Bone mineral density surveillance for childhood, adolescent, and young adult cancer survivors: evidence-based recommendations from the International Late Effects of Childhood Cancer Guideline Harmonization Group

Summary

Childhood, adolescent, and young adult cancer survivors are at increased risk of reduced bone mineral density. Clinical practice surveillance guidelines are important for timely diagnosis and treatment of these survivors, which could improve bone mineral density parameters and prevent fragility fractures. Discordances across current late effects guidelines necessitated international harmonisation of recommendations for bone mineral density surveillance. The International Late Effects of Childhood Cancer Guideline Harmonization Group therefore established a panel of 36 experts from ten countries, representing a range of relevant medical specialties. The evidence of risk factors for very low and low bone mineral density and fractures, surveillance modality, timing of bone mineral density surveillance, and treatment of very low and low bone mineral density were evaluated and critically appraised, and harmonised recommendations for childhood, adolescent, and young adult cancer survivors were formulated. We graded the recommendations based on the quality of evidence and balance between potential benefits and harms. Bone mineral density surveillance is recommended for survivors treated with cranial or craniospinal radiotherapy and is reasonable for survivors treated with total body irradiation. Due to insufficient evidence, no recommendation can be formulated for or against bone mineral density surveillance for survivors treated with corticosteroids. This surveillance decision should be made by the survivor and health-care provider together, after careful consideration of the potential harms and benefits and additional risk factors. We recommend to carry out bone mineral density surveillance using dual-energy x-ray absorptiometry at entry into long-term follow-up, and if normal (Z-score > −1), repeat when the survivor is aged 25 years. Between these measurements and thereafter, surveillance should be done as clinically indicated. These recommendations facilitate evidence-based care for childhood, adolescent, and young adult cancer survivors internationally.

Introduction

The survival of children, adolescents, and young adults with cancer has greatly improved over recent decades, with current 5-year overall survival rates approximating 80% in high-income countries.1, 2 However, childhood, adolescent, and young adult cancer survivors often experience long-term side effects.3, 4 Previous studies suggest an increased proportion of survivors with low (Z-score ≤–1) and very low (Z-score ≤–2) bone mineral density compared with the general population5, 6 as well as an increased fracture rate.7, 8 Bone mineral density deficits could occur due to the cancer itself, its treatment, or consequences such as endocrine defects (eg, hypogonadism, growth hormone deficiency, malnutrition or consequences such as endocrine defects (eg, hypogonadism, growth hormone deficiency), malnutrition or malabsorption, and sedentary lifestyles.9, 10, 11 These factors can lead to impaired bone accrual, resulting in a lower peak bone mass, usually achieved in people aged between 20 and 30 years.12, 13 Because peak bone mass predicts osteoporosis in adulthood and affects the age of osteoporosis onset,¹⁴ it is hypothesised that as the current childhood, adolescent, and young adult cancer survivor population ages, more survivors might experience fragility fractures at relatively young ages.¹⁵ These fragility fractures could cause substantial morbidity such as reduced mobility, chronic pain, and difficulty with performing activities of daily living.¹⁶

General population studies have shown that early detection and treatment of very low and low peak bone mass acquisition might overcome suboptimal peak bone density acquisition and prevent fractures.17, 18 Therefore, several North American and European groups have implemented bone mineral density surveillance in their clinical practice survivorship guidelines.19, 20, 21, 22 However, these guidelines have not systematically analysed the literature. Thus, definitions of high-risk groups, timing of surveillance, and treatment recommendations vary considerably, which impedes effective international implementation and adherence. To overcome such limitations, the International Late Effects of Childhood Cancer Guideline Harmonization Group (IGHG) was established.²³ This collaborative endeavor aimed to establish a common vision and integrated strategy for surveillance of chronic health problems in childhood, adolescent, and young adult cancer survivors. This IGHG report summarises available evidence and provides the first harmonised recommendations for bone mineral density surveillance among childhood, adolescent, and young adult cancer survivors.