This large cohort of childhood cancer survivors identified osteopenia in 45% of CCS. This indicates that greater awareness is warranted, especially in survivors who are older than 30 years, male, have underweight and were treated with cranial-spinal radiotherapy and/or steroids.

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Purpose: Osteopenia is a potential complication of childhood cancer treatment, but the magnitude of this problem in survivors is unknown. We examined (determinants of) bone mineral density (BMD) status in long-term survivors of adult childhood cancer (CCS). Methods: This retrospective single-center cohort study included 346 subjects with the most common types of childhood cancer. Acute leukemia or lymphoma was diagnosed in 273 (81%) of the patients. All subjects had a median age at diagnosis of 7.0 years (range: 0.1-16.8 years) and a median follow-up time of 16.7 years (range 5.6-39.9 years). Total body BMD (BMDTB) and BMD of the lumbar spine (BMDLS) were measured by dual-X-ray absorptiometry. Osteopenia was defined as BMD standardized deviation score (SDS) below -1. Twelve candidate single nucleotide polymorphisms (SNPs) in 11 genes (COL1A1, TNFSF11, TNFRSF11, TNRFSA11B, VDR, ESR1,WLS, LRP5, MTHFR, MTRR, IL6) were investigated. Results: Survivors had a lower BMDTB and BMDLS (mean SDS: -0.55, p<0.001; and -0.30, p<0.001, respectively) as compared to healthy peers. This was similar in cancer survivors of leukemia and lymphoma (mean SDS: -0.49, p<0.001; and -0.32, p<0.001, respectively). Osteopenia (BMDTB and/or BMDLS) was present in 45% of the survivors (46% of the leukemia and lymphoma survivors). Multivariate logistic regression analyses identified age at diagnosis <12 years, age >30 years at follow-up, male gender, underweight at follow-up, carriers of the minor allele of rs2504063 (LRP5), treatment with cranial-spinal radiotherapy and prednisone as independent prognostic factors for osteopenia. In survivors of leukemia and lymphoma, we identified low BMI at follow-up, carriers the minor allele of rs2504063 (LRP5), treatment with cranial-spinal radiotherapy and cyclophosphamide use as prognostic factors for osteopenia. Conclusions: This large cohort of childhood cancer survivors with the long follow-up identified osteopenia in 45% of CCS. This indicates that greater awareness for low BMD is warranted, especially in survivors who are older than 30 years, male, have underweight, have a genetic predisposition, and who were treated with cranial-spinal radiotherapy and/or steroids. Disclosures No relevant conflicts of interest to declare.

4296 Background Aim of this study was to investigate status and longitudinal evolvement of BMD in long-term adult survivors. Patients and methods A single-center cohort of 410 adult long-term survivors (171 females) was included in this retrospective study. Age at diagnosis was 6.6 years (0.0–16.8 yrs), and at follow up 24.5 years (18.0–49.3 yrs). Median follow-up time was 15.2 years (5.1–39.8 yrs). BMD of the lumbar spine (BMDLS) and total body (BMDTB) were measured. Results were compared with healthy age matched controls. Results Overall BMDTB and BMDLS were low in long-term survivors (median standard deviation score (SDS) −0.60, P < 0.001 and median SDS −0.40, P < 0.001 respectively). In ALL survivors both BMDTB (median SDS −0.65, P < 0.001) and BMDLS (median SDS −0.48, P < 0.001) were low. Backwards elimination of the multivariate linear regression analysis showed that both cranial irradiated and/or total body irradiated survivors were at significant risk for low BMDTB. BM(A)DLS was not different between survivors and controls and no risk factors were identified for low BM(A)DLS. In general, a slight but significant improvement of BMDTB and BMDLS was found in our sequential measurement. This BMD improvement was not found for ALL survivors alone. Conclusions Our study shows low BMD in childhood cancer survivors treated with cranial or total body irradiation. However, sequential DXA analysis shows ongoing recovery of bone mass, which suggests a potential for reaching peak bone mass later in life. Disclosures: No relevant conflicts of interest to declare.