Chronic multifocal osteomyelitis is a long-lasting inflammation of several bones that comes and goes over time. It usually happens in children and teenagers, and it is not caused by germs such as bacteria. Instead, it is part of a group of “autoinflammatory” bone diseases, where the immune system attacks the bone by mistake.
Chronic multifocal osteomyelitis (also called chronic non-bacterial osteomyelitis or chronic recurrent multifocal osteomyelitis) is a long-lasting, autoinflammatory bone disease. It causes repeated episodes of bone pain, swelling, and sometimes fractures, usually in children and teenagers. Medicines are the main treatment, but non-drug therapies, diet, surgery, and careful follow-up are also important. Current recommendations are based on expert consensus, case series, and small studies rather than large trials.
Doctors often use the name “chronic multifocal osteomyelitis” when there is more than one bone spot that is inflamed and the problem lasts for months or years. Many experts now use the wider name “chronic nonbacterial osteomyelitis (CNO)” for the whole group of these sterile bone inflammations, and “chronic recurrent multifocal osteomyelitis (CRMO)” for the more severe form with repeated attacks at many bone sites.
Other names you may see
Chronic multifocal osteomyelitis can appear in medical books and articles under different names. These include: chronic nonbacterial osteomyelitis (CNO), chronic recurrent multifocal osteomyelitis (CRMO), chronic non-bacterial osteitis, chronic sterile osteomyelitis, and autoinflammatory bone disease. All of these describe bone inflammation without infection that tends to last a long time and may affect many bones.
Types of chronic multifocal osteomyelitis
Doctors now think of chronic multifocal osteomyelitis as part of a “spectrum” of chronic nonbacterial osteomyelitis. This means there are milder and more severe forms, and some forms are linked with genetic syndromes or other inflammatory diseases.
Single-focus CNO – Only one bone is inflamed. Pain and swelling stay in one place, such as one leg bone. This can later spread to more bones and become multifocal.
Chronic multifocal osteomyelitis / CRMO – Several bones are affected at the same time or in repeated episodes. Pain can move from one area to another, and flares may come and go over years.
Spinal-involving CNO/CRMO – In some patients, the spine bones (vertebrae) are inflamed. This can cause back pain and, in severe cases, small fractures that may change the shape of the spine.
Syndromic forms (with a known gene change) – Some rare inherited conditions include chronic multifocal osteomyelitis as part of a larger syndrome, for example Majeed syndrome (LPIN2 mutation) or deficiency of the IL-1 receptor antagonist (DIRA). These children often have bone inflammation plus other problems like anemia or skin rashes.
CNO/CRMO associated with other inflammatory diseases – Many patients also have psoriasis, inflammatory bowel disease, acne, or arthritis. In these patients, chronic multifocal osteomyelitis is one sign of a wider inflammatory condition in the body.
Causes of chronic multifocal osteomyelitis
Doctors agree that there is no single simple cause, like one germ or one injury, for chronic multifocal osteomyelitis. Instead, the disease seems to happen when genes, the immune system, and outside triggers all act together. Many of the “causes” below are better described as risk factors or underlying mechanisms.
Autoinflammatory bone disease mechanism
Chronic multifocal osteomyelitis is now classed as an autoinflammatory bone disease. This means cells of the “innate” immune system, which normally fight early infections, become overactive and cause bone inflammation without germs.Genetic susceptibility
Studies in affected families and animal models show that changes in several genes can make bone inflammation more likely. These genes affect pathways such as TLR4, MAPK, and the NLRP3 inflammasome, which control how strongly the immune system reacts.Imbalance of inflammatory cytokines (IL-1, TNF-α, IL-10)
Patients often show too much pro-inflammatory cytokines like IL-1 and TNF-α and too little anti-inflammatory cytokines like IL-10. This imbalance may let inflammation in the bone continue for a long time instead of switching off.Family history of autoimmune or autoinflammatory disease
Chronic multifocal osteomyelitis is more common in families where close relatives have psoriasis, inflammatory bowel disease, arthritis, or other autoimmune illnesses. This suggests shared genetic and immune risk factors.Psoriasis and psoriatic arthritis
Many patients have skin psoriasis or psoriatic arthritis along with multifocal osteomyelitis. In these cases, the same immune pathways that inflame the skin and joints may also inflame the bone.Inflammatory bowel disease (IBD)
Chronic multifocal osteomyelitis is reported in children with Crohn’s disease or ulcerative colitis. Gut inflammation and bone inflammation seem to be linked through shared immune signals and microbes in the intestine.Arthritis and spondyloarthritis
Some patients have juvenile idiopathic arthritis or spondyloarthritis (spine-related arthritis). The same inflammatory cells that damage joints can also attack nearby bone, leading to chronic multifocal osteomyelitis.SAPHO-like disease (synovitis, acne, pustulosis, hyperostosis, osteitis)
In older children and adults, chronic multifocal osteomyelitis may be part of SAPHO syndrome, which combines bone inflammation with severe acne or palmoplantar pustulosis. Here, bone osteitis is one part of a wider inflammatory syndrome.Majeed syndrome (LPIN2 mutation)
Majeed syndrome is a rare inherited disease where children have chronic multifocal osteomyelitis, anemia, and skin inflammation. A change in the LPIN2 gene leads to over-active inflammasome pathways and sterile bone inflammation.Deficiency of IL-1 receptor antagonist (DIRA)
In DIRA, a mutation stops the body from making a natural blocker of IL-1. Without this protector, IL-1 activity is unchecked, causing severe sterile bone inflammation and skin disease in infancy that resembles aggressive multifocal osteomyelitis.Other monogenic autoinflammatory syndromes
Other very rare genetic syndromes that affect the inflammasome or related immune pathways can also present with recurrent multifocal bone lesions. In these children, bone disease is one manifestation of a broader autoinflammatory problem.Minor bone trauma as a trigger
Some patients report that pain started after a minor injury, such as a sports knock. Small injuries may not cause the disease by themselves but can trigger an attack in someone whose immune system is already at risk.Infections elsewhere in the body (possible trigger, not direct cause)
A viral or bacterial infection in another site, like the throat or gut, may wake up the immune system. In genetically susceptible people, the immune system might then mistakenly attack bone, even though no germs are found in the bone itself.Hormonal and growth changes in puberty
The disease most often begins around 10–12 years of age. Rapid growth, hormonal changes, and changing bone turnover during puberty may make bones more sensitive to abnormal immune signals.Female sex as a risk factor
Chronic multifocal osteomyelitis is more common in girls than in boys. This suggests that female hormones or other sex-related factors may increase risk, although the exact reason is not yet known.Abnormal bone remodeling
Inflammation in the bone changes the normal balance between bone-building cells (osteoblasts) and bone-resorbing cells (osteoclasts). This leads to areas of bone destruction and new bone formation, which can be seen on imaging.Association with low-grade chronic systemic inflammation
Many patients have raised inflammatory blood markers, such as ESR and CRP, even when they feel only mild symptoms. This shows that a wider low-grade inflammation in the body contributes to ongoing bone disease.Environmental triggers (unknown)
Research suggests that yet-unknown environmental triggers, such as infections, diet, or other exposures, may help start or worsen the disease in people with genetic risk, but no clear single factor has been proven.Vitamin D and bone health factors (possible modifiers)
Vitamin D is important for healthy bone and immune function. Some reports show low vitamin D levels in patients with chronic osteomyelitis, but it is better seen as a factor that may influence severity, not as a direct cause.Idiopathic nature (cause still unknown)
Even with all these risk factors, in many children no clear single trigger is found. For this reason, chronic multifocal osteomyelitis is still labeled an “idiopathic” condition, meaning that the exact root cause is unknown.
Symptoms of chronic multifocal osteomyelitis
Symptoms can be very different from one patient to another. Some children have only a few painful bone spots, while others have many lesions and general symptoms. Pain often comes in flares that last weeks or months and then calm down.
Deep bone pain
The most common symptom is deep, aching pain in a bone, often in the legs, pelvis, spine, or collarbone. The pain may be constant or may worsen with movement or weight-bearing.Pain worse at night
Many patients say the pain is stronger at night and may wake them from sleep. Night pain can be worrying because it is also seen in infections and tumors, which is one reason doctors investigate carefully.Local swelling over the bone
The skin and tissues over the affected bone may look puffy or swollen. This happens because inflammation brings extra fluid and blood cells into the area.Warmth and redness of the skin
The skin over an active bone lesion may feel warm to the touch and sometimes looks reddish. This is a sign of increased blood flow and inflammation in the area.Limited movement of nearby joints
Because movement hurts, a child may avoid bending a nearby joint, such as the knee or hip. Over time this can make the joint stiff and the muscles weaker unless treated with exercise and therapy.Limping or abnormal gait
When leg bones are affected, the child may limp or refuse to bear weight on that leg. Parents may first notice that their child avoids sports or walks differently.Back pain
If the spine is involved, the child may have persistent back pain. This is important because spinal lesions can sometimes cause compression fractures, which need close monitoring.Chest or shoulder pain and swelling
The clavicle (collarbone) and nearby chest bones are common sites. Pain and swelling here can make it hard to lift the arm or sleep comfortably.Fever
Some children have low-grade fevers during flares. Fever is due to chemicals released by the immune system and can make the child feel unwell, though blood cultures are usually negative.Fatigue and low energy
Chronic pain and inflammation can cause tiredness, poor concentration, and lower school performance. Children may appear more sleepy or less active than before.Weight loss or poor appetite
In some cases, ongoing inflammation and pain reduce appetite, so the child may lose weight or fail to gain weight as expected.Growth problems or limb length difference
When bone lesions affect growth plates, especially in the legs, the affected limb can become slightly shorter or deformed if not treated early.Joint swelling or arthritis
Some patients develop true arthritis in joints close to the bone lesions. Joints may become swollen, stiff, and painful, adding to disability.Skin problems (psoriasis, acne, pustules)
In syndromic forms, there may be psoriasis patches, severe acne, or pustules on the palms and soles. These skin signs can help doctors suspect an underlying autoinflammatory disease.Emotional distress and mood changes
Long-lasting pain, investigations, and limits on activity can cause sadness, anxiety, or anger. Good psychological support is important because this is a chronic disease.
Diagnostic tests for chronic multifocal osteomyelitis
There is no single “one test” that proves chronic multifocal osteomyelitis. Diagnosis is made by putting together symptoms, examination, imaging, and lab results, and by ruling out infections and cancers. Often, bone biopsy is needed to exclude other serious causes.
Physical exam tests
1. General physical and musculoskeletal examination
The doctor looks at the whole child, checking weight, height, temperature, posture, and how the muscles and joints move. This helps to see how widespread the problem is and whether there are signs of other diseases such as psoriasis or arthritis.
2. Local inspection of painful areas
The doctor carefully inspects the painful limb, spine, or chest area for swelling, skin color changes, differences in size, or deformity. Visible swelling or asymmetry can point to active bone lesions or past damage.
3. Palpation for bone tenderness and swelling
By gently pressing on the bone, the doctor checks for spots that are especially tender. This helps locate the exact site of inflammation, which later guides imaging and biopsy decisions.
4. Joint range-of-motion assessment
The doctor moves nearby joints through their full range to see if movement is limited or painful. Reduced movement can signal involvement of joints or muscles around the affected bone.
5. Neurological screening examination
Simple tests of strength, reflexes, and skin sensation are done, especially when the spine is involved. Changes in reflexes or weakness can suggest pressure on nerves from a vertebral lesion or fracture.
Manual and functional tests
6. Gait and functional tests (walking assessment)
The doctor watches the child walk, run, and stand on toes or heels. A limp, guarding of one leg, or poor balance can show which bones or joints are painful and how much daily function is affected.
7. Spine flexibility tests
Simple bedside tests, such as bending forward, backward, and side-to-side, help check spine flexibility and pain. Limited movement or pain during these actions suggests that vertebrae may be inflamed.
8. Provocative orthopedic maneuvers around affected joints
The doctor may perform special joint tests, such as rotating the hip or performing a straight-leg raise, to see if pain comes from the bone, joint, or soft tissues. This helps separate chronic multifocal osteomyelitis from other orthopedic problems.
Laboratory and pathological tests
9. Complete blood count (CBC)
A CBC measures red and white blood cells and platelets. In chronic multifocal osteomyelitis, white cells may be normal or mildly raised, and anemia can be mild. Very abnormal results may point to leukemia or other conditions instead.
10. Erythrocyte sedimentation rate (ESR)
ESR is a simple blood test that shows how much inflammation is in the body. Many patients have a raised ESR, but this test is not specific and can be high in infections, cancers, and other inflammatory diseases too.
11. C-reactive protein (CRP)
CRP is another marker of inflammation. A raised CRP supports the idea that inflammation is active. However, CRP can be normal in some patients, so a normal value does not rule out chronic multifocal osteomyelitis.
12. Autoimmune and inflammatory panel (e.g., ANA, RF, HLA-B27)
Tests such as antinuclear antibodies (ANA), rheumatoid factor (RF), and HLA-B27 may be done to look for associated autoimmune diseases. Positive results may point to related conditions like juvenile arthritis or spondyloarthritis that occur with the bone disease.
13. Blood cultures
Blood cultures check for bacteria in the blood. They are usually negative in chronic multifocal osteomyelitis, but they are important to rule out true bacterial osteomyelitis, which needs urgent antibiotics.
14. Bone biopsy – histopathology
A small piece of bone is taken under anesthesia and examined under a microscope. In chronic multifocal osteomyelitis, the biopsy shows chronic inflammation with immune cells but no signs of cancer. This step is often essential to exclude tumors and other serious diseases.
15. Microbiological culture of bone tissue
Part of the biopsy sample is sent to the microbiology lab to look for bacteria, mycobacteria, or fungi. In chronic multifocal osteomyelitis, cultures are typically negative, confirming that the inflammation is “sterile.”
Electrodiagnostic test
16. Nerve conduction studies and electromyography (EMG)
These tests are not routine for every patient, but they may be used if spinal lesions cause numbness, weakness, or other nerve symptoms. They measure how well nerves carry signals and help check if bone damage is pressing on the spinal cord or nerve roots.
Imaging tests
17. Plain X-rays of affected bones
X-rays are often the first imaging test. Early X-rays can be normal, but later they may show areas of bone destruction, sclerosis (hardening), or changes around the growth plate. X-rays help exclude fractures and obvious tumors.
18. MRI of the painful area
MRI is very sensitive for detecting bone marrow inflammation and soft tissue swelling. It can show bone lesions before they appear on X-ray and helps guide biopsy to the most active area.
19. Whole-body MRI
Whole-body MRI lets doctors see all bones in one study. It is especially useful in chronic multifocal osteomyelitis because it can detect silent lesions in bones that do not yet hurt, giving a full picture of disease extent without radiation.
20. Bone scintigraphy (bone scan)
A nuclear medicine bone scan uses a small amount of radioactive tracer to show areas of high bone activity. Before whole-body MRI was widely available, bone scans were commonly used to find multiple lesions in chronic multifocal osteomyelitis. They are still helpful when MRI is not available.
Non-pharmacological treatments
1. Education and reassurance for patient and family
A clear explanation of chronic multifocal osteomyelitis helps reduce fear and confusion. The doctor explains that this is a sterile inflammation of bone (not a typical infection) and that many children improve with time and treatment. Understanding the disease makes it easier to follow long-term therapy, attend appointments, and notice early flares. This “therapeutic alliance” between family and care team is the base for all other treatments and can directly lower perceived pain and anxiety.
2. Activity modification and paced rest
During flares, painful bones may need short periods of reduced sports or heavy physical activity. The goal is not complete bed rest, but “pacing”: planning rest breaks between activities so pain does not suddenly become severe. Gentle daily movement is still encouraged to protect joints, muscles, and bone strength. This approach reduces mechanical stress on inflamed bone while preventing stiffness and deconditioning, which would make pain worse later.
3. Individualized physiotherapy (physical therapy)
Physiotherapists teach stretching, strengthening, posture training, and balance exercises adapted to pain level. These exercises keep muscles strong around affected bones, improve joint range of motion, and help the child or adult return safely to school, sports, and daily life. Physio can also correct movement patterns that developed due to limping or guarding, which can otherwise cause new pain in hips, back, or opposite limb.
4. Hydrotherapy or pool-based exercise
Exercising in warm water allows joints and bones to move with less weight and impact. Many patients with bone pain feel they can move more freely in a pool, which helps maintain fitness and flexibility without overloading painful sites. Warm water also relaxes muscles, reduces spasm, and can provide gentle pain relief. Regular pool sessions may improve mood and confidence in physical ability.
5. Occupational therapy (school and daily life support)
Occupational therapists help adapt school, play, and home tasks to pain and fatigue levels. They may suggest ergonomic chairs, writing aids, backpacks with wheels, or modified PE participation plans. The aim is to maintain school attendance and independence while protecting painful bones. They also teach energy-saving strategies so the patient can plan their day and avoid severe end-of-day pain crashes.
6. Custom orthotics, insoles, and braces
Foot orthotics, ankle-foot orthoses, or spinal braces may be used when bone lesions affect the legs, feet, or spine. These devices redistribute weight, improve alignment, and stabilize painful segments. For example, a brace for vertebral involvement can help protect weakened vertebrae and reduce risk of compression fractures while medical treatment lowers inflammation. Any brace should be fitted by a specialist and combined with exercises.
7. Heat and cold therapy
Warm packs, warm showers, or heating pads can relax tense muscles around painful bones and reduce stiffness, especially in the morning. Cold packs or cool gel packs may help during acute flares by numbing pain and reducing swelling. These simple methods are low-risk when used correctly (wrapped in cloth, limited time) and can be repeated several times a day as part of a home pain plan.
8. Cognitive-behavioural therapy (CBT) for chronic pain
Chronic pain changes how the brain processes signals. CBT helps patients notice unhelpful thoughts (“I will never get better”) and replace them with coping skills and realistic goals. Relaxation techniques, distraction, and positive activity scheduling can reduce pain intensity, improve sleep, and support school and social life. Psychological support is especially important in long-lasting diseases like chronic multifocal osteomyelitis.
9. Mind-body techniques (relaxation, breathing, mindfulness)
Slow breathing, progressive muscle relaxation, guided imagery, and simple mindfulness exercises help calm the nervous system. When the body is less tense and anxious, pain messages are often felt as less intense. These techniques can be taught by psychologists, nurses, or apps and used at home before sleep, during flares, or before procedures such as MRI scans.
10. Structured sleep hygiene programme
Poor sleep amplifies pain and fatigue. A regular sleep schedule, limiting screens before bed, keeping the bedroom dark and quiet, and avoiding large late-night meals are basic but powerful tools. Sometimes, timing of medicines (for example, taking anti-inflammatory drugs with the evening meal) can also support better night-time comfort, following doctor advice. Better sleep can reduce daytime pain and improve school performance.
11. Weight-bearing and strengthening for bone health
Under medical guidance, gentle weight-bearing activities like walking, light step-ups, and age-appropriate resistance exercises help maintain bone mineral density. This is important because inflammation, reduced activity, and some medicines (like steroids) can weaken bones. A tailored exercise plan protects against fractures and deformity while avoiding over-loading painful lesions.
12. School and exam accommodations
Letters from the rheumatology team can support extra test time, rest breaks, flexible PE, and help with carrying books. These adjustments reduce stress and physical strain, which can otherwise worsen pain. Staying engaged with education also protects mental health and future opportunities, which are key parts of long-term quality of life.
13. Social work and family support services
Chronic disease can affect finances, travel to hospitals, and family stress. Social workers help connect families with transport support, financial help, school counselling, and peer support groups. Reducing practical stress makes it easier to keep up with treatment and attend specialist appointments, which indirectly improves disease control.
14. Peer support and patient groups
Meeting other patients with chronic non-bacterial osteomyelitis (in person or online, through safe and moderated groups) can reduce loneliness and fear. Families can share tips about daily life, school, and coping with flares. Peer experiences never replace medical advice, but they can improve hope and resilience, which are crucial in a long-lasting, fluctuating disease.
15. Falls-prevention and safety training
When bones are painful or weakened, balance may be affected. Simple safety strategies—good lighting at home, avoiding slippery floors, using handrails on stairs, and choosing appropriate footwear—can help prevent falls and fractures. Physiotherapists may add balance exercises like single-leg stands to further reduce risk.
16. Pain education (“pain neuroscience education”)
Explaining how chronic pain works in the nervous system—using simple language, drawings, or videos—helps patients understand that pain does not always mean new damage. This reduces fear of movement and supports gentle exercise. When patients know that inflammation, nervous system sensitivity, and mood all interact, they are more likely to follow a combined treatment plan instead of relying only on medicines.
17. Nutritional counselling for bone and overall health
Dietitians can build a balanced eating plan rich in calcium, vitamin D, protein, fruits, and vegetables, with limited ultra-processed foods and sugary drinks. This supports bone repair, immune function, and healthy weight. Adequate nutrition also helps the body tolerate long-term medicines and reduces the risk of deficiency-related complications.
18. Smoking cessation and avoidance of second-hand smoke
In older teens and adults, stopping smoking is vital. Tobacco smoke harms blood vessels, reduces bone healing, and increases infection risk. Second-hand smoke also reduces overall health in children living in the same household. Stopping exposure supports better response to all other treatments and lowers long-term cardiovascular risk.
19. Vaccination optimisation
Because some patients need immune-modifying drugs, updating routine vaccines (especially influenza and pneumococcal vaccines) is important. Doctors follow national guidelines about live vaccines in patients on biologic therapies. Good vaccination status lowers risk of serious infections, which can complicate treatment or be confused with infection-related bone disease.
20. Regular multidisciplinary follow-up in a specialist centre
Best outcomes usually occur when rheumatologists, orthopaedic surgeons, radiologists, physiotherapists, psychologists, and nurses work together in a structured clinic. They monitor pain, imaging, growth, and side effects, and adjust therapy step by step (NSAIDs, then bisphosphonates or DMARDs/biologics). A standardised follow-up plan helps detect vertebral involvement early and protect the growing skeleton.
Drug treatments
Important: All medicines and doses must be chosen by a qualified doctor or paediatric rheumatologist. Never start, stop, or change any medicine on your own. Information below is simplified and often based on adult label data; real doses depend on age, weight, kidney function, and other illnesses.
1. Ibuprofen (NSAID)
Ibuprofen is a non-steroidal anti-inflammatory drug that blocks cyclo-oxygenase (COX) enzymes and lowers prostaglandin production, which reduces pain, swelling, and fever. It is often used as a first-line medicine for chronic multifocal osteomyelitis, given several times a day with food at an anti-inflammatory dose decided by the doctor. Common side effects include stomach upset, ulcers, kidney strain, and increased cardiovascular risk at high long-term doses, so monitoring is needed.
2. Naproxen (NSAID)
Naproxen is another NSAID used as a core treatment in many patients who have chronic bone inflammation. It works in a similar way to ibuprofen by blocking COX-mediated prostaglandin synthesis, but has a longer half-life, so it is often given twice daily with food. Doctors balance the benefit in pain and stiffness against risks such as stomach bleeding, kidney problems, and cardiovascular events described in the FDA label.
3. Other NSAIDs or COX-2 inhibitors (e.g., diclofenac, celecoxib)
If standard NSAIDs fail or cause side effects, doctors may try alternative NSAIDs or COX-2 selective drugs to find a better tolerated option. These medicines still target prostaglandin pathways but may have different gastrointestinal and cardiovascular risk profiles. The choice depends on patient age, history of ulcers, heart disease, and local guidelines. Regular review is essential because many children still flare on NSAIDs alone.
4. Short courses of oral corticosteroids (e.g., prednisone)
Glucocorticoids like prednisone are sometimes used in short “bursts” to quickly control severe flares or spinal lesions. They act by broadly suppressing inflammatory cytokines and immune cell activity, which can rapidly reduce pain and swelling. Because long-term steroids cause weight gain, high blood pressure, diabetes, osteoporosis, and infection risk, most guidelines recommend the lowest effective dose for the shortest time, then tapering as other drugs take effect.
5. Methotrexate (conventional DMARD)
Methotrexate is a conventional disease-modifying anti-rheumatic drug (DMARD) used off-label for chronic non-bacterial osteomyelitis when NSAIDs are not enough. It interferes with folate metabolism in rapidly dividing immune cells, reducing inflammation over weeks to months. It is usually given once weekly by mouth or injection, together with folic acid to reduce side effects such as nausea, mouth ulcers, liver enzyme elevations, and bone-marrow suppression. Regular blood tests are mandatory.
6. Sulfasalazine (conventional DMARD)
Sulfasalazine combines an aspirin-like molecule with a sulfa component and is used for some children with peripheral joint involvement or coexisting inflammatory bowel disease. In the gut, it is broken down into active parts that modulate the immune response and lower inflammatory mediators. It can help reduce bone pain and systemic symptoms in some patients but may cause rash, low blood counts, or liver issues, so monitoring is required.
7. Pamidronate (intravenous bisphosphonate)
Pamidronate is a bisphosphonate that binds strongly to bone mineral and inhibits osteoclast-mediated bone resorption. In chronic multifocal osteomyelitis, intermittent intravenous infusions of pamidronate have been shown to rapidly reduce pain and MRI inflammation, especially in vertebral disease, and to improve vertebral shape and density. Treatment cycles are spaced weeks to months apart in hospital. Possible side effects include flu-like symptoms after infusion, low calcium, and rare jaw bone problems, as described in its FDA label.
8. Zoledronic acid (intravenous bisphosphonate)
Zoledronic acid is a more potent bisphosphonate sometimes used in place of pamidronate in specialist centres. It has similar mechanisms—binding to bone and blocking osteoclast activity—but can be given less often. Small series suggest benefit in pain and bone lesions in CNO/CRMO, but data are more limited, and the same risks (hypocalcaemia, flu-like reaction, rare osteonecrosis of the jaw) require careful monitoring and dental assessment beforehand.
9. Etanercept (TNF-α inhibitor)
Etanercept is a biologic drug that blocks tumour necrosis factor-alpha (TNF-α), a key inflammatory cytokine in many autoinflammatory and autoimmune diseases. Case reports and series show that etanercept can help children with CRMO who did not respond to NSAIDs, DMARDs, or bisphosphonates, leading to improved pain and imaging findings. It is given by regular subcutaneous injection. FDA labeling for etanercept warns about serious infections, malignancy risk, and injection-site reactions, so screening for tuberculosis and ongoing monitoring are essential.
10. Adalimumab (TNF-α inhibitor)
Adalimumab is another TNF-α blocking antibody used in similar situations, sometimes preferred when there is coexisting inflammatory bowel disease, psoriasis, or arthritis. It is injected subcutaneously every 1–2 weeks, with doses adjusted by weight and age according to approved indications. Its mechanism and major risks (serious infections, TB reactivation, rare demyelinating disease and malignancy) are similar to other TNF inhibitors, so pre-treatment screening and close follow-up are required.
11. Infliximab (TNF-α inhibitor, intravenous)
Infliximab is a chimeric monoclonal antibody against TNF-α given by intravenous infusion. It is sometimes chosen when rapid systemic control is needed or when other biologics have not worked. Case reports describe significant improvement in CRMO patients resistant to standard therapy. Infusions are given in hospital, with observation for infusion reactions, and the same infection and malignancy warnings as other TNF blockers apply.
12. Anakinra (IL-1 receptor antagonist)
Anakinra is a biologic that blocks interleukin-1 (IL-1), another strong inflammatory cytokine. Small studies and cohorts of children with chronic non-bacterial osteomyelitis report that daily subcutaneous anakinra can induce rapid and sustained remission in some refractory patients, especially those with strong systemic features. Common side effects include injection-site reactions and increased infection risk, so vaccinations and lab monitoring are important.
13. Canakinumab (IL-1β monoclonal antibody)
Canakinumab is a long-acting antibody that neutralises IL-1β. It is approved for other autoinflammatory diseases but used off-label in particularly severe or syndromic cases of CNO/CRMO. In case reports and small series, monthly or 8-weekly injections have improved pain and inflammation where other therapies failed. Because it strongly modifies immune responses, there is a risk of serious infections, so it is reserved for highly selected patients in expert centres.
14. Tocilizumab (IL-6 receptor inhibitor)
Tocilizumab blocks the interleukin-6 receptor and is sometimes tried in CRMO patients with marked systemic inflammation or overlapping systemic juvenile idiopathic arthritis. Evidence in CNO is limited to case reports, but it may help some individuals when TNF and IL-1 blockers are unsuitable. Main risks include infections, liver enzyme elevation, and abnormal cholesterol, so regular blood tests and clinical checks are necessary.
15. Other biologics (e.g., ustekinumab, secukinumab in selected cases)
In rare, complex cases with coexisting psoriasis, inflammatory bowel disease, or spondyloarthritis, other biologics targeting IL-12/23 or IL-17 pathways have been used off-label. Data in chronic multifocal osteomyelitis are extremely limited, so these are considered experimental rescue options chosen case by case by experienced teams after standard biologics fail.
16. Antibiotics (only when true infection is present or diagnosis uncertain)
Because chronic multifocal osteomyelitis is usually non-bacterial, long courses of antibiotics generally do not help and can cause harm. However, short antibiotic treatment may be started early when doctors are not yet sure whether there is a true bone infection, or when biopsy cultures show bacteria. Once non-bacterial CNO/CRMO is confirmed, guidelines advise focusing on anti-inflammatory and immunomodulatory drugs instead of antibiotics.
17. Proton pump inhibitors (PPIs) or other gastro-protection
PPIs such as omeprazole are not treatments for the bone disease itself but are often prescribed together with long-term high-dose NSAIDs or steroids to protect the stomach and upper intestine from ulcers and bleeding. They work by strongly reducing stomach acid. Doctors balance the benefits against potential long-term risks, such as nutrient malabsorption or infection, and use the lowest effective dose.
18. Vitamin D and calcium supplements (as medicines when deficient)
When blood tests show low vitamin D or low calcium, doctors may prescribe medicinal-strength supplements. Vitamin D helps the body absorb calcium and supports normal bone mineralisation, while calcium is a basic building block for bone. Correcting deficiencies is essential when bisphosphonates are used, because these drugs rely on normal mineral balance and can cause low calcium if reserves are poor.
19. Low-dose aspirin or anticoagulants in selected high-risk cases
Very rarely, if there is severe immobility, central venous lines, or other risk factors, doctors may use low-dose aspirin or other blood-thinning medicines to prevent clots. This is not routine for all CRMO patients but may be considered individually. Any anticoagulant requires careful dosing and monitoring to avoid bleeding complications.
20. Pain-modulating medicines (e.g., gabapentin, amitriptyline in selected older patients)
When pain remains high despite good control of bone inflammation, doctors may sometimes use medicines that alter how the nervous system processes pain, such as gabapentin or low-dose amitriptyline. These do not treat the underlying bone lesions but can reduce nerve hypersensitivity and improve sleep. They are usually used short-term, with careful monitoring for drowsiness, mood changes, or other side effects.
Dietary molecular supplements (10 examples – only under medical advice)
1. Vitamin D
Vitamin D supports calcium absorption and bone mineralisation. In chronic bone inflammation, low vitamin D is common and may worsen bone weakness. A doctor may prescribe a specific daily or weekly dose based on blood levels. The main mechanism is acting on vitamin D receptors in gut, bone, and immune cells to improve calcium balance and modulate immune responses.
2. Calcium
Calcium is essential for strong bones and normal muscle and nerve function. When dietary intake is low or bone density is reduced, supplements may be recommended. Calcium works together with vitamin D to rebuild bone matrix, especially important if the patient receives bisphosphonates or steroids. Doses are kept within safe limits to avoid kidney stones or vascular calcification.
3. Omega-3 fatty acids (EPA/DHA)
Omega-3 fats from fish oil or algae have mild anti-inflammatory effects by shifting the balance of eicosanoids and specialised pro-resolving mediators. In chronic inflammatory diseases, they may slightly reduce joint pain and stiffness. A typical supplement provides standardised amounts of EPA/DHA daily; side effects are usually mild (fishy taste, loose stool) but bleeding risk can increase at very high doses.
4. Protein supplements (whey or plant protein when diet is insufficient)
Adequate protein intake supports muscle repair and bone health. If pain or fatigue leads to poor appetite, dietitians may use shakes or powders to reach daily protein targets. Protein provides amino acids for collagen and other bone matrix components and helps maintain muscle mass, which stabilises joints and reduces fall risk.
5. Magnesium
Magnesium is involved in bone mineralisation and more than 300 enzyme reactions. When dietary intake is low, supervised supplementation can support bone and muscle function and may help with cramps. Excess magnesium from supplements can cause diarrhoea or, in severe kidney disease, dangerous levels, so dosing is always individualised.
6. Vitamin K (mainly K2 forms)
Vitamin K helps activate proteins such as osteocalcin that bind calcium in bone. Some data suggest K2 forms may support bone density when combined with vitamin D and calcium. In patients on blood thinners like warfarin, vitamin K supplements are usually avoided or carefully managed because they can interfere with anticoagulant action.
7. Antioxidant-rich polyphenol supplements (e.g., curcumin)
Curcumin (from turmeric) and other polyphenols show anti-inflammatory and antioxidant effects in laboratory studies by influencing NF-κB and other signalling pathways. In real patients, evidence is modest, and supplements vary in quality and absorption. If used, they are considered complementary to standard therapy, not replacements. They should be discussed with the doctor due to possible interactions with medicines.
8. Probiotics
Because the gut microbiome interacts with the immune system, probiotics are sometimes explored as supportive therapy in autoinflammatory conditions. They aim to promote a healthier microbial balance, which might indirectly reduce systemic inflammation. Evidence in chronic multifocal osteomyelitis is still experimental, so probiotics are seen as optional and low-risk when chosen from reputable brands.
9. Multivitamin with trace elements (e.g., zinc, selenium)
When diet is restricted or appetite is low, a broad multivitamin may be used to prevent deficiency of micronutrients important for immune balance and healing. Zinc and selenium support antioxidant defences and immune function. Doses are usually kept within recommended daily allowances to avoid toxicity.
10. Evidence-based medical nutrition shakes
In underweight or highly fatigued patients, medically formulated nutrition drinks can provide balanced calories, protein, vitamins, and minerals. They help maintain growth in children and support recovery after hospital stays or surgery. The mechanism is simple: providing complete, easy-to-digest nutrition when normal eating is hard. Choices are personalised by a dietitian.
Immunity-booster, regenerative and stem-cell-related drugs
These are not over-the-counter “immune boosters”. They are powerful medical treatments used only in specialist centres and, in many cases, still experimental for chronic multifocal osteomyelitis.
1. TNF-α inhibitors as “regenerative protectors” of bone
TNF blockers like etanercept, adalimumab, and infliximab not only reduce inflammation but may allow bone to remodel and heal, especially in vertebrae. By turning down TNF-α, they reduce osteoclast activation and cytokine-driven bone damage, giving the skeleton a chance to repair itself over months. They are considered disease-modifying agents rather than simple painkillers.
2. Bisphosphonates as bone-strengthening regenerative agents
Pamidronate and zoledronic acid powerfully inhibit bone resorption by osteoclasts. In CRMO, repeated cycles have been shown to improve vertebral shape and overall bone density, acting as a form of “pharmacologic bone regeneration support.” They do not cure the immune problem but protect against fractures and deformity while the disease is controlled.
3. IL-1 blockers (anakinra, canakinumab) as deep immune resetters
By cutting IL-1 signalling, these biologics target a central driver of inflammasome-mediated disease in some CNO patients. Successful treatment can normalise inflammatory markers and imaging, suggesting a deeper reset of the autoinflammatory process. Because they strongly modify immunity, they require strict infection monitoring and are usually reserved for severe, refractory cases.
4. IL-6 inhibitors (tocilizumab) in systemic and refractory disease
In patients whose disease overlaps with systemic autoinflammatory syndromes, IL-6 blockade can reduce fever, CRP, and bone pain. By dampening IL-6, these drugs may lower osteoclast activation and improve bone turnover, indirectly supporting structural healing. Use in CRMO remains off-label and carefully monitored.
5. Future mesenchymal stem-cell (MSC) therapies (experimental)
Research in other bone and immune diseases is exploring mesenchymal stem-cell infusions to modulate immune responses and promote tissue repair. In theory, MSCs can home to inflamed sites and release anti-inflammatory factors, but this is not standard care for CRMO/CNO. Any stem-cell-based approach should be offered only within properly regulated clinical trials, not commercial unproven clinics.
6. Optimised vaccination and infection prevention as “immune support”
While not drugs in the usual sense, vaccines and infection-prevention plans are critical when patients take immunomodulating medicines. They reduce infection triggers that might worsen systemic inflammation or mimic new bone flares. This whole-system approach helps the immune system focus on healing rather than fighting preventable infections.
Surgical treatments
1. Diagnostic bone biopsy
Sometimes a small piece of bone is taken surgically to confirm the diagnosis and rule out cancer or true infection. The surgeon uses imaging guidance to minimise damage and risk. Biopsy tissue is checked by pathology and cultured for bacteria. This procedure is usually done once, early in the disease course, and guides later medical treatment.
2. Curettage and debridement of isolated lesions (rare)
If a single lesion causes persistent pain or structural problems despite medical therapy, a surgeon may scrape out inflamed tissue (curettage) and clean the area. This is uncommon because most CNO/CRMO lesions respond to medicines, but in selected cases it can reduce pain and help the area fill in with healthy bone, under continued medical treatment.
3. Stabilisation of fractures (internal fixation)
When weakened bones fracture, especially in weight-bearing areas, metal plates, screws, or rods may be needed to keep bone aligned while it heals. This does not treat the underlying inflammation, but it prevents deformity and allows earlier mobilisation. Post-operative rehabilitation is important to restore strength and flexibility.
4. Spinal bracing and, rarely, corrective spinal surgery
If vertebral bodies collapse or deform because of inflammation, bracing is usually the first step. In very severe or unstable cases that threaten the spinal cord, spinal fusion surgery may be considered. Surgeons stabilise the spine using rods and bone grafts. This is a last resort after maximal medical therapy has been tried.
5. Corrective osteotomy for limb deformity
Long-standing lesions near growth plates can cause angulation or limb length differences. Corrective osteotomy is a planned surgical cut of the bone to realign it, sometimes adding plates or external frames. It is usually done when disease activity is under better control, to restore function and reduce pain from abnormal loading.
Prevention and long-term protection
Early diagnosis and treatment – recognising chronic bone pain and swelling early and referring to rheumatology can prevent long delays and reduce permanent bone damage.
Strict adherence to treatment plans – taking medicines as prescribed and attending infusions and follow-ups reduce flares and protect bones.
Regular monitoring with blood tests and imaging – this allows doctors to adjust therapy before major flares or fractures happen.
Protecting bone health (diet, supplements, exercise) – adequate calcium, vitamin D, and weight-bearing exercise help bones stay strong.
Avoiding smoking and excessive alcohol – these habits weaken bone and increase complications.
Routine vaccinations and infection control – lowers infection risk during immunosuppressive treatment.
Body-weight management – keeping a healthy weight reduces stress on painful joints and bones.
Safe physical activity – choosing low-impact sports and gradually increasing intensity can maintain fitness without overloading lesions.
Mental health and stress management – counselling and coping skills protect against depression and anxiety, which can worsen perceived pain.
Strong communication between family, school, and medical team – sharing information and plans helps everyone respond quickly to flares and needed adjustments.
When to see a doctor or seek urgent help
You should contact your doctor or specialist promptly if:
Pain, swelling, or limp suddenly worsens or spreads to new bones.
There is new fever, chills, or feeling very unwell, which might suggest infection.
Weakness, numbness, or problems controlling bladder or bowel appear (possible spinal cord pressure).
A new deformity, shortening, or obvious bend in a limb or back is noticed.
Medicines cause strong side effects such as severe stomach pain, black stools, shortness of breath, chest pain, jaundice (yellow eyes), or unusual bruising or bleeding.
There is any worry about mood, depression, or thoughts of not wanting to live – this always deserves immediate professional support.
In an emergency (severe breathing problems, sudden inability to walk, loss of consciousness, or suspected spinal cord compression), emergency services should be called immediately.
What to eat and what to avoid
Eat plenty of calcium-rich foods – milk, yoghurt, cheese, fortified plant milks, tofu, and some leafy greens to support bone strength.
Include vitamin-D-rich foods – oily fish (if appropriate), fortified dairy or plant milks, and eggs, alongside doctor-recommended supplements.
Choose lean protein sources – fish, poultry, beans, lentils, and nuts help repair muscle and bone tissue.
Fill half the plate with colourful fruits and vegetables – they provide antioxidants and fibre which support immune function and overall health.
Prefer whole grains over refined grains – brown rice, whole-wheat bread, and oats stabilise energy and support gut health.
Limit sugary drinks and sweets – high sugar intake can worsen weight gain and inflammation, and replace more nutritious foods.
Reduce ultra-processed and fast foods – these often contain high salt, unhealthy fats, and additives which are not helpful for long-term health.
Avoid excess caffeine and energy drinks – they may interfere with sleep and can affect bone health if they replace milk or other nutrient-dense drinks.
Keep salt intake moderate – too much salt may stress the cardiovascular system and kidneys, especially on NSAIDs.
Discuss special diets with the medical team – extreme diets (very low-carb, very restrictive “anti-inflammatory” plans) can cause nutritional gaps and are rarely needed for chronic multifocal osteomyelitis.
Disclaimer: Each person’s journey is unique, treatment plan, life style, food habit, hormonal condition, immune system, chronic disease condition, geological location, weather and previous medical history is also unique. So always seek the best advice from a qualified medical professional or health care provider before trying any treatments to ensure to find out the best plan for you. This guide is for general information and educational purposes only. Regular check-ups and awareness can help to manage and prevent complications associated with these diseases conditions. If you or someone are suffering from this disease condition bookmark this website or share with someone who might find it useful! Boost your knowledge and stay ahead in your health journey. We always try to ensure that the content is regularly updated to reflect the latest medical research and treatment options. Thank you for giving your valuable time to read the article.
The article is written by Team RxHarun and reviewed by the Rx Editorial Board Members
Last Updated: January 25, 2025.
