{"doi":"10.1111/bjh.16589","title":"Incidence of hip and knee osteonecrosis and their associations with bone mineral density in children with acute lymphoblastic leukaemia","abstract":"Patients undergoing treatment for acute lymphoblastic leukaemia (ALL) are at risk for bone morbidities such as osteonecrosis and low bone mineral density (BMD). We evaluated the incidence of hip and knee osteonecrosis (scored as ≥30% or <30% epiphyseal involvement), identified prospectively by magnetic resonance imaging (MRI) regardless of symptoms, and the associated risk factors in 334 children (aged 2–18 years at diagnosis) with ALL who were enrolled on the Total Therapy Study XV (clinicaltrials.gov identifier: NCT00137111).1 We also studied the association of hip and knee osteonecrosis with BMD Z-scores as evaluated with quantitative computed tomography at the first and second lumbar vertebral levels. The Total XV treatment, evaluations of osteonecrosis and BMD, and statistical analysis are described in the supporting document. MRI screening was performed at the completion of reinductions I and II and at the completion of therapy.2 BMD was determined at diagnosis, after 120 weeks of continuation therapy, and two years after the completion of therapy, and was standardised to age- and sex-specific Z-scores.3 We defined a BMD Z-score of –2.0 or lower as indicating profoundly low BMD. The demographics of 334 patients are shown in Table I and Figure S1. Hip osteonecrosis was seen in 40 patients (12.0%): 24 (7.2%) with ≥30% epiphyseal involvement, and 16 (4.8%) with <30% epiphyseal involvement. Knee osteonecrosis was observed in 198 patients (59.3%): 51 (15.3%) with ≥30% epiphyseal involvement, and 147 (44.0%) with <30% epiphyseal involvement, with a prevalence of 2.1 and 5.0 times that of the respective hip osteonecrosis (Tables I and SI). Multivariable analysis showed that older age (≥10 years) at diagnosis was significantly associated with higher incidences of osteonecrosis with ≥30% epiphyseal involvement of the hip (P = 0.007), any epiphyseal involvement of the hip (P <0.001), and ≥30% epiphyseal involvement of the knee (P <0.001), when compared to incidences in patients aged 2–9.9 years (Table I). For knee osteonecrosis, standard/high-risk disease was significantly associated with higher incidences of ≥30% epiphyseal involvement (P = 0.001) and any epiphyseal involvement (P = 0.032) when compared to the low-risk disease. Table II shows the associations between the degree of osteonecrosis and the BMD Z-score after adjustment for BMD Z-score at diagnosis and race. The median BMD Z-score at diagnosis for patients with knee osteonecrosis involving ≥30% of the epiphysis was significantly higher than that for the combined cohorts with <30% or no epiphyseal involvement (P = 0.026). At week 120 of continuation therapy, hip and knee osteonecrosis were associated with median BMD Z-scores that were significantly lower than those of other groups, regardless of the degree of epiphyseal involvement (P ≤0.007 for all). At two years off therapy, patients with any knee epiphyseal involvement had median BMD Z-scores which were significantly lower than those of patients without osteonecrosis (P = 0.026). When the median BMD Z-score changes from week 120 of continuation therapy to two years off therapy were evaluated, the increases in Z-scores were significantly greater for patients with ≥30% epiphyseal involvement of the hip (P = 0.018), any epiphyseal involvement of the hip (P = 0.004), and any epiphyseal involvement of the knee (P = 0.031) than for other groups. Figure S2, Table SII, and the supplemental document show the association of BMD Z-scores with hip and knee osteonecrosis categorised into three groups (none, <30%, and ≥30% epiphyseal involvement). The median BMD Z-scores were decreased at week 120, relative to the Z-scores at diagnosis, but showed subsequent improvement at two years off therapy; these changes were more prominent in those individuals with ≥30% epiphyseal involvement. Knee osteonecrosis with ≥30% epiphyseal involvement as well as with any epiphyseal involvement was significantly associated with profoundly low BMD Z-","journal":"British Journal of Haematology","year":2020,"id":86008,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":15,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.955,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":395545,"name":"Xueyuan Cao","orcid":"0000-0002-4396-7460","position":1,"is_corresponding":false},{"id":439364,"name":"Jennifer Y. Chang","orcid":"0000-0002-2152-5071","position":2,"is_corresponding":false},{"id":254764,"name":"Seth E. Karol","orcid":"0000-0001-8113-8180","position":3,"is_corresponding":false},{"id":285755,"name":"John C. Panetta","orcid":"0000-0003-1308-7208","position":4,"is_corresponding":false},{"id":255612,"name":"Kirsten K. Ness","orcid":"0000-0002-2084-1507","position":5,"is_corresponding":false},{"id":439365,"name":"Cheng Cheng","orcid":"0000-0001-9226-1547","position":6,"is_corresponding":false},{"id":254773,"name":"Ching‐Hon Pui","orcid":"0000-0003-0303-5658","position":7,"is_corresponding":false},{"id":258248,"name":"Mary V. Relling","orcid":"0000-0002-3720-9591","position":8,"is_corresponding":false},{"id":257205,"name":"Sue C. Kaste","orcid":null,"position":9,"is_corresponding":false},{"id":285762,"name":"Hiroto Inaba","orcid":"0000-0003-0605-7342","position":0,"is_corresponding":true}],"reference_count":5,"raw_metadata":null,"created_at":"2026-07-18T21:58:41.997408Z","pmid":"32207157","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}