Vitamin D and bone health: a practical clinical guideline for management in children and young people

National Osteoporosis Society


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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 should be restricted to children and young people with a clear indication for measurement
  • Primary prevention via safe sunlight exposure, advice regarding dietary sources of vitamin D and multivitamin supplements are recommended for high-risk groups
  • Treatment should consist of oral preparations of vitamin D2 or D3 given daily for 8 to 12 weeks
  • Many children with vitamin D deficiency have a poor dietary calcium intake and therefore may also require higher dietary calcium intake or 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 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 serum 25 hydroxyvitamin D (25(OH)D) of less than 25 nmol/l to define vitamin D deficiency
  • Serum 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 a vitamin D level
  • 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 serum calcium
    • seizures due to low serum calcium (usually in infancy)
    • infantile cardiomyopathy
  3. Abnormal investigations:
    • low serum calcium or phosphate, high alkaline phosphatase (greater than the local age-appropriate reference range)
    • radiographs—showing osteopenia, rickets or pathological fractures 
  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. Bone diseases in children where correcting vitamin D deficiency prior to specific treatment would be indicated:
    • osteogenesis imperfecta
    • idiopathic juvenile osteoporosis
    • osteoporosis secondary to glucocorticoids, inflammatory disorders, immobility and other metabolic bone conditions
  • In the absence of the above indicators, measurement of vitamin D is not indicated

Primary prevention

  • Primary preventative measures (at minimum) should be undertaken in patients at high risk. These include advice about safe sunlight exposure, dietary intake of vitamin D, and multivitamin supplements

Indications for vitamin D supplements

  • The Department of Health recommends daily vitamin D supplements to the following:
    • all children between 6 months and 5 years (unless they are receiving over 500 ml of formula milk per day)
    • breast-fed infants from the age of 1 month if the mother has not taken vitamin D supplements during her pregnancy
  • In many cases, vitamin supplementation may be available for free through the Healthy Start programme (see www.healthystart.nhs.uk for more information)
  • Other indications for vitamin D supplements:
    • children and young people previously shown to be vitamin D deficient or with a serum 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 lifestyle advice is not adhered to

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 (see full guideline) or with generally poor diets
    • exclusively breast-fed babies from the age of 6 months, especially if the mother is also at risk of vitamin D deficiency or the infant has not started to take a good range of solid foods
    • exclusively breast-fed babies from 1 month if the mother has not taken vitamin D supplements in pregnancy, or if she is known to be vitamin D deficient or insufficient
    • children and young people with limited sun exposure (e.g. veiled and photosensitive patients)
    • disabled children and young people who spend very little time outdoors
    • children and young people who have darker skin, for example people of African, African-Caribbean or South Asian origin, because their bodies are not able to make as much vitamin D
    • 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 should be treated?

  • In those patients where 25(OH)D is tested (see the previous section) the results should be acted upon as follows:
    • serum 25(OH)D <25 nmol/l:
      • treatment recommended.
    • serum 25(OH)D 25–50 nmol/l:
      • give advice on safe sun exposure and diet
      • 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
    • serum 25(OH)D >50 nmol/l:
      • provide reassurance and give advice on maintaining adequate vitamin D status through safe sunlight exposure and diet

Indications for referral to secondary care

  • The following circumstances indicate referral to secondary care is warranted:
    • repeated low serum 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 serum phosphate or low/high alkaline phosphatase

How should vitamin D deficiency be treated?

Either vitamin D3 or vitamin D2

  • Although there are data to show that vitamin D3 is more bioavailable than vitamin D2, both forms have been shown to cure rickets and we would not recommend any difference in the doses used
  • The doses 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:
    • 1–6 months: 3,000 IU orally daily for 8–12 weeks
    • 6 months to 12 years: 6,000 IU orally daily for 8–12 weeks
    • 12–18 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

Calcium supplements

  • 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 full guideline). The recommendations below are from the BNFC:
    • birth to 4 years: 0.25 mmol/kg calcium q.d.s
    • 5–12 years: 0.2 mmol/kg calcium q.d.s
    • 12–18 years: 5-10 mmol calcium q.d.s
  • Dosing also needs to take into account dietary 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 and renal disease

Monitoring

  • Bone profile and vitamin D tests (and a parathyroid hormone test if the patient has rickets or hypocalcaemia) should 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:
    • give advice on safe sun exposure and diet
    • advise multivitamin containing vitamin D 400–600 IU/day. This should be continued 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

  • Serum 25(OH)D concentrations of above 375 nmol/l have been associated with hypercalcaemia and hyperphosphataemia but there is no agreement on the threshold concentration or amount of vitamin D that results in toxicity
  • 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)

References

full guideline available from…
www.nos.org.uk/professionals/publications

National Osteoporosis Society. Vitamin D and bone health: a practical clinical guideline for management in children and young people. June 2015


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