St. Luke’s College of Medicine – William H.

Quasha Memorial
PHYSIOLOGY BLOCK 1

Lecture: 13- Bone Physiology Date: August 26, 2015

Lecturer: Irving Tan, MD, FPCS Trans Team: Lim, V., Luces, Macaraig, Magadia

Topic Outline Steps:

I. Objectives 1. Mesenchymal cells differentiate into osteoblasts and starts to
secrete organic substances (collagen monomers) to form a
II. Types of Bone matrix, where calcium, phosphate and other inorganic
III. Bone Structure substances will precipitate and turn into hydroxyapatite crystals.
A. Organic bone matrix 2. Osteoblasts become trapped in the calcified matrix and
B. Inorganic bone crystals become osteocytes in spaces called lacunae.
3. Periphery starts to harden into solid compact bone while the
IV. Initial Bone Formation middle remains spongy or cancellous bone.
A. Intramembranous 3. Other mesenchymal cells differentiate into fibroblasts that will
B. Intracartilaginous (endochondral) form blood vessels and peripheral mesenchymal cells become
V. Bone Growth the periosteum.
A. Interstitial growth
B. Appositional growth
VI. Bone Formation and Resorption
VII. Bone Remodeling
VIII. Calcium Metabolism

I. Objectives

● To learn the make-up of bone

● To differentiate between intramembranous and
intracartilaginous bone formation
● To know the steps in bone formation
● To differentiate between interstitial and appositional bone
growth
● To understand epiphyseal plate closure
● To differentiate between bone formation and resorption Figure 2. Intramembranous Ossification
● To know the different factors that favor bone formation or
resorption B. Intracartilaginous (endochondral)
● Ex. long bones
II. Types of Bone ● Periosteal bud - osteoprogenitor cells
● Spongy bone and marrow develops
A. Compact/Cortical Bone - dense area of the bone ● Epiphyses - secondary ossification center
B. Spongy/Medullary/Trabecular Bone - interconnecting cavities Steps:
inside the bone 1. Mesenchymal cells differentiate into chondroblasts that will
C.Long bones - composed of a shaft called diaphysis and two secrete the hyaline cartilage, which serves as the scaffold for
terminal heads called epiphysis bone growth.
D.Flat bone - composed of two compact surfaces called plates 2. Cartilage elongates as it grows. Its outer part will start to form
and the interweaving medullary center called diploe the osteoblasts which will secrete and form the bone matrix. It
will calcify into the bone collar, which is the primary ossification
center of the diaphysis.
3. As the bone starts to calcify, blood supply is cut off but
fibroblasts from mesenchymal cells forms blood vessels which
penetrate into the center of the bone.
4. The center becomes cancellous and forms secondary
ossification center at the epiphysis.
5. In between the diaphysis and the epiphysis is the metaphysis
Figure 1. Types of bone where the epiphyseal plate is found.
III. Bone Structure
A. Organic Matrix
1. collagen (90-95%)- tensile strength
2. ground substance - ECF, chondroitin sulfate, hyaluronic
acid (these help in the control of the deposition of calcium
salts)
B. Inorganic Substances
1. hydroxyapatite crystals- Calcium & Phosphate
■ compressional strength -shaped as long flat plates
arranged like overlapping bricks in a brick wall preventing
shear and tear and providing strength to the bone
■ Na, Mg, etc - conjugated to hydroxyapatite

- Normally, there is a high concentration of Calcium in

extracellular matrix but there is no precipitation because of Figure 3. Intracartilaginous Ossification
the presence of pyrophosphate (an inhibitor). However, there
is no pyrophosphate in bone that is why calcification occurs.
V. Bone Growth
IV. Initial Bone Formation A. Linear or Interstitial growth - Increase in length
Begins in 6th and 7th week embryonic life The epiphyseal plate is made up of cartilage layers:
A. Intramembranous (1) Resting cartilage layer, (2) Proliferating cartilage layer
● Ex. skull (towards metaphysis), (3) Maturing cartilage layer, (4) Calcified
● Mesenchymal - chondroblasts cartilage layer and (5) Metaphysis layer.
● Chondroblasts - cartilage -As cartilage is proliferating, the bone becomes longer (linear
● Osteoblast - bone collar growth) through the pushing of the cartilage layers towards the
● Cartilage cells calcify matrix ends.
● Matrix turns into marrow cavity
-Bone formation direct from mesenchymal cells. Doesn't need
model bone.

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Bone remodeling processes:

- Ideally, formation and resorption rates are equal. If there’s
imbalance, where in formation > resorption, the bone will
become denser. If Resorption > formation, bones become brittle.
-Old bones are brittle so we need to continuously form new
bones.
VIII. Calcium Metabolism
● Osteoclasts mobilize Ca2+ in to the plasma
● Osteocytes deposit Ca2+ back to the bone

-Excess calcium (hypercalcemia) is deposited in the bone via

bone formation by osteoblasts or is eliminated out of the body.
Figure 4. Cartilage layers in interstitial growth -Significant decrease of calcium in ECF (hypocalcemia) will
result to increase irritability of nerve and muscles. To increase
B. Appositional growth - Increase in diameter size. the calcium in the plasma, it will be remove from the bones via
- The periosteum forms ridges. They grow until these periosteal bone resorption of osteoclasts.
ridges meet and fuse together. The center which has a space - Signs of hypocalcemia: Chvostek sign (abnormal reaction to
secretes substances for bone matrix formation. Crystallization the stimulation if facial nerve) and carpopedal spasm.
occurs and then the space of the bone closes up of again.
- The epiphyseal plate closes as we mature. X-ray of the wrist
could determine the age of a person. Around 10 years, the
epiphyseal plate of the humerus starts to close followed by the
radius and so on. Females' epiphyseal plate closes earlier.

Figure 8. Osteoblast-Osteoclast

-Origin of osteoclasts are myeloid like blood (monocytes)

-Osteoblasts were mesenchymal cells
Figure 5. Appositional growth
Other factors involved in Calcium Metabolism:
VI. Bone Formation and Resorption o PTH
A. Bone Formation ▪ Binds to osteoblasts and osteocytes - calcium diffuses
● Osteoblasts form a membrane separating bone fluid into cell - ECF - increase [Ca]
from ECF ▪ Activation of osteoclasts
● Solubility product - calcium phosphate precipitates
● Alkaline phosphatase hydrolyze phosphate esters -
- Osteoblasts have receptors for PTH and it activates the
osteoclasts to cause bone resorption causing calcium to the
increase [phosphate]
released out of the bone into the plasma. Osteoblasts
releases Osteoprotegerin Ligand (OPGL; also known as
B. Bone Resorption
RANKL) which activates the receptors in the preosteoclast
● Osteoclast
cells, causing them to differentiate into mature Osteoclasts.
○ Proteolytic enzyme – dissolves the matrix
○ Citric and Lactic Acid - solution of bone salts o Calcitonin
● Rate of formation = resorption ▪ Decrease formation of new osteoclasts
▪ Decrease [Ca]
o Vitamin D
▪Large quantities - bone resorption
▪Small quantities - bone formation
-Important for the absorption of Ca in the diet.

o Testosterone
Figure 6. Bone Formation and Resorption ▪ Increase bone matrix and Ca retention
▪ Increase size and strength
VII. Bone Remodeling ▪ But causes epiphyses to close
-Testosterone favors formation & growth
-Hastens the closure of epiphyseal plates.

o Estrogen
▪ Inhibits osteoclastic activity – thus favors bone formation
and growth
▪ It causes early closure of the epiphyseal plate greater
than testosterone.
▪ Menopause (decrease estrogen level) – may cause
osteoporosis
● Increase osteoclastic activity
● Decrease bone matrix formation
● Decrease deposition of calcium and phosphate
-RANK binds to RANKL for the formation of the mature
Figure 7. Bone remodeling
osteoclast which favors bone resorption. RANKL is produced by
the osteoblast and RANK receptor is found in the osteoclast.
● Maintains toughness of the bone
Binding together, they cause bone resorption. But sometimes
● Re-shaping to support mechanical forces
osteoblasts & stroma cells secrete OPG (osteoprotegerin), a
● Adjusts strength to amount of stress

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“decoy” receptor which binds to the RANK receptor. RANKL

couldn't bind with RANK hence, osteoclast formation is inhibited,
favoring bone formation.
-PTH binds to the osteoblasts inhibiting the OPG formation and
letting RANKL bind with RANK. Mature osteoclasts are then
produced causing bone resorption, hence, the increase in
calcium in ECF.

Figure 9. Factors affecting bone formation and resorption

Figure 10. RANKL and RANK fusion

References
 Guyton and Hall Textbook of Medical Physiology, 13th Ed
(Chapter 80)
 Junquiera’s Basic Histology: Text and Atlas, 13th Ed.
(Chapter 8)
 Dr. Tan’s Lecture

QUIZ
1. What will result if there’s a significant decrease of
calcium in the ECF?
2. Give three importance of bone remodeling.
3. This is found in the metaphysis and allows the bone to
grow in length.
4. Give the two signs of hypocalcemia.
5. What is the substance secreted by the osteoblast
when PTH is bonded to it?
6. This is where the primary ossification center of the
bone is located.

Answers:
1. Increase irritability of nerves and muscle and/or
Tetany
2. Bone remodeling maintains toughness, re-shapes the
bone to support mechanical forces and adjusts the
bone strength to amount of stress.
3. Epiphyseal plate
4. Chvostek sign and carpopedal spasm
5. RANK-Ligand
6. Diaphysis

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