Is There An Association Between Bone Marrow Edema Syndrome And Vitamin D Deficiency?

Bone marrow edema (BME) is a common radiographic finding of increased intraosseous fluid signal on magnetic resonance imaging (MRI) or even ultrasound (US) that clinicians see with various types of bone injury. However, bone marrow edema may present without injury in cases of infection, osteonecrosis, neurologic disorder, degenerative lesion, metabolic disorders, and neoplasm.¹

Interestingly, Curtiss and Kincaid first described bone marrow edema as “transient osteoporosis” in pregnant women in 1959.² However, this term was later modified to bone marrow edema to more accurately reflect the findings observed on MRI. Oddly enough, histopathological examination of bone marrow edema does not demonstrate actual true edema but rather fibrosis, areas of necrosis and demineralization, and microfractures.³

Bone marrow edema may progress clinically to bone marrow edema syndrome with prolonged chronicity of pain. This may present in a transient, recurrent or even migratory manner, and primarily affects the lower extremities. Oehler and colleagues showed that bone marrow edema syndrome almost exclusively influences weightbearing joints and areas of high bone turnover.⁴ In the foot and ankle, it is predominant in the talus, calcaneus, cuboid and navicular bones, and consistently affects the cancellous portion of bone.^5,6 While old habits die slowly, musculoskeletal radiologists have been slow to change bone marrow edema syndrome to bone marrow lesion, which would seem to be a more descriptive term.

Current Perspectives On The Pathomechanics Of Bone Marrow Edema Syndrome

Controversy exists in terms of the exact pathomechanics of bone marrow edema syndrome although theories include increased pressure in the intramedullary canal, microtrauma and incomplete venous outflow.⁷ No theory, though, has surfaced to definitively show the etiology for bone marrow edema syndrome to date.

Some argue that bone marrow edema syndrome is an early and mild form of osteonecrosis.⁸ However, histologic features of bone marrow edema syndrome include increased osteoid volumes, decreased hydroxyapatite content and increased concentration of undermineralized bone, which all differ from the features of osteonecrosis.⁹ Geith and colleagues compared the imaging patterns of osteonecrosis versus bone marrow edema syndrome and found distinct differences on dynamic contrast-enhanced MRI.¹⁰ They showed osteonecrosis presented as a “rim of high plasma flow surrounding a subchondral area without detectable perfusion” whereas bone marrow edema syndrome showed “a subchondral spot of marked hyperperfusion.” Also, a study conducted by Klontzas and coworkers showed that out of the 155 patients with bone marrow edema syndrome, no patients developed osteonecrosis.¹¹

Still, others have found a close association between vitamin D deficiency and bone marrow edema syndrome. Alsaed and colleagues presented a 47-year-old male with recurrent bone marrow edema syndrome in bilateral knees, who was diagnosed with low bone mineral density secondary to vitamin D deficiency.¹² Sprinchorn and coworkers found reduced bone mineral density as well as vitamin D deficiency in 90 percent of the patients with bone marrow edema syndrome in their cohort.¹³ Other literature suggests that vitamin D deficiency may play a significant role in not only the presence but also the progression of bone marrow edema syndrome. Horas and colleagues detected low serum vitamin D levels in 90 percent of their cohort of 31 patients with bone marrow edema syndrome.¹⁴ Miller and coworkers found that 83 percent of their patients with foot and ankle stress fracture had suboptimal serum Vitamin D levels, a known risk factor for stress fracture.¹⁵ Additionally, Kaspiris and coworkers reported on a pediatric patient with bone marrow edema syndrome, who had low serum vitamin D.¹⁶

Assessing The Treatment Options

Although bone marrow edema syndrome is weakly understood at this juncture, there are multiple therapeutic interventions for this condition. Surgical core decompression, injectable bone graft substitution, extracorporeal shock wave therapy, bisphosphonates, prostaglandin derivatives and administration of TNF-inhibitors have all shown some value in treating these patients.^1,6 Kaspiris and coworkers treated a patient with bone marrow edema syndrome conservatively with NSAIDs, modified weightbearing and vitamin D supplementation and achieved complete clinical and radiographic resolution after just six months.¹⁶

Perhaps successful treatment with vitamin D supplementation, minimized ambulation and inhibitors of osteoclastic activity can help correct and maintain bone homeostasis, and shield against microtrauma in demineralized bone to allow sufficient healing and prevent further injury.

In Conclusion

Bone marrow edema syndrome represents a unique progression of symptoms with or without a history of acute or remote trauma or injury. Our current understanding of bone marrow edema syndrome is that is multifactorial and thus more difficult to diagnose and treat. Therefore, maintaining an index of suspicion with any chronic idiopathic foot and ankle pain is key.

One’s threshold to pursue advanced imaging in the form of MRI should be low in order to provide a more thorough evaluation for bone marrow edema syndrome. In the senior author’s experience, bone stimulation with long periods of immobilization have failed to yield adequate results in resolving bone marrow edema syndrome. Finally, the use of therapeutic vitamin D supplementation, although weakly supported in the literature at this time, may represent not only a benefit in pathology resolution but may also substantiate an association of bone marrow edema syndrome with vitamin D deficiency.

Future research should seek a stronger evidence of relation between bone marrow edema syndrome and vitamin D deficiency in order to more efficiently screen and treat these patients. It is our hope that as technology and understanding evolves, we can ultimately improve our ability to more accurately diagnose, treat and even provide prophylaxis for patients with bone marrow edema syndrome.  

This DPM Blog was co-written with Liang-Chieh Ko, DPM, a first-year resident within the PMSR/RRA program at Tower Health/Phoenixville Hospital in Phoenixville, Pa, and Jayson N. Atyes, DPM, a Fellow with the Pennsylvania Intensive Lower Extremity Fellowship at Premier Orthopaedic and Sports Medicine and the Pennsylvania Orthopaedic Center in Malvern, Pa.

References

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3. Hunter DJ, Gerstenfeld L, Bishop G, et al. Bone marrow lesions from osteoarthritis knees are characterized by sclerotic bone that is less well mineralized. Arthritis Res Ther. 2009; 11(1):R11.
4. Oehler N, Mussawy H, Schmidt T, Rolvien T, Barvencik F. Identification of vitamin D and other bone metabolism parameters as risk factors for primary bone marrow oedema syndrome. BMC Musculoskelet Disord. 2018;19(1):451.
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7. Rosen RA. Transitory demineralization of the femoral head. Radiology. 1970; 94(3):509-12
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10. Geith T, Niethammer T, Milz S, Dietrich O, Reiser M, Baur-Melnyk A. Transient bone marrow edema syndrome versus osteonecrosis: perfusion patterns at dynamic contrast-enhanced MR imaging with high temporal resolution can allow differentiation. Radiology. 2017; 283(2):478-485.
11. Klontzas ME, Vassalou EE, Zibis AH, Bintoudi AS, Karantanas AH. MR imaging of transient osteoporosis of the hip: An update on 155 hip joints. Eur J Radiol. 2015; 84(3):431-436.
12. Alsaed O, Hammoudeh M. Recurrent migratory transient bone marrow edema of the knees associated with low vitamin D and systemic low bone mineral density: a case report and literature review. Case Reps Rheumatol. 2018; 2018:7657982.
13. 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 Int. 2011; 32(5):508-12.
14. Horas K. Response to “Letter regarding: high prevalence of vitamin D deficiency in patients with bone marrow edema syndrome of the foot and ankle.” Foot Ankle Int. 2017; 38(7):768.
15. Miller JR, Dunn KW, Ciliberti LJ Jr., et al. Association of Vitamin D with stress fractures: a retrospective cohort study. J Foot Ankle Surg. 2016; 55(1):117-20.
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