Bone mineralization after treatment of growth hormone deficiency in survivors of childhood malignancy

Abstract

Having noted symptomatic osteoporotic vertebral collapse in young adult survivors of childhood malignancy, bone mineral density (BMD) was examined at three sites by dual‐energy X‐ray absorptiometry in 64 patients treated in childhood for intracranial malignancy (group 1; n = 21) or acute leukaemia (group 2; n = 43). Patients in group 1 were selected for growth hormone deficiency (GHD) by auxological and biochemical criteria before the end of puberty (Tanner stage V). Seven patients (six men; mean (± SEM) age at study, 28.0 ± 2.9 years; mean age at diagnosis, 8.7 ± 1.5 years) in this group had been treated with human pituitary growth hormone (GH) for 1–12 years; and 14 patients (nine men; mean age at study, 26.8 ± 1.0 years; mean age at diagnosis, 10.7 ± 1.4 years) had not received GH. Bone densities in group 1 were normal in the GH‐treated patients at the femoral neck (98.4 ± 3.8% of control), lumbar spine (100.4 ± 6.1% of control) and Ward's triangle (101.0 ± 6.1% of control) but markedly reduced in the untreated group (femoral neck, 81.2 ± 2.6% of control (p= 0.002); lumbar spine, 79.1 ± 4.1% of control (p= 0.04); Ward's triangle, 80.1 ± 3.6% of control (p= 0.01)). The majority of patients in group 2 had been treated for acute lymphoblastic leukaemia (ALL) and were in three subgroups. Fifteen (ten men; mean age at study, 22.1 ± 0.8 years; mean age at diagnosis, 5.7 ± 0.8 years) had no auxological evidence of GHD, ten (six men; mean age at study, 18.8 ± 0.7 years; mean age at diagnosis, 6.6 ± 1.2 years) received GH therapy for a mean of 2.6 years (range, 0.5–5.0 years), while 14 patients (three men; mean age at study, 20.9 ± 0.4 years; mean age at diagnosis, 5.1 ± 0.8 years) had GHD but did not receive GH. A small group of four patients (three men; mean age at study, 23.2 ± 2.1 years; mean age at diagnosis, 8.0 ± 2.3 years) who had been treated for acute myeloid leukaemia (AML) in childhood was also studied. The patients with AML had normal bone densities at all three sites (femoral neck, 106 ± 6.1% of control; lumbar spine, 96.5 ± 3.0% of control; Ward's triangle, 110.8 ± 9.3% of control), as did the patients with ALL who did not have GHD (femoral neck, 102.3 ± 2.9% of control; lumbar spine, 98.6 ± 1.7% of control; Ward's triangle, 108.3 ± 3.2% of control). The patients with ALL and GHD not treated with GH had markedly reduced BMD at all three sites (femoral neck, 90.5 ± 2.6% of control; lumbar spine, 88.4 ± 2.5% of control; Ward's triangle, 94.5 ± 3.7% of control), but those treated with GH had a BMD no different from control (femoral neck, 100.6 ± 3.3% of control; lumbar spine, 95.7 ± 4.6% of control; Ward's triangle, 106.2 ± 4.9% of control). It is concluded that GHD during childhood and adolescence predisposes to osteopenia.

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.…”

Bone mineral density in patients undergoing bone marrow transplantation for myeloid malignancies

“…10 Growth hormone presumably acts through changes in the production of insulinlike growth factor I (somatomedin C), which is a potent stimulator of skeletal growth, 25 thus suggesting a role for growth hormone in determining bone density. Children with acute leukemia who have received cranial radiation therapy and subsequently undergone BMT are at an increased risk for growth failure and growth hormone deficiency.…”

“…[5][6][7] Moreover, cranial irradiation 8,9 and growth hormone deficiency might be associated with decreased bone mineral density. 10 Sensitive methods are needed to demonstrate subCorrespondence: S Bhatia, at his current address: Division of Pediatric Hematology/Oncology, City of Hope National Medical Center, 1500, East Duarte Road, Duarte, CA 91010-3000, USA 5 Current address: University of Missouri Hospital and Clinics, Columbia, MI, USA Received 15 December 1997; accepted 10 February 1998 tle changes in bone accurately and assess therapeutic measures to correct demineralization. Several clinical and laboratory methods are typically used to assess osteopenia, but they have shortcomings.…”

Osteopenia and cancer in children and adolescents

“…Survivors of brain tumors may be especially vulnerable to osteopenia as a result of growth hormone deficiency and hypogonadotropic hypogonadism due to cranial irradiation. 54 The large Childhood Cancer Survivor Study reported on more than 1600 survivors of brain tumors. Only 29 of them self-reported osteoporosis, and this disorder was more frequent than in their healthy siblings only in those who had received combined modality therapy 55 (surgery, radiation, and chemotherapy).…”

“…It should be noted that, in the initial report by Nussey et al, the determination of growth hormone deficiency was made in the majority of patients by clinical assessment and some of them had received spinal irradiation, 54 so the pathogenesis of osteopenia in that study was less than clear. Furthermore, retardation of height velocity and bone age during treatment occur in both irradiated and nonirradiated patients, and in both groups there is some catch-up after the completion of treatment, 114 emphasizing that, in children who receive multimodality therapy, cranial irradiation may not be the only contributor to osteopenia.…”