Osteopenia in young adult survivors of childhood cancer

Abstract

Background Improved survival of children with malignant diseases is in part due to the application of intensive, multimodality therapies, including radiotherapy, surgery, glucocorticoids, and cytotoxic agents. Such interventions have the potential to induce complex hormonal, metabolic and nutritional effects that may interfere with skeletal mass acquisition during childhood and adolescence: it is possible that such childhood cancer survivors may therefore reach adulthood with diminished peak bone mass and be at increased risk for clinically significant osteoporosis later in their life. Procedure A bone mineral density (BMD) was measured in 26 unselected former cancer patients attending the Pediatric Long‐Term Clinic at M.D. Anderson Cancer Center. BMD was measured at the lumbar spine and the hip using dual X‐ray absorptiometry (Hologic QDR‐4500W). In addition, the patients' complete medical records were reviewed with particular attention to disease type, age modalities of treatment, and hormonal residual deficiencies. Results The median age of patients at the time of cancer diagnosis was 8 years (range, 0.3 to 16 years). Median age at BMD determination was 23 years (range, 18 to 41 years), and the median interval since cancer diagnosis and BMD was 18 years (range, 5 to 29). Overall, their BMD was decreased relative to peak bone mass at all sites: osteopenia was especially pronounced in patients with a history of cranial irradiation who had developed evidence of pituitary insufficiency during childhood or adolescence. Overall, the median BMD T‐score was −1.41 at the lumbar spine, −1.04 at the femoral neck, and −1.06 for total hip. For patients with prior cranial irradiation, T‐score at the lumbar spine was −2.18 (range, −4.06 to −0.98), at the femoral neck −1.92 (range, −4.11 to +1.10), and for total hip −1.67 (range, −4.79 to +0.56); BMD for irradiated patients was significantly lower than BMD of patients without cranial irradiation. We could not discern an independent impact of other disease characteristics or treatment modalities in this small group of patients. Conclusions Osteopenia is a prominent finding in young adults who are survivors of childhood cancers; it is likely that antineoplastic treatments during childhood and adolescence impede peak bone mass acquisition. We suggest that systematic attention to this potential complication is needed in order to identify what subgroups of children may require regular surveillance and what interventions are required for its prevention or treatment. Med. Pediatr. Oncol. 32:272–278, 1999. © 1999 Wiley‐Liss, Inc.

Density and structural changes in the bone of growing rats after weekly alendronate administration with and without a methotrexate challenge

“…Because MTX is utilized in the treatment of childhood cancers, the present findings suggest that its effects on growing bones are complex and in need of further study. [36][37][38][39][40][41][42][43] While the clinical risk factors are multifactorial, specific chemotherapeutic agents, including high-dose MTX, ifosfamide, and bleomycin, have been implicated in causing bone loss. [43][44][45][46] By contrast, low-dose MTX in rats of age similar to ours (6 weeks) did not have a significant reduction in lumbar or femoral BMD.…”

Reduced Bone Mineralization in Adolescent Survivors of Malignant Bone Tumors: Comparison of Quantitative Ultrasound and Dual-Energy X-Ray Absorptiometry

“…If decreased bone mineralization is detected early, factors that might contribute to the low value should be recognized and if possible treated. Few patients with bone tumors have been included in previous studies of bone mass after childhood cancer (11,12).…”

“…In several studies, decreased bone mineralization has been demonstrated in long-term survivors of childhood acute lymphoblastic leukemia (2,5,6) and in children with a malignancy at completion of their chemotherapy (7)(8)(9). However, recent studies are controversial with respect to bone mass status in this group of patients (10), and few studies have included patients with bone tumors (11,12).…”

“…Low levels of bone alkaline phosphatase throughout treatment for acute lymphoblastic leukemia have been described, suggesting impaired osteoblast differentiation (8,16). Prolonged bedrest, poor nutrition, alterations in vitamin D metabolism, growth hormone deficiency, gonadal failure, and changes in insulin-like growth factors and their binding proteins might also influence bone mineralization in children with malignancies (1,11,17).…”

Seqüelas endócrinas da radioterapia no tratamento do câncer na infância e adolescência

“…Outra hipótese seria a perda aguda da DMO pela irradiação per se (39). Quimioterapia, incluindo o uso de corticosteróides e metotrexate, deficiências de hormônio do crescimento, de esteróides sexuais e de hormônio tireoidiano, além de deficiência nutricional, são outros fatores que podem estar envolvidos na patogênese da osteopenia (40).…”