Neuromuscular disorders: prophylaxis and treatment guidelines for calcium and vitamin D for children and young people with neuromuscular disorders in the UK

The purpose of this guideline is to provide information on prophylaxis and treatment guidelines for calcium and vitamin D for children and young people with neuromuscular disorders in the UK.

Prophylaxis of vitamin D deficiency

Prophylactic vitamin D should be given to those who are at are at risk of vitamin D deficiency and poor bone mineralisation. These include the following:

  1. Children with mobility and poor weight bearing ability such as children with Neuromuscular Disorders (Rationale 1).
  2. Children with reduced exposure to sunlight (such as those who have poor mobility, those with clothing that limits exposure (Rationale 2).
  3. Children (particularly those with Duchenne Muscular Dystrophy) who are at increased risk of fracture as a result of long term steroid use (Rationale 3).
  4. Children with pigmented skin (Rationale 4).
  5. Children who were commenced on vitamin D treatment and now on maintenance therapy.
  6. Prepubescent children undergoing growth spurt (Rationale 5).
  7. Children following vegan diet (Rationale 6).
  8. Children who are obese (Rationale 8).

Current vitamin D requirements for children and young people in UK.

The Scientific Advisory Committee on Nutrition (SACN) 2016 has revised the 1991 Dietary Reference Values (DRV) and Safe Intakes (SI) for vitamin D in the light of new evidence. For children and young adults the new recommendations are to consume 10μg vitamin D daily in order to protect musculoskeletal health (see table 1 below).

Table 1: Daily vitamin D requirements (SACN Guidelines 2016): 

Age Vitamin D ug/day
Months (all breastfed): RNI 
0-3 8.5-10* (340-400IU)
4-6 8.5-10* (340-400IU)
7-10 8.5-10* (340-400IU)
10-12  8.5-10* (340-400IU)
Years:  RNI 
1-3 10* (400IU)
4-6 10 (400IU)
7-10 10 (400IU)

11-14 (Boys)

11-14 (Girls)

10 (400IU)

10 (400IU)

15-18 (Boys)

15-18 (Girls) 

10 (400IU)

10 (400IU)

*safe intakes (SI) Note: 1  IU = 0.025 µg  1 µg = 40 IU

Prophylactic dosage of vitamin D

The nutritional requirements for children with a neuromuscular disorder, or those children on steroid medication is not known, but they may have increased requirement for vitamin D supplementation. Therefore recommendations should follow those as below.  

Suitable preparations for prophylactic dosages.

All babies and toddlers:

  • Healthy Start = 300 IU vitamin D (but availability problems) 
  • 0.3 mls Abidec = 200 IU vitamin D 
  • 0.1 ml ProD3Forte = 300 IU vitamin D

Babies/toddlers not requiring prophylactic vitamin D

  • Babies drinking volumes of 700 mls/day and above of formula milk.
  • For partially breastfed babies an individual recommendation will be made.

Sunshine exposure

It is recommended that children spend a few hours outside particularly during the summer, autumn and spring months (Rationale 2). Exposure of arms and legs for 5 to 30 minutes (depending on time of day, season, latitude, and skin pigmentation) between the hours of 10am and 3pm is recommended. 

Treatment with Vitamin D

Biochemical evidence of Vitamin D deficiency

Diagnosis of deficiency and insufficiency states are as follows:

Table 2: Biochemical levels of vitamin D deficiency (Pearce and Cheetam 2010):

  Deficiency Insufficient Adequate Ideal / optimum
Vitamin D level (nmol/l) <25 25-50 50-75 >75

Note:  2.5 nmol/l  = 1 ng/ml

There is no agreed definition for vitamin D deficiency (Jackson 2007).

Currently, there is debate as to what is considered the acceptable minimal level of vitamin D. Some sources suggest >50 nmol/l (Holick M, 2011) whilst others say >75 nmol/l (Jackson 2007). Vitamin D plays more of an important role for children taking steroids as these children do not absorb vitamin D as well as children who do not take steroids. Therefore, vitamin D helps bone accrual and is therefore likely to be particularly advantageous for those children on steroids. 

For patients on long-term steroid therapy the best pragmatic approach would be to maintain a vitamin D level at, or around, 75 nmol/l. 

Individuals with 25(OH)-D levels of >250nmol/l (100ng/ml) have been arbitrarily designated as having vitamin D excess and as being at risk for vitamin D intoxication.  However, sunbathers and lifeguards achieve 25(OH)-D levels of >250nmol/l (100ng/ml) without evidence of intoxication (Misra et al, 2008).

Toxic levels of vitamin D: according to UCLH laboratory reports, toxic levels very much depend on the patient and their ability to handle calcium. Some individuals may have very high levels of vitamin D showing no signs of toxicity, but this can vary per patient. As a general rule, if vitamin D levels >200 nmol/L: consider dose reduction. 

Treatment and maintenance dosages with Vitamin D

Table 3a. Deficiency - Treatment dosages with vitamin D for boys with Duchenne Muscular Dystrophy and/or on steroid therapy (Alshaikh et al 2016):
Dosage (IU)/day

Deficiency 

<25 nmol/l 

Replenishment

Maintenance therapy 

following 

deficiency

1-3 years 11 months 3000* 400-800*
4-18 years  6000 daily for 3 months 1000

* Upper dose for a child who is steroid treated or with an increased risk of fracture (e.g. Duchenne Muscular Dystrophy). Consider lower dose for children with neuromuscular disorders with limited mobility but without concomitant corticosteroid treatment. 

Table 3b. Insufficiency - Treatment dosages with vitamin D for boys with Duchenne Muscular Dystrophy and/or on steroid therapy (Alshaikh et al 2016):
Dosage (IU)/day

Insufficiency

25-50 nmol/l

Replenishment

Maintenance therapy

following 

insufficiency

1-3 years 11 months 3000 400
4-18 years 3000 1000-1500
Table 4a. Deficiency - Treatment dosage with Vitamin D for all other Neuromuscular Children (not Duchenne or steroids). (Pearce and Cheetam  2010, Holick et al 2011):
Dosage (IU)/day

Deficiency

<25 nmol/l

replenishment

Maintenance therapy

following 

deficiency

1 to 6 months 3000 200-400
6 months to 12 years 6000 400-800
12 to 18 years 10000 400-800
Table 4b. Insufficiency - Treatment dosage with Vitamin D for all other Neuromuscular Children (not Duchenne or steroids). (Pearce and Cheetam  2010, Holick et al 2011):

Dosage (IU)/day

Insufficiency 

<25 nmol/l

replenishment

Maintenance therapy

following 

insufficiency 

1 to 6 months  

2000  --------
6 months to 12 years 2000  --------
12 years to 18 years  2000  --------

(for 3 months)

0 to 1 year

 --------  400-600
1 to 18 years   --------  600-1000

If a child is treated/replenished for deficiency, then they are likely to be on a high dose of vitamin D. Treatment/replenishment should remain at this level of dosage for a minimum of 3 months. Vitamin D is administered as either D2 or D3. Both D2 ergocalciferol and D3 colecalciferol are physiologically inactive and have to be hydroxlyated in the liver and kidneys to form active compounds. Ideally the preparation should be as D3 and not D2 (Rationale 9).

After this time, levels of vitamin D should be taken again to ensure levels are replete. If they are not and the levels are in the insufficient range then continue on high dose until levels are replete.  

Children who have been successfully treated with vitamin D will need a maintenance dosage of vitamin D that will keep their vitamin D levels in the optimum range: this may be between 200 IU and 1000 IU/day depending on their level of deficiency.

There appears to be no data on treatment or maintenance dosages for adequate levels of vitamin D.

Dosage preparations

As said above, colecalciferol has better bioavailability than ergocalciferol. The hydroxylation of these metabolites is controlled by PTH and therefore reduces the risk of hypercalcaemia. Alpha-calcidol and calcitriol have different modes of action.

The Neuromuscular team’s preferred preparations are:  

  • Sunvite (exists in D3 form). Holland and Barratt. Available in 1000 IU (or 25 ug). No milk, porcine, fish, soya (but uses animal by-products in processing). 
  • ProD3 Forte. Liquid/oral solution 3000 IU/ml (800 IU given as 0.26 ml. Oral syringes can be calibrated for 0.26 ml. GOSH stock these as do community pharmacists). Available through UK distributor AAH Pharmaceuticals or Martindale and Aurum Pharmaceuticals. Free from gelatin, soya, peanut oil, lactose, yeast, alcohol. Unlicensed for children so given at the GP discretion.
  • ProD3.  Liquid 2000 IU/ml.
  • Vigantoletten 1000 IU dispersible tablets from specials Manufacturer UL Medicines, Watford. Contains soya.
  • Fultium D3, drops: 2740 IU/ml: 900 IU/0.3 ml.
  • Abidec multivitamins (D2): 400 IU (10 ug) vitamin D (the drops contain peanut oil.). May possibly contain residues of egg/nut/soya protein.

DEXA scan

Boys with Duchenne Muscular Dystrophy will need an annual vitamin D and bone profile tested.

Calcium

All children need to meet their Reference Nutrient Intake (RNI) for calcium. 

Calcium is less of a concern than vitamin D as this mineral is present in many foods. However, children (particularly boys) entering growth spurt, who have high requirements for calcium (Rationale 7), or those children who have allergy/intolerance or dislike of milk and milk-containing foods, may need a calcium supplement.

If children are not meeting their calcium requirements then either dietary or proprietary products can be recommended. Supplements may be appropriate in situations where minimising the amount of calories in the diet is paramount (for example for children who are obese).

Assessment and treatment for children requiring additional calcium:

  • Underweight child: If a child is underweight and there is a suspicion that the child needs additional calcium it is preferable to refer the child to a dietitian if she/he is underweight. The dietitian will take a diet history or ask parents to complete a 4-day food diary which is analysed for its energy, protein and calcium content.  For the underweight child, dietary sources of calcium are likely to be recommended because they also provide additional calories for weight gain. The richest sources of calcium are from dairy sources. Dairy sources of calcium are better absorbed than from supplements.  
  • Appropriate weight for height child: Dietary sources of calcium should be recommended but they need to be reduced-fat varieties to prevent excess weight gain. In practice, many children have already made the adaptation to low-fat products but remain overweight. Such children may require a calcium supplement. 
  • Overweight/obese child: These children are likely to need a calcium supplement if the child has already changed to reduced fat products and remains overweight. A previous audit at GOSH (Ricotti et al 2010, unpublished data) of 22 boys with Duchenne muscular dystrophy aged >11 years showed that all (100%) boys were taking insufficient amounts of calcium (Rationale 7) when assessed using food diary. In addition, many Duchenne muscular dystrophy children at this age are likely to be wheelchair bound and very overweight, thus conferring two risk factors for poor vitamin D status.

Calcium dosage

Dosage of calcium depends on a child’s individual requirement which is age dependent:

Table 5: Dietary Reference Values for calcium (Department of Health, 1991). 

Age

RNI (Recommended Nutrient Intake) 

(mg/day)

Birth to 12 months 525
Infants 1 to 3 years 350
4 to 6 years 450
7 to 10 years 550
11 to 18 year 1000 (boys) 800 (girls)

Prescribable calcium supplements usually contain around 500 mg calcium. Some calcium supplements also provide a source of vitamin D (see Appendix 1). Some vitamin D and calcium supplements can be purchased over-the-counter.  

Glossary

RNI (Recommended Nutrient Intake). Reference Nutrient Intake (RNI) the intake that will be adequate to meet the needs of 97.5% of the population

Safe Intake:  Set for some nutrients if there are insufficient reliable data to set dietary reference values.  Represents a level or intake range at which it is considered that there is no risk of deficiency and below a level where there is a risk of undesirable effects

Rationale

Rationale 1: Weight bearing is important for maintaining bone strength. Many children with Neuromuscular disorders are unable to weight bear.

Rationale 2: The skin has a large capacity to produce vitamin D and exposure of about 20% of the body’s surface to either direct sunlight or equivalent tanning bed radiation is effective in increasing the plasma concentration of 25 (OH)D in both young adults and older adults (Holick, 2011). Children with poor exposure to sunlight are unable to produce sufficient quantities of vitamin.  However, the use of tanning beds is not recommended. 

Rationale 3: Children on steroids. Corticosteroids affect calcium and bone metabolism in many ways: 

  • Steroids decrease the amount of calcium absorbed by the intestine. 
  • Steroids increase calcium excretion through the kidneys. These two factors combine to produce a decline in the circulating ionized calcium concentration. This triggers the parathyroid glands to increase the secretion of parathyroid hormone, a condition known as secondary hyperparathyroidism. Elevated PTH levels result in increased bone breakdown, as the body attempts to rectify low circulating calcium levels by releasing calcium from the bones into the blood.

Rationale 4: Pigmented skin requires longer exposure to ultraviolet light in order to synthesise equivalent quantities of colecalciferol. Skin pigmentation can affect vitamin D3 production because the melanin absorbs UV radiation in the 290-320nm range and functions as a light filter determining the amount of incident radiation available for the cutaneous production of pre-vitamin D3 (Department of Health, 1998). A sun protection cream with SPF15 will reduce synthesis of vitamin D by 99% (Macin et al 2011). 

Rationale 5: A pre-adolescent’s daily requirements for calcium greatly increases. For boys the amount is almost doubled. For calcium to be utilised adequate vitamin D is therefore essential. 

Rationale 6: A vegan eats no animal products. Vitamin D is found in animal-based products such as dairy foods, beef liver, eggs, fish, and fish oils. 

Rationale 7: Children >11 years are at risk of calcium deficiency as this is the time for rapid skeletal growth. 

Rationale 8: Insulin secretion is dependent on vitamin D. In obese adults circulating levels of vitamin D are decreased (possibly due to its accumulation in visceral adipose tissue). Obese adolescents with the lowest vitamin D concentration show the highest pancreatic fat deposition and the lowest fasting insulin level (Norman, 1998). 

Rationale 9: Colecalciferol has been reported to raise vitamin D concentrations more effectively than ergocalciferol due to higher affinities of colecalciferol and its metabolites for liver enzymes, plasma vitamin D binding protein and vitamin D receptors.  It has been suggested that this difference in potency makes colecalciferol the drug of choice.
.

References

Alshaikh N, Andreas Brunklaus, Tracey Davis et al.  (2016) Vitamin D in Corticosteroid-naïve and corticosteroid-treated Duchenne Muscular dystrophy: what dose achieves optimal 25 (OH) vitamin D levels. Arch Dis child.

British National Formulary. London: British Medical Association and the Royal Pharmaceutical Society of Great Britain. No.64. September 2016/17.

Department of Health (1998). Nutrition and bone health with particular reference to calcium and vitamin D: Report of the Subgroup on Bone Health (Working Group on the Nutritional Status of the Population) of the Committee on Medical Aspects of Food and Nutrition Policy. Report on health and social subjects 49. London, The Stationery Office. 

Department of Health (1991). 41 Dietary Reference Values for Food Energy and Nutrients for the United Kingdom. Report of the Panel on Dietary Reference Values of the Committee on Medical Aspects of Food Policy.

Holick MF, Binkley NC, et al. (2011) Evaluation, treatment and prevention of vitamin D deficiency: an endocrine society clinical practice guideline. Journal of Clinical Endocrinology and Metabolism; 96(7):1911-1930.

Jackson AA (chair) (2007) Update on vitamin D; Position Statement by the scientific advisory committee on nutrition. Scientific Advisory committee on nutrition. London. [Last accessed 03.07.2017].

Macin et al. (2011) Abstract presented at 44th Annual Meeting of the European Society of Paediatric Gastroenterology, Hepatology and Nutrition. 25-28th Vitamin D is related to Pancreatic Fat Fraction and Fasting Serum Insulin in Obese Adolescents. 

Misra M, Pacaud D, Petryk A, Collett-Solberg. (2008) Vitamin D Deficiency in Children and Its Management: Review of Current Knowledge and Recommendations Pediatrics;122;398-417.

Norman AW. (1998). Sunlight, season, sun protection, vitamin D and 25-hydroxyvitamin D: integral components of the vitamin D endocrine system. Am J Clin Nutri.67(6): 1108-1110. [Last accessed 03.07.2017].

Pearce SHS, Cheetham TD. (2010) Diagnosis and management of vitamin D deficiency. BMJ; 340: 142-147.

Ricotti V,  Davis T,  Manzur A Y,  Muntoni, Robb SA, (2010). Dietary calcium intake in boys with Duchenne Muscular Dystrophy. The Dubowitz Neuromuscular Centre, Great Ormond Street Hospital and Institute of Child Health, University College, London, UK.

Scientific Advisory Committee on Nutrition.  Vitamin D and Health. (2016). [Last accessed 03.07.2017].

Appendices

Appendix 1: Prescribable calcium supplements and calcium supplements with vitamin D (BNF for children 2016-2017)

Calcium Supplements 

(Solution better absorbed than tablets)

Calcium 

(mg)

Vitamin D

(ug)

Sandocal + D (effervescent tablet, orange flavour) 1000  25 (1000 IU)
Alliance Calcium Syrup (1ml) 20.4 x
Adcal- D3 (caplet). Not licensed for use in children <12 years 600 10 (400 IU)
Calceos (chewable lemon tablet) 500 10 (400 IU)
Cacit D3 (effervescent granules, lemon) Not licensed for use in children <12 years 500 11 (440 IU)
Cacit (suitable >6 years) 500 x
Calcichew (chewable tablet, orange) 500  x
Calcichew FORTE 2500 x
Calcichew D3 (chewable tablet) 500 5 (200 IU)
Calcichew D3 (caplet). Not licensed for use in children.  500 10 (400 IU)
Calcichew D3 FORTE (chewable tablet) 500 10 (400 IU)
Calfovit D3 (powder lemon flavour) 1200 20 (800 IU)
Natecal D3 (chewable tablet, aniseed, peppermint, molasses flavour)  600 10 (400 IU)
Fultium D3 Solution: 2740 IU/ml  0.1 ml x 22.5 (900 IU)
ProD3 Forte liquid 3000 IU/ml  0.1 ml x 7.5 (300 IU)
ProD3 Forte liquid 3000 IU/ml  0.2ml x 15 (600 IU)
At GOSH: Colecalciferol: 1000 IU dispersable tablet OR 5000 IU capsule  x 75 (3000 IU)

Document control information

Lead Author(s)

Trak Davis, Specialist Dietician, Dietetics

Additional Author(s)

Vanessa Shaw, Head of Dietetics
Dr Ros Quinlivan, Consultant in Neuromuscular disease
Dr Adnan Manzur, Consultant in Neuromuscular Disease

Document owner(s)

Trak Davis, Specialist Dietician, Dietetics

Approved by

Guideline Approval Group

Reviewing and Versioning

First introduced: 
01 July 2013
Date approved: 
30 June 2017
Review schedule: 
Three years
Next review: 
30 June 2020
Document version: 
3.0
Previous version: 
2.0