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Bone Marrow Edema Syndrome

Editor: Steven M. Kane Updated: 6/5/2023 9:42:06 PM

Introduction

Bone marrow edema syndrome is a diagnosis of exclusion that is characterized by pain and increased interstitial fluid within bone marrow without an obvious cause. It is frequently misdiagnosed as its clinical presentation is highly variable and nonspecific. As such, it may be referred to by a plethora of terms, including "transient osteoporosis," "regional migratory osteoporosis," and "algodystrophy."[1][2][3]

Etiology

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Etiology

While bone marrow edema syndrome is by definition pain and marrow edema of unknown etiology, there is evidence that this phenomenon is associated with metabolic disturbances, including vitamin D deficiency. Bone marrow edema syndrome was originally described in pregnant women during the third trimester. Other reviews have cited cirrhosis and type IV hyperlipoproteinemia as being associated with an increased incidence of bone marrow edema syndrome.[1][4]

Epidemiology

Bone marrow edema syndrome is a condition in the lower extremities in 98% of presentations and rarely appears in the upper limbs.[5] Middle-aged men (aged 30 to 60) and young women (aged 20 to 40) are most likely to be affected with an incidence of 3 to 1 in men and women.[6][7] Bone marrow edema syndrome is often a migratory phenomenon and occurs bilaterally in 41% of patients.[1][5][8]

Pathophysiology

The pathogenesis of bone marrow edema syndrome remains unknown. Vascular anomalies, decreased fibrinolysis (especially in pregnant women), and thromboembolism have all been proposed as possible etiologies, but a definitive cause remains elusive. Ultimately, the pain is likely caused by the aggravation of neurovascular bundles within the bone marrow due to increased intraosseous pressure caused by the increased fluids in the bone marrow interstices.[1][7]

Histopathology

Histologic examination of the bone in this syndrome shows bony trabeculae containing osteoid seams, new bone formation, and vascular reconstruction with under-mineralized bone. The capacity of bone to repair itself through turnover is likely the reason for the natural regression of the symptoms associated with bone marrow edema syndrome.[9]

History and Physical

Patients with bone marrow edema syndrome often present with complaints of severe pain that limits functionality and daily activities. Patients will also report pain and swelling during rest and activity, which may occur suddenly or insidiously.[2][10][11] Patients are often point-tender and have noticeable swelling in the area of the syndrome. Frequently, joint spaces are intact, as arthralgia and joint effusion are not common in the presentation.[12][13]

Classically, bone marrow edema syndrome can be divided into three phases: The first month is characterized by initial pain and dysfunction. The next one to two months are characterized by maximum pain levels. Finally, symptoms regress over the next few months following the period of maximal pain, but it should be noted that the presentation and resolution of symptoms are highly variable.[1]

Evaluation

Radiographs will typically begin to show osteopenia a month or two after the presentation of symptoms.[14][15] Computed tomography (CT) scans may be ordered to assess local demineralization, as well as to rule out other causes of pain and swelling such as malignancy or infection. Nevertheless, magnetic resonance imaging (MRI) is a much better test for the assessment of bone marrow edema syndrome, as edema can be detected within two days of symptom onset.[7][13] MRI will show a decreased signal on T1 weighted images and an increased signal on T2 and STIR images.[16]

Blood work is typically benign, but there may be decreased levels of vitamin D. This finding may also warrant bone mineral density testing and treatment if necessary.[1]

Treatment / Management

As bone marrow edema syndrome is self-limiting, the goal of treatment is primarily symptom management. Offloading of the affected region can help control pain while nonsteroidal anti-inflammatory drugs (NSAIDs) and physical therapy remain the mainstays of symptomatic management.[1] There is also evidence that treatment with nifedipine (a calcium channel blocker) and sympathetic nerve blockade may provide substantial relief in the treatment of bone marrow edema syndrome.[17][18](B3)

Iloprost is a prostacyclin analog that has historically been used in the treatment of critical ischemia but has also been shown to improve functionality and pain in patients with bone marrow edema syndrome.[19][20] Of note, prostacyclin analogs are contraindicated in patients receiving anticoagulants and during pregnancy, a common comorbidity for bone marrow edema syndrome.[1](B2)

A regimen of bisphosphonates and vitamin D supplementation may also be used to increase anabolism and revascularization of bone. Ibandronate and other nitrogen-containing bisphosphonates have been shown to have an analgesic effect in addition to their anabolic effects within bone tissue.[1][21](B3)

Differential Diagnosis

Bone marrow edema syndrome is a diagnosis of exclusion, and therefore diagnosticians must have a broad differential when considering this diagnosis. Trauma, malignancy, infection, osteonecrosis, complex regional pain syndrome, and stress fractures are some of the many diagnoses that must be considered in a patient with pain and increased bone marrow edema.[1]

Prognosis

Bone marrow edema syndrome is self-limiting with pain typically peaking at about one to two months after onset and resolving within three to nine months. Symptoms generally resolve completely without a residual deficit.[1]

Complications

The pain associated with bone marrow edema is often debilitating and may limit function and activities of daily living. Even though the condition will eventually regress on its own, the distress associated with debilitating pain often takes a serious toll on the mental and emotional well-being of patients.

Deterrence and Patient Education

While there are many theories as to the cause of bone marrow edema syndrome, the fact remains that this is a rare condition with a highly variable presentation. Therefore, clinicians may not arrive at the correct diagnosis quickly without excluding all other reasonable possibilities. However, if a patient is diagnosed with bone marrow edema syndrome, the mainstay of treatment remains symptom management. Physical therapy and offloading techniques will be most effective in reducing pain. NSAIDs also play an important role in decreasing the inflammatory response of bone marrow edema syndrome. Over time, symptoms will likely resolve, and patients should be counseled to avail themselves of coping mechanisms or assistance which may be needed to overcome both the physical and mental stress that may occur during their recovery.

Enhancing Healthcare Team Outcomes

Arriving at a diagnosis of bone marrow edema syndrome can be difficult and requires the cooperation of the diagnostician and clinicians across specialties to rule out all other possible sources of pain. Therapists play an essential role in assisting patients with appropriate off-loading techniques which can ameliorate their symptoms. As noted above, mental health professionals will, at times, be very important for patients suffering from emotional or mental distress associated with what can be a relatively debilitating, albeit temporary process. A supportive interprofessional medical team that is able to work in conjunction with the patient is the most important factor in guiding a patient through this disorder. [Level 5]

References


[1]

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