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.
Nasu–Hakola disease also known as polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy is a rare disease characterised by early-onset dementia and multifocal bone cysts. It is caused by autosomal recessive loss of function mutations in either the TREM2 or TYROBP gene that are found most frequently in the Finnish and Japanese populations. Signs and symptoms
Four stages are recognised in this condition. The first (latent stage) show no symptoms or signs. This stage typically lasts up to the early 20s. This is followed by the osseous stage. This is characterised by recurrent bone pain usually affecting the long bones of the limbs. This is usually followed by pathological fractures of these bones. The third stage (early neurological) is marked by the onset of symptoms typical of a frontal lobe syndrome (euphoria, lack of concentration, loss of judgment and social inhibitions) with memory loss. Epilepsy may occur. This stage usually has its onset in the late 20s and early 30s. The final stage is characterised by severe dementia and paralysis. Death usually occurs in the late 40s or early 50s. Genetics
This condition has been associated with mutations in the TYRO protein tyrosine kinase binding protein (TYROBP) gene and in the triggering receptor expressed on myeloid cells 2 (TREM2) gene. TYROBP is located on the long arm of chromosome 19 (19q13.12) and TREM2 is located on short arm of chromosome 6 (6p21.1). Pathopysiology
This is not understood but appears to involve the microglia. Diagnosis
This syndrome may be suspected on clinical grounds.