Low turnover bone disease in Egyptian children with acute leukemia

Abstract

The aim of this work was to study bone turnover markers, calcium homeostasis and bone mineral density (BMD) in children with acute leukemia at diagnosis, after induction chemotherapy, and during maintenance therapy to delineate abnormalities present. After evaluation of L2-L4 BMD using dual-energy X-ray absorptiometry in patients with acute myeloid and lymphoid leukemia at presentation and after treatment, the results were compared to 352 healthy age- and sex-matched Egyptian controls. Calcium homeostasis parameters and bone turnover biochemical markers (serum osteocalcin and urinary deoxypyridinoline) were also assayed and the results were compared to 12 healthy age- and sex-matched controls. Osteopenia was observed at diagnosis and during treatment in patients with acute leukemia. At diagnosis osteopenia was observed in 27 patients (62.8%): 10 (23.3%) had non severe osteopenia and 17 (39.5%) had severe osteopenia. This low BMD persisted in those who were followed up. Parathyroid hormone (PTH) (pg/ml) levels demonstrated non significant differences between children with acute leukemia at different stages of therapy and controls, while, 25 (OH) D3 (ng/ml) was significantly lower in acute leukemia patients at different stages of therapy compared to controls (p<0.001). Osteocalcin (ng/ml) is significantly lower in patients at different stages of the disease compared to controls (p<0.001) but there was no significant difference between patients at different stages of therapy. Deoxy-pyridoline cross links showed non-significant difference between the different types of acute leukemia and with controls. Osteopenia is a significant problem in children with acute leukemia at presentation and after chemotherapy. Osteopenia in acute leukemia appears to be of the low turnover type (decreased osteoblastic activity and decreased bone mineralization).

Inhibition of leukemia cell engraftment and disease progression in mice by osteoblasts

“…Notably, a decrease in disease burden following chemotherapy appeared to correlate with an increase in osteoblast activity and an improvement in bone mass, despite corticosteroid treatment. 50,51,54 These reports are consistent with our observations in mice that reinstatement of osteoblast functions reduces disease progression.…”

“…[49][50][51][52][53] All these reports correlate osteopenia or osteoporosis with decreased For personal use only. on August 29, 2018.…”

Mapping and targeting of the leukemic microenvironment

“…This agrees with clinical reports of osteopenia or osteoporosis, due to a decrease in osteoblast function, noted in newly diagnosed children or adults with acute leukemia (El-Ziny et al, 2005;Fitter et al, 2008;Haddy et al, 2001;Sala and Barr, 2007;Shalet, 1996;Sinigaglia et al, 2008). In several of these studies, improvement of disease burden following chemotherapy correlated with an increase in osteoblast activity and bone mass, in spite of whether corticosterone treatment was also used (Crofton et al, 1998;El-Ziny et al, 2005;Fitter et al, 2008). In stromal cells from MDS and AML patients, expression of cell surface molecules involved in interaction with HSCs is decreased (Geyh et al, 2013), whereas the population of CD271 + MSCs, which favor blast expansion through up-regulation of CXCL12, is increased.…”

“…MDS and AML patients show a reduction in osteoblast numbers, reflecting a corresponding reduction in bone formation rate without any changes in osteoclast numbers (Krevvata et al, 2014). This agrees with clinical reports of osteopenia or osteoporosis, due to a decrease in osteoblast function, noted in newly diagnosed children or adults with acute leukemia (El-Ziny et al, 2005;Fitter et al, 2008;Haddy et al, 2001;Sala and Barr, 2007;Shalet, 1996;Sinigaglia et al, 2008). In several of these studies, improvement of disease burden following chemotherapy correlated with an increase in osteoblast activity and bone mass, in spite of whether corticosterone treatment was also used (Crofton et al, 1998;El-Ziny et al, 2005;Fitter et al, 2008).…”

Bicycle ergometer versus treadmill on balance and gait parameters in children with hemophilia

“…The incidence of hemophilia in Egypt is 1:10,000 live births [2]. Depending on the concentration of factor VIII or IX coagulant activity in blood, the disorders may be classified as severe (<1% of normal activity), moderate (1-4%) or mild (5-25%) [3].…”