Introduction: Osteonecrosis can be a debilitating consequence of treatment for acute lymphoblastic leukaemia (ALL), most commonly affecting patients aged between 10 and 20 years at diagnosis of malignancy. Patients may have asymptomatic lesions that spontaneously regress, and little is known about the natural history of lesions. There is also limited understanding of the relationship between osteonecrosis and other markers of bone health.
Aims: The aims of the British OsteoNEcrosis Study (BONES) are to determine:
The incidence of symptomatic and asymptomatic osteonecrosis in patients aged between 1025 years undergoing treatment for acute lymphoblastic leukaemia (ALL) or lymphoblastic lymphoma, and variation in incidence at different time points in their treatment
Risk factors for progression and development of symptomatic osteonecrosis in this population
Specific radiological features predicting for progression or regression of osteonecrosis, with validation of a classification system for osteonecrosis
Vertebral fracture incidence and bone mineral density in these patients
Study Design: BONES is a multi-centre prospective, longitudinal cohort study based at tertiary childrens hospitals around the UK. Research Population: Patients aged 10 to 25 years with a first diagnosis of acute lymphoblastic leukaemia (ALL) or lymphoblastic lymphoma. Anticipated recruitment: 50 patients over 2 years. Methodology: Magnetic resonance imaging of lower limbs for assessment of osteonecrosis within 4 weeks of diagnosis, at the end of delayed intensification, and 1, 2 and 3 years after the start of maintenance therapy. Physiotherapy assessment will occur at the same time-points, with completion of the child health assessment questionnaire. Additional collection of clinical and biochemical data will include demographic information, prognostic and diagnostic data, BMI and phase of puberty, bone and lipid profile, PTH and vitamin D status. Bone mineral density and lateral vertebral assessment will be assessed at diagnosis and annually thereafter to a total of 4 assessments. Data analysis: A central review panel will assess MRI and DXA assessments. Vertebral fracture prevalence will be assessed using the Genant semi-quantitative method. Chi squared tests will be used for categorical variables to compare baseline characteristics between patients with and without osteonecrosis. The two sample t-test will be used for continuous variables with a normal distribution and the Mann-Whitney U test will be used for continuous variables with a skewed distribution. We will examine effect modification by risk factors such as age, sex, ethnicity and risk group by performing stratified analyses. Ethics: ethical approval has been obtained: REC ref: 16/YH/0206.
27 - 29 Sep 2018
European Society for Paediatric Endocrinology