Rod Hughes Rheumatology ASPH 6th Oct 2011 Vitamin D for the GP Rod Hughes Rheumatology ASPH 6th Oct 2011

Surrey data 50% of the population is Vitamin D deficient 150,000 ‘potential’ cases Exponential rise in ordering of Vitamin D testing Cost per test - £2.90 ASPH

Vitamin D NHS Surrey

The size of the problem No-one is sure how to treat No-one is sure when to treat No-one is sure who to treat No-one is sure how long you treat for

Vitamin D – clinical issues Should we be restricting access to testing? Should we be testing everyone? When to test What time of year When to treat What with and for how long How to reassure the worried well

Vitamin D deficiency – an epidemic

Sources of Vitamin D Vitamin D2 – ergocalciferol – synthesised by plants Vitamin D3 – cholecalciferol the analyte – colecalciferol the drug – from UVB effect on skin of invertebrates – naturally in fish Vitamin D measurement = 25 hydroxy Vit D – raised by both Vit D2 and D3

Sources of Vitamin D 2-3 exposures of 20-30 mins sunlight per week should provide enough Vit D for adults in the UK Sun exposure due to latitude in the UK insufficient to provide needs Oct through to April Diet – oily fish, egg yolks, light exposed mushrooms and liver + fortified products

Vitamin D – the media

Some facts Half the world’s population is Vit D deficient Holick MF. Vitamin D deficiency. N Engl J Med. 2007; 357:266-81 The Institute of Medicine (IOM)Nov 2010 recommends increasing the daily vitamin D intake for children and adults to 600 IU per day for people ages 1 to 70, and 800 IU for people over age 70. A combined analysis of multiple studies found that taking 700 to 1,000 IU of vitamin D per day lowered the risk of falls by 19 percent, but taking 200 to 600 IU per day did not offer any such protection. Bischoff-Ferrari HA, Dawson-Hughes B, Staehelin HB, et al. Fall prevention with supplemental and active forms of vitamin D: a meta-analysis of randomised controlled trials. BMJ. 2009; 339:b3692. Low vitamin D levels might somehow increase colon cancer risk Garland CF, Garland FC. Do sunlight and vitamin D reduce the likelihood of colon cancer? Int J Epidemiol. 1980; 9:227-31.

Osteomalacia Impaired mineralisation phase of remodelling Spinal bone pain Pelvic pain Leg pain Muscle weakness Hypocalaemia Pelvic flattening Low trauma fractures Bone softening and bending of bones

Clinical presentation Insidious onset Lumbar pain Lordosis and pelvic flattening Waddling gait Low trauma fractures Bone sensitivity on pressure Easy fatiguability

Osteomalacia images

Assays Assay of serum 25-hydroxy Vit D by measuring 25-hydroxy D3 or total 25 hydroxy D2 and D3 <25 nmol/L – severely deficient – below this level PTH starts to rise and bone turnover increases 25-50 nmol/L – insufficient 50-75 nmol/L - adequate >75 nmol/L – normal and replete Highest levels at the end of summer and lowest in the early Spring

Case 1 34 year old doctor 28 weeks pregnant 1st pregnancy Tired – aching – feels unwell Sees her GP and asks for Vitamin D levels Measured 2.07.2011 37nmol/L Wants to be treated as she feels that her risks for foetal abnormality are increased

Case 1 Management advice What would you tell her? What treatment would you give? What follow up would you give?

Case 2 47 year old asian lady presents with proximal myalgia and leg pain Vitamin D levels June 2011 – 6 nmol/L No clear cause for deficiency X rays suggest Looser’s zones tibia bilaterally Seen at the request of the GP in Rheumatology

Case 2 – Management advice What would you treat her with? Specific product Dose Duration What follow up instructions would you give

Case 3 54 year old lady with ulcerative colitis Vitamin D levels via GP 18nmol/L Feels tired Joints and muscles ache

Case 3 – management advice What would you treat her with? Product Dose Duration Route

Who should you test? Features of symptomatic deficiency Insidious-onset widespread bone pain and tenderness Proximal muscle weakness Swelling and tenderness at pseudo-fracture sites Fractures at osteoporotic sites Myalgia with raised CPK

Predisposing features Black and ethnic minorities with dark skin Elderly patients in residential care and housebound Intestinal malabsorption Wearing of a veil or habitual sunscreen Vegan/ vegetarian Liver or renal disease Anti-convulsants / cholestyramine / rifampicin / steroids / anti- retrovirals

Pregnancy Non-evidence based advice Pregnant women and women with a baby under 1 yr old and children from six months to age 4 are entitled to free vitamins under Healthy Start programme Treat severe deficiency in pregnancy to avoid foetal risk

Assessing Vit D status Serum calcium PTH (unstable – on site phlebotomy) Alkaline Phosphatase Phosphate Renal function Liver function FBC (exclude malabsorption)

Treatment Colecalciferol (D3) is the preferred form of treatment Colecalciferol may raise Vit D levels more effectively than ergocalciferol as it binds better to liver enzymes, plasma Vit D binding protein and vitamin D receptors Some assays only measure metabolites of colecalciferol

What to use? Deficiency – colecalciferol when less than 25nmol/L Drug Preparation and manufacturer Distributors and price 6000iu per day for one month Lamberts Vit D3 1000 units Lamberts healthcare or via Alliance Healthcare £7.65 /120 60,000iu orally once per week for 12 weeks Dekristol 20,000iu capsule Martindale pharma £16.47 +p/p for 50 2 x IM injections of 300,000iu 3 months apart Colecalciferol 300,000 Streuli Switzerland Pack of 10 injections £47.30 + p/p 150,000iu (50 mls of 3000iu/ml liquid) once daily for 2 days Special liquid products are not commercially available Martindale pharma 100mls £71.89

What to use? Insufficient 25-50 nmol/L – oral supplementation of 1000 -2000 units of colecalciferol for 12 weeks Preferred product is Lambert’s Vit D3 tablets 1000 units As a fat soluble vitamin D tablets should be taken with food to enhance absorption Test Vit D after treatment – 3 months later

What to use? Maintenance after treatment 800 – 1000 units daily sometimes for life Adcal D3 (calcium carbonate 1.5g & colecalciferol 400units) one tablet twice daily

Vitamin D Surrey

Alfacalcidol 1 – alpha hydroxy colecalciferol With kidney failure or after parathyroidectomy 0.25 microgm or 1 microgm capsules Dose – initial 1 – 3 microgm daily to achieve calcium normality then maintain at 0.25 – 1 microgm daily Itching / urticaria / hypercalcaemia / kidney stones

Calcitriol (rocaltrol) 1, 25 dihydroxy colecalciferol Greater chance of inducing hyper calcaemia Some data in osteoporosis management Use with dialysis Start at 0.25 microgm daily and titrate upwards to 0.5 – 1.0 microgm daily

Vitamin D NHS Surrey

Case 1 Reassure 80% pregnant women have Vit D levels below 75 nmol/L Suggest supplementation with adcal D3 2 tablets daily Repeat Vit D 3 months after pregnancy

Case 2 Preferred treatment Lamberts Vit D3 600iu daily for 1 month Repeat Vit D levels Start maintenance supplementation as adcal D3 for life

Case 3 IM Vit D3 300,000iu 2 x 3 months apart Repeat Vit D assay Repeat treatment?

Vitamin D guidelines Guidance on testing and results interpretation Help with treatment choice and availability Avoidance of expensive and sub optimal treatments Standardise replacement and testing across primary and secondary care