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J R Soc Med. 2001 December; 94(12): 635–636.
PMCID: PMC1282297

Bilateral osteonecrosis of the tarsus coincident with glioblastoma multiforme

Manolis Heliotis, MSc FDSRCS, Eleftherios Tsiridis, MSc FRCS,1 Simon T Donell, BSc FRCS(Orth),2 Thomas J Marshall, FRCR,2 and David G Scott, MD FRCP2

The presence of two rare conditions in a single patient—bilateral osteonecrosis of the tarsal bones and glioblastoma multiforme of the brain—raises the possibility of a causal association.

CASE HISTORY

A woman of 55 reported pain in both ankles for three months. There was no history of trauma or vascular disease and she had not taken any prescription medication for several years. Nothing abnormal was found on general physical examination. The ankle and hindfoot had diffuse discomfort, without swelling or increase in temperature. Ankle, hindfoot, and midfoot movements were normal. Blood analyses including haematological, rheumatological, and bone screening were unremarkable. Bilateral plain radiographs of the hands and the ankles were normal. A bone scan demonstrated focal areas of increased uptake in the tarsal bones bilaterally. A magnetic resonance imaging (MRI) scan of the feet revealed bone oedema in the right medial cuneiform and left navicular bones consistent with ischaemic necrosis. A biopsy specimen from the left navicular bone, taken under fluoroscopic control, showed no organisms or crystals and no bacterial growth was obtained on culture. Histopathological examination demonstrated thickened bony trabeculae with evidence of remodelling in the past, but the process appeared inactive.

The patient was diagnosed as having avascular necrosis of the right medial cuneiform and left navicular bones and was treated for six weeks with a left below-knee non-weight-bearing fibreglass cast.

Five months later she developed headaches with dizziness, and soon afterwards she was admitted with a Glasgow coma score of 5. Computerized tomography revealed a heterogeneous lesion in the right frontal lobe with a marked midline shift and contralateral ventricular dilatation. She underwent a right frontal lobectomy and the histopathological diagnosis was glioblastoma multiforme WHO grade IV. She subsequently received postoperative radical radiotherapy but died after about three months.

COMMENT

Avascular necrosis of the navicular bone may have no apparent cause or be secondary to trauma or an underlying medical condition1. In almost all cases with an underlying medical disorder the lesion is bilateral; many patients give a history of chronic steroid use1. Avascular necrosis is believed to arise from disruption to the microvasculature of the bone2,3, with resultant infarction3. Corticosteroid therapy, familial thrombophilia, hyperlipidaemia and tissue factor release (from inflammatory bowel disease, malignancy) all predispose to avascular necrosis2,3, and cytokines such as tumour necrosis factor α and transforming growth factor β (TGF-β)5 have been proposed as mediators by inhibiting angiogenesis.

Several cytokines and their receptors have been identified as important in glioblastoma multiforme, among which TGF-β is pivotal6. In normal glial cells it functions as an autocrine factor, inhibiting cell proliferation, differentiation and matrix synthesis7. It also inhibits the growth of endothelial cells, activates coagulation and inhibits fibrinolysis8. By contrast, in glioblastomas and other central nervous system tumours TGF-β acts as a progression factor and mitogen6. We suggest that, in the case reported here, TGF-β, released by the glioma, could have caused the avascular necrosis through its antiangiogenic and prothrombotic effects. Why involvement of the tarsus and not some other bone? This may reflect the specificity of TGF-β for particular extracellular matrices7.

References

1. Haller J, Sartoris DJ, Resnick D, et al. Spontaneous osteonecrosis of the tarsal navicular in adults: imaging findings. Am J Roentgenol 1988;151: 355-8 [PubMed]
2. Glueck CJ, Freiberg R, Tracy T, Stroop D, Wang P. Thrombophilia and hypofibrinolysis: pathophysiologies of osteonecrosis. Clin Orthop 1997;334: 43-56 [PubMed]
3. Smith DW. Is avascular necrosis of the femoral head the result of inhibition of angiogenesis? Med Hypoth 1997;49: 497-500 [PubMed]
4. Kirchhofer D, Tschopp TB, Hadvary P, Baumgartner HR. Endothelial cells stimulated with tumor necrosis factor-alpha express varying amounts of tissue factor resulting in inhomogenous fibrin deposition in a native blood flow system. Effects of thrombin inhibitors. J Clin Invest 1994;93: 2073-83 [PMC free article] [PubMed]
5. Ray Chaudhury A, D'Amore PA. Endothelial cell regulation by transforming growth factor-β. J Cell Biochem 1991;47: 224-9 [PubMed]
6. Jennings MT, Pietenpol JA. The role of transforming growth factor beta in glioma progression. J Neurooncology 1998;36: 123-40 [PubMed]
7. Ripamonti U, Duneas N, Van Den Heever B, Bosch C, Crooks J. Recombinant transforming growth factor-beta 1 induces endochondral bone in the baboon and synergizes with recombinant osteogenic protein-1 (bone morphogenetic protein-7) to initiate rapid bone formation. J Bone Miner Res 1997;12: 1584-95 [PubMed]
8. Jones JP, Jr. Coagulopathies and osteonecrosis. Acta Orthop Belg 1999;65(suppl 1): 5-8 [PubMed]

Articles from Journal of the Royal Society of Medicine are provided here courtesy of Royal Society of Medicine Press