Vitamin D deficiency

Around 50% of adults have low vitamin D levels. Dr Louise R Newson discusses investigation and prevention of vitamin D deficiency in primary care and provides advice on managing rickets and osteomalacia.

Most of the body’s daily vitamin D requirement is obtained from skin exposure to UVB
Most of the body’s daily vitamin D requirement is obtained from skin exposure to UVB

Vitamin D is important for calcium homeostasis and normal bone metabolism. About 90% of the daily requirement is usually obtained from skin photosynthesis following UVB exposure, and the remainder is from the diet (including oily fish, liver, eggs and fortified breakfast cereals). In the UK, only infant formula milk and margarine have statutory vitamin D supplementation.

Production of metabolically active vitamin D requires hydroxylation, which occurs first in the liver and then in the kidneys to produce 1,25-dihydroxyvitamin D3 or calcitriol.

Around 20 minutes of sunlight exposure on the face and forearms at midday is estimated to generate the equivalent of around 2,000 IU vitamin D.

Exposure to this amount of sunlight two or three times a week is usually sufficient to achieve healthy vitamin D levels for fair-skinned people in the UK. However, those with pigmented skin require greater exposure time or frequency. Even this amount of regular sunlight exposure is rarely achieved. It is estimated that around one billion people worldwide suffer from vitamin D deficiency.

Deficiency

Vitamin D deficiency in children can manifest as rickets. In adults it results in osteomalacia. Deficiency can contribute to the development of osteoporosis by decreasing intestinal calcium absorption.

One UK survey showed that more than half of the adult population has inadequate vitamin D levels and 16% have severe deficiency during winter and spring.1 Risk factors for vitamin D deficiency are listed in the box below.

Risk factors
  • Dark skin (especially south Asian, African-Caribbean and Middle Eastern)
  • Using sunscreen (SPF >15) or concealing clothing when outdoors
  • For babies, breastfeeding (there are only minimal amounts of vitamin D in breast milk)
  • Childhood and older age (vitamin D production in the skin declines with age)
  • Pregnancy
  • Being housebound
  • Vegetarianism
  • Alcoholism
  • Chronic disease (liver/kidney disease, malabsorption)

Vitamin D deficiency can be secondary to other underlying causes, such as reduced GI absorption of vitamin D (because of stomach and bowel resections, chronic pancreatic disease, or Crohn's disease). Liver disease and some drugs (such as anticonvulsants and rifampicin) can also lead to vitamin D deficiency.

Children usually present with rickets which most commonly leads to bowing of the legs; knock knees can also occur. There may be bony deformities of the chest, pelvis and skull, delayed dentition, poor growth and bone pain. Those affected may be irritable and reluctant to weight bear due to bone and joint pains.

Adults most commonly present with pain (usually in the ribs, hips, pelvis, thighs and feet) and proximal muscle weakness. More diffuse muscular aches and weakness can also occur. Lethargy is a common symptom. There may be multiple fractures that are often bilateral and symmetrical. Skeletal deformities can occur, leading to scoliosis or kyphosis.

Rickets, osteomalacia, and vitamin D and calcium deficiencies are preventable global public health problems in infants, children, and adolescents.2

Investigations

Vitamin D status is best determined by measuring serum 25-hydroxyvitamin D levels. Those with osteomalacia or rickets have levels <25nmol/L; those with vitamin D insufficiency 25-50nmol/L. The optimum is >75nmol/L.

Blood should also be taken for calcium, phosphate and alkaline phosphatase. Parathyroid hormone levels are sometimes checked. Elevation of plasma parathyroid hormone is typically seen in osteomalacia; however, it is not seen in around 20 per cent of people with vitamin D deficiency.3

Anaemia should be excluded by measuring haemoglobin level. Any other relevant investigations to determine a secondary cause for vitamin D deficiency should be undertaken, if necessary. Any areas of focal pain in adults should be X-rayed, especially if they worsen or persist during treatment.

Vitamin D insufficiency has been shown to be associated with an increased risk of mortality and also an increased risk of several diseases, including cardiovascular disease, type-2 diabetes, and bowel and breast cancer.4,5 Low 25(OH)D concentrations are also associated with an increased risk of mortality.6

Managing rickets

All children with rickets should be referred to a paediatrician. Adults should be referred to a specialist if there is no obvious cause, unexplained weight loss or anaemia, if the patient has hepatic or renal disease, or if there is no symptomatic improvement after taking supplements for two months.

Oral calciferol in the bioequivalent forms of either ergocalciferol (yeast derived vitamin D2) or colecalciferol (fish or lanolin derived vitamin D3) is the treatment of choice for children with rickets.

Once vitamin D stores have been replenished, patients continue on a lower maintenance dose. Children usually respond rapidly and their alkaline phosphatase levels normalise within three months.

It is likely that the mother, siblings and other family members of a child with rickets are also vitamin D deficient.

Managing osteomalacia

The current loading regimens for treatment of deficiency up to a total of approximately 300,000 international units (IU) given either as weekly or daily split doses. The exact regimen will depend on the local availability of vitamin D preparations but include:7

  • 50,000 IU capsules, one given weekly for 6 weeks (300,000 IU)
  • 20,000 IU capsules, two given weekly for 7 weeks (280,000 IU)
  • 800 IU capsules, five a day given for 10 weeks (280,000 IU)

Maintenance regimens may be considered 1 month after loading with doses equivalent to 800–2000 IU daily (occasionally up to 4000 IU daily), given either daily or intermittently at a higher equivalent dose.

Treatment is usually lifelong as few adults have reversible risk factors for vitamin D deficiency.

Caution is required when prescribing vitamin D for patients also taking certain drugs, including thiazide diuretics (which impair calcium excretion) and digoxin (vitamin D can enhance the effect of digoxin). The combination of calcium and vitamin D should be avoided in the long term as the calcium component is unnecessary, especially in those people who have adequate calcium in their diets.

Preventing deficiency

The key groups to target for treatment are infants, children, adolescents and pregnant women, particularly those with dark skin.2 Education about appropriate sunlight exposure, use of vitamin D supplements and eating oily fish should be more readily available to the general population.

All pregnant women should be informed at the booking appointment about the importance of maintaining adequate vitamin D stores during pregnancy and while breastfeeding. In order to achieve this, women should be advised to take 10 micrograms of vitamin D per day.8

The Scientific Advisory Committee on Nutrition (SACN) has recently published its recommendations on vitamin D.9 In a change to previous advice, SACN is now recommending a Reference Nutrient Intake (RNI) for vitamin D of 10 μg/d (400 IU/d), throughout the year, for everyone in the general UK population aged 4 years and above. This dose includes pregnant and lactating women and population groups at increased risk of vitamin D deficiency.

For children SACN recommends the following:

  • 8.5-10 μg/340-400 IU per day for all infants aged under 1 year
  • 10 μg/400 IU per day for ages 1 up to 4 years.

These recommendations have been developed to ensure that the majority of the UK population has a satisfactory vitamin D status (as measured in the blood) throughout the year, in order to protect musculoskeletal health.

Clear evidence of benefit over harm for vitamin D has not been proved, so vitamin D supplements should not be recommended solely for the prevention of chronic diseases (such as cardiovascular disease, cancer, chronic obstructive lung disease, or diabetes) until more definitive research evidence is available.10

The SACN recommendations are different to the current NOS guidelines, which state that in addition to recommending supplements to pregnant women, the following patients are also recommended to take routine vitamin D supplements: breastfed babies, children under the age of five years, people over the age of 65 years and those not exposed to much sun (for example, those who cover their skin, and housebound individuals).10

Key learning points
  • Most of the body’s daily vitamin D requirement is obtained from skin exposure to UVB: the rest is from the diet
  • Deficiency manifests as rickets in children and osteomalacia in adults
  • Vitamin D insufficiency is associated with an increased risk of morbidity and mortality
  • Vitamin D status is best determined by measuring serum 25-hydroxyvitamin D levels
  • All children with rickets should be referred to a paediatrician
  • Oral calciferol is the treatment of choice for vitamin D deficiency
  • Recent recommendations are for everyone over 1 year of age to receive 10mcg vitamin D daily
  • Dr Newson is a GP in the West Midlands

This is an updated version of an article that was first published in 2011.

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References

  1. Hypponen E, Power C. Hypovitaminosis D in British adults at age 45 y: nationwide cohort study of dietary and lifestyle predictors. Am J Clin Nutr 2007; 85: 860-8
  2. Munns CF, Shaw N, Kiely M, et al. Global Consensus Recommendations on Prevention and Management of Nutritional Rickets. J Clin Endocrinol Metab. 2016 Feb; 101(2): 394-415
  3. Pearce SH, Cheetham TD. Diagnosis and management of vitamin D deficiency. BMJ 2010; 340: b5664
  4. Pilz S, Verheyen N, Grübler MR, et al. Vitamin D and cardiovascular disease prevention. Nat Rev Cardiol. 2016 Jul;13(7):404-17
  5. Muscogiuri G, Altieri B, Annweiler C, et al. Vitamin D and chronic diseases: the current state of the art. Arch Toxicol. 2016 Jul 18. [Epub ahead of print]
  6. Pilz S, Grübler M, Gaksch M, et al. Vitamin D and mortality. Anticancer Res. 2016 Mar; 36(3): 1379-87
  7. National Osteoporosis Society. Vitamin D and bone health: a practical clinical guideline for patient management. NOS, April 2013
  8. NICE. Antenatal care: routine care for the healthy pregnant woman. CG62. London, NICE, 2008 (updated March 2016)
  9. Scientific Advisory Committee on Nutrition. Vitamin D and health. July 2016.
  10. Meyer HE, Holvik K, Lips P. Should vitamin D supplements be recommended to prevent chronic diseases? BMJ. 2015 Jan 29;350:h321

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