Rickets needs Vitamin D and Calcium - Global Consensus Jan 2016

Global Consensus Recommendations on Prevention and Management of Nutritional Rickets.

Horm Res Paediatr. 2016 Jan 8. [Epub ahead of print]
Munns CF, Shaw N, Kiely M, Specker BL, Thacher TD, Ozono K, Michigami T, Tiosano D, Mughal MZ, Mäkitie O, Ramos-Abad L, Ward L, DiMeglio LA, Atapattu N, Cassinelli H, Braegger C, Pettifor JM, Seth A, Idris HW, Bhatia V, Fu J, Goldberg G, Sävendahl L, Khadgawat R, Pludowski P, Maddock J, Hyppönen E, Oduwole A, Frew E, Aguiar M, Tulchinsky T, Butler G, Högler W.

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.

Summary of Consensus Recommendations from PDF

Grading of evidence: 1 = strong recommendation; 2 = weak recommendation.
Quality of evidence: ®®® = high; ®® O = moderate; ® OO = low quality.

 Download the PDF from VitaminDWiki

Definition and Diagnosis of Nutritional Rickets

• Nutritional rickets (NR), a disorder of defective chondrocyte differentiation and mineralization of the growth plate and defective osteoid mineralization, is caused by vitamin D deficiency and/or low calcium intake in children. (1 ®® ®)

The diagnosis of NR is made on the basis of history, physical examination, and biochemical testing, and is confirmed by radiographs. (1 ®® ®)

Vitamin D Status

The panel recommends the following classification of vitamin D status, based on serum 25-hydroxyvitamin D (25OHD) levels: (1®®®)
Sufficiency, >50 nmol/l
Insufficiency, 30-50 nmol/l
Deficiency, <30 nmol/l

Vitamin D Toxicity

Toxicity is defined as hypercalcemia and serum 25OHD >250 nmol/l, with hypercalciuria and suppressed parathyroid hormone (PTH). (1 ® ®®)

Dietary Calcium Intake to Prevent Rickets

For infants 0-6 and 6-12 months of age, the adequate calcium intake is 200 and 260 mg/day, respectively. (1®®®)
For children over 12 months of age, dietary calcium intake of <300 mg/day increases the risk of rickets independently of serum 25OHD levels. (1 ®® O)
For children over 12 months of age, the panel recommends the following classification of dietary calcium intake: (1®®O)
Sufficiency, >500 mg/day
Insufficiency, 300-500 mg/day
Deficiency, <300 mg/day

Vitamin D Deficiency and Fractures

Children with radiographically confirmed rickets have an increased risk of fracture. (1 ®® O)
Children with simple vitamin D deficiency are not at increased risk of fracture. (1 ® ® O)

Vitamin D Supplementation for the Prevention of Rickets and Osteomalacia

• 400 IU/day (10 gg) is adequate to prevent rickets and is recommended for all infants from birth to 12 months of age, independently of their mode of feeding. (1 ®®®)
• Beyond 12 months of age, all children and " id="6305" icon="1")}Dow nutritional requirement for vitamin D through diet and/or supplementation, which is at least 600 IU/day (15 gg), as recommended by the Institute of Medicine (IOM). (1®®®)

Target for Vitamin D Supplementation

• In healthy children, routine 25OHD screening is not recommended, and consequently, no specific 25OHD threshold for vitamin D supplementation is targeted in this population. (1 ®®®)

Candidates for Preventative Vitamin D Supplementation beyond 12 Months of Age

In the absence of food fortification, vitamin D supplementation should be given to:
Children with a history of symptomatic vitamin D deficiency requiring treatment (1 ®® ®)
Children and adults at high risk of vitamin D deficiency, with factors or conditions that reduce synthesis or intake of vitamin D (1 ® ®®)
Pregnant women (see section 3.1)

Dose of Vitamin D and Calcium for the Treatment of Nutritional Rickets

• For the treatment of NR, the minimal recommended dose of vitamin D is 2,000 IU/day (50 gg) for a minimum of 3 months. (1 ® ®®)
• Oral calcium, 500 mg/day, either as dietary intake or supplement, should be routinely used in conjunction with vitamin D in the treatment regardless of age or weight. (1®®®)

Appropriate Route of Administration and Duration of Therapy

• We recommend oral treatment, which more rapidly restores 25OHD levels than intramuscular treatment. (1®®®)
• For daily treatment, both D2 and D3 are equally effective. (1®®®)
• When single large doses are used, D3 appears to be preferable compared to D2 because the former has a longer half-life. (1 ®®®)
• Vitamin D treatment is recommended for a minimum of 12 weeks, recognizing that some children may require a longer treatment duration. (1 ©©©)

Dietary Practices and Nutrient Intakes among Mothers Associated with Nutritional Rickets in Infants

• Maternal vitamin D deficiency should be avoided by ensuring that women of childbearing age meet intakes of 600 IU/day recommended by the IOM. (1 ©©©)
• Pregnant women should receive 600 IU/day of vitamin D, preferably as a combined preparation with other recommended micronutrients such as iron and folic acid. (2©©0)

Early Feeding, Supplementation, Complementary Feeding, and Nutrient Intake Associated with Rickets in Infants

• In addition to an intake of 400 IU/day of vitamin D, complementary foods introduced no later than 26 weeks should include sources rich in calcium. (1 ©©©)
• An intake of at least 500 mg/day of elemental calcium must be ensured during childhood and adolescence. (1©©©)

Association of Sunlight Exposure with Nutritional Rickets

• Because ultraviolet B (UVB) rays trigger epidermal synthesis of previtamin D3, restricted exposure to sun increases the risk of vitamin D deficiency and NR. (1©©©)
• Environmental factors, such as latitude, season, time of day, cloud cover, and pollution affect the availability of UVB, whereas personal factors, such as time spent outdoors, skin pigmentation, skin coverage, age, body composition, and genetics affect the dose response of UVB exposure and circulating 25OHD. (2©©0)
• No safe threshold of UV exposure allows for sufficient vitamin D synthesis across the population without increasing skin cancer risk. (2© © O)
  VitaminDWiki - data disagrees with this

The Relationship between Vitamin D during Pregnancy and Infant Growth and Bone Mass

• Pregnant women should receive 600 IU/day of supplemental vitamin D.
  This will ensure adequacy of maternal 25OHD, especially in women at risk of deficiency, to prevent elevated cord blood alkaline phosphatase (ALP), increased fontanelle size, neonatal hypocalcemia and congenital rickets, and to improve dental enamel formation. (2©©0)
• There is little evidence that maternal supplementation with vitamin D will protect or improve birth anthropometry (2© OO) and
  no evidence that supplementation with vitamin D will protect or improve short- or long-term growth or bone mass accretion. (2©© O)

The Effect of Calcium Supplementation during Pregnancy on Infant Bone Mass

Pregnant women do not need calcium intakes above recommended nonpregnant intakes to improve neonatal bone. (1 ©©©)

Influence of Calcium or Vitamin D Supplementation in Pregnancy or Lactation on Breast Milk Calcium or Vitamin D

• Lactating women should ensure they meet the dietary recommendations for vitamin D (600 IU/day) for their own needs, but not for the needs of their infant. (1©©©)
• Lactating women should not take high amounts of vitamin D as a means of supplementing their infant. (2©©0)
• Pregnant and lactating women should meet the recommended intakes of calcium. Maternal calcium intake during pregnancy or lactation is not associated with breast milk calcium concentrations. (1 ©©©)

Causes and Therapy of Congenital Rickets

• Supplementing mothers with 600 IU/day of vitamin D and ensuring they receive recommended calcium intakes, or appropriate therapy of maternal conditions predisposing to hypocalcemia or vitamin D deficiency, prevent congenital rickets. (2© 00)

Assessment of Disease Burden

The prevalence of rickets should be determined by population-based samples, by case reports from sentinel centers, or by mandatory reporting. (1 ©©©)
Screening for NR should be based on clinical features, followed by radiographic confirmation of suspected cases. (1©©©)
Population-based screening with serum 25OHD, serum ALP, or radiographs is not indicated. (1 ©©©)

Public Health Strategies for Rickets Prevention

• Universally supplement all infants with vitamin D from birth to 12 months of age, independently of their mode of feeding. Beyond 12 months, supplement all groups at risk and pregnant women. Vitamin D supplements should be incorporated into childhood primary health care programs along with other essential micronutrients and immunizations (1®®®), and into antenatal care programs along with other recommended micronutrients. (2®®0)
• Recognize NR, osteomalacia, and vitamin D and calcium deficiencies as preventable global public health problems in infants, children, and adolescents. (1®®®)
• Implement rickets prevention programs in populations with a high prevalence of vitamin D deficiency and limited vitamin D and/or calcium intakes, and in groups of infants and children at risk of rickets. (1®®®)
• Monitor adherence to recommended vitamin D and calcium intakes and implement surveillance for NR. (1®®®)
• Fortify staple foods with vitamin D and calcium, as appropriate, based on dietary patterns. Food fortification can prevent rickets and improve vitamin D status of infants, children, and adolescents if appropriate foods are used and sufficient fortification is provided, if fortification is supported by relevant legislation, and if the process is adequately monitored.
  Indigenous food sources of calcium should be promoted or subsidized in children. (1 ®®®)
• Promote addressing the public health impact of vitamin D deficiency as both a clinical and a public health issue. (1®®®)

Economic Cost/Benefits of Prevention Programs

The cost-effectiveness of supplementation and food fortification programs needs further study. (1 ®® O) Nutritional rickets (NR), secondary to vitamin D deficiency and/or dietary calcium deficiency, remains a significant global, public health problem despite the availability of supplementation and numerous published guidelines for its prevention [1-8]. This is concerning because NR can have a major impact on the health of infants, children, and adolescents, with ramifications that persist into adulthood. The morbidity and mortality associated with NR can be devastating, with substantial but poorly recognized consequences for society and health economics.
Features of NR and osteomalacia include:

• (1) hypocalcemic seizures and tetanic spasms;
• (2) life-threatening hypocalcemic cardiomyopathy;
• (3) bone pain and muscle weakness;
• (4) limb and pelvic deformities;
• (5) failure to thrive;
• (6) developmental delay, and
• (7) dental anomalies [9, 10].

Alarmingly, NR can also lead to death from heart failure caused by hypocalcemic cardiomyopathy, even in developed countries [11]. In addition, narrowing of the pelvic outlet after NR in childhood can result in obstructed labor and maternal and fetal death [12].
Despite an intense focus around the role of vitamin D status in health and disease, there has been a worldwide failure to implement public health guidance and eradicate the severest manifestations of vitamin D and calcium deficiency in our most vulnerable population - NR and osteomalacia of childhood. Therefore, the goal of this Consensus Statement is to provide clinicians with clarity and recommendations on the recognition, societal burden, and treatment of NR and osteomalacia, and to enable clinicians and health policy leaders to establish appropriate clinical and public health interventions to prevent this debilitating, costly, and underrecognized global health problem

© 2016 S. Karger AG, Basel and The Endocrine Society.

PMID: 26741135