Growth and Development of
Bone
Fall 2006
Introduction

Bone (Latin: "os") is a type of hard endoskeletal
connective tissue found in many vertebrate animals.
Bone is the main tissue of body organs; organs that
support body structures, protect internal organs, (in
conjunction with muscles) facilitate movement; and are
involved with cell formation, calcium metabolism, and
mineral storage. The bones of an animal are,
collectively, known as the skeleton. Bone has a
different composition than cartilage, and both are
derived from mesoderm. In common parlance,
cartilage can also be called "bone", certainly when
referring to animals that only have cartilage as hard
connective tissue
Introduction
Bone is a relatively hard and lightweight
composite material, formed mostly of
calcium phosphate
 Bone can be either compact or
cancellous (spongy). Cortical (outer
layer) bone is compact
 Cortical bone accounts for 80% of the
total bone mass of the adult skeleton

Introduction

Long bones are tubular in structure (e.g. the
tibia). The central shaft of a long bone is called
the diaphysis, and has a hollow middle—the
medullary cavity filled with bone marrow.
Surrounding the medullary cavity is a thin layer
of cancellous bone that also contains marrow.
The extremities of the bone are called the
epiphyses and are mostly cancellous bone
covered by a relatively thin layer of compact
bone.
Introduction

Short bones (e.g. finger bones) have a similar
structure to long bones, except that they are shorter.
 Flat bones (e.g. the skull and ribs) consist of two
layers of compact bone with a zone of cancellous
bone sandwiched between them.
 Irregular bones are bones which do not conform to any
of the previous forms (e.g. vertebrae).
 All bones consist of living cells embedded in a
mineralised organic matrix that makes up the main
bone material
Bone cells

Osteoblasts are typically viewed as
bone forming cells. They are located
near to the surface of bone and their
functions are to make osteoid and
manufacture hormones, such as
prostaglandins, which act on bone itself.
Bone cells

Osteocytes originate from osteoblasts which have
migrated into and become trapped and surrounded by
bone matrix which they themselves produce.

The space which they occupy is known as a lacuna.

Their functions include to varying degrees: formation
of bone, matrix maintenance and calcium
homeostasis.

They possibly act as mechano-sensory receptors—
regulating the bones' response to stress.
Bone cells


Osteoclasts are the cells responsible for bone
resorption. Osteoclasts are large, multinucleated cells
located on bone surfaces in what are called Howship's
lacunae.
The process of bone resorption releases stored
calcium into the systemic circulation and is an
important process in regulating calcium balance. As
bone formation actively fixes circulating calcium in its
mineral form, resorption actively unfixes it thereby
increasing circulating calcium levels. These processes
occur in tandem at site-specific locations and are
known as bone turnover or remodeling. Osteoblasts
and osteoclasts, coupled together via paracrine cell
signalling, are referred to as bone remodeling units.
Origin of Bone cells

Osteogenesis

Endochondral ossification


Intramembranous ossification


Lack of cartilaginous template
Axial Skeleton


Requires a cartilaginous template
Formed from sclerotome cells
Appendicular Skeleton

Formed from cells derived from the lateral plate
mesoderm
Origin of cells
Osteoblasts come from mesenchymal
cells and are directly involved in the
bone matrix production
 Osteocytes are mature osteoblasts are
responsible for maintenance of the bone
matrix


In adult bone, osteocytes out number
osteoblasts
Origin of cells
Chondroblasts- form cartilage which is
associated with bone required for bone
growth
 Osteoclasts are involved in bone
resorption (breakdown) and remodeling.
The number in adults is small
 Bone lining cells – inactive cells found on
the surface of the bone and may used as
precursors for osteoblasts

Terms
Tendons- connective tissue that
connects muscle to bone
 Ligaments – connective tissue that
connects bone to bone

Endochondral Ossification

Occurs with the replacement of cartilage with
bone
 Both axial and appendicular skeletons develop
cartilaginous structures prenatally and serves
as a template for ossification
 The cartilagenous matrix near the shaft of the
bone begins to calcify as chondrocytes mature
and enlarge
 This calcification prevents nutrients from
reaching the chondrocytes, thus they die, thus
preventing new growth (ossification)
Endochondral Ossification
The perchondrium is converted into
periosteum and ostioblasts become
apparent in the inner layer of the
periosteum. These form a layer of bone
around the diaphysis.
 Primary ossification center is established
in the central portion of the shaft as a
result of capillaries and osteblasts that
migrate into that region

Endochondral Ossification

The calcified cartilage matrix in the center is
broken down and action of the osteoblasts
replaces the cartilage with new bone
 Bone is formed from the center of ossification
until the entire diaphysis is filled with spongy
bone
 As the bone grows, osteoclasts increase the
inside diameter of the hollow central protion of
the diaphysis so that the marrow cavity results
Endochondral Ossification
Secondary center of ossification occurs
at each epiphysis
 Osteoblasts in this area produce spongy
bone that replaces the cartilage at the
epiphyses.
 A thin layer of articular cartilage to
reduce the friction at joints (bone to
bone)

Endochondral Ossification
The epiphyseal plate or growth plate is a
thin region of cartilage between the
diaphysis and epiphysis of long bones
 Increased length of long bones involves
action of both chondrocytes and
osteoblasts at the growth plate
 The chondrocytes closest to the
epiphyseal side of the growth plate are a
part of the reserve zone (stem cell zone)

Endochondral Ossification

Proliferating chondrocytes produce
extracellular matrix such as collagens and
proteoglycans
 Mature chondrocytes eventually die and leave
behind a calcified matrix which is replaced with
bone via invading capillaries and osteoblasts
 Chondroosseous junction is the region of
growth between the cartilage and new bone
Endochondral Ossification
Degradation of the growth plate cartilage
is important in allowing bone formation to
occur at a normal rate
 Growth plate turnover is the rate at which
the condrocytes progress through the
varying zones

Termination of long bone growth
The diaphysis of long bone will continue
to lengthen as long as the rate of
cartilage growth remains faster than the
rate of osteoblast invasion at the growth
plate – as long as it does not ossify
 Cartilage growth stops or slows to a rate
that allows it to be overcome with
ossification – epiphyseal closure

Termination of long bone growth
Break joint in sheep – separation is at
the distal end of the epiphyseal plate of
the metacarpal bone
 The distal end of the metacarpus is
referred to as the spool joint

Intramembranous ossification
Increases in diameter of growing bone
through appositional growth
 Osteoblasts that differentiate from the
periosteum deposit new bone matrix
within the periosteum
 Osteoblast activity is highest for those
cells that surround the periosteal blood
vessels

Intramembranous ossification
New osteons are produced as a result of
the concentric deposition of bone that
results from the action of osteoblasts and
the formation of osteocytes
 These new osteons contribute to
compact bone and increase the overall
outside diameter of the bone

Bone Resorption

While osteoblasts and osteocytes are adding
new bone to the outer surface, osteoclasts are
removing bone at th einner surface and
enlarging the marrow cavity
 Osteoclasts make contact with the bone
through a region referred to as ruffled border
and subsequently have the ability to degrade
both inorganic and organic matrices of the
bone
Bone Resorption

The degradation of the inorganic matrix is
accomplished by solubilization of crystalline
hydroxapatite crystals.
 Osteoclasts appear to be capable of creating an acidic
environment
 The resulting decrease in pH in the local region is key
to the solubilization process
 This process results in the mobilization of minerals
 Degradation of the organic matrix is accomplished with
enzymes, including collagenase and proteinases
Bone Resorption

Types of marrow
Red marrow – chief blood cell forming organ
of the adult and is found in spongy bone of
the epiphysis of long bones and main
bodies of ribs, sternum and vertebrae
 Yellow marrow – composed mainly of
adipose tissue and found in the medullary
cavity of bones

Bone Remodeling
Osteoblasts form osteons (basic
functional unit of compact bone) by
osteogenesis whereas osteoclasts
destroy osteons by resorption.
 The balance between these two yields
net bone deposition
 As animals age, bone resorption may
exceed formation and bone mass
decreases

Bone Remodeling

Bone remodeling provides a mechanism for
bone to adapt to new stresses especially
heavily stressed bone that actually helps it
become stronger
 Remodeling is initiated through osteoclast
activation to removal of bone matrix and is
followed by osteoblast formation for the
production of new bone.
 Osteoblasts respond to the stress on bones
and deposit additional bone in locations of
stress to make bones stronger
Bone Remodeling
Increased force of muscles will result in
increased bone growth where tendons
connect to bones
 The amount of stress is closely related to
the degree of mineralization and porosity

Factors affecting bone growth and
remodeling
A lot of bone remodeling is a result of
hormonal action.
 Hormones involved in bone growth and
remodeling is PTH and Calcitonin
 Calcitonin is released by the thyroid
gland that decreases osteoclasts yielding
decreased mobilization of calcium from
bone and decreasing blood calcium
concentrations

Factors affecting bone growth and
remodeling

PTH acts on bone, kidney, and gastrointestinal
tract to increase blood calcium
 Action on bone includes an increase in
osteoclast activity
 This is mediated through signals from
osteoblasts and osteocytes and often
mobilization of calcium out of bone via
osteoclasts
 Also, PTH regulates phosphorus metabolism
Factors affecting bone growth and
remodeling

Other hormones that regulate bone growth
and remodeling are testosterone and estrogen
 Both estrogen and testosterone hasten
ossification and have an effect on epiphyseal
closure
 As a result, castration yields longer bones
(longer, taller animals) because of slower
closure processes
 Estrogens are more effective in mediating
closure of the growth plate than testosterone,
thus females are smaller statured than males