Management of Nutritional Rickets in Indian Children: A Randomized Controlled Trial
ABSTRACT Introduction: Rickets is usually attributed to vitamin D deficiency. However, recent studies have implicated dietary calcium deficiency in its etiology. Information on relative efficacy of calcium, vitamin D or both together in healing of rickets is limited.Objective: To study effect of treatment with calcium, vitamin D or a combination of these two on healing of nutritional rickets in young children.Design: Randomized controlled trial.Methods: Sixty-seven cases of nutritional rickets in the age group of 6 months to 5 years were randomly allocated to receive vitamin D (600 000 IU single intramuscular dose), calcium (75 mg/kg/day elemental calcium orally) or a combination of the above two for a period of 12 weeks. The demographic parameters, nutritional status, dietary calcium and phytate intake were assessed for all. Radiographs (wrist and knee) and biochemical parameters (serum calcium, inorganic phosphate, alkaline phosphatase, 25-hydroxycholecalciferol and parathyroid hormone) were evaluated at baseline, 6 and 12 weeks for evidence of healing.Results: Mean dietary intake of calcium in all cases was low (204 ± 129 mg/day). Mean serum 25-hydroxycholecalciferol D level was 15.9 ± 12.4 ng/ml, and 82.1% of patients had serum vitamin D levels <20 ng/ml, indicative of vitamin D deficiency. After 6 and 12 weeks of treatment, radiological and biochemical evidence of healing rickets was observed in all treatment groups, albeit to a variable extent. The combined end point of normal serum alkaline phosphatase and complete radiological healing at 12 weeks was observed in 50% subjects on combination therapy as compared with 15.7% subjects on vitamin D alone and 11.7% on calcium alone.Conclusions: Children with rickets had a low serum vitamin D level and a low dietary calcium intake. The best therapeutic response was seen with a combination of vitamin D and calcium than either of them given alone.Trial registration number: CTRI/2010/091/000448.
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ABSTRACT: Objective: Radiological scoring is particularly useful in rickets, where pre-treatment radiographical findings can reflect the disease severity and can be used to monitor the improvement. However, there is only a single radiographic scoring system for rickets developed by Thacher and, to the best of our knowledge, no study has evaluated radiographic changes in rickets based on this scoring system apart from the one done by Thacher himself. The main objective of this study is to compare and analyse the pre-treatment and post-treatment radiographic parameters in nutritional rickets with the help of Thacher's scoring technique. Methods: 176 patients with nutritional rickets were given a single intramuscular injection of vitamin D (600 000 IU) along with oral calcium (50 mg kg(-1)) and vitamin D (400 IU per day) until radiological resolution and followed for 1 year. Pre- and post-treatment radiological parameters were compared and analysed statistically based on Thacher's scoring system. Results: Radiological resolution was complete by 6 months. Time for radiological resolution and initial radiological score were linearly associated on regression analysis. The distal ulna was the last to heal in most cases except when the initial score was 10, when distal femur was the last to heal. Conclusion: Thacher's scoring system can effectively monitor nutritional rickets. The formula derived through linear regression has prognostic significance. Advances in knowledge: The distal femur is a better indicator in radiologically severe rickets and when resolution is delayed. Thacher's scoring is very useful for monitoring of rickets. The formula derived through linear regression can predict the expected time for radiological resolution.The British journal of radiology 02/2014; 87(1036):20130648. DOI:10.1259/bjr.20130648 · 1.53 Impact Factor
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ABSTRACT: To determine whether children with calcium-deficiency rickets have a better response to treatment with vitamin D and calcium than with calcium alone. Randomised controlled trial. Jos University Teaching Hospital, Jos, Nigeria. Nigerian children with active rickets treated with calcium carbonate as limestone (approximately 938 mg elemental calcium twice daily) were, in addition, randomised to receive either oral vitamin D2 50 000 IU (Ca+D, n=44) or placebo (Ca, n=28) monthly for 24 weeks. Achievement of a 10-point radiographic severity score ≤1.5 and serum alkaline phosphatase ≤350 U/L. The median (range) age of enrolled children was 46 (15-102) months, and baseline characteristics were similar in the two groups. Mean (±SD) 25-hydroxyvitamin D (25(OH)D) was 30.2±13.2 nmol/L at baseline, and 29 (43%) had values <30 nmol/L. Baseline alkaline phosphatase and radiographic scores were unrelated to vitamin D status. Of the 68 children (94% of original cohort) who completed 24 weeks of treatment, 29 (67%) in the Ca+D group and 11 (44%) in the Ca group achieved the primary outcome (p=0.06). Baseline 25(OH)D did not alter treatment group effects (p=0.99 for interaction). At the end of 24 weeks, 25(OH)D values were 55.4±17.0 nmol/L and 37.9±20.0 nmol/L in the Ca+D and Ca groups, respectively, (p<0.001). In the Ca+D and Ca groups, the final 25(OH)D concentration was greater in those who achieved the primary outcome (56.4±17.2 nmol/L) than in those who did not (37.7±18.5 nmol/L, p<0.001). In children with calcium-deficiency rickets, there is a trend for vitamin D to improve the response to treatment with calcium carbonate as limestone, independent of baseline 25(OH)D concentrations. ClinicalTrials.gov NCT00949832.Archives of Disease in Childhood 04/2014; 99(9). DOI:10.1136/archdischild-2013-305275 · 2.91 Impact Factor
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ABSTRACT: Vitamin D deficiency may represent a modifiable risk factor to improve outcome in severe illness. The efficacy of high-dose regimens in rapid normalization of vitamin D levels is uncertain. We conducted a systematic review of pediatric clinical trials administering high-dose vitamin D to evaluate 25-hydroxyvitamin D (25[OH]D) response and characteristics associated with final 25(OH)D levels by using Medline, Embase, and the Cochrane Central Register of Controlled Trials, including reference lists of systematic reviews and eligible publications. Uncontrolled and controlled trials reporting 25(OH)D levels after high-dose (≥1000 IU) ergocalciferol or cholecalciferol were selected. Two reviewers independently extracted and verified predefined data fields. We identified 88 eligible full-text articles. Two of 6 studies that administered daily doses approximating the Institute of Medicine's Tolerable Upper Intake Level (1000-4000 IU) to vitamin D-deficient populations achieved group 25(OH)D levels >75 nmol/L within 1 month. Nine of 10 studies evaluating loading therapy (>50 000 IU) achieved group 25(OH)D levels >75 nmol/L. In meta-regression, baseline 25(OH)D, regimen type, dose, age, and time factors were associated with final 25(OH)D levels. Adverse event analysis identified increased hypercalcemia risk with doses >400 000 IU, but no increased hypercalcemia or hypercalciuria with loading doses <400 000 IU (or 10 000 IU/kg). Few studies in adolescents evaluated loading dose regimens >300 000 IU. Rapid normalization of vitamin D levels is best achieved by using loading therapy that considers disease status, baseline 25(OH)D, and age (or weight). Loading doses >300 000 IU should be avoided until trials are conducted to better evaluate risk and benefit. Copyright © 2015 by the American Academy of Pediatrics.Pediatrics 12/2014; 135(1). DOI:10.1542/peds.2014-1703 · 5.30 Impact Factor