Bones are rigid organs that form the endoskeleton and have several important functions, including movement, support, protection and storage of minerals. There are two types of ossification that form bones - intramembranous and endochondral ossification. Intramembranous ossification forms some flat bones directly in fibrous membranes, while endochondral ossification first forms cartilage templates that are later replaced by bone. Long bones develop primarily through endochondral ossification, beginning as cartilage that is later invaded by blood vessels and replaced with spongy bone. Growth plates allow bones to lengthen, and remodeling allows bones to increase in thickness. Calcium homeostasis and bone health rely on adequate vitamin D, which facilitates intestinal

1. Bones

2. Define Bone ?
Bones are rigid organs that form part of the endoskeleton of vertebrates.
They function to move, support, and protect the various organs of the body,
produce red and white blood cells and store minerals
Define Bone ?

3. 3
Ossification
Ossification is the process by which bone is formed
from cartilage. The cartilage cells die off and are
calcified to produce bone.
As a baby grows the cartilage
becomes bone and hardens. This is
part of the process of bone growth.
In the womb the skeleton of the
foetus is initially formed from an
elastic tissue called cartilage
(except for the clavicle and parts
of the cranium).

4. 4
Types of Ossification
Intramembranous Ossification
&
Endochondral Ossification

5. Intramembranous Ossification
• Some bones of the skull (frontal, parietal, temporal, and occipital
bones), the facial bones, the clavicles, the pelvis, the scapulae, and
part of the mandible are formed by intramembranous ossification
• Prior to ossification, these structures exist as fibrous membranes
made of embryonic connective tissue known as mesenchyme.
• Some bones of the skull (frontal, parietal, temporal, and occipital
bones), the facial bones, the clavicles, the pelvis, the scapulae, and
part of the mandible are formed by intramembranous ossification
• Prior to ossification, these structures exist as fibrous membranes
made of embryonic connective tissue known as mesenchyme.

6. 6
Formation of the Bony Skeleton
• Mesenchymal cells first
cluster together and start
to secrete the organic
components of bone
matrix which then
becomes mineralized
through the crystallization
of calcium salts. As
calcification occurs, the
mesenchymal cells
differentiate into
osteoblasts.
• The location in the tissue
where ossification begins
is known as an ossification
center.
• Some osteoblasts are
trapped w/i bony pockets.
These cells differentiate
into osteocytes.

7. 7
• The developing bone grows outward from the ossification
center in small struts called spicules.
• Mesenchymal cell divisions provide additional osteoblasts.
• The osteoblasts require a reliable source of oxygen and
nutrients. Blood vessels trapped among the spicules meet
these demands and additional vessels branch into the area.
These vessels will eventually become entrapped within the
growing bone.

8. 8
• Initially, the intramembranous bone consists only of spongy
bone. Subsequent remodeling around trapped blood vessels
can produce osteons typical of compact bone.
• As the rate of growth slows, the connective tissue around the
bone becomes organized into the fibrous layer of the
periosteum. Osteoblasts close to the bone surface become the
inner cellular layer of the periosteum.
• Initially, the intramembranous bone consists only of spongy
bone. Subsequent remodeling around trapped blood vessels
can produce osteons typical of compact bone.
• As the rate of growth slows, the connective tissue around the
bone becomes organized into the fibrous layer of the
periosteum. Osteoblasts close to the bone surface become the
inner cellular layer of the periosteum.

9. Endochondral Ossification
• Begins with the formation of a hyaline cartilage model which
will later be replaced by bone.
• Most bones in the body develop via this model.
• More complicated than intramembranous because the hyaline
cartilage must be broken down as ossification proceeds.
• We’ll follow limb bone development as an example.

10. Endochondral Ossification – Step 1
• Chondrocytes near the center
of the shaft of the hyaline
cartilage model increase
greatly in size. As these cells
enlarge, their lacunae expand,
and the matrix is reduced to a
series of thin struts. These
struts soon begin to calcify.
• The enlarged chondrocytes are
now deprived of nutrients
(diffusion cannot occur through
calcified cartilage) and they
soon die and disintegrate.

11. Endochondral Ossification – Step 2
• Blood vessels grow into the perichondrium surrounding the shaft of
the cartilage. The cells of the inner layer of the perichondrium in this
region then differentiate into osteoblasts.
• The perichondrium is now a periosteum and the inner osteogenic
layer soon produces a thin layer of bone around the shaft of the
cartilage. This bony collar provides support.

12. Endochondral Ossification – Step 3
• Blood supply to the periosteum, and
capillaries and fibroblasts migrate
into the heart of the cartilage,
invading the spaces left by the
disintegrating chondrocytes.
• The calcified cartilaginous matrix
breaks down; the fibroblasts
differentiate into osteoblasts that
replace it with spongy bone.
• Bone development begins at this
primary center of ossification and
spreads toward both ends of the
cartilaginous model.
• While the diameter is small, the
entire diaphysis is filled with spongy
bone.
Notice the primary
ossification centers in the
thigh and forearm bones
of the above fetus.

13. Endochondral Ossification – Step 4
• The primary ossification center enlarges
proximally and distally, while osteoclasts
break down the newly formed spongy bone
and open up a medullary cavity in the center
of the shaft.
• As the osteoblasts move towards the
epiphyses, the epiphyseal cartilage is growing
as well. Thus, even though the shaft is
getting longer, the epiphyses have yet to be
transformed into bone.

14. Endochondral Ossification – Step 5
Around birth, most long bones have a
bony diaphysis surrounding remnants
of spongy bone, a widening medullary
cavity, and 2 cartilaginous epiphyses.
At this time, capillaries and osteoblasts
will migrate into the epiphyses and
create secondary ossification centers.
The epiphysis will be transformed
into spongy bone. However, a small
cartilaginous plate, known as the
epiphyseal plate, will remain at the
juncture between the epiphysis and
the diaphysis.
Articular
cartilage Epiphyseal plate

16. Growth in Bone
Length
• Epiphyseal cartilage
(close to the
epiphysis) of the
epiphyseal plate
divides to create more
cartilage, while the
diaphyseal cartilage
(close to the
diaphysis) of the
epiphyseal plate is
transformed into bone.
This increases the
length of the shaft.

17. •As a result osteoblasts begin
producing bone faster than the
rate of epiphyseal cartilage
expansion. Thus the bone grows
while the epiphyseal plate gets
narrower and narrower and
ultimately disappears. A remnant
(epiphyseal line) is visible on X-
rays (do you see them in the
adjacent femur, tibia, and fibula?)
At puberty, growth in bone length
is increased dramatically by the
combined activities of growth
hormone, thyroid hormone, and
the sex hormones.

18. Growth in Bone Thickness
• Osteoblasts beneath the periosteum secrete
bone matrix on the external surface of the
bone. This obviously makes the bone thicker.
• At the same time, osteoclasts on the
endosteum break down bone and thus widen
the medullary cavity.
• This results in an increase in shaft diameter
even though the actual amount of bone in the
shaft is relatively unchanged.

19. 19
Functions of the skeleton
The skeleton performs many functions in the body.
Shape – The skeleton gives us our
shape and determines our size.
Blood cell production – blood
cells are made in the bone marrow.
Movement – The skeleton allows us to move. Muscles
are attached to the bones and move them as levers.
Protection – The skeleton protects delicate
parts of the body like the brain and lungs.
Support – The skeleton
supports muscles and organs.
1
2
3
4
5

20. Bone
• 206 bones in the human skeleton
• Provide support, anchorage for muscles and protection for organs eg
ribs
• Bone is a storage area for calcium and phosphorous salts and has an
important role in blood formation
• Before birth the skeleton is made of cartilage most of which is
gradually replaced by bone via a process called ossification.
• Bones of the human skeleton can be divided into long bone and flat
bones
• Long bones are tubular and weight bearing and are made of a dense
outer layer of compact (cortical) bone and central region (medulla)
made up of trabecular (spongy) bone
• Trabecular bone makes up most of the short, flat and irregular shaped
bones and the epiphyses (ends) of the long bones
• It is much lighter than cortical bone and has a good strength to weight
ratio

21. 21
1. Less calcium intake
2. Age
3. Smoking
4. Diet
5. Long use of corticosteroids
6. High body mass
What are the reason for bone
loss ?
Bone loss in women occurs fastest in the first few years after menopause, but
bone loss continues into old age

22. 22
Issues ?
Arthritis
&
osteoporosis

23. 23
Arthritis and osteoporosis are two distinct conditions
that are very common, especially in older
individuals. While osteoporosis generally affects
older women who are of postmenopausal age,
arthritis can affect any individual at any time. In
some cases, the conditions can be combined into a
disease which is known as arthritis osteoporosis or
osteoarthritis. Arthritis osteoporosis is a disease
that attacks the bone joints as well as bone mass.

24. 24
Osteoporosis
)
• Osteoporosis is a chronic disease that has late clinical
consequences and has been referred to as a silent epidemic
because there are no associated signs or symptoms before
fracture.

25. Risk factors for Osteoporosis
• Age- bone mineral density (BMD) decreases with age
• Hormones- lower levels of oestrogen after menopause
accelerate bone loss due to increased activity of
osteoclasts.
• Premature menopause or hysterectomy causes earlier
acceleration of bone loss. Likewise surgical or chemical
castration in men
• Gender- women are at increased risk of osteoporosis as
they start out with smaller bones and bone mass
compared to men
• Genetic factors- family history of osteoporotic fracture,
especially hip fracture, increases risk

26. 26
CALCIUM

27. 27
The Role of Calcium
Calcium is needed for our heart, muscles, and nerves to
function properly and for blood to clot. Inadequate calcium
significantly contributes to the development of osteoporosis.
Many published studies show that low calcium intake
throughout life is associated with low bone mass and high
fracture rates. National nutrition surveys have shown that
most people are not getting the calcium they need to grow
and maintain healthy bones. To find out how much calcium
you need, see the Recommended Calcium Intakes (in
milligrams) chart
Calcium is needed for our heart, muscles, and nerves to
function properly and for blood to clot. Inadequate calcium
significantly contributes to the development of osteoporosis.
Many published studies show that low calcium intake
throughout life is associated with low bone mass and high
fracture rates. National nutrition surveys have shown that
most people are not getting the calcium they need to grow
and maintain healthy bones. To find out how much calcium
you need, see the Recommended Calcium Intakes (in
milligrams) chart

29. Calcium Homeostasis

30. First, Let’s Take a Look at This
Diagram…… Homeostasis of Calcium

31. Where Do I Get My Calcium?
% 70 inorganic matrix composed
of Calcium Salts in
Hydroxyapatite
Ca10(PO4)6(OH)2.
The skeleton is resevoir for the
minerals Calcium (and
phosphorous).
Resorption: the process of
dissolving bone and releasing
its minerals into the blood for
other uses. The
OSTEOCLAST secretes
ACID PHOSPHATASE or
sometimes HCL to digest
bone matrix. Secreted by
lysosomes.

32. Resorption and Remodeling
Resorption
Osteoclasts do
this using HCL
and ACID
PHOSPHATASE
to dissove bone
matrix
Remodeling
Ostoblasts do this
Collagen fibers and
hydroxyapatite
matrix

33. Calcium alone is not enough
• Important co-factor nutrients that work with calcium
for healthy bones
Vitamin D3
Magnesium
Vitamin C
Folic Acid, B12, B6
Silicon
Boron
Vitamin K
Selenium
Zinc, Copper, Manganese
Lycopene

34. Its Role in Calcium
Homeostasis
VITAMIN D
TThe vitamin That Works
Like a hormone

36. To Make Me D, Warm Me Up and
Hydroxylate Me..3X!

38. Vitamin D3 Recommendation
• Vitamin D3 continues to be overlooked – despite standard
medical care, research shows that over 50% of North
Americans with osteoporosis have inadequate Vitamin D
status!
• Supplementation studies at 800 IU (the exact dosage in the
bone builder blend) show reduced fracture incidence and
decreases cancer risk
• National Osteoporosis Foundation recommends 400-800
IU Vitamin D3 daily.
• Health Canada is now recommending increasing upwards
to 2000 IU daily

39. Vitamin D3 at work
• Drives bone health, measured best by 25OH)D test
• Helps calcium be absorbed into bone-building cells
• Inhibits formation of bone breakdown cells
• Helps to prevent Calcium loss through the kidneys
• Assists in the absorption of Calcium from the intestines.
(Holick M. Mayo Clin Proc 2006)

40. Vitamin D Deficiency Diseases
• 16 different types of cancer
• 62% increased risk of heart disease & stroke
• Multiple sclerosis
• Juvenile Diabetes
• Influenza
• Osteoporosis
• Fracture Incidence
• Large population studies show that dietary Vitamin D3
(or sunlight exposure) is associated with protection
against osteoporosis and fractures.
(Nieves. Am J Clin Nutr 2005)
(Circulation: Jan 7, 2008)

41. How Does “D” Compare To
Hormones?
Vitamin D3 is not secreted by a classical endocrine
gland, the active form of the hormone is released
from the kidney and acts at distant sites or locally.
Each of the forms of vitamin D is hydrophobic, and is
transported in blood bound to carrier proteins.
Only a very remains in a free form in the circulation
and has a serum t1/2 of about 5 hours small proportion
of vitamin D

42. So..Exposure to Sun and Then, Fortified
Foods….Give Us the D We Need

43. How Does Vitamin D Facilitate
Calcium Absorption in the Intestines??

44. IN THE INTESTINE
It facilitates intestinal absorption of calcium, as
well as stimulates absorption of phosphate and
magnesium ions.
In the absence of vitamin D, dietary calcium is not
absorbed at all efficiently.
Vitamin D stimulates the expression of a number
of proteins involved in transporting calcium
from the lumen of the intestine, across the
epithelial cells and into blood.

45. The vitamin D form, 1,25-
dihydroxcholecalciferol [1,25(OH)2D3],
1. stimulates the synthesis of the epithelial
calcium channels in the plasma membrane
calcium pumps , and
2. induces the formation of the calbindins.

46. Structure and Synthesis-Vitamin D
The term vitamin D actually refers to a group
of steroid molecules. Vitamin D3, also
known as cholecalciferol is generated in the
skin of animals when light energy is
absorbed by a
precursor molecule 7-dehydrocholesterol.

47. Structure and Synthesis-Vitamin D
Vitamin D is thus not a true vitamin, because individuals
with adequate exposure to sunlight do not require
dietary supplementation.
There are dietary sources of vitamin D, including egg yolk,
fish oil and a number of plants.
The plant form of vitamin D is called vitamin D2 or
ergosterol. However, natural diets typically do not
contain adequate quantities of vitamin D, and exposure
to sunlight or consumption of foodstuffs purposefully
supplemented with vitamin D are necessary to prevent
deficiencies.

48. Vitamin D, as either D3 or D2, does not have significant biological
activity.
Rather, it must be metabolized within the body to the hormonally-
active form.
This transformation occurs in 2 steps, as depicted in the diagram on
the next slide
Within the liver, cholecalciferal is hydroxylated
to 25-hydroxycholecalciferol by the enzyme 25-
hydroxylase.
Within the kidney, 25-vitamin D serves as a substrate for
1-alpha-hydroxylase, yielding 1,25-
dihydroxycholecalciferol, the biologically active form of
vitamin D.

50. Physiological Effects of Vitamin D
Vitamin D is well known as a
hormone involved in mineral
metabolism and bone growth.
Its most dramatic effect is to
facilitate intestinal absorption of
calcium, although it also stimulates
absorption of phosphate and
magnesium ions.

51. Physiological Effects of Vitamin D
In the absence of vitamin D, dietary calcium
is not absorbed at all efficiently.
Vitamin D stimulates the expression of a
number of proteins involved in
transporting calcium from the lumen of the
intestine, across the epithelial cells and into
blood. The best-studied of these calcium
transporters is calbindin, an intracellular
protein that ferries calcium across the
intestinal epithelial cell.

52. Physiological Effects of Vitamin D
Vitamin D receptors are present in most if
not all cells in the body. Additionally,
experiments using cultured cells have
demonstrated that vitamin D has potent
effects on the growth and differentiation of
many types of cells.
Hence, vitamin D has physiologic effects
much broader that a role in mineral
homeostasis & bone function.

53. Diseases and Conditions
that Vitamin D Helps Prevent
• Rickets and other bone diseases
• Internal cancers
• Multiple sclerosis
• Helps in pregnacy to make bone
stronger

54. Vitamin D3
 Must be Vitamin D3, also known as
cholecalciferol.
 Dose is 75 IU per pound body weight or 165
IU per kilogram body weight.
 Children with blood levels of 25-hydroxy
exceeding 80 ng/mL have shown the most
improvement in immune response.
 Very important in immune function.

55. Outline
• Historical science perspective
• Diseases and conditions affected by
vitamin D
• Sources of vitamin D
• How much we need in our blood
• Concerns regarding ultraviolet
radiation
• Sources of additional information

56. Any Question