Application of Bone Mineral Density Study Guidelines across California Pediatric Oncology Survivorship Programs
Authors: Joshirao Mrinal , Torno Lilibeth , Lin Carol Hwang , Panigrahi Arun Ranjan , Raphael Robert , Alvarez Griselda , Goldsby Robert , Kuo Dennis John 
Published: December 2024

INTRODUCTION
Advances in the treatment of children and adolescents with cancer have resulted in an increased percentage of pediatric cancer survivors (PCSs). However, PCSs are at increased risk of bone health issues from prolonged therapy with corticosteroids, higher cumulative corticosteroid dose, hematopoietic stem cell transplant (HCT), total body irradiation and cranial/craniospinal radiation which can decrease bone mineral density (BMD). Low BMD in PCS is associated with osteoporosis and osteopenia in adult life. The Children's Oncology Group's (COG) long-term follow-up (LTFU) guidelines (Version 6.0) recommend a baseline evaluation of BMD by DXA (Dual-energy X-ray absorptiometry) for PCS who received corticosteroids or HCT at entry into LTFU clinic (2 to 5 years after completion of therapy). Based on Z-scores the guidelines may recommend evaluation for endocrine defects and/or consultation with a bone health specialist with a repeat DXA after 2 years and thereafter as clinically indicated. Although there have been reports of fracture risk in pediatric cancer patients during or shortly after therapy, the fracture risk in PCS with low BMD for chronologic age based on Z-scores has not been established. The aim of this study is to review the extent of the clinical application of bone mineral density study guidelines across six California pediatric oncology cancer survivorship programs and determine the variation in practices based on low BMD.

METHODS
We performed a multicenter, retrospective chart review of PCSs from January 1, 2015, to Dec 31, 2019, at six children's hospitals in California affiliated with the University of California. Each participating site collected its own data from their institutional electronic medical records to analyze the utilization patterns of DXA scans in screening for low BMD in PCS. The study was approved by the Institutional Review Board of each hospital. Patients included were between 0-25 years of age at the time of cancer diagnosis, who had a DXA scan performed as part of off-therapy care and were followed at the LTFU clinic at the participating sites. Demographic, clinical and treatment data were collected, along with the DXA scan results (whole body, lumbar spine or femoral neck adjusted for age and gender) and the actions taken based on DXA scan results such as referrals to other subspecialties or pharmacotherapy. The number of new diagnoses in 2018 was included to estimate the relative sizes of the programs.

RESULTS
A total of 529 PCS patients met inclusion criteria at the six participating hospitals over the period of 5 years. The percentage of patients who were referred to other specialties based on DXA scan results varied from 0% to 46% at the different hospitals. The number of patients who were started on bisphosphonates across all the hospitals varied from 0% to 10%. The most common diagnosis overall in PCS who had DXA scans was acute lymphoblastic leukemia.

CONCLUSION
The study findings demonstrate that the current guidelines are neither universally nor uniformly applied. Practices regarding ordering DXA scans and ordering referrals based on the results varied in the different participating hospitals across California. We suggest updating the guidelines to be more targeted to more effectively direct resources to those most likely to benefit from screening and referral. Further research is necessary to determine the prevalence of treatment-related bone health issues and the most effective strategies for minimizing risk of osteopenia and osteoporosis during adulthood in PCS.