Bone Mineral Density in Young Adult Survivors of Childhood Cancer

Aisenberg, Javier; Hsieh, Ken; Kalaitzoglou, George; Whittam, Elizabeth H.; Heller, Glenn; Schneider, Robert J.; Sklar, Charles A.

doi:10.1097/00043426-199805000-00010

Cited by 108 publications

(66 citation statements)

References 18 publications

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“…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.…”

Section: Discussionmentioning

confidence: 99%

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

Spadaro¹,

Damron²,

Horton³

et al. 2006

Journal Orthopaedic Research

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Alendronate (ALN) and other bisphosphonates have been used successfully in pediatric patients with osteopenia secondary to connective tissue diseases. Loss of growth in height has not been reported, but concerns remain regarding the effect of these potent antiresorptive agents when used in children and adolescents. High-dose methotrexate (MTX) and other chemotherapy drugs have been implicated in osteoporosis and a high fracture incidence in survivors of childhood cancers and are also associated with osteopenia in adult animals. The effect of high dose MTX on bone density during rapid skeletal growth, however, has not been widely studied, nor has the potentially therapeutic effect of bisphosphonates in this setting. We examined the effects of ALN and MTX administration, alone and in combination, on bone density, morphology, mechanical strength, and longitudinal growth in normal growing rats. Sprague-Dawley rats were given ALN once weekly (0.3 mg/kg) from 5 to 11 weeks of age, with and without a course of methotrexate (MTX) given daily in weeks 1 and 3 (0.75 mg/kg/day). Twenty-four animals were randomly divided into four groups: Control (vehicle), ALN alone, ALN þ MTX, and MTX alone. After 6 weeks, the femora, tibiae, and lumbar spine were studied by dual-energy X-ray absorptiometry, peripheral quantitative computed tomography, mechanical strength testing, microradiography, light microscopy, and by determination of ash weights and bone lengths. ALN treatment increased bone mineral density (BMD) by 23% to 68%. The largest increases in the femur occurred in the distal third where endochondral bone growth was greatest and included large increases in trabecular bone and total cross-sectional area. ALN þ MTX produced similar effects to ALN alone. MTX only reduced BMD by 8% in the vertebrae, but not significantly at other sites. MTX also led to femoral length reductions of 2.9%. The small reductions in BMD due to MTX were overwhelmed by the increases due to ALN, whereas the length loss was unaffected. Transverse density banding corresponding to weekly ALN administrations were clearly evident radiographically throughout the growing skeleton, likely due to decreased resorption and possibly increased mineralization in the bands. ALN or ALN þ MTX treatment also led to increases in mechanical strength in the femora. Although MTX administration during growth leads to some BMD reduction, ALN given with MTX eliminates this reduction and in fact bone density and strength increase above control levels. ß

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Section: Discussionmentioning

confidence: 99%

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

Spadaro¹,

Damron²,

Horton³

et al. 2006

Journal Orthopaedic Research

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“…Children with hematologic and oncologic malignancies have reduced BMD after conventional chemotherapy 16,17 and long-term survivors of childhood cancer have a significantly reduced bone mass at a mean age of 25. 18 Because peak bone mass is attained at age 25 to 30, and peak bone mass is a major determinant of BMD at older age, it can be assumed that these patients have an increased risk for osteoporosis in later life.…”

Section: Discussionmentioning

confidence: 99%

Loss of bone mass and vitamin D deficiency after hematopoietic stem cell transplantation: standard prophylactic measures fail to prevent osteoporosis

et al. 2001

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“…However, a considerable proportion of these reports consist of small numbers of subjects who have had a wide variety of malignant diseases and an even greater heterogeneity of treatments administered, all contributing to difficulties in assessing the validity of conclusions. [48][49][50][51][52][53] Stronger evidence (Table 1) is available on survivors of primary brain tumors, osteogenic sarcoma and Ewing sarcoma, soft tissue sarcomas, and malignant lymphomas (Hodgkin and non-Hodgkin lymphomas). Survivors of brain tumors may be especially vulnerable to osteopenia as a result of growth hormone deficiency and hypogonadotropic hypogonadism due to cranial irradiation.…”

Section: Bone Mineral Loss and Cancer In Early Lifementioning

confidence: 99%

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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Bone Mineral Density in Young Adult Survivors of Childhood Cancer

Abstract: Young adult survivors of childhood cancer have reduced BMD. Because age at study coincides with the normal age of attainment of peak bone mass and peak bone mass is a major determinant of BMD later in life, many of these patients are at increased risk for osteoporosis and fractures.

Cited by 108 publications

References 18 publications

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

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

Loss of bone mass and vitamin D deficiency after hematopoietic stem cell transplantation: standard prophylactic measures fail to prevent osteoporosis

Osteopenia and cancer in children and adolescents

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