Xanthogranulomatous osteomyelitis (XO) is a peculiar aspect of osteomyelitis characterized by prevalent histiocytic infiltrate and foamy macrophage clustering.

As of 2011 five cases had been reported, involving rib, tibial epiphysis, ulna, distal tibia and femur. Young individuals are prevalently affected but one case involved a 50-year-old woman. Pain, swelling of possibly long duration, fever and increased ESR are some of the main clinical findings. X-ray examination shows lytic foci with sclerotic margins. A neoplastic process can be suspected.

The Xanthogranulomatous Process (XP), also known as Xanthogranulomatous Inflammation is a form of acute and chronic inflammation characterized by an exuberant clustering of foamy macrophages among other inflammatory cells. Localization in the kidney and renal pelvis has been the most frequent and better known occurrence followed by that in the gallbladder but many others have been subsequently recorded. The pathological findings of the process and etiopathogenetic and clinical observations have been reviewed by Cozzutto and Carbone.

The xanthogranulomatous type of inflammation is most-commonly seen in pyelonephritis and cholecystitis, although it has more recently been described in an array of other locations including bronchi, lung, endometrium, vagina, fallopian tubes, ovary, testis, epydidymis, stomach, colon, ileum, pancreas, bone, lymph nodes, bladder, adrenal gland, abdomen and muscle. Telling apart clinically a XP from a tumor condition can be challenging as pointed out by several authors. Cozzutto and Carbone suggested that a wide array of entities characterized by a large content of histiocytes and foamy macrophages could be traced back at least in part to a xanthogranulomatous inflammation. These include such varied disturbances as xanthoma disseminatum, ceroid granuloma of the gallbladder, Whipple's disease, inflammatory pseudotumor of the lung, plasma cell granuloma of the lung, malakoplakia, verruciform xanthoma, foamy histiocytosis of the spleen in thrombocytopenic purpura, isolated xanthoma of the small bowel, xanthofibroma of bone, and gastric xanthelasma.

A pathogenetic model might be suggested as follows:

1. suppuration, hemorrhage and necrosis,

2. granulomatous tissue with granular histiocytes and foamy macrophages,

3. fibrohistiocytoma-like or plasma cell granuloma-like patterns,

4. possible myofibroblast metaplasia.

A reactive fibrohistiocytic lesion simulating fibrous histiocytoma has been reported by Snover et al. Reactive granular cells in sites of trauma have been regarded of histiocytic nature. Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease) might share several aspects of the XP. Likewise there might be some superimpositions between the XP and the plasma cell granuloma/histiocytoma-inflammatory myofibroblastic tumor complex.> The XP might be an important stage of this complex.

CRMO was once considered strictly a childhood disease, but adults have been diagnosed with it. The affected tends to range from 4 to 14 years old, with 10 as the median age. As stated above, CRMO occurs 1:1,000,000 and primarily in girls with a 5:1 ratio. That means out of six million, there will probably be 5 girls and 1 boy with the condition.

Prognosis will depend on your child's individual disease and response to treatment. It is best to discuss the prognosis with your child's pediatric rheumatologist.

OM is usually a polymicrobial, opportunistic infection, caused primarily by a mixture of alpha hemolytic streptococci and anaerobic bacteria from the oral cavity such as "Peptostreptococcus", "Fusobacterium" and "Prevotella", (in contrast to OM of the long bones, usually caused by isolated "Staphylococcus aureus" infection). These are the same as the common causative organisms in odotonogenic infections. However, when OM in the jaws follows trauma, is the likely cause is still staphylococcal (usually "Staphylococcus epidermis".

Other risk factors can be any familial hypercoagulation tendency, including for example, Factor V (Five) Leiden heterozygosity.

Peripheral arthritis has been reported in 92% of cases of SAPHO as well.

In children, the SAPHO syndrome is most likely to affect the metaphysis of long bones in the legs (tibia, femur, fibula), followed by clavicles and spine.

Pathologic fracture of the mandible is a possible complication of OM where the bone has been weakened significantly.

Erdheim–Chester disease is associated with high mortality rates. In 2005, the survival rate was below 50% at three years from diagnosis. More recent reports of patients treated with Interferon therapy describe an overall 5-year survival of 68%. Long term survival is currently even more promising, although this impression is not reflected in the recent literature.

Garre's sclerosing osteomyelitis is a type of chronic osteomyelitis also called proliferative periostitis, periostitis ossificans and Garré's sclerosing osteomyelitis.

It is a rare disease. It mainly affects children and young adults. It is associated with a low grade infection, which may be due to dental caries (cavities in the teeth).

The body of the mandible may show irregular lucent/opaque changes with subperiosteal opaque layering along inferior border. It is a chronic osteomyelitis with subperiosteal bone and collagen deposition.

There is no suppuration and sinus formation.

It was first described by the Swiss surgeon Carl Garré.

The disease has been reported to affect 3 per 1000 infants younger than 6 months in the United States. No predilection by race or sex has been established. Almost all cases occur by the age of 5 months. The familial form is inherited in an autosomal dominant fashion with variable penetrance. The familial form tends to have an earlier onset and is present at birth in 24% of cases, with an average age at onset of 6.8 weeks. The average age at onset for the sporadic form is 9–11 weeks.

Cortical hyperostosis is a potential side effect of long-term use of prostaglandins in neonates.

Bisphosphonate therapy has been suggested as a first-line therapeutic option in many case reports and series.

Treatment with tumor necrosis factor alpha antagonists (TNF inhibitors) have been tried in few patients with limited success. Other drugs that are used in psoriatic arthritis, to which SAPHO syndrome is closely related, have also been used in this condition. They include NSAIDs, corticosteroids, sulfasalazine, methotrexate, ciclosporin and leflunomide.

Some patients have responded to antibiotics. The rationale for their use is that Propionibacterium acnes, a bacterium known for its role in acne, has been isolated from bone biopsies of SAPHO patients.

In children, the long bones are usually affected. In adults, the vertebrae and the pelvis are most commonly affected.

Acute osteomyelitis almost invariably occurs in children because of rich blood supply to the growing bones. When adults are affected, it may be because of compromised host resistance due to debilitation, intravenous drug abuse, infectious root-canaled teeth, or other disease or drugs (e.g., immunosuppressive therapy).

Osteomyelitis is a secondary complication in 1–3% of patients with pulmonary tuberculosis. In this case, the bacteria, in general, spread to the bone through the circulatory system, first infecting the synovium (due to its higher oxygen concentration) before spreading to the adjacent bone. 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 (fungal) 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, Pott's disease.

The "Burkholderia cepacia" complex has been implicated in vertebral osteomyelitis in intravenous drug users.

In the pediatric age group, the marrow in the phalangeal bones are still active, a conducive place for the tuberculous bacilli to multiply. Slowly, the whole marrow space gets involved and this underlying granulomatous disease leads to expansion of the overlying soft cortex. Finally there is a fusiform dilation of the bone, with thinned out cortex and destruction of the marrow space leading to a balloon like shape; this cystic type of expansion of the bone is termed as spina ventosa.

There is debate as to the cause, although hematogenous seeding of the offending organism is favored as well as direct spread. It is important to differentiate between spontaneous discitis which is usually from hematologic spread from a urinary or respiratory infection versus that from a post-operative complication which usually involves skin flora such as staph aureus.

It can be caused due to spinal tuberculosis and spread along spinal ligament to involve the adjacent anterior vertebral bodies, causing angulation of the vertebrae with subsequent kyphosis.

The cause may be aseptic.

Tuberculous dactylitis is a skeletal manifestation of tuberculosis, one of the commonest bacterial osteitis. It affects children more often than adults. The first radiological description of the condition is credited to Feilchenfeld in 1896; however, the first histological description was given by Rankin in 1886. Multiple bones are involved in children and usually only a single bone is involved in adults suffering from tuberculous dactylitis. Tuberculous dactylitis affects the short tubular bones of the hands and feet in children. It often follows a mild course without fever and acute inflammatory signs as opposed to acute osteomyelitis. There may be a gap of a few months to 2 to 3 years from the time of initial infection to the point of diagnosis.

Spina ventosa is the term given for tuberculous dactylitis. Nearly 85% of the patients of spina ventosa are below 6 years of age.The bones of hands are more commonly involved than those of the feet. Proximal phalanx of the index and middle fingers are the commonest sites of involvement.Up to nearly 7% of children with pulmonary tuberculosis may develop this condition. Spread to the skeletal system is believed to occur via blood and lymphatics.

Osteomyelitis (OM) is an infection of bone. Symptoms may include pain in a specific bone with overlying redness, fever, and weakness. The long bones of the arms and legs are most commonly involved in children while the feet, spine, and hips are most commonly involved in adults.

The cause is usually a bacterial infection and rarely a fungal infection. It may occur via spread from the blood or from surrounding tissue. Risks for developing osteomyelitis include diabetes, intravenous drug use, prior removal of the spleen, and trauma to the area. Diagnosis is typically suspected based on symptoms. This is then supported by blood tests, medical imaging, or bone biopsy.

Treatment often involves both antimicrobials and surgery. In those with poor blood flow, amputation may be required. With treatment outcomes are often generally good when the condition has only been present a short time. About 2.4 per 100,000 people are affected a year. The young and old are more commonly affected. Males are more commonly affected than females. The condition was described at least as early as the 300s BC by Hippocrates. Before the availability of antibiotics the risk of death was significant.

An infectious bone disease is a bone disease primarily associated with an infection.

An example is osteomyelitis.

Erdheim–Chester disease (also known as Erdheim–Chester syndrome or polyostotic sclerosing histiocytosis) is a rare disease characterized by the abnormal multiplication of a specific type of white blood cells called histiocytes, or tissue macrophages (technically, this disease is termed a non-Langerhans-cell histiocytosis). Onset typically is in middle age. The disease involves an infiltration of lipid-laden macrophages, multinucleated giant cells, an inflammatory infiltrate of lymphocytes and histiocytes in the bone marrow, and a generalized sclerosis of the long bones.

Discitis or diskitis is an infection in the intervertebral disc space that affects different age groups. In adults it can lead to severe consequences such as sepsis or epidural abscess but can also spontaneously resolve, especially in children under 8 years of age. Discitis occurs post surgically in approximately 1-2 percent of patients after spinal surgery.

A Brodie abscess is a subacute osteomyelitis, which may persist for years before converting to a frank osteomyelitis. Classically, this may present after conversion as a draining abscess extending from the tibia out through the shin. Occasionally acute osteomyelitis may be contained to a localized area and walled off by fibrous and granulation tissue. This is termed Brodie's abscess.

Most frequent causative organism is Staphylococcus aureus.

Overall, the incidence of dry socket is about 0.5–5% for routine dental extractions, and about 25–30% for impacted mandibular third molars (wisdom teeth which are buried in the bone).

Females are more frequently affected than males, but this appears to be related to oral contraceptive use rather than any underlying gender predilection. The majority of dry sockets occur in individuals aged between 20 and 40 which is when most dental extractions occur, although for any given individual it is more likely to occur in with increasing age.

Other possible risk factors include periodontal disease, acute necrotizing ulcerative gingivitis, local bone disease, Paget's disease of bone, osteopetrosis, cemento-osseous dysplasia, a history of previously developing a dry socket with past extractions and inadequate oral hygiene. Other factors in the postoperative period that may lead to loss of the blood clot include forceful spitting, sucking through a straw, and coughing or sneezing.

Other factors such as toxicants can adversely impact bone cells. Infections, chronic or acute, can affect blood flow by inducing platelet activation and aggregation, contributing to a localized state of excess coagulability (hypercoagulability) that may contribute to clot formation (thrombosis), a known cause of bone infarct and ischaemia. Exogenous estrogens, also called hormonal disruptors, have been linked with an increased tendency to clot (thrombophilia) and impaired bone healing.

Heavy metals such as lead and cadmium have been implicated in osteoporosis. Cadmium and lead promotes the synthesis of plasminogen activator inhibitor-1 (PAI-1) which is the major inhibitor of fibrinolysis (the mechanism by which the body breaks down clots) and shown to be a cause of hypofibrinolysis. Persistent blood clots can lead to congestive blood flow (hyperemia) in bone marrow, impaired blood flow and ischaemia in bone tissue resulting in lack of oxygen (hypoxia), bone cell damage and eventual cell death (apoptosis). Of significance is the fact that the average concentration of cadmium in human bones in the 20th century has increased to about 10 times above the pre-industrial level.

The first three cases of bisphosphonate-associated osteonecrosis of the jaw were spontaneously reported to the FDA by an oral surgeon in 2002, with the toxicity being described as a potentially late toxicity of chemotherapy. In 2003 and 2004, three oral surgeons independently reported to the FDA information on 104 cancer patients with bisphosphonate-associated osteonecrosis of the jaw seen in their referral practices in California, Florida, and New York. These case series were published as peer-reviewed articles — two in the "Journal of Oral and Maxillofacial Surgery" and one in the "Journal of Clinical Oncology". Subsequently, numerous instances of persons with this ADR were reported to the manufacturers and to the FDA. By December 2006, 3607 cases of people with this ADR had been reported to the FDA and 2227 cases had been reported to the manufacturer of intravenous bisphosphonates.

The International Myeloma Foundation's web-based survey included 1203 respondents, 904 patients with myeloma and 299 with breast cancer and an estimate that after 36 months, osteonecrosis of the jaw had been diagnosed in 10% of 211 patients on zoledronate and 4% of 413 on pamidronate. A population based study in Germany identified more than 300 cases of osteonecrosis of the jaw, 97% occurring in cancer patients (on high-dose intravenous bisphosphonates) and 3 cases in 780,000 patients with osteoporosis for an incidence of 0.00038%. Time to event ranged from 23–39 months and 42–46 months with high dose intravenous and oral bisphosphonates. A prospective, population based study by Mavrokokki "et al.". estimated an incidence of osteonecrosis of the jaw of 1.15% for intravenous bisphosphonates and 0.04% for oral bisphosphonates. Most cases (73%) were precipitated by dental extractions. In contrast, safety studies sponsored by the manufacturer reported bisphosphonate-associated osteonecrosis of the jaw rates that were much lower.

Although the majority of cases of ONJ have occurred in cancer patients receiving high dose intravenous bisphosphonates, almost 800 cases have been reported in oral bisphosphonate users for osteoporosis or Pagets disease. In terms of severity most cases of ONJ in oral bisphosphonate users are stage 1–2 and tend to progress to resolution with conservative measures such as oral chlorhexidine rinses.

Owing to prolonged embedding of bisphosphonate drugs in the bone tissues, the risk for BRONJ is high even after stopping the administration of the medication for several years.

This form of therapy has been shown to prevent loss of bone mineral density (BMD) as a result of a reduction in bone turnover. However, bone health entails quite a bit more than just BMD. There are many other factors to consider.

In healthy bone tissue there is a homeostasis between bone resorption and bone apposition. Diseased or damaged bone is resorbed through the osteoclasts mediated process while osteoblasts form new bone to replace it, thus maintaining healthy bone density. This process is commonly called remodelling.

However, osteoporosis is essentially the result of a lack of new bone formation in combination with bone resorption in reactive hyperemia, related to various causes and contributing factors, and bisphosphonates do not address these factors at all.

In 2011, a proposal incorporating both the reduced bone turnover and the infectious elements of previous theories has been put forward. It cites the impaired functionality of affected macrophages as the dominant factor in the development of ONJ.

In a systematic review of cases of bisphosphonate-associated ONJ up to 2006, it was concluded that the mandible is more commonly affected than the maxilla (2:1 ratio), and 60% of cases are preceded by a dental surgical procedure. According to Woo, Hellstein and Kalmar, oversuppression of bone turnover is probably the primary mechanism for the development of this form of ONJ, although there may be contributing co-morbid factors (as discussed elsewhere in this article). It is recommended that all sites of potential jaw infection should be eliminated before bisphosphonate therapy is initiated in these patients to reduce the necessity of subsequent dentoalveolar surgery. The degree of risk for osteonecrosis in patients taking oral bisphosphonates, such as alendronate (Fosamax), for osteoporosis is uncertain and warrants careful monitoring. Patients taking dexamethasone and other glucocorticoids are at increased risk.

Matrix metalloproteinase 2 may be a candidate gene for bisphosphonate-associated osteonecrosis of the jaw, since it is the only gene known to be associated with bone abnormalities and atrial fibrillation, both of which are side effects of bisphosphonates.