Links To PedsCases’ “Chronic Nonbacterial Osteomyelitis (CNO)”: Evaluation Of Bone And Joint Pain

Today I reviewed and link to PedsCasesChronic Nonbacterial Osteomyelitis (CNO).

All that follows is from the above resource.

This podcast will give you an approach to chronic nonbacterial osteomyelitis (CNO). In this episode, the listener will be able to 1) discuss the differential diagnosis for pediatric patients presenting with non-traumatic bony pain, 2) suggest appropriate investigations for these patients, 3) list the Bristol diagnostic criteria for CNO, and 4) outline two options in the treatment of patients with CNO. The podcast was created by Iain Sander, a 3rd year medical student at the University of Alberta, in collaboration with Dr. Dax G. Rumsey, a Pediatric Rheumatologist from the Stollery Children’s Hospital and the Division Director of the Pediatric Rheumatology Program at the University of Alberta in Edmonton.

Excerpts From The Script

The Case:

You are completing an elective in pediatric emergency medicine and have been asked to see Sierra, an 8-year-old girl presenting with pain below her right knee and a swollen left clavicle. She is afebrile and the rest of her vitals are normal. There is no history of mechanical trauma preceding her presentation. The patient is not visibly in pain or distress. Her parents tell you that they initially thought their daughter was having growing pains, but are now worried that she has something far more sinister like cancer, as her pain has not gone away. What is your differential diagnosis? How would you approach this patient?

Differential Diagnosis:

Because the differential diagnosis for bony pain is long (pardon the pun), it is important to prioritize the most likely and most sinister diagnoses. Some causes of non-traumatic pediatric bony pain might include:
1) Infection
– Infectious osteomyelitis or septic arthritis
2) Malignancy:
– Primary bone malignancy, such as Ewing Sarcoma or Osteosarcoma
– Hematologic malignancy, including Acute Lymphocytic Leukemia (ALL)
– Metastatic malignancy
3) Benign bone tumor:
– Osteoblastoma
– Osteoid Osteoma
4) Growing pains
5) CNO

Back to the Case:

The patient’s parents state that she has had the pain below her right knee for the past 2.5 months, with pain and swelling of her left clavicle starting about 3 weeks ago. The parents state that their daughter has experienced pain in the affected regions every day since onset and that the pain remains constant throughout the day, but seems to be most noticeable at night when she is going to bed. They often give her a dose of ibuprofen and a heating pad, which seem to help with the pain. However, overall, the pain has not improved over the past 2.5 months but has also not worsened. She is still active, going to gymnastics twice a week and has not missed school due to the pain. The patient denies having pain in other parts of her body and is otherwise healthy. There has been no joint swelling noted. Review of systems and the remainder of the history is unremarkable, apart from the patient’s father having ulcerative colitis.

Physical Examination:

Like questions from the history, the physical exam will be focused around evaluating for infectious, malignant, and inflammatory causes of the bony pain.

MSK exam:

o One of the most important parts of physical exam for        patients with this presentation
o Important to examine all joints for range of motion (ROM), pain with movement, and the presence of effusions
o Check for tenderness to palpation of the metaphyseal regions of all long bones (e.g. around the shoulders, elbows, wrists, hips, knees, and ankles).
o Check for tenderness to palpation along the spine, clavicles (especially medial clavicles), and mandibles, which are all common sites of involvement in CNO.
o Muscle atrophy, loss of strength, especially around affected areas.
o Check for sternal tenderness, often a feature of leukemia/infiltrative disease.
o Check for the presence of enthesitis, or tenderness at the sites of attachment of tendons, ligaments, or fascia to bone.

Back to the Case:

The physical exam you perform is largely normal, apart from an enlarged and exquisitely tender medial left clavicle and tenderness to palpation at the right tibial tuberosity.

You are less concerned about arthritis, given the lack of morning stiffness, joint effusion(s), or limitation of joint ROM. An acute infection or hematologic malignancy are also less likely (but not impossible), given the otherwise benign history and lack of constitutional symptoms, but you want to be cautious and avoid missing anything serious. So, you will need to decide what lab work and imaging to order.


For laboratory tests, an appropriate starting point might include:

● CBCd to investigate for signs of inflammation, including thrombocytosis and leucocytosis
● Acute phase reactants, including CRP, ESR, and Ferritin for inflammation in active disease
● ALT, AST, ALP, Albumin, and Bilirubin for liver function and to rule out associated autoimmune disease. It is also helpful to know baseline values of these in case the patient ends up on medications
● Urea, LDH, Creatinine, and Electrolytes, as tumour lysis can occur with rapidly progressive hematologic malignancies

In pediatric medicine, it is important to balance the risks of radiation exposure against the usefulness of the test. Let’s discuss the role of different imaging modalities for investigating bony pain.

● In many cases, if the history and physical point clearly toward growing pains or
similar benign cause as a diagnosis, then no imaging is necessary.
● Ultrasound is a quick bedside test that does not involve radiation exposure. It is unfortunately of little diagnostic value in the evaluation of bony pain and should therefore not be ordered.
● X-rays can be a useful starting point in the diagnostic workup of bony pain and are quicker and easier to access than CT or MRI. In CNO, x-rays can show osteolytic lesions and sclerosis in affected areas. However, it is important to consider that this modality does involve radiation exposure and is not particularly
sensitive or specific.
● CT scans involve significant radiation exposure should only be used when necessary. They can be useful to look for signs of occult fracture. Also, a dual energy CT can help diagnose gout (which is extremely rare in pediatrics). CT would not be the appropriate test in this case.
● Bone Scans are a form of low-resolution nuclear medicine imaging that help to identify areas of high metabolic activity within bone. However, they involve significant doses of radiation and can be difficult to interpret in children, whose
bones have active growth plates. Since bone scans do not show much detail, it is difficult to differentiate among infection, malignancy, osteomyelitis, and normal growing bones. For these reasons, they are not typically used unless MRI is not
easily accessible.
● MRI is the gold standard imaging tool for the diagnosis of musculoskeletal and soft tissue lesions in pediatrics. These scans offer the best balance of high resolution images, absence of radiation, and sensitivity and specificity in identifying bone lesions. There are drawbacks to consider, however, such as limited availability, the need to sedate young children during imaging, and high cost. In tertiary care pediatric hospitals, this is the recommended imaging modality for a case such as this. For cases of suspected or confirmed CNO, there is a whole-body MRI protocol involving coronal T1 and STIR images that
takes about 30 minutes to complete.

Back to the Case:

After completing laboratory investigations and diagnostic imaging, you receive the results back. Lab investigations are unremarkable, with no evidence of inflammation, electrolyte imbalances, or abnormal cell counts. You choose to start with some x-rays (which come back normal) and order an outpatient whole-body MRI scan for this patient. Lab work and initial imaging further reassure you that there is likely no infectious or malignant process at play here. You reassure the patient and family and let them know the plan. You discharge them from the ED and instruct them to give Sierra Tylenol as needed for now.

A few weeks later, Sierra has the whole-body MRI. Your preceptor lets you know that it demonstrated widening of the left clavicle, with periosteal reaction and bone marrow
edema and a lytic lesion at the right tibial tuberosity. It also showed similar inflammatory-appearing lesions at the bilateral distal tibiae and a lesion at the right proximal femur. These lesions were asymptomatic in Sierra. If radiologic findings were
identified at only one site, a bone biopsy may be useful to rule out malignancy or infection.

The type of lesions identified on imaging is inconsistent with malignancy or benign bone tumours, and growing pains would have yielded normal imaging. Also, if this was infectious osteomyelitis at multiple sites throughout the body, you would expect the patient to be sicker and for the labs to be more remarkable (e.g. elevated inflammatory markers). Thus, you begin to wonder if this could be chronic nonbacterial osteomyelitis (CNO) and look into how this condition can be diagnosed and managed.


CNO is a disease characterized by osteomyelitis, or inflammation that occurs in the bone. It is a chronic condition, persisting for 6 or more weeks. It is a non-bacterial
condition, meaning that there is no microbial infection. CNO can have multiple recurrences and/or can occur in multiple bony sites simultaneously. For these reasons, a subset of CNO is termed CRMO, or chronic recurrent multifocal osteomyelitis. Many of the involved sites can be asymptomatic and just show up on imaging.


In contrast to autoimmune conditions, which occur due to dysfunctions of B and T cells in the adaptive immune system, CNO is an autoinflammatory condition characterized by dysfunction of the innate immune system. The exact mechanism of this condition is not fully understood, but it is thought to involve increased expression of proinflammatory cytokines, such as IL-1β, IL-6, and TNF-α, and dysregulated osteoclast behaviour [1].


CNO is a rare disorder and, while its exact prevalence and incidence remain unknown, one study estimated an incidence of up to 80 per 100,000 children [1]. CNO is primarily a disease of children and young adolescents, with peak onset between 7-12 years of age. Girls are thought to be affected 2-4 times more frequently than boys. CNO does not have a clearly identified genetic inheritance pattern but is associated with inflammatory bowel disease (IBD), psoriasis, ankylosing spondylitis, and
autoinflammatory conditions, such as pyoderma gangrenosum (which is also known to be associated with IBD).

Diagnostic Criteria:

Start here.


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