OBJECTIVE: Compare the efficacy and safety of daily versus fortnightly oral vitamin D3 in treating symptomatic vitamin D deficiency in children aged 1-10 years.
METHODS: Open labelled randomized controlled trial.
METHODS: Eighty children with symptomatic vitamin D deficiency were randomized into group daily (D) and group bolus (B) [40 in each group] to receive oral vitamin D3, 4000 IU daily or 60,000 IU fortnightly for 12 weeks respectively. Both groups received daily oral calcium of 500 mg/day.
METHODS: Serum calcium (Ca), phosphate (P), alkaline phosphatase (ALP), 25-hydroxy cholecalciferol (25(OH)D), parathyroid hormone (PTH) levels, urine calcium: creatinine ratio and radiological score were assessed at baseline, 4 weeks and 12 weeks. At the end of 12 weeks, 74 children were available for evaluation of the efficacy and safety of both regimens.
RESULTS: Both regimens led to a significant increase in Ca and P levels and a fall in ALP and PTH levels from baseline to 4 and 12 weeks of therapy, with no intergroup difference. At 4- and 12-week assessments, all children in both treatment arms achieved 25(OH)D level in sufficiency range, with no significant difference in their geometric mean. Both regimens were associated with asymptomatic transient hypercalcemia [group D-51.4% vs. group B-34.3%; p -0.14] and hypercalciuria (5.7%) in group D that resolved spontaneously on follow-up.
CONCLUSIONS: Daily and fortnightly oral vitamin D3 in similar cumulative doses are efficacious for treating symptomatic vitamin D deficiency in children (1-10 years). Treated children should be monitored for serum 25(OH)D, Ca and urinary calcium creatinine ratio.

A 15-month-old African American male patient presented to the pediatric clinic to establish care. The patient had been seen and treated by a previous pediatrician who had diagnosed him with failure to thrive, anemia, and hepatosplenomegaly, according to the patient\'s parents. Upon physical examination, the patient was determined to be less than the first percentile for height and in the eighth percentile for weight. Frontal bossing was also observed. The patient\'s hemoglobin level was measured in the office to help confirm the previous anemia diagnosis and was determined to be 6.3 g/dL (normal: 10.5-13.0 g/dL). At this point, the patient was sent to a pediatric emergency department for continued treatment and workup. At the emergency department, the patient received an extensive laboratory workup for the evaluation of anemia, revealing iron deficiency anemia (hemoglobin: 5.6 g/dL (normal: 10.5-13 g/dL), mean corpuscular volume: 51.4 fl (normal: 70-84 fl), iron: 18 mcg/dL (normal: 30-70 mcg/dL), total iron binding capacity: 598 mcg/dL (normal: 100-400 mcg/dL), and hematocrit: 23.7% (normal: 33-38%)) and decreased levels of vitamin D (<6 ng/mL, normal: >30 ng/mL), ionized calcium (1.17 mg/dL, normal: 4.4-5.2 mg/dL), and phosphorus (2.4 mg/dL, normal: 2.9-5.9 mg/dL). These studies, paired with X-ray images of the patient\'s shoulders and wrists, further confirmed the diagnosis of rickets. Rickets is a disease in pediatric patients defined as a condition in which the mineralization of epiphyseal plates is defective. A nutritional deficiency in vitamin D, calcium, or phosphate causes acquired rickets. This condition is most commonly found in developing countries; some predisposing factors include poor sun exposure, high altitude, and breastfeeding. The patient was seen in the outpatient pediatric setting after the hospitalization, in which he received a blood transfusion, where he was managed on supplementation of calcium carbonate suspension, polysaccharide iron complex/novaferrum drops, and cholecalciferol drops with referral to endocrinology, hematology, and dietetics. This case serves as an example of how the diagnosis of nutritional deficiencies, such as rickets, can also be found in developed countries like the United States. Other conditions considered in the differential diagnosis were cystic fibrosis, necrotizing enterocolitis, metabolic disorders, inadequate absorption, and mechanical feeding difficulties, each of which must be ruled out to ensure that even an unlikely finding was not missed.

Rickets results from impaired mineralization of growing bone due to alterations in calcium and phosphate homeostasis. Clinical signs of rickets are related to the age of the patient, the duration of the disease, and the underlying disorder. The most common signs of rickets are swelling of the wrists, knees or ankles, bowing of the legs (knock-knees, outward bowing, or both) and inability to walk. However, clinical features alone cannot differentiate between the various forms of rickets. Rickets includes a heterogeneous group of acquired and inherited diseases. Nutritional rickets is due to a deficiency of vitamin D, dietary calcium or phosphate. Mutations in genes responsible for vitamin D metabolism or function, the production or breakdown of fibroblast growth factor 23, renal phosphate regulation, or bone mineralization can lead to the hereditary form of rickets. This position paper reviews the relevant literature and presents the expertise of the Bone and Mineral Metabolism Group of the Italian Society of Pediatric Endocrinology and Diabetology (SIEDP). The aim of this document is to provide practical guidance to specialists and healthcare professionals on the main criteria for diagnosis, treatment, and management of patients with rickets. The various forms of rickets are discussed, and detailed references for the discussion of each form are provided. Algorithms to guide the diagnostic approach and recommendations to manage patients with rare forms of hereditary rickets are proposed.

UNASSIGNED: Nutritional rickets remains a significant concern in certain countries, with increasing prevalence attributed to factors such as limited sunlight exposure and undernourishment. This study aimed to identify the factors associated with rickets due to nutritional deficiency in children from Jazan Province, southwestern Saudi Arabia.
UNASSIGNED: A retrospective cross-sectional study was conducted using descriptive data from medical records at a tertiary hospital in Jazan Province. Records of patients diagnosed with rickets between January 2010 and December 2020 were analyzed. Symptomatic rickets cases from pediatric clinics were included, and diagnoses were based on biochemical and clinical tests. Risk factors were assessed using patient medical records. Data were analyzed using percentages, mean, and standard deviation.
UNASSIGNED: The study included 84 patients with rickets (53 females and 31 males), primarily between 11-18 years old. The mean body mass index (BMI) of the participants was 21.21. The most common risk factor was nutritional deficiencies, including vitamin D deficiency or calcium deficiency, with 75 patients reporting a family history of vitamin D deficiency. The children had limited sunlight exposure and low levels of calcium and vitamin D. Malnutrition was identified as the highest risk factor for rickets in the study population.
UNASSIGNED: Nutritional rickets appears to be prevalent in the Jazan Province, emphasizing the need for government organizations to address this preventable disease. Adequate sun exposure and recommended dietary vitamin D intake are crucial to prevent rickets, as this study detected inadequate levels of calcium and vitamin D in children. National studies are required to further identify risk factors and develop appropriate strategies.

Muscle atrophy, weakness, and loss of ambulation in the pediatric population are signs of progressive neuromuscular diseases. Rapid identification of such diseases is important to prevent further progression. In pediatric neurology, it is well understood to include neuromuscular disorders in the differential for such presentations. We report a case of severe nutritional rickets that mimicked the presentation of spinal muscular atrophy type III and discuss the importance of including rickets in the differential for muscle atrophy and loss of ambulation. A 33-month-old African American boy with several months of gait abnormality was referred to outpatient neurology. The initial diagnostic evaluation focused primarily on neuromuscular disorders, specifically SMA type III, given the absence of reflexes on examination and the history of prior ambulation. After an unfruitful genetic workup, it was elucidated that the child had very poor dietary intake and minimal sun exposure causing nutritional rickets that improved with intervention.

Nutritional rickets (NR) is still a major problem and is exacerbated by an increasing influx of immigrants. In this study, Turkish and immigrant cases followed with the diagnosis of NR in our pediatric endocrinology clinic were retrospectively evaluated.
Detailed data of cases diagnosed with NR between 2013 and 2020 and followed for at least six months were reviewed.
In the study period, 77 cases of NR were identified. Turkish children constituted 76.6% (n=59) while 18 (23.4%) were immigrant children. The mean age at diagnosis was 8.1±7.8 months, 32.5% (n=25) were female, and 67.5% (n=52) were male. The 25-hydroxyvitamin D3 was below normal in all patients, with a mean value of 4.3±2.6 ng/mL. Parathyroid hormone (PTH) was above normal in all and the mean value was 301.7±139.3 pg/ mL. While there were 3.9 cases of NR in 10,000 endocrine clinic patients in 2013, this rate increased more than four-fold to 15.7 patients in 2019.
Despite the vitamin D prophylaxis program in Türkiye, NR is seen significantly more frequently in recent years, which may be associated with an increasing number of refugees. High PTH levels indicate the severity of NR cases admitted to our clinic. However, clinically significant NR is only the tip of the iceberg and the true burden of subclinical rickets is unknown. Increasing compliance with the vitamin D supplementation program in refugee and Turkish children is important for the prevention of nutritional rickets.

Rickets is the disease of a growing skeleton and results from impaired apoptosis of hypertrophic chondrocytes and mineralization of the growth plate. Nutritionally induced rickets, secondary to vitamin D and/or calcium deficiency, remains a major global problem. In this review, we discuss pathogenesis, clinical signs, investigation and management of nutritional rickets.

Nutrition-acquired osteomalacia is a bone mineralization disorder associated with dietary calcium and/or solar vitamin D deficiency, risk factors considered common in the Middle Eastern region. Establishing less invasive, cheap, and widely available diagnostic markers for this underdiagnosed entity is essential, in particular for screening in high-risk groups. This study assessed the prevalence of biochemical osteomalacia in Arab adolescents. In this cross-sectional study performed between September 2019 and March 2021, adolescents aged 12−17 years from 60 different secondary and preparatory year schools in Riyadh, Saudi Arabia were included. Anthropometrics and fasting blood samples were collected. Biochemical osteomalacia was defined as any two of the following four serum markers of hypomineralization, namely low 25 hydroxyvitamin D (25OHD < 30 nmol/L), high alkaline phosphatase (ALP), low calcium (Ca), and/or inorganic phosphorous (Pi). A total of 2938 Arab adolescents [1697 girls; mean age (years) 14.8 ± 1.8; 1241 boys; mean age 15.1 ± 1.6] were recruited. Vitamin D deficiency was noted in 56.2% (n = 953) of girls and 27.1% (n = 336) of boys (p < 0.001). The overall prevalence of biochemical osteomalacia was 10.0% (n = 295/2938) and was higher in girls than boys (14.7% vs. 3.6%, p < 0.001). The prevalence of low serum Ca and/or Pi was also higher in girls than in boys (24.2% vs. 12.5%, respectively, p < 0.001), as well as elevated ALP (5.1% vs. 1.5%, p < 0.001). Overall, girls were 4.6 times (95% CI 3.3−6.4) more likely to have biochemical osteomalacia than boys. Screening of apparently healthy Arab adolescents revealed a high prevalence of deranged mineralization markers suggestive of biochemical osteomalacia, which was significantly more common in girls than boys and was likely associated with Arab traditional clothing and diet. The proposed combination of typically altered mineralization markers for the diagnosis of osteomalacia is, at best, suggestive until further comparisons with established diagnostic tools (histological analysis of bone biopsies) are conducted.

UNASSIGNED: Rickets is typically characterized by bone deformities due to defective bone mineralization and chondrocyte maturation in growing bones. However, infantile rickets often goes unrecognized, because the skeletal abnormalities are more subtle and often can only be detected radiologically. Nutritional rickets is a major public health concern in several regions worldwide. It is most commonly caused by vitamin D and/or calcium deficiency.
UNASSIGNED: We provide an overview of historical perspective, epidemiology, and pathophysiology of nutritional rickets. Additionally, we outline diagnostic approaches and highlight challenges in radiographic diagnosis of rickets. Finally, we present strategies for prevention and treatment of rickets.
UNASSIGNED: Despite the evidence from clinical databases that rickets is a rare disease, it is likely that rickets is clinically underdiagnosed as studies designed to screen healthy children for radiographic evidence of rickets reported surprisingly much higher prevalence. It has been reported that some of the radiologic features of rickets can be misinterpreted as fractures. To prevent nutritional rickets, most if not all infants and young children, should receive vitamin D from formulas and foods that are fortified with vitamin D or supplementation to achieve a serum 25-hydroxyvitamin D of at least 20 ng/mL as recommended by the Institute of Medicine. It has been recommended by the Endocrine Society that to achieve maximum bone health for children and adults, a serum concentration of 25-hydroxyvitamin D should be at least 30 ng/mL and preferably 40-60 ng/mL. Pregnant women who are unable to obtain an adequate amount of vitamin D from sunlight exposure and natural and fortified diets should take a vitamin D supplement of 1500-2000 IUs daily as recommended by the Endocrine Society since it has been demonstrated that 600 IUs daily will not maintain a circulating 25-hydroxyvitamin D of at least 20 ng/mL and most pregnant women. If lactating women take approximately 6400 IUs of vitamin D daily, they provide enough vitamin D in their milk to satisfy their infant\'s requirement thereby preventing rickets.

Vitamin D is essential for the normal mineralization of bones during childhood. Although diet and adequate sun exposure should provide enough of this nutrient, there is a high prevalence of vitamin D deficiency rickets worldwide. Children with certain conditions that lead to decreased vitamin D production and/or absorption are at the greatest risk of nutritional rickets. In addition, several rare genetic alterations are also associated with severe forms of vitamin-D-resistant or -dependent rickets. Although vitamin D3 is the threshold nutrient for the vitamin D endocrine system (VDES), direct measurement of circulating vitamin D3 itself is not a good marker of the nutritional status of the system. Calcifediol (or 25(OH)D) serum levels are used to assess VDES status. While there is no clear consensus among the different scientific associations on calcifediol status, many clinical trials have demonstrated the benefit of ensuring normal 25(OH)D serum levels and calcium intake for the prevention or treatment of nutritional rickets in childhood. Therefore, during the first year of life, infants should receive vitamin D treatment with at least 400 IU/day. In addition, a diet should ensure a normal calcium intake. Healthy lifestyle habits to prevent vitamin D deficiency should be encouraged during childhood. In children who develop clinical signs of rickets, adequate treatment with vitamin D and calcium should be guaranteed. Children with additional risk factors for 25(OH)D deficiency and nutritional rickets should be assessed periodically and treated promptly to prevent further bone damage.