Bisphosphonate treatment in children with acute lymphoblastic leukemia and osteonecrosis – radiological and clinical findings in a national cohort

Abstract

Osteonecrosis (ON) is a recognized complication of childhood ALL, but its optimal management remains unestablished. This study evaluated the effect of bisphosphonate (BP) treatment on evolution of ON lesions in childhood ALL.We included a national cohort of ALL patients diagnosed with symptomatic ON before 18 years of age and treated with BPs (N=10; five males). Patients were followed both clinically and with serial MRIs. ON lesions were graded according to the Niinimäki classification.The 10 patients had a total of 55 ON lesions. The median age was 13.3 years at ALL diagnosis and 14.8 years at ON diagnosis. Four patients had received HSCT before the ON diagnosis. BPs used were pamidronate (N=7), alendronate (N=2) and ibandronate (N=1). The duration of BP treatment varied between 4 months and 4 years. In 4/10 patients, BP treatment was given during the chemotherapy. BPs were well tolerated, with no severe complications or changes in kidney function. At the end of follow up 13/55 (24%) ON lesions were completely healed both clinically and radiographically; all these lesions were originally graded 3 or less. In contrast, ON lesions originally classified as grade 5 (joint destruction; N=4) remained at grade 5. All grade 5 hip joint lesions needed surgical treatment. During BP treatment, pain was relieved in 7/10 patients. At the end of follow up, none of the patients reported severe or frequent pain.BP treatment was safe and seemed effective in relieving ON-induced pain in childhood ALL. After articular collapse (Grade 5) lesions did not improve with BP treatment.Randomized controlled studies are needed to further elucidate the role of BPs in childhood ALL-associated ON.

Bisphosphonate treatment for skeletal complications in paediatric cancer—Experience from a single tertiary centre

“…There is no evidence, however, for an effect on the healing of the osteonecrosis per se in this patient group. Our previous study in children with ALL‐related osteonecrosis also indicates that bisphosphonate treatment does not help if it has already led to joint damage 15 . The effect of bisphosphonates on the healing process of osteonecrosis lesions cannot be confirmed with the current study setting.…”

“…Our previous study in children with ALL-related osteonecrosis also indicates that bisphosphonate treatment does not help if it has already led to joint damage. 15 The effect of bisphosphonates on the healing process of osteonecrosis lesions cannot be confirmed with the current study setting. Whether the bisphosphonates can prevent the osteonecrosis lesions from progressing joint collapse remains unanswered.…”

“…4 In most patients, there was a marked delay between the diagnosis of the skeletal complication and application of the bisphosphonate treatment, as was also seen in our previous study on 10 children with ALL-related osteonecrosis treated with bisphosphonates. 15 The potential beneficial effects of bisphosphonate treatment are probably compromised if administered too late when the active metabolic process in the bone has already ceased.…”

Supportive methods for childhood acute lymphoblastic leukemia then and now: A compilation for clinical practice

“…The management of osteonecrosis in childhood ALL is risk-stratified and ranges from observation and adaptation of therapy with cytostatics and corticosteroids to pharmaceutical and surgical approaches ( 110 ). It has been shown that therapy with bisphosphonates (combined with dietary calcium, vitamin D and physical therapy) was able to reduce pain and thus increase mobility, but not stop the destruction of joints ( 31 , 111 ). In addition, new conservative therapeutic methods such as hyperbaric oxygen therapy have been used further to ameliorate the outcome ( 108 ).…”