Growth
factors of Bone
Osteoconductive
This
term describes factors which help form bone by providing a scaffold on which
cells, such as osteoblasts, lay down vascularized new bone. Perhaps the most simple example is freeze
dried bone graft, which is devoid of living tissue but contains the inherent
framework to build new bone. Ceramics
also possess this ability and are frequently utilized. Ceramics are usually fundamentally composed
of calcium phoshate in the form of hydroxyapatite and/or tricalcium
phosphate. Both of these substances
provide a framework for bone formation; additionally, they are reabsorbed and
remodeled at varying rates. Recently,
combinations have been produced that provide structural stability for several
months and have been useful in fracture care.
Synthetic polymers such as polylactic acid (PLA) and polyglycolic acid
(PGA) possess osteoconductive properties and are used frequently as plates and
screws for stabilizing fractures and graft placement.
Osteoinductive
Osteoinductive
is a term used to describe substances that are capable of inducing bone to
grow. Unlike osteoconductive
substances, these factors are capable of causing extraskeletal tissue to form
bone. This class of compounds include
Bone Morphogenic Proteins, TGF-Beta family, Insulin-Like growth factors,
fibroblastic growth factors (FGFs), and Platelet Derived Growth Factors (PDGFs)
TGF-Beta family
TGF-Beta
family of proteins induces the production of type II collagen and proteoglycans
that are instrumental in fracture healing.
This protein has dramatic effects on callus formation and regulation and
can be found throughout the early fracture hematoma within 24 hours from
fracture. It is deposited in the
hematoma by platelets; however, the protein is found throughout mesenchymal
cells, chondrocytes, and osteoblasts.
TGF-Beta has been used clinically as a coating for porous implants and
has demonstrated the ability to enhance bone ingrowth.
Bone Morphogenic Protein (BMP)
A
cytokine that induces undifferentiated perivascular mesenchymal cell to
transform into osteoblasts. This low
molecular weight hydrophobic glycoprotein is highly “osteoinductive” meaning
that the substance can induce bone growth.
This induction is powerful enough that it can cause bone to form in
extraskeletal sites. BMPs were first
discovered in demineralized bone matrix and several different types have been
found. BMP-7 (also known as OP-1) is
often mixed with a collagen carrier and utilized frequently as an adjuct in
spinal fusion and non-union surgeries.
BMP-2 and BMP-3 (also called osteogenin) have similar effects with
variable potency. In addition, BMPs
help regulate bone matrix formation and BMP-1 has an important function in the
processing of collagen from its procollagen precursors.
Platelet Derived Growth Factor (PDGF)
A
protein found within platelets that has many functions. Most importantly, it has a chemotactic
function that attracts inflammatory cells to the fracture hematoma. In vitro, it appears to stimulate
replication of osteoblasts and increase production of type I collagen. While it can induce bone formation, no
experiment has shown it to increase callus strength.
Fibroblast Growth Factor and Insulin Like Growth Factor both have varying effects on fracture callus and appear to enhance fracture healing.