: blood-cell production.
• Medullary cavity
  • Large hollow central cavity in the shaft.
• Yellow marrow
  • Located mainly inside the medullary cavity.
  • Rich in fat, so it acts mainly as an energy store.
• Epiphyseal line
  • Remnant of the previous growth plate.
  • Shows where lengthwise bone growth occurred before adulthood.

🔑 KEY CONCEPT

Compact bone = dense strength outside
Spongy bone = light supporting network inside
Red marrow = blood-cell formation
Yellow marrow = fat storage

One-line memory

“Hard outside, spongy inside, red marrow makes blood, yellow marrow stores fat.”

PRECIPITATION AND ABSORPTION OF CALCIUM AND PHOSPHATE IN BONE—EQUILIBRIUM WITH THE EXTRACELLULAR FLUIDS

Hydroxyapatite Does Not Precipitate in Extracellular Fluid Despite Supersaturation of Calcium and Phosphate Ions

• Extracellular fluid contains enough calcium and phosphate to form hydroxyapatite crystals.
• However, normal tissues contain inhibitors, especially pyrophosphate, that prevent this precipitation.
• Therefore, hydroxyapatite normally forms mainly in bone, not in other tissues.

Mechanism of Bone Calcification

• Osteoblasts first secrete:
  • Collagen monomers
  • Ground substance, mainly proteoglycans
• Collagen monomers join to form collagen fibers.
• This newly formed material is called osteoid.
• Osteoid resembles cartilage but allows calcium salts to precipitate easily.
• Some osteoblasts become trapped in osteoid and become inactive osteocytes.
• Within a few days:
  • Calcium salts begin depositing on collagen fibers.
  • Small deposits called nidi appear.
  • These deposits grow over days to weeks into hydroxyapatite crystals.
• The first calcium salts deposited are amorphous, noncrystalline salts, including: CaHPO₄·2H₂O Ca₃(PO₄)₂·3H₂O
• Over weeks to months, these salts are converted into hydroxyapatite crystals.
• A small percentage remains permanently in the amorphous form.
• These amorphous salts are important because they can be rapidly absorbed when extracellular calcium is needed.
• Pyrophosphate inhibits hydroxyapatite formation and bone calcification.
• Tissue-nonspecific alkaline phosphatase (TNAP) breaks down pyrophosphate.
• Osteoblasts release TNAP into osteoid: ↑ TNAP → ↓ pyrophosphate → hydroxyapatite crystallization → bone calcification
• When TNAP is deficient:
  • Pyrophosphate becomes too high.
  • Bone calcification decreases.
  • Bones remain soft and poorly mineralized.
• Osteoblasts also produce:
  • NPP1 → produces extracellular pyrophosphate.
  • ANK → transports pyrophosphate from inside the cell to the extracellular surface.
• Deficiency of NPP1 or ANK causes:
  • ↓ Extracellular pyrophosphate
  • Excessive calcification
  • Bone spurs or abnormal calcification of tendons and ligaments

Precipitation of Calcium in Nonosseous Tissues Under Abnormal Conditions

• Normally, calcium salts do not precipitate in tissues outside bone.
• Under abnormal conditions, calcium may deposit in:
  • Arterial walls in arteriosclerosis
  • Degenerating tissues
  • Old blood clots
• This probably occurs when normal inhibitors of calcium deposition are lost or reduced.

CALCIUM EXCHANGE BETWEEN BONE AND EXTRACELLULAR FLUID

• If blood calcium suddenly rises, it usually returns toward normal within about 30–60 minutes.
• If calcium is suddenly removed from body fluids, calcium also returns toward normal within about 30 minutes to 1 hour.
• This rapid control occurs because bone contains exchangeable calcium that remains in equilibrium with extracellular Ca²⁺.
• Most exchangeable calcium is found in bone and represents about 0.4%–1% of total bone calcium.
• It is stored mainly as easily mobilized salts such as:
  • CaHPO₄
  • Other amorphous calcium salts
• A smaller amount is also present in tissue cells, especially cells of the:
  • Liver
  • Gastrointestinal tract
• Exchangeable bone calcium acts as a rapid calcium buffer:
  • ↑ Extracellular Ca²⁺ → calcium moves toward storage.
  • ↓ Extracellular Ca²⁺ → calcium is rapidly released.
• This prevents large short-term changes in extracellular calcium concentration.

KEY CONCEPT

• Pyrophosphate prevents unwanted calcium-phosphate precipitation.
• TNAP ↓ pyrophosphate → allows bone calcification.
• NPP1 and ANK ↑ extracellular pyrophosphate → help limit excessive calcification.
• Bone formation: Osteoblast → collagen + ground substance → osteoid → calcium salt deposition → hydroxyapatite
• A small pool of exchangeable bone calcium rapidly buffers extracellular Ca²⁺.
• Bone therefore acts as both a mineral store and a rapid calcium-buffering system.

Conceptual Examples

• Bone calcification:
  Osteoblast forms osteoid → TNAP reduces pyrophosphate → calcium phosphate crystallizes as hydroxyapatite.
• TNAP deficiency:
  ↓ TNAP → ↑ pyrophosphate → ↓ mineralization → soft, poorly calcified bone.
• NPP1/ANK deficiency:
  ↓ Pyrophosphate → excessive calcium deposition → abnormal calcification.
• Sudden fall in blood Ca²⁺:
  Exchangeable calcium leaves bone → blood Ca²⁺ returns toward normal within about 30–60 minutes.

DEPOSITION AND RESORPTION OF BONE—REMODELING OF BONE

Deposition of Bone By the Osteoblasts

• Bone is continuously being formed by osteoblasts and continuously being resorbed by osteoclasts (Fig. 80.6).
• Osteoblasts are located:
  • On the outer surfaces of bones
  • In the trabecular cavities
• A small amount of osteoblast activity occurs continuously in all living bones.
• In adults, osteoblasts are active on about 4% of all bone surfaces at any given time.
• Therefore, some new bone is always being formed.

KEY CONCEPT

• Osteoblasts → bone deposition / new bone formation.
• Osteoclasts → bone resorption.
• Bone is therefore a continuously remodeling tissue.
• In adults, osteoblast activity occurs on about 4% of bone surfaces at one time.

Conceptual Examples

• Bone formation:
  Osteoblast becomes active → new bone is deposited.
• Bone removal:
  Osteoclast becomes active → old bone is resorbed.
• Normal adult bone:
  Bone deposition + bone resorption continue together → constant remodeling.

Figure 80.6 — Osteoblasts vs Osteoclasts

Easiest Concept

Think of bone as a building that is continuously repaired:

Osteoclasts remove old bone → Osteoblasts build new bone.

Each part of the figure

• Osteoblasts = bone builders
  • Small cells lining the bone surface.
  • They deposit new bone matrix.
  • So: Osteoblast → bone formation ↑
• Osteoclasts = bone breakers
  • Large cells sitting on bone surfaces.
  • They resorb/dissolve old bone.
  • They create small excavated areas while removing bone.
  • So: Osteoclast → bone resorption ↑
• Bone
  • Pink solid area represents existing mineralized bone.
  • It is continuously being removed and replaced.
• Fibrous periosteum
  • Tough connective-tissue covering on the outer surface of bone.
  • Protects and supports the bone.
• Vein
  • Blood vessel running through the bone.
  • Helps carry nutrients and substances such as calcium to and from bone tissue.

What is the figure really showing?

Both processes can occur in the same bone at the same time:

Old/damaged bone → osteoclast removes it → osteoblast replaces it with new bone

This continuous process is called bone remodeling.

🔑 KEY CONCEPT

Osteoclast = CUTS bone
Osteoblast = BUILDS bone

When their activities are balanced:

Bone removed ≈ Bone formed → bone mass stays stable

One-line memory

“Osteoclast clears the old bone; osteoblast builds the new bone.”

Resorption of Bone—Function of the Osteoclasts

• Osteoclasts continuously resorb bone.
• They are large multinucleated phagocytic cells, sometimes containing up to 50 nuclei.
• Osteoclasts arise from monocytes or monocyte-like cells in bone marrow.
• In adults, osteoclasts are normally active on less than 1% of bone surfaces.
• PTH is an important regulator of osteoclast-mediated bone resorption.
• During bone resorption, osteoclasts form villus-like projections called a ruffled border against the bone (Fig. 80.7).
• From this ruffled border, osteoclasts release:
  • Proteolytic enzymes → digest the organic bone matrix.
  • Acids, including citric and lactic acids → dissolve the mineral salts of bone.
• Osteoclasts also phagocytose small particles of bone matrix and crystals, digest them, and release their products into the blood.
• PTH stimulates osteoclasts indirectly because osteoclasts do not have PTH receptors.
• Instead, PTH acts on osteoblasts.
• Osteoblasts then stimulate osteoclast precursor cells using:
  • RANKL
  • Macrophage colony-stimulating factor
• These signals are required for formation of mature osteoclasts.
• The main pathway is: PTH → osteoblast → ↑ RANKL → RANK on preosteoclast → mature osteoclast → bone resorption
• PTH binds to osteoblast receptors and increases formation of RANKL, also called OPGL.
• RANKL binds to RANK receptors on preosteoclasts.
• This causes preosteoclasts to become mature, multinucleated osteoclasts.
• Mature osteoclasts then form a ruffled border and release enzymes + acids, producing bone resorption.
• Osteoblasts also produce osteoprotegerin (OPG).
• OPG inhibits osteoclast formation and therefore decreases bone resorption.
• OPG acts as a decoy receptor by binding RANKL.
• This prevents RANKL from binding to RANK on preosteoclasts. ↑ OPG → less RANKL reaches RANK → ↓ mature osteoclasts → ↓ bone resorption
• OPG therefore opposes the bone-resorbing effect of PTH.
• Genetic deficiency of OPG causes a marked decrease in bone mass.
• Vitamin D and PTH promote osteoclast formation by:
  • ↑ RANKL
  • ↓ OPG
• Glucocorticoids also increase bone resorption by:
  • ↑ RANKL
  • ↓ OPG
• Estrogen has the opposite effect by increasing OPG production.
• Therefore, the balance between RANKL and OPG strongly determines osteoclast activity and bone resorption.
• Drugs that mimic OPG by blocking the interaction between RANKL and RANK can reduce bone loss.
• Such treatment may be useful in postmenopausal bone loss and some patients with bone cancer.

KEY CONCEPT

• Osteoclast = bone-resorbing cell.
• Osteoclasts use:
  • Enzymes → digest organic matrix
  • Acids → dissolve bone minerals
• PTH acts indirectly: PTH → osteoblast → RANKL → RANK → mature osteoclast → ↑ bone resorption
• RANKL promotes osteoclast formation.
• OPG blocks RANKL → inhibits osteoclast formation.
• PTH, vitamin D, glucocorticoids → favor bone resorption.
• Estrogen → ↑ OPG → opposes bone resorption.

Conceptual Examples

• PTH effect:
  ↑ PTH → ↑ osteoblast RANKL → ↑ mature osteoclasts → ↑ bone resorption.
• OPG effect:
  OPG binds RANKL → RANKL cannot activate RANK → fewer osteoclasts form.
• Estrogen effect:
  ↑ Estrogen → ↑ OPG → ↓ osteoclast formation → ↓ bone resorption.
• Osteoclast action:
  Ruffled border releases enzymes + acids → matrix digested + minerals dissolved → bone resorbed.

Figure 80.7 — How Osteoclasts Resorb Bone

Easiest Concept

Think of osteoblasts as the controllers and osteoclasts as the bone-removing workers.

PTH/Vitamin D → osteoblast signals → preosteoclast becomes osteoclast → bone is resorbed

Follow the figure step by step

• PTH acts mainly on the osteoblast, not directly on the osteoclast.
• Vitamin D also promotes signals from osteoblasts that favor osteoclast formation.
• Stimulated osteoblasts produce:
  • RANKL
  • M-CSF

RANKL–RANK pathway

• RANKL is present on the osteoblast.
• RANK is its receptor on the preosteoclast.
• RANKL binds RANK → preosteoclast develops into a mature osteoclast.
• M-CSF also helps preosteoclasts survive and mature.

What is OPG?

• OPG (osteoprotegerin) = protective brake.
• Osteoblasts can release OPG.
• OPG grabs RANKL before RANKL can bind RANK.
• Therefore:

↑ OPG → ↓ osteoclast formation → ↓ bone resorption

• PTH decreases OPG, removing this brake.

Mature osteoclast

Once formed, the osteoclast attaches tightly to bone and develops a ruffled membrane/border.

It releases:

• Acid (H⁺) → dissolves the mineral part of bone.
• Lysosomal enzymes → digest the organic bone matrix.

The hollow area beneath it is the area of bone resorption.

Osteocytes

• Osteocytes are former osteoblasts trapped inside bone matrix.
• They form an interconnected network throughout the bone.

🔑 KEY CONCEPT

PTH → osteoblast → ↑ RANKL + M-CSF and ↓ OPG → RANK activation → ↑ osteoclasts → ↑ bone resorption

One-line memory

“RANKL turns osteoclasts ON; OPG blocks RANKL; osteoclast acid + enzymes eat bone.”

Bone Deposition and Resorption Are Normally in Equilibrium

• Except during bone growth, the rates of bone deposition and bone resorption are normally equal.
• Therefore, total bone mass usually remains constant.
• Osteoclasts usually act in small, concentrated groups.
• Once activated, they resorb bone for about 3 weeks.
• This creates a tunnel about:
  • 0.2–1 mm in diameter
  • Several millimeters long
• After about 3 weeks, the osteoclasts disappear.
• Osteoblasts then enter the tunnel and begin forming new bone.
• Bone deposition continues for several months.
• Osteoblasts lay down new bone in successive concentric layers called lamellae.
• These lamellae gradually fill the resorbed tunnel.
• Bone formation stops when the new bone approaches the blood vessels supplying the area.
• The small remaining canal containing these blood vessels is called the Haversian canal.
• Each complete new unit of bone formed by this remodeling process is called an osteon (Fig. 80.8).

KEY CONCEPT

• Normal adult bone maintains: Bone resorption ≈ Bone deposition → constant bone mass
• Remodeling sequence: Osteoclasts remove old bone → tunnel forms → osteoblasts enter → concentric lamellae form → osteon develops
• Haversian canal = central remaining canal containing blood vessels.

Conceptual Examples

• Old bone removal:
  Osteoclasts work for about 3 weeks → create a bone tunnel.
• New bone formation:
  Osteoblasts enter the tunnel → deposit concentric lamellae for several months.
• Final structure:
  Lamellae surround the remaining blood-vessel canal → Haversian canal + surrounding bone = osteon.

Figure 80.8 — Structure of Cortical (Compact) Bone

Easiest Concept

Think of compact bone like many tiny strong cylinders packed together.

Each cylinder is called an osteon.

Understand every label

• Epiphyseal line
  • Remnant of the old growth plate.
  • Shows where bone lengthening occurred during growth.
• Osteon
  • Basic structural unit of compact bone.
  • Made of circular layers of bone arranged around a central canal.
  • Gives compact bone great strength.
• Haversian canal
  • Central canal running through an osteon.
  • Contains blood vessels and nerves.
  • Supplies nutrients to bone cells.
• Lacunae
  • Tiny spaces inside the bone matrix.
  • Each lacuna normally contains an osteocyte.
• Canaliculi
  • Very tiny channels connecting the lacunae with each other and with the Haversian canal.
  • Allow nutrients, oxygen, and wastes to move between osteocytes and blood vessels.

Magnified section

The enlarged circle shows that compact bone is not a completely solid block.

It contains:

Haversian canals → surrounded by osteons → lacunae containing osteocytes → connected by canaliculi

🔑 KEY CONCEPT

Osteon = structural unit
Haversian canal = blood vessels + nerves
Lacuna = home of osteocyte
Canaliculi = tiny communication/nutrient channels

One-line memory

“Osteon is the unit, Haversian canal is the supply tunnel, lacuna houses the osteocyte, and canaliculi connect everything.”

Value of Continual Bone Remodeling

• Continuous bone deposition and resorption have several important functions.
• Bone adjusts its strength according to the amount of stress placed on it.
• Therefore, bones become thicker and stronger when exposed to heavy loads.
• Bone remodeling can also change the shape of bone so it can better support mechanical forces.
• Old bone gradually becomes brittle and weak, so it must be replaced with new organic matrix.
• This continual replacement helps maintain the normal toughness of bone.
• Children have rapid bone deposition and resorption, so their bones are less brittle.
• In older people, remodeling is slower, so bones become more brittle.

Control of the Rate of Bone Deposition By Bone “Stress”

• Bone deposition increases according to the compressional load placed on the bone.
• Therefore, athletes usually develop heavier and stronger bones than nonathletes.
• If one leg is kept in a cast and is not used:
  • Its bone becomes thinner.
  • It may lose as much as 30% of its calcium within a few weeks.
• Meanwhile, the actively used opposite leg remains thick and normally calcified.
• Therefore: Continual physical stress → ↑ osteoblast activity → ↑ bone deposition and calcification
• Mechanical stress can also gradually change bone shape.
• If a fractured long bone heals at an angle:
  • The compressed inner side undergoes increased bone deposition.
  • The less-compressed outer side undergoes increased bone resorption.
• Over many years, this remodeling can make the bone almost straight again.
• This correction is especially effective in children, because their bone remodeling is faster.

Repair of a Fracture Activates Osteoblasts

• A bone fracture strongly activates periosteal and intraosseous osteoblasts near the break.
• Large numbers of new osteoblasts are also rapidly formed from osteoprogenitor cells, which are bone stem cells.
• These cells produce:
  • New osteoblastic tissue
  • New organic bone matrix
  • Followed by deposition of calcium salts
• This new tissue between the broken bone ends is called a callus.
• Orthopedic surgeons may use mechanical fixation to keep the broken ends together while allowing the bone to experience stress.
• Stress at the fracture site increases osteoblast activity, accelerates healing, and may shorten recovery time.

KEY CONCEPT

• Bone remodeling keeps bone strong, properly shaped, and less brittle.
• ↑ Mechanical stress → ↑ osteoblast activity → ↑ bone deposition.
• ↓ Mechanical stress → bone thinning and decalcification.
• Bone shape can change through deposition on stressed areas + resorption on less-stressed areas.
• Fracture → osteoblast activation → callus formation → bone repair.

Conceptual Examples

• Athlete:
  Repeated heavy loading → ↑ bone stress → thicker, stronger bone.
• Leg in a cast:
  ↓ Bone use → ↓ stress → bone thinning + up to 30% decalcification within weeks.
• Angulated fracture:
  Compression side → bone deposition.
  Outer side → bone resorption → gradual straightening.
• Fracture healing:
  Break → osteoblast activation → new matrix + calcium deposition → callus formation.

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