| Abstract |
Acute lymphoblastic leukemia is the most common pediatric cancer and the survival rates today reaches΄&γτ 80%. Disorder of bone mass is recognized as one of the most important side effects of treatment and the disease itself. The assessment of bone metabolism is taking place by imaging and biochemical parameters. The test of choice for imaging remains the measurement of bone density by DEXA, the assessment in children should be based according to age BMD z-score and when the value is ΄&λτ-2 to be considered as low value for the patient's age. From the biochemical parameters the most basic are markers of bone metabolism (IOM), which are divided into markers of bone formation and markers of bone resorption.
Clinically osteoporosis is defined as a reduction in bone mineral density to such an extent that even normal movements or loads can cause bone fractures. The diagnosis of osteoporosis in children requires the presence of clinically significant fracture history and low BMC or BMD.
The medications currently on treatment of osteoporosis include antiresorptive agents that reduce the activity of osteoclasts and anabolic agents that increase the activity of osteoblasts. As an adjunct to the above formulations calcium and vitamin D are used. Few data are available concerning the treatment indication when a child has reduced bone density or even further if a fracture has occurred, more over choice of medication is extremely difficult as there is no long-term experience.
The population of our study comprised of 36 children with ALL who were treated according to protocol ALL-BFM. Patients were studied in three groups: 1) newly-diagnosed, 2) patients receiving chemotherapy for at least 12 months and 3) patients completed chemotherapy at΄&λτ4 years from initiation of the study. Monitoring was based on clinical parameters and laboratory parameters with specific biochemical tests of bone metabolism in serum (ALP - bone ALP, osteocalcin, C-propeptide of collagen-I, PTH) and 24-hr urine (NTX, Pyrilinks, D-pyrilinks). Bone mineral density assessment was done by DEXA-scan at the lumbar spine and the estimation was based on the z-score. The cumulative dose corticosteroids as analogous prednisone was gradually increased from 0.8 to 4.3 and 5 g/m2 respectively for groups 1, 2 and 3. No patients experienced bone fracture with low BMD during the study. A gradual decrease in bone density (BMD z-score) was recorded from Group 1 (-0.74) in group 2 (-1.59) and group 3 (-2.03). This difference is statistically significant (p = .022)
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between
group 1 and group 3, while not statistically significant between group 1 and 2 (p = .13), nor in group 2 and 3 (p = .25 ). Despite the small number of patients, the proportion of patients showing a significant decrease in bone mineral density (BMD z-score΄&λτ-2) increased from 17% (n = 3) in group 1 in 25% (n = 4) in group 2 and 50% (n = 5) in group 3.
From a total of 36 patients reliable results of the bone turnover markers had only 26 patients. A decrease in their levels is recorded in diagnosis when bone metabolism in children has been suppressed by neoplastic disease. A gradual recovery in their levels after the 6th month of chemotherapy was noted, sooner as expected from the restoration of bone density which usually has objective changes detected by measurements after 1-2 years. Normalization of prices, in most markers, is observed as the period from the completion of chemotherapy increases. Only bone fraction of alkaline phosphatase remained quite low despite the upward trend and the D-pyrilinks, thus a marker of bone formation and a marker of bone resorption.
When the Z-score was ΄&λτ-1.0 calcium alone was administered as treatment in group 1 and calcium plus vitamin D in group 2 and 3, but despite a clear improvement in all patients, the number (n = 7) is not sufficient for statistical analysis of results. For patients with BMD Z-score ΄&λτ-2.5, in the original study design, administration of bisphosphonates was planned. This never applied because: a) there was no child with BMD Z-score΄&λτ-2.5, b) no fracture was documented in patients with low BMD, c) a decreasing influence on bone mineral density of newer, less toxic chemotherapy protocols was obvious.
The assessment of bone health for children ALL-survivors is very important to take place at the right time, with the most accurate method available in order to allow not only the restoration of possible disorders but their prevention too. With this goal in mind this study was designed, aiming at early detection of bone loss in order to create a baseline for monitoring therapeutic intervention but mainly design protocols to prevent further complications on the health status of the skeleton at a delicate and critical age development.
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