NORD gratefully acknowledges Olivia Ganescu, MD Candidate, McGill University School of Medicine, and Michael Anderson, MD, Infectious Disease Physician, Kankakee, IL, for assistance in the preparation of this report.
Osteomyelitis can be broken down into “osteo” meaning bone, and “myelitis”, meaning inflammation of the fatty tissues within the bone. Osteomyelitis is caused by an infection of the bone or joint, and can be both acute and chronic. It can occur at any age and involve any bone. These infections can be due to one, or many types of bacteria and/or fungi. In order of frequency, osteomyelitis can be the result of a trauma, surgery, or joint insertion or any type of prosthetic material; it can be due to lack of blood flow in diabetes associated foot infections, or it can be the result of an infection that has spread via the blood and has reached the bone (seen mostly in prepubescent children or the elderly).
Among children and teens, the long bones of the legs and arms are most frequently affected. In adults, osteomyelitis most often affects the vertebrae of the spine and/or the hips. However, extremities are frequently involved due to skin wounds, trauma and surgeries. The prevalence of this disease depends on the age group and disease category in question. With respect to the blood-related spread of infection to the bone, which is the most common type in children, the United States estimates 2-5 cases per 10,000 people, with an estimated higher incidence in developing countries. Older adults are more prone to osteomyelitis because they experience more disorders that can lead to infection, namely orthopedic surgeries and diabetes mellitus.
The overall observed trend in osteomyelitis is that it has been increasing over the last few decades. This could be because we have gotten better at diagnosing osteomyelitis, but also because the prevalence of certain risk factors is increasing, namely diabetes. Osteomyelitis patients may present with many symptoms, ranging from an open wound that exposes fractured bone, to no obvious skin lesion but with associated swelling, bone pain, lower extremity warmth, and tenderness when examined. With the appropriate diagnostics, antibiotics can make up the effective treatment regimen, but may include the surgical removal of dead bone in chronic osteomyelitis.
Osteomyelitis is one of the oldest diseases ever recorded. Evidence of the disease has been found in the fractured spine of a Permian reptile, close to 250 million years ago. This evidence consisted of bone inflammation based on the roughened swollen area above the fracture, hinting that the injury was in fact infected. Hippocrates (460-370 BC) also recognized infection after bone fracture, but it was only in 1773 that an Englishman named William Bromfield published on the observed “abcessus in medulla”, referring to the infected fatty tissues within the inner cavity of the bone. In 1844, French physician and renowned surgeon Auguste Nélaton coined the term “osteomyelitis”, which described an infectious condition of the entire bone, but included “itis” in the word so as to make reference to the inflammatory damage. Bone is usually good at fighting infection, but trauma, bacteremia, surgery, or foreign body insertion may disrupt blood flow and lead to the development of osteomyelitis. Early diagnosis is very important because fast antibiotic delivery may prevent permanent bone loss.
Acute osteomyelitis is a serious bone inflammation that can result from a previous trauma, puncture wound, surgery, bone fracture, abscessed tooth, or infection of soft tissue, the ear or sinus. Osteomyelitis can be the result of a spreading infection in the blood (hematogenous) and occurs more often in children than adults. In prepubescent children, it usually affects the long bones: the tibia and the femur. The most common site of infection is the metaphysis, which is the narrow portion of the long bone). In adults, the bones of the spinal column (vertebra) are often affected.
Initially there may be several days of fever, pain at the site of infection, and a generalized feeling of ill health (malaise). This may be followed by an increase in fever (104-105 degrees Fahrenheit), deep localized bone pain, chills, sweating, swelling and painful or limited movement of the nearby joints. The skin near the affected bone may be red (erythema) and there may be a purulent buildup (pus), loss of calcium, destruction of the surrounding tissue (necrosis) and bone deterioration or deformity. However, patients with osteomyelitis involving the hip, vertebrae, and/or pelvis are less likely to present with many signs other than pain. In long bone infections, if the infection spreads from the metaphysis through the bone cortex and within the joint capsular reflection of knee, any discharge of pus into the joint can present as septic arthritis secondary to osteomyelitis. These joints include the knees, wrists hip, ankles, symphysis pubis, and shoulders.
Chronic osteomyelitis usually occurs after an acute episode of osteomyelitis when the infection has not been totally cured, and is sometimes associated with a draining sinus tract. There may be bone pain, swelling, redness and tenderness of the affected area. A discharge of pus from an opening to the infected bone is often the first symptom. There may also be destruction of the bone with pieces of the infected bone separating from the healthy bone. When this occurs, surgery to remove the bone fragments may be necessary.
Spinal infections, referring to vertebral osteomyelitis, are most commonly distributed or spread by way of the bloodstream, or present as post-surgical complications. These spinal infections are often characterized by chronic back pain not relieved by ordinary treatment, including bed rest, heat or pain relievers. There may be fever, localized tenderness, pain, muscle spasms and limited movement. Any patients with known fever, weight loss, bacteremia and/or endocarditis should be sent for spinal imaging if they are experiencing new or worsening back pain. This form of osteomyelitis usually affects people over 50 years of age, and is usually caused by a previous injury, urinary tract infection, inflammation of the lining of the heart (endocarditis) or drug addiction. (For more information on this disorder, choose “Endocarditis” as your search term in the Rare Disease Database.)
Anaerobic osteomyelitis often affects the lower jawbone (mandible), skull or feet. It is characterized by ulceration and swelling, foul smelling drainage and redness of the affected area.
Diabetic foot infections can progress into osteomyelitis as a result blood vessel insufficiency. These infections usually occur following skin ulcerations in patients with nerve damage (neuropathy). This phenomenon is more common in people with diabetes mellitus or vascular diseases affecting the extremities, especially the toes and small bones of the feet. It is usually seen in people over 50 years old and is characterized by pain and redness of the affected area (erythema), swelling, ulcerations, and drainage of pus. This type of osteomyelitis is difficult to treat because of the underlying vascular disorder that can impair the therapeutic effect of antibiotic treatment.
Traditionally, osteomyelitis is a bone infection that has been classified into three categories: (1) a bone infection that has spread through the blood stream (Hematogenous osteomyelitis) (2) osteomyelitis caused by bacteria that gain access to bone directly from an adjacent focus of infection (seen with trauma or surgery) and (3) osteomyelitis that is the result of diabetic foot infection or any other reason for diminished blood supply to the bones. Therefore, risk factors of bone vulnerability to osteomelitis include recent trauma, having diabetes, being on hemodialysis, intravenous drug abuse, and having had one’s spleen removed. Osteomyelitis is an infection frequently caused by Staphylococcus bacteria. While some cases of osteomyelitis are of unknown causes, the infection is usually transmitted through the bloodstream from one area of the body to another (Hematogenous osteomyelitis). These blood infections are commonly due to Staphylococcus aureus, Streptococcus species, and aerobic Gram-negative bacilli. If the patient has a compromised immune system, M tuberculosis, Brucella species and fungi should be included as possible causing agents in the disease work-up.
Polyarticular septic arthritis can be associated with osteomyelitis, and is the result of pus discharge into the joints. The deposition of pus therefore leads to septic arthritis, and so the patient can experience chills, fatigue, fever, inability to move the limb with the infected joint because of severe pain, swelling, and warmth to the touch. Septic arthritis is more common in patients with inflammatory joint disease or those experiencing an overwhelming systemic bacterial infection (sepsis). Injection drug use is also a risk factor for septic arthritis, and is often also associated with endocarditis.
Osteomyelitis is a prevalent condition that affects males and females in equal numbers. Osteomyelitis more commonly affects people younger than 20, or adults older than 50 years of age. While there is a higher incidence of bone infections in adults that live in developing countries, hemodialysis patients, injection drug users, and patients with diabetes are also more susceptible to this infection. Osteomyelitis that is the result of an infection that has spread through the blood occurs more commonly in children than adults. Inoculation or direct osteomyelitis tends to happen more in younger individuals in the setting of trauma and related surgery. When direct osteomyelitis does occur in adults, it is usually secondary to an infected ulcer from diabetes or an infection from a total joint replacement.
Making the appropriate osteomyelitis diagnosis is critical to providing fast and adequate treatment. Different imaging techniques play a key role in early diagnosis and follow-up. Symptoms of osteomyelitis can resemble those of many other bone disorders. Bone scans and bone biopsies are tests that help diagnose this disorder so that treatment can be started immediately.
The diagnosis of osteomyelitis is usually established using a bacterial culture from a bone biopsy, in combination with markers from the histology report, and findings of inflammations and/or osteonecrosis. In the setting of a positive bacterial culture and radiographic findings indicative of osteomyelitis, a bone biopsy may not be required.
Diagnosing chronic osteomyelitis can prove to be challenging when prosthetic material, skin or soft tissue ulceration, or vascular insufficiency is present. However, a draining sinus tract is almost always diagnostic of chronic osteomyelitis. Additional presentations of chronic osteomyelitis include fractures that do not heal, and Brodie’s abscess (a particular form of chronic osteomyelitis that follows an acute attack of an organism whose virulence is evenly matched by the patients’ resistance). Brodie’s abscess is also referred to as a distinct form of subacute osteomyelitis.
Clinical Testing and Work-Up
The clinical approach of patients presenting with suspected osteomyelitis including obtaining a proper history and physical exam, and assessing for any predisposing factors, including diabetes, vascular pathologies, any history of recent procedures, injection drug use, and any associated trauma. If osteomyelitis is suspected based on clinical history and other physical findings, plain radiographs of the involved bones, laboratory evaluation for inflammation, and blood cultures can be ordered. If the patient is diabetic and has symptoms referable to the foot, or if the patient has symptoms referable to the spine, then magnetic resonance imaging (MRI) is the test of choice.
In diabetic patients, the probe-to-bone test can also be used as a screening tool for suspected osteomyelitis. The basis of this test is if a probe can reach the bone, so might bacteria. The probe-to-bone test has been shown to help rule in diabetic foot osteomyelitis in high-risk patients, and help rule it out in low-risk patients. It is however not a diagnostic tool.
Radiographic findings do not indicate the need for a bone biopsy unless the blood cultures are positive for bacteria such as Staphylococcus aureus or Pseudomonas aeruginosa. Bacterial culture from a bone biopsy can then be used to direct antimicrobial therapy. In the absence of any evidence found on the MRI or CT scan, osteomyelitis is unlikely.
The treatment of osteomyelitis depends on the extent of the infection. It might be necessary to drain and clean the infected area surgically and then continue treatment with antibiotic therapy. In some cases, a bone graft may be necessary.
In order to prevent osteomyelitis in adults following open trauma, prophylactic antibiotics should be given intravenously (via IV) to reduce the risk of soft tissue infection. If possible, antibiotic therapy should be tailored to the findings of the tissue culture. However, if the patient is not stable, and the culture results are not obtainable, then broad-spectrum antibiotics should be given. If and after the infectious organism has been identified, osteomyelitis is usually treated with massive doses of the appropriate antibiotic regiment. Treatment with intravenous delivery of antibiotics is not uncommon, even though some of the newer antibiotics are effective when administered orally.
The antibiotic treatment may last from several days to a few weeks, but the therapy duration is not certain and is usually individualized based on a given patient’s progress. Antibiotic therapy of osteomyelitis usually requires prolonged regimen of medication, typically in the form of outpatient IV antibiotics. Many experts favor IV antimicrobial therapy for up to 6 weeks from when the site of infection was drained and cleaned surgically. This is especially true in patients with vascular diseases, because the antibiotics have more trouble reaching the bone, and so a prolonged regime is favored.
It is most important that diabetics and those with vascular disorders be treated as quickly as possible for suspected osteomyelitis. If left untreated, this disorder can result in destruction of the bone and surrounding tissue and may lead to amputation of the affected toes or foot. Other treatment is symptomatic and supportive. Any prosthetic joint infection must be treated with immediate prosthesis removal and re-implantation.
Additional therapies include hyperbaric oxygen and negative pressure wound therapy (vacuum-assisted closure). This is because the oxygen may help the immune cells to function, since osteomyelitis is associated with reduced blood flow and limited oxygen access in the infected bone tissue.
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