Long-term outcomes of children and adolescents who had cerebral palsy with secondary osteoporosis

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Abstract
To investigate the long-term efficacy and index of treatment with vitamin D alone or with a bisphosphonate in children and adolescents who have cerebral palsy (CP) with secondary osteoporosis. Thirty patients diagnosed with CP and secondary osteoporosis were analyzed for 5 years, and the efficacy of treatment was compared. Treatment was divided into three groups: The monotherapy group, consisting of patients taking only alfacalcidol (0.03 µg/kg/day); the polytherapy group, consisting of those taking alfacalcidol and risedronate (0.05 mg/kg/day); and the control group, consisting of patients who discontinued taking their medications for reasons unrelated to these therapies. Bone mineral density (BMD), bone-specific alkaline phosphate (BAP), and N-telopeptides of type I collagen (NTX/Cr) were measured on each patient just before and at discontinuation of treatment, after 6 months, and again at 1 and 3 years, respectively. The changes in BMD (ΔBMD), BAP (ΔBAP), and NTX/Cr (ΔNTX/Cr) were evaluated at these intervals, because the normal value of each parameter varies over time during childhood. ΔBMD significantly increased in the polytherapy group at ≥1 year (p = 0.006), and the difference in BMD between the polytherapy and the control groups at ≥1 year was also significant (p = 0.005). ΔBAP was increased in the monotherapy and polytherapy groups at ≥1 year (p = 0.021 and p = 0.033). ΔNTX/Cr decreased in the polytherapy group at ≥1 year, which was consistent with the polytherapy group of the period from 1 month to 1 year (p = 0.033). The relation between ΔBMD to ΔBAP was a positive correlation in the second period in the monotherapy group (r = 0.46). And the relations between ΔBMD to ΔNTX/Cr were not recognized negative correlations in the monotherapy and polytherapy groups. Thus, ΔBMD reflected ossification of secondary osteoporosis in patients with CP, and ΔBAP and ΔNTX/Cr was significantly related to the increase and decrease of ΔBMD. There were no effects of other factors except sexual maturity. Limitations of this study include that each index of examination was the evaluation according to rate of change. Therefore, the results of this study were limited to longitudinal evaluations. Evaluation according to ΔBMD and both methods of monotherapy and polytherapy were useful for CP patient taking antiepileptic drugs (AEDs) and regardless of sex. Especially, polytherapy for longer than 1 year led to improvement in BMD in children who had CP with secondary osteoporosis. BAP and NTX/Cr were useful for the index of the progression osteoporosis with or without these therapies.

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