PATHOPHYSIOLOGY ACUTE HEMATOGENOUS OSTEOMYELITIS Aetology and Pathogenesis Acute haematogenous osteomyelitis is mainly a disease of children.

When adults are affected it is usually because their resistance is lowered. Trauma may determine the site of infection, possibly by causing a small haematoma or fluid collection in a bone, in patients with concurrent bacteraemia. The incidence of acute haematogenous osteomyelitis in western European children is thought to have declined in recent years, probably a reflection of improving social conditions. A study from Glasgow, Scotland, covering the period 199099, suggests that it is less than 3 cases per 100 000 per year (Blyth et al., 2001). However, it is almost certainly much higher among less affluent populations. The causal organism in both adults and children is usually Staphylococcus aureus (found in over 70% of cases), and less often one of the other Gram-positive cocci, such as the Group A beta-haemolytic streptococcus (Streptococcus pyogenes) which is found in chronic skin infections, as well as Group B streptococcus (especially in new-born babies) or the alphahaemolytic diplococcus S. pneumoniae. In children between 1 and 4 years of age the Gramnegative Haemophilus influenzae used to be a fairly common pathogen for osteomyelitis and septic arthritis, but the introduction of H. influenzae type B vaccination about 20 years ago has been followed by a much reduced incidence of this infection in many countries. In recent years its place has been taken by Kingella kingae, mainly following upper respiratory infection in young children. Other Gram-negative organisms (e.g. Escherichia coli, Pseudomonas aeruginosa, Proteus mirabilis and the anaerobic Bacteroides fragilis) occasionally cause acute bone infection. Curiously, patients with sickle-cell disease are prone to infection by Salmonella typhi. Anaerobic organisms (particularly Peptococcus magnus) have been found in patients with osteomyelitis, usually as part of a mixed infection. Unusual organisms are more likely to be found in heroin addicts and as opportunistic pathogens in patients with compromised immune defence mechanisms. The blood stream is invaded, perhaps from a minor skin abrasion, treading on a sharp object, an injection point, a boil, a septic tooth or in the newborn from an infected umbilical cord. In adults the source of infection may be a urethral catheter, an indwelling arterial line or a dirty needle and syringe.
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In children the infection usually starts in the vascular metaphysis of a long bone, most often in the proximal tibia or in the distal or proximal ends of the femur. Predilection for this site has traditionally been attributed to the peculiar arrangement of the blood vessels in that area (Trueta, 1959): the non-anastomosing terminal branches of the nutrient artery twist back in hairpin loops before entering the large network of sinusoidal veins; the relative vascular stasis and consequent lowered oxygen tension are believed to favour bacterial colonization. It has also been suggested that the structure of the fine vessels in the hypertrophic zone of the physis allows bacteria more easily to pass through and adhere to type 1 collagen in that area (Song and Sloboda, 2001). In infants, in whom there are still anastomoses between metaphyseal and epiphyseal blood vessels, infection can also reach the epiphysis. In adults, haematogenous infection accounts for only about 20% of cases of osteomyelitis, mostly affecting the vertebrae. Staphylococcus aureus is the commonest organism but Pseudomonas aeruginosa often appears in patients using intravenous drugs.

Adults with diabetes, who are prone to soft-tissue infections of the foot, may develop contiguous bone infection involving a variety of organisms. Pathology Acute haematogenous osteomyelitis shows a characteristic progression marked by inflammation, suppuration, bone necrosis, reactive new bone formation and, ultimately, resolution and healing or else intractable chronicity. However, the pathological picture varies considerably, depending on the patients age, the site of infection, the virulence of the organism and the host response. Acute osteomyelitis in children The classical picture is seen in children between 2 and 6 years. The earliest change in the metaphysis is an acute inflammatory reaction with vascular congestion, exudation of fluid and infiltration by polymorphonuclear leucocytes. The intraosseous pressure rises rapidly, causing intense pain, obstruction to blood flow and intravascular thrombosis. Even at an early stage the bone tissue is threatened by impending ischaemia and resorption due to a combination of phagocytic activity and the local accumulation of cytokines, growth factors, prostaglandin and bacterial enzymes. By the second or third day, pus forms within the bone and forces its way along the Volkmann canals to the surface where it produces a subperiosteal abscess. This is much more evident in children, because of the relatively loose attachment of the periosteum, than in adults. From the subperiosteal abscess pus can spread along the shaft, to re-enter the bone at another level or burst into the surrounding soft tissues. The developing physis acts as a barrier to direct spread towards the epiphysis, but where the metaphysis is partly intracapsular (e.g. at the hip, shoulder or elbow) pus may discharge through the periosteum into the joint. The rising intraosseous pressure, vascular stasis, small-vessel thrombosis and periosteal stripping increasingly compromise the blood supply; by the end of a week there is usually microscopic evidence of bone death. Bacterial toxins and leucocytic enzymes also may play their part in the advancing tissue destruction. With the gradual ingrowth of granulation tissue the boundary between living and devitalized bone becomes defined. Pieces of dead bone may separate as sequestra varying in size from mere spicules to large necrotic segments of the cortex in neglected cases. Macrophages and lymphocytes arrive in increasing numbers and the debris is slowly removed by a combination of phagocytosis and osteoclastic resorption. A small focus in cancellous bone may be completely resorbed, leaving a tiny cavity, but a large cortical or
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cortico-cancellous sequestrum will remain entombed, inaccessible to either final destruction or repair.

Another feature of advancing acute osteomyelitis is new bone formation. Initially the area around the infected zone is porotic (probably due to hyperaemia and osteoclastic activity) but if the pus is not released, either spontaneously or by surgical decompression, new bone starts forming on viable surfaces in the bone and from the deep layers of the stripped periosteum. This is typical of pyogenic infection and fine streaks of subperiosteal new bone usually become apparent on x-ray by the end of the second week. With time this new bone thickens to form a casement, or involucrum, enclosing the sequestrum and infected tissue. If the infection persists, pus and tiny sequestrated spicules of bone may discharge through perforations (cloacae) in the involucrum and track by sinuses to the skin surface. If the infection is controlled and intraosseous pressure released at an early stage, this dire progress can be halted. The bone around the zone of infection becomes increasingly dense; this, together with the periosteal reaction, results in thickening of the bone. In some
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cases the normal anatomy may eventually be reconstituted; in others, though healing is sound, the bone is left permanently deformed. If healing does not occur, a nidus of infection may remain locked inside the bone, causing pus and sometimes bone debris to be discharged intermittently through a persistent sinus (or several sinuses). The infection has now lapsed into chronic osteomyelitis, which may last for many years. Acute osteomyelitis in infants The early features of acute osteomyelitis in infants are much the same as those in older children. However, a significant difference, during the first year of life, is the frequency with which the metaphyseal infection spreads to the epiphysis and from there into the adjacent joint. In the process, the physeal anlage may be irreparably damaged, further growth at that site is severely retarded and the joint will be permanently deformed. How this comes about is still argued over. Following Trueta (1957) it has long been held that, during the first 69 months of life, small metaphyseal vessels penetrate the physeal cartilage and this permits the infection to spread into the cartilaginous epiphysis. Others have disagreed with this hypothesis (Chung, 1976), but what is indisputable is that during infancy osteomyelitis and septic arthritis often go together. Another feature in infants is an unusually exuberant periosteal reaction resulting in sometimes bizarre new bone formation along the diaphysis; fortunately, with longitudinal growth and remodelling the diaphyseal anatomy is gradually restored. Acute osteomyelitis in adults Bone infection in the adult usually follows an open injury, an operation or spread from a contiguous focus of infection (e.g. a neuropathic ulcer or an infected diabetic foot). True haematogenous osteomyelitis is uncommon and when it does occur it usually affects one of the vertebrae (e.g. following a pelvic infection) or a small cuboidal bone. A vertebral infection may spread through the end-plate and the intervertebral disc into an adjacent vertebral body. If a long bone is infected, the abscess is likely to spread within the medullary cavity, eroding the cortex and extending into the surrounding soft tissues. Periosteal new bone formation is less obvious than in childhood and the weakened cortex may fracture. If the bone end becomes involved there is a risk of the infection spreading into an adjacent joint. The outcome is often a gradual slide towards subacute and chronic osteomyelitis.

SUBACUTE HAEMATOGENOUS OSTEOMYELITIS

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Typically there is a well-defined cavity in cancellous bone usually in the tibial metaphysis containing glairy seropurulent fluid (rarely pus). The cavity is lined by granulation tissue containing a mixture of acute and chronic inflammatory cells. The surrounding bone trabeculae are often thickened. The lesion sometimes encroaches on and erodes the bony cortex. Occasionally it appears in the epiphysis and, in adults, in one of the vertebral bodies. POST-TRAUMATIC OSTEOMYELITIS Open fractures are always contaminated and are therefore prone to infection. The combination of tissue injury, vascular damage, oedema, haematoma, dead bone fragments and an open pathway to the atmosphere must invite bacterial invasion even if the wound is not contaminated with particulate dirt. This is the most common cause of osteomyelitis in adults. Staphylococcus aureus is the usual pathogen, but other organisms such as E. coli, Proteus mirabilis and Pseudomonas aeruginosa are sometimes involved. Occasionally, anaerobic organisms (clostridia, anaerobic streptococci or Bacteroides) appear in contaminated wounds. CHRONIC OSTEOMYELITIS Bone is destroyed or devitalized, either in a discrete around the focus of infection or more diffusely along the surface of a foreign implant. Cavities containing pus and pieces of dead bone (sequestra) are surrounded by vascular tissue, and beyond that by areas of sclerosis the result of chronic reactive new bone formation which may take the form of a distinct bony sheath (involucrum). In the worst cases a sizeable length of the diaphysis may be devitalized and encased in a thick involucrum. Sequestra act as substrates for bacterial adhesion in much the same way as foreign implants, ensuring the persistence of infection until they are removed or discharged through perforations in the involucrum and sinuses that drain to the skin. A sinus may seal off for weeks or even months, giving the appearance of healing, only to reopen (or appear somewhere else) when the tissue tension rises. Bone destruction, and the increasingly brittle sclerosis, sometimes results in a pathological fracture. The histological picture is one of chronic inflammatory cell infiltration around areas of acellular bone or microscopic sequestra.