Chronic Sclerosing Osteomyelitis of Garré

The eponym. The name comes from Carl Garré (1893), and it has been applied loosely ever since. The chronic, non-suppurative sclerosing process now called Garré's is not the entity his paper described, which is why the examiner's real question is "what do you actually mean when you say Garré's?"

The entity. A non-suppurative sclerosing osteitis in which the bone reacts to chronic low-grade irritation with dense periosteal and endosteal new bone rather than with pus and necrosis. All of these defining features must be present:

• Chronic, low-grade, indolent bone inflammation
• Dense cortical thickening with medullary sclerosis and canal narrowing
• Smooth solid or laminated periosteal new bone
• Absence of abscess cavity, sequestrum, involucrum, cloaca or draining sinus
• Minimal systemic upset, with a near-normal white cell count and inflammatory markers

The examiner's headline. Garré's is a radiological-clinical phenotype, not a microbiological diagnosis. Imaging alone cannot separate infective from sterile disease; that requires biopsy with extended culture. Your job is to place the patient into one of three boxes, tumour, infective (culture-positive) sclerosing osteomyelitis or sterile inflammatory osteitis, because management diverges completely.

The labels. The eponym sits beside several other labels for sclerosing inflammatory bone disease, and the table maps what each one really denotes.

The infective mechanism. A low-virulence organism in a bone with intact host defences produces a chronic reactive rather than destructive response. The organisms classically implicated are Actinomyces species (especially in the mandible, where infection may follow dental extraction), Cutibacterium (Propionibacterium) acnes, coagulase-negative staphylococci, viridans streptococci and, occasionally, low-inoculum Staphylococcus aureus. Spread is by contiguous odontogenic extension in the jaw, by haematogenous seeding in long bones, and rarely after trauma.

Why the bone thickens. Chronic cytokine drive (IL-1, IL-6, TNF, RANKL/OPG shifts) stimulates periosteal and endosteal osteoblastic activity, so the bone lays down more bone than it resorbs and the result is sclerosis rather than lysis. Sclerotic, poorly vascularised bone is then a pharmacological sanctuary: antibiotic penetration is poor, which explains the need for prolonged therapy and the tendency to relapse.

The sterile autoinflammatory mechanism. CNO, CRMO and SAPHO are innate immune disorders. Dysregulated IL-1β and IL-10 signalling in monocytes, with excess TNF and IL-6, drives a sterile osteitis. Monogenic models illuminate the pathway, and all produce sterile bone inflammation:

• IL1RN mutations: deficiency of the IL-1 receptor antagonist (DIRA)
• LPIN2: Majeed syndrome
• PSTPIP1: PAPA syndrome

The associations are psoriasis, palmoplantar pustulosis, severe acne, inflammatory bowel disease and HLA-B27-related spondyloarthropathy. The osteitis passes through an inflammatory oedematous phase and then a reparative sclerotic or hyperostotic phase, hence the mixed lytic-sclerotic appearance that evolves to dense sclerosis over years.

Mechanical contributors. In the mandible, chronic masticatory overload, parafunction and occlusal disharmony are implicated in diffuse sclerosing disease, and explain its response to occlusal management. In long bones, repetitive loading may sustain the periosteal reaction; a stress reaction or fracture must be excluded, because it produces identical fusiform cortical thickening.

The pain. Local venous stasis and raised intraosseous pressure contribute to the deep, boring, night-predominant pain. That is the rationale for medullary fenestration, which provides decompression relief that is often temporary.

Biopsy is required in almost every case: to exclude malignancy, to obtain histology, and to attempt organism recovery.

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The course. The disease is relapsing-remitting over years, with flares of pain and swelling separated by quiescent intervals. Most patients burn out, with residual bone thickening and deformity but resolution of pain. In children with CRMO, a majority achieve inactive disease over several years, and a substantial minority have persistent or relapsing disease into adulthood.

Long-term morbidity. It includes vertebral compression and kyphosis in spinal CNO, limb-length discrepancy or angular deformity from physeal involvement, jaw deformity and malocclusion in mandibular disease, and chronic pain syndromes.

Follow-up. Structure follow-up around these elements:

• Clinical review with pain scores every 3 months while active
• Inflammatory markers if previously raised
• STIR MRI of symptomatic sites at flares
• Whole-body MRI at diagnosis and to assess treatment response in multifocal disease
• Spinal imaging for any back pain
• Dental review in mandibular disease
• Bone health monitoring (calcium, vitamin D, DXA) in patients on bisphosphonates

When to biopsy again. The threshold for re-biopsy is any change in pain character, rapid growth, new lytic destruction, a soft-tissue mass, or failure to respond as expected.

The modern reclassification. This is where most of these cases now belong. Chronic Recurrent Multifocal Osteomyelitis is the paediatric entity that absorbed much of what was once called Garré's, and SAPHO Syndrome is its adult counterpart - many authors now regard them as one disease at different ages, with Juvenile Idiopathic Arthritis as the commonest coexisting inflammatory diagnosis.

The must-not-miss mimics. Osteoid Osteoma is the great imitator - night pain relieved by NSAIDs with a sclerotic cortex, and CT rather than MRI is the test; Ewing Sarcoma and Osteosarcoma are the malignancies that mimic infection systemically as well as radiographically, and Langerhans Cell Histiocytosis completes the paediatric list.

True infection. Osteomyelitis Pathophysiology, Paediatric Acute Osteomyelitis and Brodie Abscess for the suppurative disease this entity is defined against, with Fungal Osteomyelitis for the culture-negative case that is not sterile after all.

Other causes of dense bone. Sclerotic Bone Lesion, Melorheostosis and Paget's Disease of Bone.

Sampling. Biopsy Principles and Techniques governs the sampling discipline that decides whether a culture-negative result means anything.

The classic vignette. An adolescent or young adult with months of deep, aching, boring pain, notably worse at night and at rest, over the mandible or the diaphysis of the tibia or femur, with a firm, fusiform, non-fluctuant swelling fixed to bone. Symptoms flare and settle over years. There is little or no fever, no malaise, no weight loss and no sinus.

History. Each question below either points towards a mimic or establishes an association.

Inspection. Expose the patient with both limbs visible, or light the face symmetrically for mandibular disease. Look for a fusiform expansion of the shaft contour against the contralateral side, and specifically for the absence of a sinus or scar: a discharging sinus excludes Garré's and means classic chronic osteomyelitis. Inspect the palms, soles, scalp and back for pustulosis, psoriasis and acne conglobata.

Palpation. Run flat fingertips along the subcutaneous border of the tibia or the mandibular body from posterior to anterior. The positive finding is a hard, smooth, non-mobile, tender expansion continuous with bone, without fluctuance and without overlying warmth or erythema. The tenderness is deep, localised to the segment and reproducible on percussion.

Regional nodes. Palpate the cervical nodes in mandibular disease and the inguinal and popliteal nodes in the lower limb. Significant lymphadenopathy raises malignancy or atypical infection.

Adjacent joints. Assess range of movement and effusion; a sterile sympathetic effusion may accompany metaphyseal CNO. In SAPHO, examine the sternoclavicular joints and anterior chest wall for hyperostotic swelling, a finding that alone reframes the whole case.

Neurovascular. In mandibular disease, test inferior alveolar nerve sensation over the lower lip and chin. Numbness (Vincent sign) is a red flag for malignancy or osteonecrosis, not simple sclerosing osteitis. In long bones, document distal pulses and nerve function before any surgery.

Spine and gait. CNO involves the spine in a meaningful minority, so assess for a kyphotic angulation from vertebra plana and for an antalgic gait.

Where it occurs. The site itself narrows the differential.

Blood tests. There is no blood test that makes the diagnosis. Normal markers never exclude low-grade infection, and raised markers never confirm it.

Radiographs. Obtain orthogonal radiographs of the whole bone, including both adjacent joints; for jaw disease, an orthopantomogram plus a PA mandible. Describe the findings systematically:

1. Fusiform cortical thickening: the cortex is expanded circumferentially over several centimetres, with a gradual (not abrupt) transition to normal bone.
2. Medullary sclerosis with narrowing or obliteration of the canal: the hallmark; the medulla becomes as dense as cortex.
3. Periosteal new bone: smooth, solid or finely laminated and continuous; it fuses with the cortex over time.
4. No sequestrum, no cloaca, no involucrum, no lytic abscess cavity.
5. No cortical destruction, no soft-tissue mass, no Codman triangle, no sunburst spiculation. The presence of a soft-tissue mass means sarcoma or atypical infection.

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CT. Thin-slice (1 mm or less) helical CT with a bone algorithm and multiplanar reformats through the sclerotic segment answers four questions:

• Is there a nidus? A rounded lucency, usually less than 1.5 cm, with a central mineralised dot, surrounded by reactive sclerosis, is an osteoid osteoma. CT is the definitive test; MRI can hide the nidus in oedema.
• Is there a sequestrum? A dense fragment of dead bone lying within a lucent cavity confirms classic chronic osteomyelitis (Brodie abscess variants) and mandates surgical debridement.
• Is there a cortical breach or a soft-tissue component? Either redirects the patient to the sarcoma pathway.
• What does the surgeon need? Cortical thickness, canal patency, a safe fenestration window and the planned biopsy trajectory.

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MRI. The protocol is T1, fluid-sensitive fat-suppressed (STIR or T2 FS) in two planes, and post-gadolinium T1 fat-suppressed sequences.

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Whole-body MRI. Coronal STIR from head to toe is the key investigation when multifocal sterile disease is suspected. It detects clinically silent lesions (clavicle, pelvis, spine, metaphyses), supports a CNO diagnosis by pattern, provides a safer biopsy target, and is radiation-free for repeated follow-up in children.

Nuclear medicine. Tc-99m bone scintigraphy shows intense uptake in all three phases; it is sensitive but non-specific, and it was historically useful for detecting multifocality before whole-body MRI largely superseded it in children. FDG-PET/CT may map multifocal disease and assess treatment response in SAPHO, but its radiation dose limits paediatric use.

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Ultrasound and genetics. Ultrasound has a limited role: it can confirm the absence of a subperiosteal collection and guide aspiration of a soft-tissue swelling. Consider genetic testing (IL1RN, LPIN2, PSTPIP1) in very early-onset, severe or syndromic disease.

Sorting the mimics. Each diagnosis below has a clinical feature that betrays it and an imaging feature that settles it. Garré's is what remains when the others have been excluded.

The cost of an error. For six of the mimics, the habit that prevents the mistake and the price of making it are worth knowing by heart.

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The decision map. The findings sort the patient into one of six pathways.

1. Aggressive imaging features or diagnostic uncertainty → sarcoma unit staging (local MRI, chest CT, bone scan/PET) and planned biopsy. Everything else waits.
2. CT nidus present → osteoid osteoma → radiofrequency ablation or en-bloc excision. Cure rate is high; recurrence is managed by repeat ablation.
3. Sequestrum, abscess or sinus present → this is secondary chronic osteomyelitis, not Garré's → radical debridement, dead space management (antibiotic-loaded carrier), stabilisation and culture-directed antibiotics.
4. Organism recovered from 2 or more deep samples → prolonged culture-directed antibiotics, typically 3 to 6 months, with agents of good bone penetration; consider adjunctive fenestration if pain persists.
5. No organism, compatible histology and course → treat as CNO/SAPHO: NSAIDs first line, escalate medically, rheumatology co-management, whole-body MRI to confirm multifocality.
6. Refractory pain despite medical escalation → consider medullary fenestration/decortication, understanding that relief is variable and often temporary; document informed consent accordingly.

Culture-positive disease. The regimen follows the organism. Give intravenous induction followed by oral step-down with high-bioavailability bone-penetrating agents, and guide duration by clinical and radiological response and inflammatory markers. No randomised evidence defines the endpoint, and practice varies beyond the typical range (see Controversies). Infectious diseases co-management is mandatory; monitor for hepatotoxicity, marrow suppression, tendinopathy (fluoroquinolones) and C. difficile.

Antibiotics are not a treatment for sterile disease. Empirical prolonged courses in culture-negative sclerosing osteitis expose patients to toxicity for no benefit and delay effective anti-inflammatory therapy.

Sterile disease is a medical problem. Once CNO, CRMO or SAPHO is established, repeated decortication, sequestrectomy or drilling produces temporary relief followed by relapse and progressive bone loss. Escalate through the drug lines below with rheumatology instead.

Corticosteroids give short-term relief but are avoided as maintenance in the young.

Mandibular disease. Eliminate odontogenic sepsis by extracting non-restorable teeth, endodontic treatment and periodontal therapy, but be cautious in patients on bisphosphonates because of the risk of medication-related osteonecrosis. Occlusal adjustment, splint therapy and management of parafunction address the mechanical driver.

Mandibular drugs and surgery. NSAIDs are first line, and intravenous bisphosphonate infusion for refractory diffuse sclerosing osteomyelitis of the mandible has good evidence of analgesic benefit. Hyperbaric oxygen has been used adjunctively, but the evidence is limited and it is not standard of care. Decortication (removal of the dense outer cortex and periosteum) is reserved for refractory disease and recurrence is common; resection with reconstruction is a last resort with substantial morbidity. Always exclude osteosarcoma of the jaw and metastatic disease before ascribing mandibular sclerosis to inflammation; lip numbness and rapid growth are red flags.

Indication. The operation is for refractory, disabling pain in a confirmed sclerosing osteitis of a long bone after failure of appropriately escalated medical therapy, or the need for a diagnostic tissue sample where core biopsy has been non-diagnostic.

Contraindications. Do not operate for suspected malignancy, which is biopsied in the sarcoma unit instead, for active multifocal sterile disease that is responding to medical therapy, or where the patient has unrealistic expectations of cure.

Why this operation. It decompresses raised intraosseous pressure, removes a segment of avascular sclerotic bone, permits definitive tissue sampling and, where infection exists, improves antibiotic delivery. Reamed intramedullary nailing is an alternative in the tibia or femur when canal reaming is wanted with immediate stabilisation, but it seeds any organism along the whole canal and is generally reserved for infective disease with a mechanical need.

Position. Supine on a radiolucent table, with a sandbag under the ipsilateral buttock for the tibia and a tourniquet high on the thigh; it is used, but consider deflating it before closure to secure haemostasis. The image intensifier comes in from the contralateral side.

Preparation. Confirm that no antibiotics have been given preoperatively unless the patient is septic, and brief the scrub team on the "clean instrument per sample" protocol. Consent for possible conversion to the sarcoma pathway, and send a group and save. Have fluoroscopy available and the preoperative CT reformats on screen, defining the sclerotic segment and canal. The kit is an oscillating saw, fine osteotomes, a high-speed burr, flexible reamers, a bone biopsy trephine, multiple sterile specimen pots, and an antibiotic-loaded carrier (calcium sulphate beads) if infection is suspected.

Approach. For the tibia, a direct anteromedial incision over the subcutaneous border, 1 cm medial to the anterior crest so that the wound does not lie over bone. For the femur, a lateral approach splitting the iliotibial band, with vastus lateralis elevated anteriorly off the lateral intermuscular septum.

Dissection. Preserve periosteum where possible: incise it longitudinally and elevate only the width of the intended window, because excessive stripping devascularises an already compromised cortex.

The window. Mark a rectangular window with rounded corners, since stress risers at sharp corners cause fracture. It is typically 1 cm wide and no more than 30 to 50 percent of the bone diameter, sited away from the tension side. Outline it with drill holes and cut with a fine osteotome or saw under continuous irrigation to avoid thermal necrosis, then harvest the cortical block as a specimen.

Decompression and sampling. Open the sclerotic medullary canal with a burr and gentle reaming until healthy bleeding bone is seen. Take the five deep samples, irrigate with saline, and consider a local antibiotic carrier if infection is confirmed.

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At-risk structures. In the tibia, the saphenous nerve and vein are at risk medially, and the anterior tibial artery deep to the interosseous membrane with lateral over-penetration. In the femur, the perforating branches of the profunda femoris run along the linea aspera and are controlled with diathermy or ligation before they retract into the septum; the sciatic nerve is at risk if dissection strays posteriorly.

Fixation. Usually none. If more than 50 percent of the diameter or more than 30 percent of the circumference is removed, or the bone is a weight-bearing femur, prophylactic intramedullary nailing or plating should be considered.

Closure. Close in layers, over a drain if there is bleeding, and avoid a tight closure over the subcutaneous border of the tibia.

Aftercare. Protected weight bearing with crutches for 6 to 8 weeks, with progressive loading, and no impact or torsion for 3 months given the cortical window. Radiographs at 6 weeks and 3 months confirm that the window is healing. Continue medical therapy: surgery does not replace it.

Pitfalls. The avoidable errors are these:

• A sharp-cornered window causing fracture
• Over-resection
• Sampling burnt-out sclerosis, giving false-negative histology
• Operating for sterile inflammatory disease without medical escalation
• Failing to send tissue for mycobacterial culture

Salvage of failure. Recurrent pain calls for repeat imaging to look again for a missed nidus or malignancy before relapse is assumed, then escalation of medical therapy. A postoperative fracture is treated with intramedullary nailing. Established segmental infection may require resection with bone transport or vascularised fibular reconstruction.

Complications. Each has a preventive step and a plan if it happens.

Global epidemiology. Sclerosing osteitis is uncommon everywhere but the balance of underlying causes varies markedly by setting. In high-income systems with early antibiotic access, sterile chronic non-bacterial osteomyelitis accounts for the majority of chronic sclerosing long-bone lesions in children and adolescents; incidence estimates for CNO are broadly comparable to those for other rare paediatric rheumatological diseases and it is likely under-recognised. In regions with high tuberculosis burden, restricted early antibiotic access, or a high incidence of untreated odontogenic disease, genuinely infective sclerosing osteomyelitis — including actinomycosis and tuberculous osteitis — remains proportionally far more common, and empirical antituberculous therapy is a legitimate consideration where testing is unavailable.

Society and consensus guidance that genuinely addresses this topic:

Registries. There are no implant registries relevant to this condition. Evidence comes instead from national and multinational CNO/CRMO patient registries and inception cohorts, which have driven the shift from empirical antibiotics and repeated surgery towards protocolised anti-inflammatory therapy, and from bone and joint infection registries which document culture yield and duration of therapy in low-virulence infection.

Practice variation by resource setting.

• Well-resourced settings: whole-body MRI, molecular microbiology, biologic therapy and multidisciplinary rheumatology-orthopaedics-radiology-microbiology meetings are available; the risk is over-investigation and delayed treatment.
• Intermediate settings: CT and conventional MRI available; extended culture may be, but broad-range PCR often is not; a pragmatic sequential trial of culture-directed or empirical antibiotics followed by NSAIDs is common.
• Limited-resource settings: radiographs and histology only. Here the priorities are (1) exclude malignancy by histology, (2) exclude tuberculosis, (3) trial NSAIDs before committing to prolonged empirical antibiotics with real toxicity and cost.

1. Is Garré's osteomyelitis a real infective entity at all? Many authorities argue that most historic long-bone cases were sterile autoinflammatory osteitis, and that the eponym should be retired in favour of "chronic non-bacterial osteomyelitis" or "primary chronic osteomyelitis". Others maintain that a genuine low-virulence infective form exists, supported by culture-positive cases responding to antibiotics.
2. Does culture-negative mean sterile? Proponents of an occult infective aetiology point to Cutibacterium recovered by molecular methods in SAPHO lesions and to occasional antibiotic responses; sceptics regard these as contaminants or as immune triggers rather than ongoing infection. The pragmatic position: a time-limited antibiotic trial may be justified where a plausible organism is isolated, but should not be repeated indefinitely.
3. Duration of antibiotic therapy in culture-positive disease. No randomised evidence defines the endpoint; practice ranges from 3 to 12 months, guided by symptoms and markers rather than trial data.
4. Role of surgery. Decortication and fenestration give unpredictable and often temporary relief. There is no randomised comparison against medical therapy, and publication bias favours positive surgical series.
5. First-line agent in refractory CNO. Bisphosphonate versus TNF inhibitor as second line is not resolved; bisphosphonates are favoured for pain and vertebral disease, biologics where there is coexisting arthritis, skin or bowel disease.
6. Antibiotic stewardship versus diagnostic uncertainty. Prolonged empirical antibiotics in a probably sterile disease is a common real-world harm; balancing this against the small risk of missing genuine infection remains a matter of judgement.
7. Whether unifocal CNO and multifocal CRMO are the same disease at different points of expression, or biologically distinct — currently assumed to be a spectrum.