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

Abstract

Background Premature bone loss after childhood chemotherapy may be underestimated in patients with bone sarcoma. Methotrexate (MTX), a standard agent in osteosarcoma protocols, reportedly reduces bone mineral density (BMD). The literature, however, has reported cases of BMD reduction in patients with Ewing's sarcoma treated without MTX. Thus, it is unclear whether osteoporosis after chemotherapy relates to MTX or to other factors. Questions/purposes We therefore asked whether (1) young patients with a bone sarcoma had BMD reduction, (2) patients treated with MTX had lower BMD, and (3) other factors (eg, lactose intolerance or vitamin D deficiency) posed additional risks for low BMD. Methods We retrospectively reviewed 43 patients with malignancies who had dual-energy x-ray absorptiometry (DEXA) (lumbar, femoral); 18 with Ewing's sarcoma (mean age, 26 ± 8 years), and 25 with an osteosarcoma (mean age, 27 ± 10 years). The mean time since diagnosis was 8 ± 4 years in the group with Ewing's sarcoma and 7 ± 5 years in the group with osteosarcoma. At last followup we determined BMD (computing z-scores), fracture rate, and lifestyle, and performed serum analysis. Results BMD reduction was present in 58% of patients (37% had a z-score between À1 and À2 SD, 21% had a z-score less than À2 SD) in at least one measured site. Seven of the 43 patients (16%) had nontrauma or tumor-associated fractures after chemotherapy. Findings were similar in the Ewing and osteosarcoma subgroups. We found vitamin D deficiency in 38 patients (88%) and borderline elevated bone metabolism; lactose intolerance was present in 16 patients (37%). Conclusion Doctors should be aware of the possibility of major bone loss after chemotherapy with a risk of pathologic fracture. Vitamin D deficiency, calcium malnutrition, and lactose intolerance may potentiate the negative effects of chemotherapy, and should be considered in long-term patient management. Level of Evidence Level II, prognostic study. See Guidelines for Authors for a complete description of levels of evidence.

Decreased bone mineral density and alteration in biochemical bone metabolism markers in children affected by bone tumors after completion of therapy

“…Most of the existing literature data on bone mineral density in bone sarcoma patients focused on adults and reported reduced BMD values and high prevalence of osteoporosis in long-term survivors [3,15,17]. Similar to us, decreases in total and regional BMDs in young adults with bone sarcomas after anti-cancer therapy were observed by Holzer et al [4], Ruza et al [5], and PirkerFruhauf et al [12].…”

“…In another study, lower levels of bone formation markers (carboxyterminal propeptide procollagen type I -PICP, OC) and increased (in about 20%) resorption marker (carboxyterminal cross-linked telopeptide of type I collagen -ICTP) in bone cancer survivors were found [5]. Pirker-Fruhauf et al [12] showed increased PICP, BALP, OC, CTX, TRAP (tartrate-resistant acid phosphatase) levels, and decreased RANKL concentration in some patients with bone cancers. However, these differences were not statistically significant.…”

“…According to actual guidelines 25-hydroxyvitamin D concentrations below 20 ng/ml indicate vitamin D deficiency, concentrations of 20 ng/ml up to 30 ng/ ml reflect a suboptimal status, and concentrations higher than 30 ng/ml up to 50 ng/ml reflect adequate status of this vitamin [31]. Several studies documented a high prevalence of vitamin D deficiency in cancer patients [5,12]. The observed vitamin D deficiency in 78% and its suboptimal status in 20% of our bone cancer survivors along with low calcium levels may affect bone turnover, mineralization and loss of BMD.…”

“…However, clinical studies conducted in patients with bone cancers showed different results. Some researchers reported similar values but others found decreased bone mineral density in patients treated with chemotherapy with and without MTX [5,12]. It is unclear whether low BMD in patients with malignant bone tumors is related to high-doses of MTX or other factors.…”

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

“…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].…”