Relative Osteopenia after Treatment for Acute Lymphoblastic Leukemia

Abstract

Osteoporosis in adult life is associated with a significant morbidity and may be predisposed to by osteopenia and failure to reach peak bone mass in childhood. Children treated for acute lymphoblastic leukemia (ALL) may be at risk of osteopenia as a result of previous therapy or as a consequence of the disease process itself. Dual energy x-ray absorptiometry measurements of bone mineral content (BMC) for the whole body and at the lumbar spine and hip were taken in 35 (14 male) long-term survivors of ALL and compared with results in 20 (10 male) survivors of other malignancies and 31 (17 male) healthy sibling controls. The measured BMC was expressed as a percentage of a predicted value derived from the control group and based on the variables that had influence upon it. BMC (%) was reduced at the spine in the ALL group compared with controls [92.4 (8.0)% versus 100.4 (9.7)%, respectively; p < 0.005] and at the hip compared with both other malignancies and controls [89.0 (11.5)% versus 96.1 (11.7)% and 100.4 (9.2)%, respectively; p < 0.0005]. Increasing length of time off therapy was associated with a significant increase in %BMC at both the spine and the hip. For the spine, this association was significantly different between the ALL group and other malignancies, suggesting that any gain in %BMC after therapy was slower in children treated for ALL. Both exercise capacity and levels of physical activity were correlated with %BMC at the hip (r = 0.44, p < 0.001 and r = 0.29, p < 0.01, respectively). Previous exposure to methotrexate, ifosfamide, and bleomycin was associated with a reduction in %BMC at the spine. Exposure to 6-mercaptopurine and cisplatin was associated with a reduction at the hip. In conclusion, children treated for ALL are osteopenic. The mechanism is probably multifactorial but is partially related to previous chemotherapy, limited exercise capacity, and relative physical inactivity.

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

“…14, 15 We observed a high frequency of osteopenia and osteoporosis in 49% of patients before SCT signalling the influence of SCTindependent factors on bone metabolism. 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.…”

Improvement in Bone Mineral Density and Body Composition in Survivors of Childhood Acute Lymphoblastic Leukemia: A 1-Year Prospective Study

“…Studies on patients who were treated with cranial irradiation have shown significantly reduced BMD in TB as well as in LS, even Ͼ8 years after completion of treatment. 16,[18][19][20][21][22] Defects in the hypothalamic-pituitary axis leading to abnormalities in growth hormone and gonadotropin secretion are probable causes, leading to disturbed bone metabolism. 36 The effect of chemotherapy alone on BMD is much less clear; normal 12,14,24,25 or reduced BMD 8,23 have been reported.…”

“…[6][7][8][9][10][11][12] Cytotoxic agents and steroids have been said to affect normal bone mass accumulation and bone turnover, leading to increased risk for osteoporosis and fractures. 5,13 Although studies have consistently shown that BMD is reduced in patients after the cure of ALL using cranial irradiation during childhood, [14][15][16][17][18][19][20][21][22] few studies have investigated whether these abnormalities persist after completion of therapy in patients who are treated for ALL without the use of cranial irradiation. In such studies, decreased 23 and normal 24,25 BMD have been reported.…”

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

“…[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. 47 Clinically, low-dose MTX, as used to treat rheumatologic conditions, has not been associated with osteopenia or osteoporosis independent of corticosteroids.…”