Vitamin D and Bone Health: A Practical Clinical Guideline for Management in Children and Young People

Overview

This is a clear summary of the Royal Osteoporosis Society (ROS)'s clinical guideline for the management of vitamin D deficiency in children and young people. It provides key recommendations for primary care settings, as well as the tole of vitamin D in paediatric bone health, when vitamin D deficiency should be tested for, primary prevention treatment, and vitamin D toxicity. For the complete set of recommendation, refer of the full guideline.

The Guidelines summary of the ROS recommendations on patient management of vitamin D in both health and adults can be found here.  

Key Recommendations

• Measurement of serum 25(OH)D is the best way to estimate vitamin D status
• Routine testing of serum 25(OH)D levels is not recommended and it is advised to be restricted to children and young people with a clear indication for measurement
• Primary prevention with advice regarding dietary sources of vitamin D and multivitamin supplements as recommended for age
• Treatment is recommended to consist of oral preparations of vitamin D₃ given daily for eight to 12 weeks
• Many children with vitamin D deficiency have a poor dietary calcium intake and therefore may need to increase their dietary calcium intake or take calcium supplementation.

The Role of Vitamin D in Paediatric Bone Health

• Nutritional vitamin D deficiency can lead to health problems in children including rickets, impaired growth, muscle weakness, cardiomyopathy and seizures due to hypocalcaemia
• There is no universal consensus on the biochemical definition of vitamin D deficiency. It is current paediatric practice to use a threshold of plasma 25 hydroxyvitamin D (25(OH)D) of less than 25 nmol/l to define vitamin D deficiency
• Plasma 25(OH)D levels:
  • below 25 nmol/l is deficient
  • 25–50 nmol/l may be inadequate in some people
  • greater than 50 nmol/l is sufficient for almost the whole population.

Who Should Be Tested for Vitamin D Deficiency?

• Low levels of vitamin D are common in the UK. It is therefore important to consider whether the child’s symptoms or signs could be related to vitamin D deficiency before requesting the measurement of vitamin D
• Routine screening is not recommended.

Indications for Testing Vitamin D Status

1. Symptoms and signs of rickets:
   • progressive bowing of legs (bowing of legs can be a normal finding in toddlers)
   • progressive knock knees
   • wrist swelling
   • rachitic rosary (swelling of the costochondral junctions)
   • craniotabes (skull softening with frontal bossing and delayed fontanelle closure)
   • delayed tooth eruption and enamel hypoplasia.
2. Other symptoms or conditions associated with vitamin D deficiency:
   • long-standing (>3 months), unexplained bone pain
   • muscular weakness (e.g. difficulty climbing stairs, waddling gait, difficulty rising from a chair or delayed walking)
   • tetany due to low plasma calcium
   • seizures due to low plasma calcium (usually in infancy)
   • infantile cardiomyopathy.
3. Abnormal investigations:
   • low plasma calcium or phosphate, high alkaline phosphatase (greater than the local age-appropriate reference range)
   • radiographs—showing osteopenia, rickets or pathological fractures revealed by radiographs.
4. Chronic disease that may increase risk of vitamin D deficiency:
   • chronic renal disease, chronic liver disease
   • malabsorption syndromes (e.g. coeliac disease, Crohn's disease, cystic fibrosis)
5. Treatment with bone-targeted drugs that require vitamin D sufficiency such as bisphosphonates (used in conditions affecting bones such as osteoporosis due to steroids, immobility or inflammatory disorders)

• In the absence of the above indicators, measurement of vitamin D is not indicated.

Primary Prevention

• It is advised that primary preventative measures (at minimum) be undertaken in patients at high risk. These include advice about dietary intake of vitamin D and multivitamin supplements.

Indications for Vitamin D Supplements

• Public Health England recommends daily vitamin D supplements as follows:
  • all babies from birth to one year should consume 8.5–10 μg per day
  • babies receiving infant formula do not require supplements if receiving more than 500 ml per day
  • children from one to four years should consume 10 μg per day.
• The provision of Healthy Start multivitamin drops through primary health care services and Children’s Centres remains key to the delivery of vitamin D supplementation to children. Whilst Healthy Start multivitamins currently provide only 7.5 μg (300 IU per day), it is the understanding of the authors that this is under review.

Other Indications for Vitamin D Supplements

• Children and young people previously shown to be vitamin D deficient or with a plasma 25(OH)D of 25–50 nmol/L should take a supplement containing vitamin D. This should be continued unless there is a significant lifestyle change to improve vitamin D status
• Vitamin D supplements should be considered in other groups at high risk of vitamin D deficiency (see below), especially if they do not adhere to lifestyle advice.

Groups at High Risk of Vitamin D Deficiency

• Children and young people in the following groups are at high risk of vitamin D deficiency. Primary prevention is therefore particularly important for them:
  • children and young people with diets insufficient in calcium (e.g. vegan or low dairy intake) or with generally poor diets
  • children and young people with limited sun exposure (e.g. veiled and photosensitive patients and patients who are advised to apply high factor sun block due to malignancy risk e.g. cancer survivors)
  • children and young people who spend very little time outdoors (e.g. those with limited mobility)
  • children and young people who have dark skin, for example people of African, African-Caribbean or South Asian origin, as they may not get enough vitamin D from sunlight
  • children and young people taking anticonvulsants that induce liver enzymes such as phenytoin, carbamazepine, primidone or phenobarbitone
  • children and young people with family members with proven vitamin D deficiency.

Season

• There is a seasonal variation in vitamin D status in the UK, with lower circulating concentrations seen in the population in winter and late spring, compared to summer and autumn. It may be helpful to take into consideration the likely decline in vitamin D status when determining what to do with a child with a low 25(OH)D concentration in autumn or winter
• Having a low 25(OH)D concentration in late summer may reflect a lifestyle that places the individual at risk of vitamin D deficiency. It is important to state that the physiological significance of a given 25(OH)D concentration at a given moment is the same whatever the time of year.

Dietary Vitamin D

• Consumption of vitamin-D-rich foods can contribute to improving vitamin D status. Foods rich in vitamin D include:
  • oily fish such as sardines, pilchards, and mackerel
  • eggs, meat, and milk (in small and varying amounts)
  • most margarine, some breakfast cereal, some yoghurt, and infant formula, which are fortified with vitamin D.

Who Will Benefit From Treatment?

• It is advised that in those patients where 25(OH)D is tested (discussed in the previous section) the results be acted upon as follows:
  • plasma 25(OH)D <25 nmol/l:
    • treatment recommended.
  • plasma 25(OH)D 25–50 nmol/l:
    • give advice on dietary sources of vitamin D
    • advise oral preparations containing vitamin D 400–600 IU/day for patients aged 1 month to 18 years. This should be continued unless there is a significant lifestyle change to improve vitamin D status
    • ensure dietary calcium intake is adequate
    • retesting is not normally required if the individual is asymptomatic and compliant with multivitamin supplements.
  • plasma 25(OH)D >50 nmol/l:
    • provide reassurance and give advice on maintaining adequate vitamin D status through diet and supplements.

Indications for Referral to Secondary Care

• The following circumstances indicate referral to secondary care is warranted:
  • repeated low plasma calcium concentration with or without symptoms (irritability, brisk reflexes, tetany, seizures or other neurological abnormalities)
    • symptomatic: requires immediate referral to A&E if outpatient
    • asymptomatic: discuss treatment with paediatrician.
  • underlying complex medical disorders (e.g. liver disease, intestinal malabsorption)
  • in children, deformities or abnormalities probably related to rickets
  • poor response to treatment despite good adherence (defined as a level of 25(OH)D <50 nmol/l after 8 to 12 weeks of adherence to therapy)
  • persisting low plasma phosphate or low/high alkaline phosphatase.

How Should Vitamin D Deficiency Be Treated?

Vitamin D₃ or Vitamin D₂?

• As there is data to show that vitamin D3 is more 3 bioavailable than vitamin D₂, vitamin D₃ is recommended as the preferred treatment although treatment with vitamin D₂ is effective
• The doses of vitamin D below are based on what are currently recommended in the British National Formulary for Children (BNFC). However, these may need to be changed dependent on the availability of other vitamin D preparations and evidence of alternative dosing regimens:
  • one to five months: 3,000 IU orally daily for 8–12 weeks
  • six months to 11 years: 6,000 IU orally daily for 8–12 weeks
  • 12–17 years: 10,000 IU orally daily for 8–12 weeks; a single or divided oral dose totalling 300,000 units can be considered if there is concern about compliance.
• It is recognised that equivalent weekly or fortnightly dosing is likely to be effective in treating vitamin D deficiency

Calcium Supplementation

Table 1: Guideline on Assessing Dietary Calcium Intake

Monitoring

• Many children with vitamin D deficiency rickets have a poor dietary calcium intake. As their bones are growing, there is a greater risk of negative calcium balance. Therefore, in children consider the need for calcium supplementation. Many children with vitamin D deficiency will have a depleted calcium status and/or a poor calcium intake and may therefore benefit from advice about dietary calcium intake 
• In some cases calcium supplementation may be worthwhile over the period of vitamin D treatment (see Table 1). These recommendations represent a represent a recommended calcium intake to prevent rickets: 
  • birth to six months: 200 mg per day
  • six to 12 months: 260 mg per day
  • over 12 months: >500 mg per day.
• Dietary intake can be achieved through a combination of diet and supplementation as required. The dose of any supplements also needs to take into account dietary calcium intake and the size of the child
• There is no place for the use of 1α-hydroxylated preparations (e.g. alfacalcidol or calcitriol) in the routine management of vitamin D deficiency. Their use is limited to treating significant hypocalcaemia, disorders of malabsorption, renal disease and rare diseases of calcium and phosphate regulation.
• Bone profile and vitamin D tests (and a parathyroid hormone test if the patient has rickets or hypocalcaemia) are recommended to be repeated at the end of the course of treatment
• If the 25(OH)D level is greater than 50 nmol/l and the bone profile is normal:
  • advise multivitamins containing vitamin D 400–600 IU/day. Continue unless there is a significant lifestyle change to improve vitamin D status.
• If 25(OH)D is below 50 nmol/l:
  • consider poor compliance, drug interactions and underlying disease such as renal disease, liver disease and malabsorption
  • if poor compliance is suspected, a high-dose treatment may be considered if the patient is aged 12–18 years (e.g. 300,000 IU as a single or divided dose.
• Note: If a child's symptoms/signs have not improved despite a satisfactory 25(OH)D concentration, they are unlikely to be related to vitamin D deficiency.

Vitamin D Toxicity

• The Global consensus recommendations on prevention and management of nutritional rickets defines toxicity as hypercalcemia and a plasma 25(OH)D > 250 nmol/L with hypercalciuria and suppressed PTH. Whilst recommending a concentration of 250 nmol/L as the upper limit of 25(OH)D the paper’s authors acknowledge that this allowed a 'large safety margin' and that symptomatic toxicity from randomised control trials had only been reported at levels >500 nmol/L1
• There is no widespread agreement on the threshold concentration or amount of vitamin D that results in toxicity. This is, in part, a reflection of the paucity of studies that address the safety of vitamin D supplementation. In adults, prolonged daily intake of vitamin D up to 10,000 IU or plasma concentrations of 25(OH)D of up to 240 nmol/L appear to be safe. Although described, acute vitamin D intoxication is rare and usually results from vitamin D doses much higher than 10,000 IU per day
• However, the long-term effects of supplementation with high doses of vitamin D are not known. Risks such as nephrolithiasis cannot be excluded. Caution is required in any child or young person with a granulomatous disease (e.g. tuberculosis or sarcoidosis)