Transient Primary Bone Marrow Edema Syndrome - Systematic Review and Proposal for a Management Protocol

Background: Transient primary bone marrow edema syndrome (TPBMES), a set of conditions affecting weight-bearing joints, mostly of the lower limbs, presents acutely with severe local pain, disproportionate to the physical findings. This disease is designated by an array of terms, not all of which are in the consensus. But they seem to refer to a single disease entity, whether the hips, the knees, or the foot and ankle are affected, singly, bilaterally, or in a migratory pattern. The diagnosis of bone marrow edema of a temporary nature is based on the MRI. Moreover, systemic osteoporosis has been detected in association with some cases of TPBMES, but the significance of this combined occurrence is not clear. Moreover, whether "migratory" TPBMES represents a more aggressive expression of the disease is not yet settled.

Objectives: This study was initiated to resolve the numerous ambiguities concerning this disease entity.

Data Sources: A search in PubMed looking for TPBMES or equivalent terms.

Study Eligibility Criteria: Single or isolated case reports were excluded. Two reviews were excluded as they did not agree with the basic classification of the entity. Inclusion criteria of patients: a history of sudden onset of pain in the affected joint, in the absence of more than minimal trauma, and confirmation of bone marrow edema by MRI and follow-up evidence of the resolution, as shown by MRI. Exclusion criteria of patients: insidious onset of pain and evidence of avascular necrosis, infection, significant trauma of bone, stress fractures, or inflammatory arthropathy, based on the MRI and the laboratory. Remote studies were not based on the MRI.

Study Appraisal and Synthesis Methods: Based on a review featuring 141 patients, several clinical, radiological and pathological data were extracted into an all-inclusive table (not shown). Four tables were built thereof. Tables 2-4 were conceived to summarize independently all the variables in every recognized form of TPBMES (see Table 1). The association between TPBMES and systemic osteoporosis is shown in an additional table.

Results: Table 2 features the demographic and clinical studies, as distributed among the different TPBMES subtypes. A total of 546 patients were assigned mainly to 342 TOH patients, most of them males. Next, were 105 patients with TOH of pregnancy. A lesser subset was composed of 49 F&A patients, mainly women. Table 3 shows the allocation of clinical features and risk factors to TPBMES subsets. Pain was by far the most frequent symptom. Subchondral fractures were detected in TOH and TOH of pregnancy. Overweight and vitamin D deficiency have been suggested as additional risk factors. Table 4 depicts the treatment and follow-up of TPBMES patients. Bisphosphonates have been recommended for TOH and "migratory" osteoporosis patients. Tables 5 and 6 demonstrate the interaction between TPBMES and systemic osteoporosis and with migratory osteoporosis, highlighting the common self-limited nature of TPBMES, as well as the frequently extended course of this combined occurrence.

Limitations: See Fig. 1.

Conclusions: The different subsets in the TPBMES classification have several features in common, notably an MRI-based diagnosis and a self-limited outcome, even in the absence of modern therapy. Thus, they should be considered as belonging to a single disease entity, with some variable traits. Of note, a tendency for TPBMES to be associated with systemic osteoporosis, sometimes in addition to a "migratory" pattern, has been reported in conjunction with an abnormally extended course of the disease. These are the patients who raised our concern and who evoked the necessity for a therapeutic intervention to limit their suffering (see suggested management protocol, Fig. 2).