Commentary on “Changes in Bone Health During the First Year of Cancer Treatment in Children”

The article entitled “Changes in Bone Health During the First Year of Cancer Treatment in Children,” by Choi et al, aimed to evaluate longitudinal changes in bone mineral density (BMD) and bone mineral content in childhood cancer survivors (CCSs) (1). Bone health is an important endocrine and musculoskeletal issue in CCSs. Based primarily on cross-sectional studies, moderate-to-severe BMD deficits (Z-score < −1) have been documented with estimates indicating bone impairments in nearly 50% of CCSs (2). The main finding herein was the significant effects of cancer treatment on bone health during the first year apparent especially during the first 6 months for hematologic malignancies and the last 6 months in solid tumors. “Skeletal morbidity remains one of the most important problems for CCSs, but is often overlooked” and, as a consequence, underconsidered in disease and treatment management. This article, which demonstrates the longitudinal assessed adverse cumulative effects of cancer on bone health during arguably the most critical period in the development of the strength–structural properties of the skeleton, highlights the need for guided efforts to optimize bone health in CCSs. Chemotherapy agents (especially glucocorticoids and methotrexate), included in nearly all treatment regimens, can affect bone formation. These therapies may alter the balance between bone resorption and formation, lengthen the life span of osteoclast and/or reducing osteoblast activity and differentiation, as well as adversely affect DNA and RNA synthesis within the bone, interfere with growth hormone IGF1 and reproductive hormones, and impair the muscle-bone unit. Disturbances in calcium and magnesium metabolism in the gut and kidney are also frequent. In the current report, the serum levels of calcium and phosphorus at the time of diagnosis were significantly different compared to the normal control group.This finding might reflect tumor lysis syndrome or nutrient deficiency, or both. Radiation-associated damage to the hypothalamicpituitary adrenal axis (HPA) (during the critical developmental period) adversely affects microvasculature within the bone and its surrounding tissue, with a direct cytotoxic effect on the growth plate, particularly when radiation takes place at a younger age (3). In the article by Choi et al, the BMD Z-score of patients with hematologic cancer decreased rapidly during the first month (probably due to the corticosteroid treatment) (1). A reduction of 1 standard deviation in BMD has been associated with a doubling of the fracture risk (4). In this evaluation, although the associations were noted at baseline, the time to cancer diagnosis and effects on growth could not accurately be accounted for, presenting a limitation as likely growthrelated processes are delayed. Measuring bone Z-score without evaluating skeletal size is a confounder, yet to date, no other report integrating overall skeletal size in growing children has been conducted. Notwithstanding, to prevent the downward trend in BMD, early interventions to ameliorate impaired bone health in pediatric cancer patients are necessary. Beyond the overt obesity-related diseases that are increasingly manifested in adulthood in CCSs, metabolic “obesity” even among CCSs in the normal weight range is becoming commonplace. The greater body mass index observed by the authors in CCSs with solid tumors supports a potential additive effect of rapid growth and obesity and its relationship with cancer, and represents a new challenge in the overall health management of CCSs. An improved understanding of the relative contribution of cancer treatment, lifestyle, and genetic factors on the risk of BMD deficiency and fracture rates would promote development of intervention programs and novel therapies aimed at maximizing peak bone acquisition in childhood and adolescence. Supporting interventions delivered at any time point in the cancer journey are imperative. However, as demonstrated by this longitudinal assessment, the most effective interventions may be those implemented at diagnosis Received 06/3/16; Accepted 06/22/16. *Address correspondence to: Krista Casazza, PhD, RDN, LD, UAB Hospital, Department of Pediatrics, University of Alabama Birmingham, 1601 4th Ave South, CPPI 310, Birmingham, AL 35233. E-mail: kristac@uab.edu Journal of Clinical Densitometry: Assessment & Management of Musculoskeletal Health, vol. 20, no. 1, 3–4, 2017 © 2016 The International Society for Clinical Densitometry. 1094-6950/20:3–4/$36.00 http://dx.doi.org/10.1016/j.jocd.2016.06.011