Bone Marrow Edema Syndrome

Earn CME/CE in your profession:

Continuing Education Activity

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. This activity reviews the presentation, pathogenesis, and management of patients presenting with bone marrow edema syndrome. We examine the complications and briefly explore the impact of the disorder on patients and highlight the importance of an interprofessional team approach to treat these individuals appropriately.


  • Describe the presentation of bone marrow edema syndrome.
  • Summarize the clinical course of bone marrow edema syndrome and the best management.
  • Identify the challenges associated with the management of bone marrow edema syndrome.
  • Outline the role of an interprofessional health team in optimizing patient management of bone marrow edema syndrome.


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]


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]


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]


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]


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]


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]

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]

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]

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]


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]


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]



Steven M. Kane


6/5/2023 9:42:06 PM



Mirghasemi SA, Trepman E, Sadeghi MS, Rahimi N, Rashidinia S. Bone Marrow Edema Syndrome in the Foot and Ankle. Foot & ankle international. 2016 Dec:37(12):1364-1373     [PubMed PMID: 27587374]


Arazi M, Yel M, Uguz B, Emlik D. Be aware of bone marrow edema syndrome in ankle arthroscopy: a case successfully treated with iloprost. Arthroscopy : the journal of arthroscopic & related surgery : official publication of the Arthroscopy Association of North America and the International Arthroscopy Association. 2006 Aug:22(8):909.e1-3     [PubMed PMID: 16904599]

Level 3 (low-level) evidence


Singh D, Ferrero A, Rose B, Goldberg A, Cullen N. Bone Marrow Edema Syndrome of the Foot and Ankle: Mid- to Long-Term Follow-up in 18 Patients. Foot & ankle specialist. 2016 Jun:9(3):218-26. doi: 10.1177/1938640015609986. Epub 2015 Oct 12     [PubMed PMID: 26459365]


Pinals RS, Jabbs JM. Type-IV hyperlipoproteinaemia and transient osteoporosis. Lancet (London, England). 1972 Oct 28:2(7783):929     [PubMed PMID: 4116632]


Lakhanpal S, Ginsburg WW, Luthra HS, Hunder GG. Transient regional osteoporosis. A study of 56 cases and review of the literature. Annals of internal medicine. 1987 Mar:106(3):444-50     [PubMed PMID: 3813239]

Level 3 (low-level) evidence


Hofmann S. The painful bone marrow edema syndrome of the hip joint. Wiener klinische Wochenschrift. 2005 Feb:117(4):111-20     [PubMed PMID: 15847189]


Starr AM, Wessely MA, Albastaki U, Pierre-Jerome C, Kettner NW. Bone marrow edema: pathophysiology, differential diagnosis, and imaging. Acta radiologica (Stockholm, Sweden : 1987). 2008 Sep:49(7):771-86. doi: 10.1080/02841850802161023. Epub     [PubMed PMID: 18608031]


Aigner N, Petje G, Steinboeck G, Schneider W, Krasny C, Landsiedl F. Treatment of bone-marrow oedema of the talus with the prostacyclin analogue iloprost. An MRI-controlled investigation of a new method. The Journal of bone and joint surgery. British volume. 2001 Aug:83(6):855-8     [PubMed PMID: 11521928]


Plenk H Jr, Hofmann S, Eschberger J, Gstettner M, Kramer J, Schneider W, Engel A. Histomorphology and bone morphometry of the bone marrow edema syndrome of the hip. Clinical orthopaedics and related research. 1997 Jan:(334):73-84     [PubMed PMID: 9005898]


Sprinchorn AE, O'Sullivan R, Beischer AD. Transient bone marrow edema of the foot and ankle and its association with reduced systemic bone mineral density. Foot & ankle international. 2011 May:32(5):S508-12. doi: 10.3113/FAI.2011.0508. Epub     [PubMed PMID: 21733459]


Limaye R, Tripathy SK, Pathare S, Saeed K. Idiopathic transient osteoporosis of the talus: a cause for unexplained foot and ankle pain. The Journal of foot and ankle surgery : official publication of the American College of Foot and Ankle Surgeons. 2012 Sep-Oct:51(5):632-5. doi: 10.1053/j.jfas.2012.04.003. Epub 2012 May 18     [PubMed PMID: 22608351]


Korompilias AV, Karantanas AH, Lykissas MG, Beris AE. Bone marrow edema syndrome. Skeletal radiology. 2009 May:38(5):425-36. doi: 10.1007/s00256-008-0529-1. Epub 2008 Jul 16     [PubMed PMID: 18629460]


Radke S, Vispo-Seara J, Walther M, Ettl V, Eulert J. Transient bone marrow oedema of the foot. International orthopaedics. 2001:25(4):263-7     [PubMed PMID: 11561506]


Unay K, Poyanli O, Akan K, Guven M, Demircay C. The relationship between bone marrow edema size and knee pain. Knee surgery, sports traumatology, arthroscopy : official journal of the ESSKA. 2009 Nov:17(11):1298-304. doi: 10.1007/s00167-009-0842-9. Epub 2009 Jun 26     [PubMed PMID: 19557392]


Vanhoenacker FM, Snoeckx A. Bone marrow edema in sports: general concepts. European journal of radiology. 2007 Apr:62(1):6-15     [PubMed PMID: 17317067]


Fernandez-Canton G, Casado O, Capelastegui A, Astigarraga E, Larena JA, Merino A. Bone marrow edema syndrome of the foot: one year follow-up with MR imaging. Skeletal radiology. 2003 May:32(5):273-8     [PubMed PMID: 12679846]


Boos S, Sigmund G, Huhle P, Nurbakhsch I. [Magnetic resonance tomography of so-called transient osteoporosis. Primary diagnosis and follow-up after treatment]. RoFo : Fortschritte auf dem Gebiete der Rontgenstrahlen und der Nuklearmedizin. 1993 Mar:158(3):201-6     [PubMed PMID: 8453071]


Laroche M, Jacquemier JM, Montane de la Roque P, Arlet J, Mazières B. [Nifedipine per os relieves the pain caused by osteonecrosis of the femur head]. Revue du rhumatisme et des maladies osteo-articulaires. 1990 Oct:57(9):669-70     [PubMed PMID: 2075407]


Röhner E, Zippelius T, Steindl D, Fussi J, Perka C. Effects of intravenous iloprost therapy in patients with bone marrow oedema of the foot and ankle. European journal of orthopaedic surgery & traumatology : orthopedie traumatologie. 2014 Dec:24(8):1609-16. doi: 10.1007/s00590-013-1320-0. Epub 2013 Sep 19     [PubMed PMID: 24048706]


Baier C, Schaumburger J, Götz J, Heers G, Schmidt T, Grifka J, Beckmann J. Bisphosphonates or prostacyclin in the treatment of bone-marrow oedema syndrome of the knee and foot. Rheumatology international. 2013 Jun:33(6):1397-402. doi: 10.1007/s00296-012-2584-0. Epub 2012 Nov 10     [PubMed PMID: 23143557]


Bartl C, Imhoff A, Bartl R. Treatment of bone marrow edema syndrome with intravenous ibandronate. Archives of orthopaedic and trauma surgery. 2012 Dec:132(12):1781-8. doi: 10.1007/s00402-012-1617-1. Epub 2012 Oct 6     [PubMed PMID: 23053191]