From marrow edema to osteonecrosis
Centre for Transplant and Renal Research, Westmead Millennium Institute, Sydney, New South Wales, Australia.
Osteonecrosis, the calcineurin-inhibitor-induced pain syndrome and transient marrow oedema may occur after renal transplantation, are generally painful and can be diagnosed by X-ray, radionuclide scan or magnetic resonance imaging. They share features of increased intraosseous pressure, compromised vascular supply, marrow oedema and the development of a 'bone compartment syndrome'. Glucocorticoid dosage is the most commonly implicated risk factor for osteonecrosis. Mechanisms may include the differentiation of mesenchymal stem cells to adipocytes causing increased intraosseous pressure and collapse of marrow sinusoids, as well as increased osteoblast and osteocyte apoptosis. Some of these effects may be ameliorated by lipid lowering drugs. Calcineurin-inhibitors, particularly cyclosporine, may increase the risk of osteonecrosis because of vasoconstrictive effects and sirolimus may influence the development of osteonecrosis by potentiating the effects of calcineurin inhibitors or by influencing the lipid profile.
For osteonecrosis, early stages are generally managed conservatively or with core decompression sometimes accompanied by bone grafting and more recently the injection of bone morphogenic protein. The use of iloprost to improve blood flow and bisphosphonates and RANK-ligand inhibition to reduce osteoclastic resorption of remaining trabecular structures are as yet unproven strategies. Unfortunately, the rate of total hip arthroplasty remains high. For the calcineurin-inhibitor-induced pain syndrome and transient marrow oedema, calcium channel blockers, the reduction or withdrawal of calcineurin-inhibitors and core decompression have been used.
Although a lack of randomized controlled trials makes management decisions difficult, early recognition of these bone pain syndromes affords the best opportunity for avoiding prolonged pain or joint replacement surgery.
KEY WORDS: bone pain, calcineurin inhibitors, glucocorticoid, marrow oedema, osteonecrosis