Global Consensus Recommendations on Prevention and Management of Nutritional Rickets

"BACKGROUND: Vitamin D and calcium deficiencies are common worldwide, causing nutritional rickets and osteomalacia, which have a major impact on health, growth, and development of infants, children, and adolescents; the consequences can be lethal or can last into adulthood. The goals of this evidence-based consensus document are to provide health care professionals with guidance for prevention, diagnosis, and management of nutritional rickets and to provide policy makers with a framework to work toward its eradication. EVIDENCE: A systematic literature search examining the definition, diagnosis, treatment, and prevention of nutritional rickets in children was conducted. Evidence-based recommendations were developed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system that describes the strength of the recommendation and the quality of supporting evidence. PROCESS: Thirty-three nominated experts in pediatric endocrinology, pediatrics, nutrition, epidemiology, public health, and health economics evaluated the evidence on specific questions within five working groups. The consensus group, representing 11 international scientific organizations, participated in a multiday conference in May 2014 to reach a global evidence-based consensus. RESULTS: This consensus document defines nutritional rickets and its diagnostic criteria and describes the clinical management of rickets and osteomalacia. Risk factors, particularly in mothers and infants, are ranked, and specific prevention recommendations including food fortification and supplementation are offered for both the clinical and public health contexts. CONCLUSION: Rickets, osteomalacia, and vitamin D and calcium deficiencies are preventable global public health problems in infants, children, and adolescents. Implementation of international rickets prevention programs, including supplementation and food fortification, is urgently required."

Vitamin D prophylaxis in children with a single dose of 150000 IU of vitamin D.

OBJECTIVE: To determine the efficacy of a single oral dose of 150,000 IU of vitamin D2 at the beginning of autumn for preventing winter vitamin D deficiency in children in Ushuaia (55 degrees S). DESIGN: The study was prospective. SUBJECTS: 79 children clinically healthy with 8.6 +/- 1.4 y of age (X +/- s.d.). INTERVENTIONS: Fasting serum venous samples and 2 h urine samples were obtained immediately before and 6 w and 5 mon after the vitamin D dose. Parents informed consent was obtained previous to the study. In a subgroup of 30 children serum levels of calcium (sCa), phosphorus (sP), total alkaline phosphatase (TAP), 25 hydroxyvitamin D (25 OHD), parathyroid hormone (PTH) and the urine calcium/creatinine ratio in a 2 h urine sample (UCa/UCreat) were measured. In the whole group sCa and the ratio uCa/ucreat were measured. RESULTS: After 150,000 IU of vitamin D2 administration, serum 25 OHD levels at the end of winter (17.0 +/- 9.4 ng/ml) were similar to those at the beginning of autumn (18.7 +/- 10.7 ng/ml), but significantly higher from those obtained in a previous study without vitamin D (9.8 +/- 3.8 ng/ml, P < 0.001). PTH levels were higher at the end of winter (P < 0.02), but this augmentation was lower than the increment observed without vitamin D. Plasma calcium levels and the urine calcium/creatinine ratio were lower at 5 months after vitamin D2 dose (P < 0.02 and P < 0.05 respectively). In the total group the serum calcium was lower after the fifth month (P < 0.05). The Uca/Ucreat ratio was lower at 6 w and 5 mon (P < 0.05 and P < 0.001). CONCLUSION: A single dose of 150,000 IU of vitamin D maintained appropriate levels of 25 OHD without inducing hypercalcemia nor hypercalciuria, but a winter increment of PTH (smaller than in the group without vitamin D) was not inhibited.

Growth hormone and insulin-like growth factor I plasma levels in patients with hypophosphatemic rickets.

The cause of the growth retardation present in patients with hypophosphatemic rickets has not been totally elucidated. There has been a previous report of a growth hormone deficit in a group of these patients. To verify this abnormality we studied two groups of patients with hypophosphatemic rickets, one with (n = 6) and the other without (n = 7) treatment with calcitriol and oral phosphates. All patients in both groups showed a normal growth hormone response (> 10 micrograms/l) to standard stimulatory tests and normal IGF-I plasma levels. Mean IGF-I plasma levels were not significantly different (untreated 1.46 +/- 0.80 U/ml, treated 1.25 +/- 0.69 U/ml) and the mean logarithmic deviation of IGF-I plasma levels from both groups did not differ from normal. In summary, we found no abnormalities of the growth hormone-IGF-I axis in our patients with hypophosphatemic rickets.

Familial idiopathic hyperphosphatasia (FIH): response to long-term treatment with pamidronate (APD).

A 5-year-old child suffering from familial idiopathic hyperphosphatasia (FIH) was treated by: (1) intravenous infusion of pamidronate (APD) (3 h) (0.75 mg/kg/day) for 5 days; and (2) oral administration of APD (8 mg/kg/day) for 1 year, in association with calcium (1 g/day) as calcium gluconate. A decrease of both serum calcium and phosphate, and a slight PTH increase were observed immediately after the IV treatment; serum alkaline phosphatase did not change, but a marked and rapid decline in the hydroxyprolinuria was observed: basal 659 +/- 207 during IV treatment 169 +/- 59 (mean +/- SD mg/24 h, P < 0.005). At the end of one year of oral APD treatment clinical and radiological findings showed a remarkable improvement. Serum calcium, phosphate and PTH returned to the initial values. Plasma alkaline phosphatase levels showed a 70% decrease: basal 1370 IU/l, 1 year 410 IU/l whereas the hydroxyprolinuria values were similar to those determined at the end of the intravenous treatment (212 +/- 13 mg/24 h), but still significantly lower than the basal levels (P < 0.01). No side-effects were observed. APD appears to be a promising treatment for patients with FIH.

Bone mineral density of the spine and radius shaft in children with X-linked hypophosphatemic rickets (XLH).

X-linked hypophosphatemic rickets (XLH) is characterized by inadequate skeletal mineralization. The bone mineral density (BMD) of the radius shaft and the lumbar spine was determined in 13 children with XLH. Ten patients were on treatment, whereas three patients had discontinued treatment 20-32 months prior to this study. Two of them had radiological evidence of rickets. The radius shaft BMD was significantly diminished: Z score was -1.33 +/- 0.89 (P less than 0.001), while the BMD of lumbar spine was significantly augmented (Z score +1.95 +/- 1.17, P less than 0.001). A positive correlation was found between the Z scores for the BMD of the radius shaft and spine. The two patients with overt rickets had lower radius shaft BMD values and a lesser increment of BMD of the spine. The BMD deficit of cortical bone may be related to the lack of efficacy of the treatment and/or to an intrinsic defect of the bone on this disease. On the other hand, the augmented BMD of the lumbar spine might reflect the overabundance of partially mineralized osteoid. The determination of the BMD of the radius shaft by SPA was a sensitive method for detecting abnormalities of the bone mass in XLH patients under treatment without radiological signs of rickets.