Low bone mineral density is associated with hypogonadism and cranial irradiation in male childhood cancer survivors

Abstract

We investigated if bone mineral density was related to testosterone deficiency and/or previous cancer treatment in men who were childhood cancer survivors. Men with untreated testosterone deficiency or previous treatment with cranial irradiation were at increased risk of impaired bone health. Prevention of osteoporosis should be considered in their follow-up. Introduction Childhood cancer survivors (CCS) are at increased risk of hypogonadism. Reduced bone mineral density (BMD) has been reported in CCS but it is unclear whether this is due to hypogonadism or a direct effect of cancer therapy. This study investigated BMD in CCS, and association with hypogonadism, previous treatment and cancer type. Methods Investigation of 125 CCS (median age 33.7 at inclusion; 9.6 at diagnosis) and 125 age-matched population controls. Serum testosterone and luteinizing hormone were assayed and BMD at total hip and lumbar spine L1-L4 measured. The mean difference in BMD (g/cm 2 ; 95% CI) between CCS and controls was analysed. Odds ratios (OR; 95% CI) for low BMD were also calculated. Results Overall, BMD in the CCS cohort did not significantly differ from controls. However, compared with eugonadal CCS, the CCS with untreated hypogonadism had lower BMD at the hip (mean difference − 0.139 (− 0.210; − 0.067); p < 0.001) and spine (− 0.102 (− 0.174; − 0.030); p = 0.006). They also had a higher risk of low hip BMD (OR 4.1 (1.3; 14); p = 0.018). CCS treated with cranial irradiation also had lower BMD (hip − 0.076 (− 0.133; − 0.019); p = 0.009; spine − 0.071 (− 0.124; − 0.018); p = 0.009) compared with controls. The latter associations remained statistically significant after adjustment for hypogonadism. Conclusions CCS with hypogonadism or previously treated with cranial irradiation are at increased risk of impaired bone health. Prevention of osteoporosis should be considered as an important part in future follow-up of these men.

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

“…CAYA cancer survivors are at increased risk of low BMD (moderate-quality evidence), 6,7,[9][10][11] very low BMD (moderate-quality evidence), 6,7,9,10,[30][31][32][33][34][35][36][37][39][40][41][42][43][44][47][48][49][50][51][52][53][54][55][58][59][60][61][62]64,[66][67][68][69][70][71] and lower BMD Z-scores (moderatequality evidence) after a follow-up period ranging from 2•7 to 27•2 years. 30,31,33,38,39,41,43,<...…”

Improvement of Bone Health and Initiation of Puberty Development in Camurati-Engelmann Disease With Glucocorticoid and Losartan Treatment: A Case Report and Review of Literature

“…Estrogen exerts protective effects on bone (24), and the Tanner stage was the major determinant of BMD in girls (25). Previous studies have also reported that patients with hypogonadotropic hypogonadism had lower BMD compared with normal controls (26). We therefore proposed that low BMD in the lumbar spine and femoral neck in our patient with CED was mostly attributed to the hypogonadism.…”

Osteoporosis in Childhood Cancer Survivors: Physiopathology, Prevention, Therapy and Future Perspectives

“…In this case, the bone alteration can be related to circulating hormones and cytokines produced by the tumor. It is known that patients with primary bone tumors, including osteosarcoma (OS) and Ewing sarcoma, may have bone alteration in the affected sites [ 1 ]. Alternatively, cancer-induced OP can derive from the therapies administered to treat the primary condition.…”

“…Androgens enlarge the cross-sectional area of long bones and increase mechanical strength [ 7 ]. GH and insulin-like growth factor I are important for maintaining bone mass because both independently contribute to bone remodeling and apposition [ 1 ].…”

“…During the last decades, the childhood cancer survival rate has considerably increased, reaching 80% in Europe [ 1 , 2 ] and increasing the number of childhood cancer survivors (CCS). This amelioration in survival rate is due to chemotherapy, radiotherapy, surgical interventions’ improvement, and hematopoietic stem cell transplantation (HSCT) [ 1 ]. However, cancer treatments are responsible for the onset of long-term adverse effects.…”