Vitamin D Deficiency

1
Vitamin D Deficiency

• Dr Elizabeth Murphy
• GP Principal, Easton Family Practice
• and Salaried GP, the Haven
• Bristol

2
Definitions

• Osteoporosis- lack of bone tissue that which is
  left behind is fully calcified
• Osteomalacia poor calcification causing a delay
  or failure of bone matrix mineralization usually
  caused by Vitamin D deficiency or a disturbance
  in its metabolism
• Rickets osteomalacia happening before the
  epiphyses have fused

3
Personal turning point

• BMJ Lesson of the week 17/07/04
• Musculoskeletal pain in female asylum seekers
  and hypovitaminosis D3
• Gabrielle de Torrente de la Jara, Alain Pecoud,
  Bernard Favrat Medical OPD Lusanne, Switzerland
• Series of 11patients
• First diagnosis- somatisation,chronic back pain,
  multiple unexplained somatic symptoms
• Mean duration of symptoms before diagnosis- 38
  months
• Most complaints were typical of hypovitaminosis D
  from the outset
• With treatment most symptoms disappeared in 1-3
  months
• At diagnosis mean Vit D3 levels 10.9ug/L
  (19-57ug/L)
• Delay in diagnosis had psychosocial effects in an
  already vulnerable population
• Poor knowledge of hypovitaminosis D amongst
  doctors

4
Immediate effect

• Instantly recognised patients fitting this
  description
• Many local GPs uncertain how to diagnose and
  treat
• Lab difficulty coping with numbers of requests
  for Vit D levels expensive manual test costing
  around 50 each
• Meeting convened with interested parties- Public
  Health, GPs, Paed Endocrinologist, care of
  elderly with interest in bone health, biochemist
• Remit to increase knowledge and create local
  protocol based on current evidence
• Gaps in evidence and conflicting evidence
  identified
• Research led by Julie Mytton SpR Public Health

5
Our research

• Published as brief report in BJGP July 2007
  Vitamin D deficiency in multicultural primary
  care Julie Mytton, Alison P Frater, Giles Oakley,
  Elizabeth Murphy, Matthew J Barber, Sarah Jafar
• Review of 299 patients from 4 inner city
  practices with combined list of 34,684 patients
• Review of case notes of those diagnosed with Vit
  D deficiency from January 2003 to September 2005
• Largest case series in black African patients in
  English language literature

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Ethnicity - 206/299
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Symptoms adult- 268/299
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Symptoms children 31/299
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Vitamin D levels 272/299
10
Taking supplements?
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Conclusions

• Predominance of women of child bearing age their
  infants also at high risk as cannot complete
  their Vit D stores in the last trimester of
  pregnancy
• Limits of data in clinical record especially
  ethnicity and risk factors
• COMA (Committee on Medical Aspects of Food) 1998
  recommended supplements for lt4, pregnant and
  breast feeding women, and others at risk such as
  those over 65 or those with reduced exposure to
  sunlight
• There is conflicting advice for supplementation
  in breast feeding and pregnancy
• Withdrawal of Vitamin drops under welfare foods
  scheme important factor

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Pregnancy and Breastfeeding 1

• Scientific Advisory Committee on Nutrition
  (SACN) (formerly Committee on the Medical Aspects
  of food (COMA)) 1998
• Recommends supplements for most vulnerable groups
  including Asian pregnant women, Asian children,
  African-Caribbean children on exclusion diets,
  older housebound people, those who rarely go out
  of doors or when they do so wear concealing
  clothes
• An RNI (reference Nutrient Intake ) of 10mcg/day
  for ALL pregnant women represents a prudent
  approach. In practice this means that Vitamin D
  supplements are advised

13
Pregnancy and Breastfeeding 2

• National Institute for Clinical Excellence 2003
• There is insufficient evidence to evaluate the
  effectiveness of Vitamin D in pregnancy. In the
  absence of evidence of benefit, Vitamin D
  supplementation should not be offered routinely
  to all pregnant women
• women form the Indian subcontinent living in
  England and Wales are thought to be particularly
  vulnerable to vitamin D deficiency. Those women
  who remain indoors, whose clothing leaves little
  skin exposed, who live in sunless climates and
  who are vegetarian are also thought to be at
  higher risk of vitamin D deficiency
• No recommendation that these high risk groups
  receive supplements
• Guidance on Maternal and Child Nutrition due
  March 2008
• Guidance on Routine Care of Health Pregnant Women
  due March 2008

14
Pregnancy and Breastfeeding 3

• MIDIRS (Royal College of Midwives/National
  Childbirth Trust in collaboration with NHS Centre
  for Reviews and Dissemination) 2005
• Refers to NICE recommendation
• Recommends supplements towards the end of
  pregnancy for high risk groups (vegetarians, or
  women whose clothing covers most of their body,
  particularly in regions where there is little
  sunlight). Asian women, especially if follow a
  vegetarian diet and keep their skin covered, are
  most at risk of Vitamin D deficiency and should
  be considered for supplementation

15
Pregnancy and Breastfeeding 4

• Clarified personally with Chairman of the
  Subgroup on Maternal and Child Nutrition at the
  Scientific Advisory Committee on Nutrition
• Advised that pregnant and breastfeeding women can
  only meet the reference nutrient intake of
  10ug/day by taking a supplement

16
Healthy Start

• Replaces previous Welfare Foods Scheme
• Families with one or more children (including
  unborn) up to 4 years of age receiving certain
  benefits (IS,IB JSA,CTC, WTC)
• All pregnant women under 18
• Vouchers (fresh fruit, vegetables, milk and
  infant formula) and vitamin supplements
• Child vitamins from 6/12 to 4 years- A 233 mcg, C
  20mg, D3 7.5 mcg- 5 drops a day- 10 mls lasts 8
  weeks- can be bought for 1.70
• Adult vitamins for pregnant women- C 70 mg, D3
  10mcg, Folic acid 400 mcg- 1 tablet a day- 1 pot
  lasts 8 weeks can be bought for 65p

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Vitamin D and the Skin

• 90 of our vitamin D is made by the action of
  sunlight on skin
• Sunlight (290-320 nm UVB) converts
  7-dehydrocholesterol to cholecalciferol (Vit D3)
• What can go wrong?
• Not enough sunlight end October to end March in
  UK
• Not enough sun on skin-clothing that conceals
  skin, not going outdoors, sun block.
• Fat malabsorption
• What is enough?
• For fair skin 15mins sun exposure on hands, arms
  and face or back 2-3 times a week from April to
  September creates a store to last through the
  winter months more exposure needed in those with
  dark skin / how much??

18
Vitamin D and the Liver

• Hydroxylation at 25 position in liver makes
• 25OHD3 cholecalciferol (calcidiol or the
  medication calcifediol) 25OHD3 measured in
  laboratory endogenous colecalciferol
  supplements 25OHD2 supplements of
  ergocalciferol
• 10 from dietary sources- oily fish, eggs,
  supplemented foods (cereals, margarine, infant
  formula) liver
• What can go wrong?
• Poor diet
• Fat malabsorption
• Liver disease
• P450 hepatic induction (phenytoin, carbamazepine)

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Vitamin D and the Kidney

• Transported to kidney by specific binding protein
• Hydroxylation at 1 position to make
  1alpha,25-dihydroxycholecalciferol 1,25(OH)2D3
  (calcitriol) the most metabolically active
  compound
• Hydroxylation stimulated by low calcium, low
  phosphate, PTH
• What can go wrong?
• Deficiency 1 alpha hydroxylase enzyme- CRF,
  hereditary (Vit D dependent rickets type1)
• Suppression of action deficiency of PTH
• Resistance to Calcitriol (Vit D dependent rickets
  type 2)
• Nephrotic syndrome (causes excess Vit D binding
  protein)

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Presentation in adults

• Generalised musculoskeletal pain often
  symmetrical, of gradual onset and persistent
• Bony pain usually back or lower limbs
• Fatigue
• Muscular weakness (difficulty with stairs,
  getting up off the floor/low chair)
• Waddling gait
• Normal range of movement and absence of
  inflammatory signs in the painful areas

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Presentation in child

• Tender /swollen joints, classically wrists
• Deformed bones
• Bone pain or tenderness
• Fits or irritability
• Breathing difficulties
• Occurs during rapid growth
• Bow legs or knock knees
• Delayed walking or waddling gait
• Rickety rosary
• Tetany or convulsions
• Apnoea or stridor
• Impaired growth or delayed fontanelle closure
• Delayed eruption of teeth or enamel hypoplasia

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Investigations-adult and child

• Checking for secondary causes
• Ferritin as marker for malabsorption check for
  symptoms/other causes
• LFT isolated alkaline phosphatase may be high in
  deficiency
• Renal function
• Calcium- may be low or normal
• PTH- raised
• Vitamin D- low insufficiency/ deficiency
• x-ray left wrist - In children
• Refer if suspect secondary cause or if calcium
  high or PTH low

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Treatment Adult

• Calciferol (as ergo- or cole-) 300,000 i.u. I/M
  or orally (10ug 400 i.u.)
• Repeat after 1/12 unless symptoms of
  hypercalcaemia (thirst and polyuria) in this
  case check calcium if normal repeat treatment
  if abnormal refer
• Prevention 300,000 i.u. annually or daily
  Calchichew D3 forte 2 daily, Adcal D3 2 daily or
  Calfovit D3 1 daily
• Advise safe sun exposure and healthy diet
• Review annually or as needed
• gt65s physiological process less effective and are
  also at risk of osteoporosis so should have Vit D
  calcium long term high dose Vit D to treat
  deficiency of Vitamin D
• Takes on average 3/12 for bony symptoms and 6/12
  for muscular symptoms to resolve

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Treatment child

• Calciferol (cole- or ergo-) 150,000 oral or I/m
• Repeat after 1/12 if no new symptoms or other
  concerns if so refer
• Prevent further disease by daily or annual
  supplements ? for life ? At times of rapid growth
• Dalavit and Healthy Start drops contains vitamin
  D2 from vegetable sources and has no peanut oil
• 6/52 to 12/12 of age 0.3 ml 7 drops gt 12/12 of
  age 0.6 ml 14 drops
• Can be added to squash, juice, milk or jam
• Advise safe sun exposure and healthy diet

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Ongoing Bristol working group

• Preparing update of local protocol with guidance
  and flow charts for diagnosis and treatment in
  children and adults (will provide copy of updated
  version on request when available
  e.murphy_at_nhs.net)
• Research-what are normal values in a) bone
  healthy people having a blood test for another
  reason b) pregnant women at time of AFP test
  both groups will cover range of ethnic groups
• Public health perspectives access to Healthy
  Start vitamins midwives, HV involvement.

26
Recent reviews

• Primary Vitamin D deficiency in children Drug and
  Therapeutics Bulletin Vol 44 No 2 February 2006
• Primary Vitamin D deficiency in adults Drug and
  Therapeutics Bulletin Vol 44 No 4 April 2006