Pathogenesis
In general, microorganisms may infect bone through one or more of three basic methods

Via the bloodstream (haematogeneously) – the most common method
From nearby areas of infection (as in cellulitis), or
Penetrating trauma, including iatrogenic causes such as joint replacements or internal fixation of fractures, leading to a fracture-related infection, or secondary periapical periodontitis in teeth.The area usually affected when the infection is contracted through the bloodstream is the metaphysis of the bone. Once the bone is infected, leukocytes enter the infected area, and, in their attempt to engulf the infectious organisms, release enzymes that lyse the bone. Pus spreads into the bones blood vessels, impairing their flow, and areas of devitalized infected bone, known as sequestra, form the basis of a chronic infection. Often, the body will try to create new bone around the area of necrosis. The resulting new bone is often called an involucrum. On histologic examination, these areas of necrotic bone are the basis for distinguishing between acute osteomyelitis and chronic osteomyelitis. Osteomyelitis is an infective process that encompasses all of the bone (osseous) components, including the bone marrow. When it is chronic, it can lead to bone sclerosis and deformity.Chronic osteomyelitis may be due to the presence of intracellular bacteria. Once intracellular, the bacteria are able to spread to adjacent bone cells. At this point, the bacteria may be resistant to certain antibiotics. These combined factors may explain the chronicity and difficult eradication of this disease, resulting in significant costs and disability, potentially leading to amputation.
In tubercular osteomyelitis, the long bones and vertebrae are the ones that tend to be affected.Staphylococcus aureus is the organism most commonly isolated from all forms of osteomyelitis.Bloodstream-sourced osteomyelitis is seen most frequently in children, and nearly 90% of cases are caused by Staphylococcus aureus. In infants, S. aureus, Group B streptococci (most common) and Escherichia coli are commonly isolated; in children from one to 16 years of age, S. aureus, Streptococcus pyogenes, and Haemophilus influenzae are common. In some subpopulations, including intravenous drug users and splenectomized patients, Gram-negative bacteria, including enteric bacteria, are significant pathogens.The most common form of the disease in adults is caused by injury exposing the bone to local infection. Staphylococcus aureus is the most common organism seen in osteomyelitis, seeded from areas of contiguous infection. But anaerobes and Gram-negative organisms, including Pseudomonas aeruginosa, E. coli, and Serratia marcescens, are also common. Mixed infections are the rule rather than the exception.Systemic mycotic infections may also cause osteomyelitis. The two most common are Blastomyces dermatitidis and Coccidioides immitis.In osteomyelitis involving the vertebral bodies, about half the cases are due to S. aureus, and the other half are due to tuberculosis (spread hematogenously from the lungs). Tubercular osteomyelitis of the spine was so common before the initiation of effective antitubercular therapy, it acquired a special name, Potts disease.The Burkholderia cepacia complex has been implicated in vertebral osteomyelitis in intravenous drug users.