Bone mineral density in long-term survivors of highly malignant osteosarcoma

Holzer, Gerold; Krepler, P; Koschat, Martin A.; Grampp, S.; Dominkus, Martin; Kotz, R.

doi:10.1302/0301-620x.85b2.13257

Cited by 85 publications

(104 citation statements)

References 20 publications

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“…58 The deficit in bone mineral may persist for more than a decade. 59 A similar deficit has been noted in survivors of rhabdomyosarcoma. 60 Although the usual treatment of such bone and soft tissue tumors includes multiagent chemotherapy, methotrexate and ifosfamide have been labeled as especially toxic to bone.…”

Section: Bone Mineral Loss and Cancer In Early Lifesupporting

confidence: 56%

Osteopenia and cancer in children and adolescents

Sala

Barr

2007

Cancer

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The attainment of a satisfactory peak bone mass, which is accomplished largely by the end of adolescence, is the best protection against excessive bone mineral loss in late adulthood. Factors that influence this process include age, race, sex, body size, pubertal status, diet, physical activity, and other lifestyle elements.Cancer and its treatment in children and teenagers adversely impact bone mineralization. In particular, chemotherapy (especially glucocorticosteroids and methotrexate) and cranial irradiation (apparently by reducing growth hormone secretion and by causing hypogonadotropic hypogonadism) interfere with normal bone turnover. Resorption often exceeds formation, resulting in net bone mineral loss and providing a rational basis for the use of antiresorptive drugs. Such osteopenia may be symptomatic, with pain and abnormal gait, and increases the risk of fractures several fold. The disorder is compounded by reduced physical activity, so programs to reduce this deficit are of measurable benefit. All of those engaged in the care of children and adolescents with cancer have an opportunity to improve the bone health of these young people and to limit their risk of developing osteoporosis and fragility fractures in adult life.

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Section: Bone Mineral Loss and Cancer In Early Lifesupporting

confidence: 56%

Osteopenia and cancer in children and adolescents

Sala

Barr

2007

Cancer

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“…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].…”

Section: Discussionmentioning

confidence: 99%

“…MTX osteopathy was described in eight of 87 patients with osteosarcoma with at least three of four radiographic abnormalities including osteopenia, dense zones of provisional calcification, insufficiency fractures, and involvement of multiple bones [8]. 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].…”

Section: Introductionmentioning

confidence: 99%

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

Pirker-Frühauf

Friesenbichler

Urban

et al. 2012

Clinical Orthopaedics &Amp; Related Research

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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.

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“…A follow-up of long-term survivors of highly malignant osteosarcoma who had received high-dose chemotherapy including cyclophosphamide showed that osteoporosis was a common occurrence in these patients. 40 Thus, besides immunosuppressive therapy, the myeloablative regimen before BMT may be responsible for the decreased bone mass in long-term survivors of BMT.…”

Section: Discussionmentioning

confidence: 99%

Bone metabolism in patients more than five years after bone marrow transplantation

Kerschan‐Schindl

Mitterbauer

Füreder

et al. 2004

Bone Marrow Transplant

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Summary:We investigated the bone metabolism of 22 patients (median age 38 years) over 6 years after allogeneic bone marrow transplantation (BMT). Biplanar roentgenograms of the thoracic and lumbar spine were used to diagnose vertebral deformities caused by fractures. The actual bone mineral density (BMD) of the lumbar spine and the femoral neck were measured. Laboratory tests included calcium, phosphate, parathyroid hormone, a marker of bone resorption (beta-crosslaps, CTX), markers of bone formation (osteocalcin, bone-specific alkaline phosphatase), osteoprotegerin (OPG) -an antagonist of the osteoclast differentiation factor RANKL, and sex hormone status. One patient had a vertebral fracture. Seven patients (28%) had osteopenia in the lumbar spine while 12 patients (48%) had osteopenia in the femoral neck. Bone resorption was increased in nine patients (43%) and bone formation was increased in four patients (20%). BMT recipients had significantly increased serum levels of OPG (P ¼ 0.029). Three women (75%) and four men (25%) were hypogonadal. The data showed that BMD is reduced and bone metabolism is still disturbed more than 6 years after BMT. The RANKL/osteoprotegerin system appears to play an important role in the pathophysiology of late post transplantation osteoporosis.

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Bone mineral density in long-term survivors of highly malignant osteosarcoma

Cited by 85 publications

References 20 publications

Osteopenia and cancer in children and adolescents

Osteopenia and cancer in children and adolescents

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

Bone metabolism in patients more than five years after bone marrow transplantation

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