2. BONES are rigid organs serving various vital functions in the body. In addition to providing
shape, aiding in movement, and providing protection for vital inner organs, they are the
production house of blood cells, storage house of fat, mineral, and growth factors, and play
considerable role in detoxification and acid–base balance of blood.
A long bone has two parts:
the diaphysis and
the epiphysis.
The diaphysis is the tubular shaft that runs between the
proximal and distal ends of the bone. The hollow region in
the diaphysis is called the medullary cavity, which is filled
with yellow marrow. The walls of the diaphysis are composed
of dense and hard compact bone.
The wider section at each end of the bone is called the
epiphysis (plural = epiphyses), which is filled with spongy
bone. Red marrow fills the spaces in the spongy bone.
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3. The medullary cavity has a delicate
membranous lining called
the endosteum (end- = “inside”; oste- =
“bone”), where bone growth, repair, and
remodeling occur. The outer surface of
the bone is covered with a fibrous
membrane called the periosteum (peri–
= “around” or “surrounding”). The
periosteum contains blood vessels,
nerves, and lymphatic vessels that
nourish compact bone.
Compact bone is denser and stronger so
that it can withstand compressive forces,
while spongy (cancellous) bone has open
spaces and supports shifts in weight
distribution
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4. Bone contains a relatively small number of cells entrenched in a
matrix of collagen fibers that provide a surface for inorganic salt
crystals to adhere. These salt crystals form when calcium phosphate
and calcium carbonate combine to create hydroxyapatite, which
incorporates other inorganic salts like magnesium hydroxide,
fluoride, and sulfate as it crystallizes, or calcifies, on the collagen
fibers. The hydroxyapatite crystals give bones their hardness and
strength, while the collagen fibers give them flexibility so that they
are not brittle.
Although bone cells compose a small amount of the bone volume,
they are crucial to the function of bones. Four types of cells are
found within bone tissue: osteogenic cells, osteoblasts, osteocyte
and osteoclasts.
Bone Cells. Four types of cells are found within bone tissue.
Osteogenic cells are undifferentiated and develop into osteoblasts.
When osteoblasts get trapped within the calcified matrix, their
structure and function changes, and they become osteocytes.
Osteoclasts develop from monocytes and macrophages and differ in
appearance from other bone cells.
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5. BONE-LIMITATIONS
However, bone in general is a poorly perfused organ.
During pathological conditions, the blood supply in the local area gets further hampered, making the availability of
drug rather questionable.
Although parenteral route is expected to provide better bioavailability and avoid the possibility of hepatic first pass
metabolism as compared with oral route, bone being a poorly perfused organ is the major reason for
experiencing poor supply of drugs at the site of treatment.
BONE-DRUG DELIVERY-LIMITATIONS
Hence, the need to administer drugs at high doses and for prolonged periods, in conventional therapy, would appear
logical. Eg ceftriaxone administered at 2 g a day by i.v. for 4–6 weeks in the treatment of bone infections and
bisphosphonates as Risedronate at 5 mg per day orally at least for 6 months in case of osteoporosis.
From the drug point, delivering large amounts of drugs to the body may display an increase in
bioavailability but could result with exorbitant irrational quantities of drug getting eliminated from the body with
potential increase in undesired serious side effects as nephrotoxicity and hepatotoxicity and escalated treatment
cost, as with antimicrobials
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6. ADVANTAGES OF LOCAL DRUG DELIVERY IN BONE
• Local delivery of drugs offer various possibilities for avoiding serious side effects,
• avoiding infusions,
• decreased hospitalization,
• reduced medical expenses,
• release drug in a sustained fashion,
• maintain high drug concentrations locally,
• reduce presence of drug in systemic blood circulation, maintain drug stability for a longer period, etc.
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8. ORGANIC
- Polymers fall under this class
- May be from natural or synthetic
- Has good control on drug release
- Can be made to totally degrade out on the last
day of drug release
- Non biodegradable polymers need second
surgery
for removal of polymer system
- Polymers are highly priced, esp. biodegradable
synthetic
- Do not support new bone formation
- Cannot support the bone, mechanically
- Polymers or their biodegraded products can
cause severe immunological disturbances in
some patients
- Sterilization disturbs polymer property and
thereby drug release
INORGANIC
- Bioactive glasses, bioceramics, inorganic
materials
that form a part of bone fall under this
class
- May be from natural or synthetic
- Once placed, no need to remove later
- Sterilization does not interfere with material
properties
- Inorganics are quite cheap
- Supports new bone formation
- Supports the bone, mechanically also
- Inorganics do not cause immunological
disturbances
- Do not have good control on drug release
- Resorption cannot be tailored easily
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