Overview
Surgical treatment of a fracture changes both the biological and the mechanical environment, and these changes can strongly affect healing. Every trauma surgeon therefore needs a working knowledge of the biology and biomechanics of fracture healing. This guide reviews bone fracture, vascular supply, stages of secondary and primary healing, and the mechanics of relative and absolute stability. (AO)
AO principles have shifted over the last decades. Early methods aimed for absolute reduction and absolute stability, sometimes at a biological cost. Today both mechanics and biology are considered. The aim of fixation is fast fracture healing and, wherever possible, full function of the limb. The strongest, stiffest implant is not necessarily the best: fixation is always the balance between biology and biomechanics, and osteosynthesis provides temporary support for healing in an appropriate position, rather than replacing the bone. (AO)
Principles
Relative stability: enough motion between fragments to permit callus formation, without disturbing the reduction, during healing and early rehabilitation. Flexible fixation promotes callus formation and indirect reduction, and reduces operative trauma.
Absolute reduction and absolute stability need not be pursued in every case, and may carry a biological cost. If anatomic reduction would compromise blood supply and soft-tissue cover, partial reduction by traction on the main fragments reduces surgical trauma and keeps the bone alive.
Fracture fragments can heal with minimal motion between them, whether or not they are in contact.
Decisions are never made on radiographs alone. Patient age, expectations, comorbidities and psychosocial factors must be considered. (AO)
Bone and Fracture
Bone is stiff (little deformation under load) and strong, but brittle: it behaves like glass rather than rubber, and can fracture with very small deformation. Repeated displacement of fracture ends in early healing prevents bridging. (AO)
A fracture occurs in a fraction of a millisecond from single or repeated overload, with implosion and cavitation that damage the surrounding soft tissue. The fracture tears periosteal and intraosseous vessels, and biochemical agents released from the torn vessels stimulate healing. In a fresh fracture these signals are strong and rarely need augmentation: the role of surgery is to guide and support the process. (AO)
Early fixation restores function and relieves pain, helping to prevent complications such as complex regional pain syndrome. (AO)
Blood Supply
Fracture healing is mechanical in origin but triggers biological reactions (callus formation, resorption) that depend on adequate perfusion. Factors affecting blood supply at the fracture: (AO)
Mechanism of injury: displacement tears periosteal and endosteal vessels and strips periosteum, and cavitation and implosion cause further damage.
First aid: lack of splinting adds new injury.
Resuscitation: hypovolemia, hypoxia and coagulopathy increase soft-tissue and bone injury.
Comorbidities: peripheral vascular disease, diabetes.
Surgical approach: exposure adds damage, which careful planning, anatomic knowledge and meticulous technique can minimize.
Fixation material: implants damage vascularity depending on contact. Plates with a reduced undersurface contact (LC-DCP, LCP) were designed to reduce contact area and thereby preserve periosteal perfusion, although the real contact area also depends on the relationship between plate and bone radii. Reducing underplate contact lessens temporary osteoporosis beneath plates.
Effects of trauma: raised intra-articular pressure (such as intracapsular hematoma) can reduce epiphyseal blood flow, particularly in the young.
Necrotic bone heals only by slow remodeling, predisposes to infection, and stimulates internal (Haversian) remodeling that causes temporary weakening.
Cortical blood flow near a fracture or osteotomy drops by about 50% from vasoconstriction. During repair, hyperemia peaks at about 2 weeks, and flow in the callus region then gradually declines.
Callus perfusion: most of the blood supply to callus comes from the surrounding soft tissues (microangiography studies), a strong reason not to strip them. The vascular response appears greater after flexible fixation. Instability with a wide gap causes high strain and reduced blood flow. Reaming reduces endosteal blood flow and delays cortical perfusion recovery, but does not affect callus perfusion.
Blood flow damage is minimized by avoiding direct manipulation of fragments, using minimally invasive surgery, and using internal or external fixation. (AO)
Biology of Fracture Healing
Two types of healing: primary (direct) healing by internal (osteonal) remodeling, and secondary (indirect) healing by callus formation. (AO)
Secondary (indirect) healing with relative stability
Four stages with continuous transitions: (AO)
Inflammation (about days 1–7). Hematoma forms and torn vessels release inflammatory molecules. Bone fragment ends are necrotic. Platelet degranulation and cytokines cause vasodilation, hyperemia and recruitment of neutrophils and macrophages. Granulation tissue gradually replaces the hematoma, and osteoclasts remove necrotic bone.
Soft callus. Pain and swelling decrease. This stage corresponds roughly to weeks 2–3 after fracture. Cambial-layer and endosteal progenitor cells become osteoblasts, and woven bone forms by intramembranous ossification on the periosteal surface. Capillaries grow in, and mesenchymal cells become fibroblasts and chondrocytes. Fixation must still prevent shortening.
Hard callus. Once the ends are bridged by soft callus, intramembranous bone formation continues beneath the periosteum and the soft callus undergoes endochondral ossification to woven bone. Bone formation begins at the periphery, where strain is lowest, and progresses toward the center. This is complete at about 3–4 months.
Remodeling. Woven bone is gradually converted to lamellar bone by surface erosion and osteonal remodeling. This can take months to years and ends with restoration of the original morphology, including the medullary canal.
Growth factors: bone morphogenetic proteins (BMPs, members of the TGF-beta superfamily) are potent stimulators of bone formation. BMP-2 is the most used clinically, and up to 85% of its use is estimated to be off-label. It is used in spinal fusion with a fixation device in single-level L2–S1 degenerative disc disease and in open tibial shaft fractures (FDA approval 2004). Potential adverse effects include ectopic bone formation. (AO)
Cortical vs cancellous bone: secondary healing in cortical bone relies on external callus, whereas in cancellous bone, healing occurs without significant external callus. After inflammation, bone formation is intramembranous. This is best seen in short metaphyseal fractures. With a more stable metaphyseal fracture, trabecular bone has great angiogenic potential. With excessive motion, the gap fills with soft tissue (often fibrous). (AO)
Primary (direct) healing with absolute stability
Absolute stability eliminates strain in the repair tissue. With low strain, bone heals directly by osteonal remodeling (the same homeostatic mechanism as normal bone turnover), without visible callus. This is slower than callus healing. The implant must provide absolute stability for a long time and be strong enough to resist fatigue failure.
Direct healing is not the primary goal of the technique. It is an inevitable consequence of achieving and maintaining excellent anatomic reduction, which is the main aim in intra-articular fractures and some forearm shaft fractures. (AO)
Biomechanics
Stability terminology
A "stable" fracture does not visibly displace under physiologic load. Absolute stability means no motion at the fracture under physiologic load. Relative stability means displacement that is elastic and reversible, preserving reduction while keeping the mechanical stimulus for callus.
Aims of fixation, in order: maintain reduction, restore stiffness at the fracture site so function is possible, and minimize pain from fracture motion.
Exceptions that need no reduction: impacted metaphyseal fractures, undisplaced fractures with intact periosteum, abduction fractures of the proximal femoral neck, and greenstick fractures. (AO)
Healing is delayed at either end of the range: no motion gives no callus, and too much motion leaves the fracture unstable. (AO)
Relative stability and secondary healing
In relative stability, displacement increases with load and decreases with the stiffness of the device. All fixation methods other than compression techniques give relative stability.
Conservative treatment: closed reduction, then splinting or casting maintains reduction while callus forms. Traction reduces by ligamentotaxis. External splints rely on soft tissue and three-point contact, so they allow some motion. Too-tight casts cause compartment syndrome. In shaft fractures length, alignment and rotation must be restored. In intra-articular fractures, anatomic reduction avoids incongruity and secondary arthrosis.
External fixators generally give relative stability. Unilateral frames are eccentric and behave asymmetrically. Ring fixators behave similarly in all planes, so motion is mostly axial. Stiffness depends on rod strength and stiffness, the distance of rods from the bone (closer is stiffer), and number, position, diameter and tension of pins or wires. Dynamization can be applied by changing rod distance or number, or by axial telescoping devices.
Intramedullary nails give relative stability. Interlocking nails resist torsion and axial loading. Stability depends on nail diameter, geometry, and the number and arrangement of locking screws. Linear (non-locking) holes of locking screws allow some play, reduced by using more stable locking designs.
Bridge plating with locking plates: in multifragmentary fractures, locked screws used like an external fixator inside the body give elastic fixation. Plating with relative stability should be used only in multifragmentary fractures, because in simple fractures it causes high strain and a high rate of delayed union or nonunion. A simple fracture plated should be given absolute stability.
Mechanobiology of secondary healing. Interfragmentary motion stimulates callus. As callus matures it stiffens and fracture-site motion falls (in human tibial shaft fractures, motion under 300 N axial load decreases with time, and the fracture is stabilized by callus at about 13 weeks).
Perren's strain theory. Strain is the change in length divided by original length (delta l / l) of the repair tissue. Granulation tissue tolerates about 100% strain, whereas intact bone tolerates only about 2%. A bony bridge can form only when local strain is lower than what the newly formed woven bone can tolerate. The callus periphery has the highest local strain, so the first bone bridge forms there, and bridging progresses toward the center. The gap narrows and strain falls. Multifragmentary fractures tolerate more motion because motion is distributed among several gaps.
Delayed healing and nonunion: too much strain or too wide a gap leaves callus that does not ossify (hypertrophic nonunion). Too little strain (device too stiff, gap too wide) gives low-strain delayed union or nonunion. Dynamization (nail or external fixator) reduces the gap and increases stiffness. Weight bearing also stimulates callus.
Flexible fixation stimulates callus and accelerates healing of diaphyseal fractures treated with nails, external fixators or bridge plates. (AO)
Absolute stability and primary healing
Absolute stability is obtained by compression preload and friction between fracture surfaces. It must resist both bending and shear, and shear resistance depends on friction and on the geometry (serration) of the surfaces.
Axial compression by lag screw or plate (static) does not produce pressure necrosis in sheep studies. Smooth fracture surfaces have about 40% less friction than normal rough surfaces.
Lag screws apply compression only (head in the near cortex, threads only in the far cortex), generating forces over 2,500 N for longer than the healing period. In shaft fractures a lag screw alone is inadequate against bending and shear, so combine it with a plate (protection plate, formerly neutralization plate). A single lag screw cannot withstand excessive single loads: if the threads strip, compression is lost. Do not tighten lag or plate screws to the point of stripping: titanium screws resist torque less than steel. (AO)
Anatomic reconstruction is the key goal in articular fractures and some shaft fractures such as the forearm. (AO)
Complications of Mismatched Mechanics and Biology
Compromised biology or blood supply, or a very flexible construct with high strain, causes delayed union or nonunion. Compromised biology is a more serious problem than a simple hypertrophic nonunion, which is corrected by increasing mechanical stability. (AO)
Excessive stripping, implant contact and reaming reduce perfusion. (AO)
References
Gueorguiev-Rüegg B, Stoddart M. Biology and biomechanics in bone healing (Chapter 1.2). In: Buckley RE, Moran CG, Apivatthakakul T, eds. AO Principles of Fracture Management. 3rd ed. Thieme; 2017 (Turkish edition: AO Kırık Tedavisinin Prensipleri).