Biology of fracture healing

By Faisal Rahman

Fracture healing can be divided into two types:

primary or direct healing by internal remodeling;
secondary or indirect healing by callus formation.

Primary bone healing is process when there is no motion at the fracture site under
physiological load (i.e. absolute stability) and bone ends are compressed each other (no gap
or minimal gap).

Bone healing can be divided into four stages:

inflammation;
soft callus formation;
hard callus formation;
remodeling.

Although the stages have distinct characteristics, there is a seamless transition from one stage
to another; they are determined arbitrarily and have been described with some variation.

Inflammation
After fracture, the inflammatory process starts rapidly and lasts until fibrous tissue, cartilage,
or bone formation begins (17 days postfracture). Initially, there is hematoma formation and
inflammatory exudation from ruptured blood vessels. Bone necrosis is seen at the ends of the
fracture fragments. Injury to the soft tissues and degranulation of platelets results in the
release of powerful cytokines that produce a typical inflammatory response, ie, vasodilatation
and hyperemia, migration and proliferation of polymorphonuclear neutrophils, macrophages,
etc. Within the hematoma, there is a network of fibrin and reticulin fibrils; collagen fibrils are
also present. The fracture hematoma is gradually replaced by granulation tissue. Osteoclasts
in this environment remove necrotic bone at the fragment ends.

Soft callus formation

Eventually, pain and swelling decrease and soft callus is formed. This corresponds roughly to
the time when the fragments are no longer moving freely, approximately 23 weeks
postfracture. he soft callus stage is characterized by the growth of callus. The progenitor cells
in the cambial layer of the periosteum and endosteum are stimulated to become osteoblasts.
Intramembraneous, appositional bone growth starts on these surfaces away from the fracture
gap, forming a cuff of woven bone periosteally, and filling the intramedullary canal. Ingrowth
of capillaries into the callus and increased vascularity follows. Closer to the fracture gap,
mesenchymal progenitor cells proliferate and migrate through the callus, differentiating into
fibroblasts or chondrocytes, each producing their characteristic extracellular matrix and
slowly replacing the hematoma

Hard callus formation

When the fracture ends are linked together by soft callus, the hard callus stage starts and lasts
until the fragments are firmly united by new bone (34 months). As intramembraneous bone
formation continues, the soft tissue within the gap undergoes endochondral ossification and
the callus is converted into rigid calcified tissue (woven bone). Bone callus growth begins at
the periphery of the fracture site, where the strain is lowest. The production of this bone
reduces the strain more centrally, which in turn forms bony callus. Thus, hard callus
formation starts peripherally and progressively moves towards the center of the fracture and
the fracture gap. The initial bony bridge is formed externally or within the medullary canal,
away from the original cortex. Then, by endochondral ossification, the soft tissue in the gap is
replaced by woven bone that eventually joins the original cortex.

Remodeling

The remodeling stage begins once the fracture has solidly united with woven bone. The
woven bone is then slowly replaced by lamellar bone through surface erosion and osteonal
remodeling. This process may take anything from a few months to several years. It lasts until
the bone has completely returned to its original morphology, including restoration of the
medullary canal.