Short-Term Bisphosphonate Therapy Could Ameliorate Osteonecrosis: A Complication in Childhood Hematologic Malignancies

Abstract

Osteonecrosis (ON) is a critical complication in the treatment of childhood leukemia and lymphoma. It particularly affects survivors of acute lymphoblastic leukemia and non-Hodgkin lymphoma reflecting the cumulative exposure to glucocorticosteroid therapy. ON is often multiarticular and bilateral, specially affecting weight-bearing joints. A conventional approach suggests a surgical intervention even if pharmacological options have also recently been investigated. We reported two cases of long time steroid-treated patients who underwent Bone Marrow Transplantation (BMT) for hematological disease. Both patients developed femoral head osteonecrosis (ON) that was diagnosed by magnetic resonance imaging (MRI) and the ON was also accompanied with pain and a limp. Despite of the conventional strategies of therapy, we successfully started a short-term treatment with bisphosphonates in order to decrease the pain and the risk of fracture.

Osteonecrosis in children and adolescents with acute lymphoblastic leukemia: a therapeutic challenge

“…35 Bisphosphonates reduce osteoclast activity and prevent osteocyte and osteoblast apoptosis and thus might reduce the direct toxic effects of chemotherapy on bone cells. [36][37][38][39][40][41][42] Adrenocorticotropic hormone stimulates vascular endothelial growth factor, which enhances osteoblast activity and revascularization of necrotic bone. 43,44 The aforementioned pharmacological interventions might be of most significant impact when applied concomitant with antileukemic treatment associated with hypercoagulopathy and hyperlipidemia to prevent the occurrence of stage I ON and the progression to stage II ON.…”

“…A detailed summary of pharmacological intervention studies and their outcomes is presented in Table 2. 29,31,35,[37][38][39][40]42,47 Prospective clinical trials are needed to elucidate potential toxicities and thus to facilitate an accurate risk/benefit analysis of these pharmacological interventions. ACTH, adrenocorticotropic hormone; ALCL, anaplastic large cell lymphoma; AML, acute myeloid leukemia; ARCO, association research circulation osseous; AVN, avascular necrosis; BME, bone marrow edema; BMT, bone marrow transplantation; GCS, glucocorticosteroids; HL, Hodgkin lymphoma; HR, high risk; LMW, low molecular weight; NHL, non-Hodgkin lymphoma; n.s., not specified; ON, osteonecrosis; po, by mouth; pts, patients; SR, standard risk.…”

Management and treatment of osteonecrosis in children and adolescents with acute lymphoblastic leukemia

“…17,19,23,26,27 As no proper controls were used in these studies, the real benefit for these drugs was not shown. Side effects consisted of acute phase reactions (headache, fever, nausea, vomiting, malaise), mainly after the first infusion.…”

“…Five studies provided data on bisphosphonates, 17,19,23,26,27 one study described an intervention with hyperbaric oxygen therapy, 20 and one study reported on a prostacyclin analog. 24 No studies compared the effectiveness of different antileukemic therapy adjustments as treatment option after the onset of osteonecrosis on the symptoms or radiological progression of osteonecrosis.…”

“…A search of the Cochrane Central Register of Controlled Trials (CENTRAL) and the Clinical Practice Guidelines (NGC) did not identify additional articles or guidelines about the treatment of osteonecrosis in children and adolescents. Fourteen articles specifically described pediatric ALL patients [16][17][18][19][20][21][22][23][24][25][26][27][28][29] and 36 articles partially addressed the population of interest. Of those 14 articles specifically describing pediatric ALL patients, 7 reported the results of non-surgical interventions and 7 reported the results of surgical interventions for osteonecrosis.…”