Bone Mineral Density and Bone Metabolism In Children Treated for Bone Sarcomas

Abstract

ABSTRACT:In adolescent bone sarcoma patients, bone mass acquisition is potentially compromised at a time in which it should be at a maximum. To evaluate the problem we measured bone mineral density (BMD) and serum markers of bone formation and resorption in a series of pediatric patients with bone tumors. BMD was measured by dual-energy x-ray absorptiometry, at clinical remission, for lumbar spine and the neck of the femur in 38 osteosarcoma and 25 Ewing's sarcoma patients. Mean age was 20.65 and 19.13 y respectively. Serum markers of bone metabolism were: OC, PICP, ICTP, 25-OH vit D and 1,25-(OH) 2 vit D, IGF-I, IGFBP-3 and intact PTH. Serum was sampled throughout anti-tumoral treatments and followup. We analyzed 85 samples from 59 osteosarcoma patients and 54 samples from 36 Ewing's sarcoma patients. Patients had decreased lumbar and femoral BMD. The decrease was more pronounced in pubertal patients compared with those who had completed pubertal development at the time of disease diagnosis. Multivariate analysis indicated that sex, age, weight and BMI were significant in lumbar BMD depletion. Weight and BMI were significant in femoral BMD depletion. Serum markers of bone formation (PICP and OC) and resorption (ICTP) were, throughout, lower than reference values. Significant alterations in other markers were also observed. Up to a third of osteosarcoma and Ewing's sarcoma patients in clinical remission had some degree of BMD deficit. The corresponding increased risk of pathologic bone fractures constitutes a reduction in future quality of life. B one growth and mineralization begin during fetal development and continue, at different rates, throughout infancy and adolescence until the accrued bone mass peak in the third decade of life (1). During infancy and adolescence two processes are involved in bone mass acquisition: bone neoformation from the growth cartilage (endochondral ossification) and remodeling of previously synthesized bone (2). If an optimal peak bone mass is not attained during adolescence, the risk of osteoporosis and pathologic fractures during adulthood is increased.There are various studies of bone growth and maintenance in child cancer patients but few large series are available (3-5). Best studied have been children treated for acute lymphoblastic leukemia (ALL) who are particularly at risk for bone mineral density (BMD) deficits after cranial irradiation (6 -8). Some pediatric solid tumors have been included in the larger series, which tend to be rather heterogeneous, but there is scant BMD data for pediatric bone sarcomas, osteosarcomas and Ewing's sarcomas (9).Children undergoing anti-tumoral treatments are at risk from several factors that may interfere in bone mass acquisition and maintenance. These factors include: the suboptimal nutritional status, prolonged immobilization, hormonal disorders, hypogonadism and treatments with chemotherapy, radiotherapy and with glucocorticoids. These factors have a strong impact on patients with bone tumors because such tumours are typically diagnose...

Do Long Term Survivors of Ewing Family of Tumors Experience Low Bone Mineral Density and Increased Fracture Risk?

“…This was known for patients with postmenopausal osteoporosis [29] and sarcoma [40], and also applies to young survivors of Ewing tumors. In line with Ruza et al [34], in patients with Ewing tumors, BMI positively correlated with low BMD. Therefore BMI may be an indicator for assessing BMD in survivors of bone tumors.…”

“…During the period of bone accumulation in childhood and adolescence, a malignant tumor and its treatment can affect bone turnover and decrease bone mineral density (BMD) [18]. Reduced levels of BMD were reported in long-term survivors of childhood cancers, such as leukemia [2,17], osteosarcoma [18], and a few mixed solid pediatric tumor cohorts [3,26,30,32,34]. Therefore, in survivors of Ewing tumors, an accumulation of treatment-induced effects may compromise bone [3,25].…”

Osteoporosis in Children and Young Adults: A Late Effect After Chemotherapy for Bone Sarcoma

“…HD-MTX, a standard agent in osteosarcoma protocols, reportedly has reduced BMD [8,17]. The literature, however, shows decreased BMD in patients with Ewing's sarcoma treated without HD-MTX [33]. Thus, it is unclear whether osteoporosis after chemotherapy relates to HD-MTX or to other factors.…”

“…We also compared our data with that in the literature ( Table 7). The studies varied in study population and followup times; nevertheless, both revealed a remarkable number of patients with BMD reduction and fractures [17,33], which are often the first indicator of bone loss. The estimated lifetime-fracture risk attributable to osteoporosis reportedly is exponentially related to BMD, which decreases up to 10-fold faster if related to tumor treatment, especially in association with hypogonadism [13].…”

“…Among 48 long-term survivors who had DEXA, 10 had osteoporosis, 21 had osteopenia, and 18 had fractures after chemotherapy [17]. However, Ruza et al questioned MTX as one of the most suspect chemotherapeutics causing premature bone loss because the BMD of patients with Ewing's sarcoma treated without MTX was reportedly decreased [33]. Thus, it is unclear whether MTX is one of the main triggers of bone loss after chemotherapy or if other factors also play an important role.…”