Treatment of vitamin D deficiency: divergencebetween clinical practice and expert advice

Mark Findlay,1 Julia Anderson,2 Susan Roberts,3 Alison Almond,4 Chris Isles1

ABSTRACTBackground Current recommendations for the treatmentof vitamin D deficiency vary from calciferol 800 IU perday to loading doses of vitamin D followed bymaintenance therapy of up to 2000 IU per day.Objective To assess the preparations and doses ofvitamin D used to load and maintain patients with serum25-hydroxyvitamin D (25OHD) <25 nmol/l.Methods We examined all requests for serum 25OHDover a 12-month period, from September 2009 to 2010in southwest Scotland. We wrote to all 33 generalpractices asking whether they usually startedreplacement therapy with a loading dose and/orrecommended over-the-counter maintenancepreparations. We accessed the Emergency CareSummary for all patients with serum 25OHD <25 nmol/lto determine whether they had been prescribedmaintenance therapy.Results Serum 25OHD was requested in 1162 patients.Levels were <25 nmol/l in 282 (24%) patients, only 173(61%) of whom were receiving vitamin D replacementtherapy 3e15 months after diagnosis. Only four (1.4%)were prescribed a loading dose. One hundred and fifty-three (54%) were treated with cholecalciferol orergocalciferol and 19 (7%) with alfacalcidol or calcitriol.The median dose of chole/ergocalciferol was 800 IUper day, usually in combination with 1200 mg calciumper day.Conclusions We have shown a divergence betweenclinical practice and even the most conservative expertadvice for vitamin D replacement therapy. Possibleexplanations are conflicting advice on treatment anddifficulty obtaining suitable vitamin D preparations,particularly high dose vitamin D and vitamin D withoutcalcium, in the UK.

INTRODUCTIONOur understanding of vitamin D and the conse-quences of its deficiency have advanced consider-ably in recent years.1 2 The classic manifestations ofvitamin D deficiency are well known, namelyosteomalacia in adults and rickets in children. It isnow also appreciated that vitamin D has importantintracellular functions, and that its deficiency isassociated with an increased risk of a number ofchronic disorders including osteoporosis, multiplesclerosis, diabetes, hypertension, cardiovasculardisease and cancer.1 2 The full list of associationsextends to no fewer than 56 diseases and 17cancers, though causality has still to be establishedin all except osteomalacia and rickets.3

Vitamin D status is readily assessed bymeasuring serum 25-hydroxyvitamin D (25OHD)with most authorities defining optimal, adequate,insufficient and deficient levels as >75 nmol/l,

50e75 nmol/l, 25e49 nmol/l and <25 nmol/l,respectively.4 The threshold for normality shouldprobably be the serum 25OHD required formaximum suppression of parathyroid hormone,greatest calcium absorption and highest bonemineral density. Defined in this way, vitamin Dinsufficiency occurs when serum levels fall below50 nmol/l5 with concentrations $75 nmol/lrequired for optimal bone health.6 A further usefulrule of thumb is that a regular daily dose of 1000 IUvitamin D per day will raise serum 25OHD byaround 25 nmol/l.7

Sources of vitamin D are sunlight, food andsupplements, with sunlight being the predominantsource. In the UK, 20e30 min of sunlight to theface and forearms at midday during the monthsApril to October will generate 2000 IU per day infair-skinned individuals.4 This is likely to maintainadequate serum levels of 25OHD during summermonths, although a recent survey has shown that47% of UK adults have insufficient (<40 nmol/l)and 16% have deficient levels of serum 25OHD(<25 nmol/l) during winter and spring.8 There arelikely to be many reasons for this. Pigmented skin,sun creams with protection factor 15 or more andthe low UK winter sun all lead to lower skinvitamin D synthesis. Older people are at risk, partlybecause they spend more time indoors and partlybecause ageing skin stores less of the vitamin Dprecursor 7-dehydrocholesterol and thereforegenerates less vitamin D from sunlight. Clothingthat conceals the face and forearms also increasesthe risk of vitamin D deficiency.2 While it isgenerally assumed that the benefits of sunlight aremediated by vitamin D, other mechanisms may beinvolved.9

The average intake of vitamin D from foodpurchased by British households in 1996 was141 IU (3.35 mg) daily. The main dietary sources atthis time were fortified fats including butter andmargarine (39%), fortified cereals (17%), oily fish(16%), meat and meat products (13%).10 Someexperts in this area have since suggested that up to4000 IU daily from all sources may be required tomaintain an optimum serum level of $80 nmol/l.7

Possibly in response to such suggestions, the USInstitute of Medicine and a UK Consensus Group,representing the British Association of Dermatolo-gists, Cancer Research UK, Diabetes UK, theMultiple Sclerosis Society, the National HeartForum, the National Osteoporosis Society and thePrimary Care Dermatological Society, publishedposition statements in 2010.11 12

The US Institute of Medicine assumed minimalsun exposure when they determined that a dietaryintake of 600 IU will meet the needs of most North

1Department of Medicine,Dumfries and Galloway RoyalInfirmary, Dumfriesshire, UK2Department of Biochemistry,Dumfries and Galloway RoyalInfirmary, Dumfriesshire, UK3Pharmacy Department,Dumfries and Galloway RoyalInfirmary, Dumfriesshire, UK4Renal Unit, Dumfries andGalloway Royal Infirmary,Dumfriesshire, UK

Correspondence toProfessor Chris Isles, MedicalUnit, Dumfries Infirmary,Dumfriesshire DG1 4AP, UK;chris.isles@nhs.net

Received 8 August 2011Accepted 16 January 2012

Findlay M, Anderson J, Roberts S, et al. Postgrad Med J (2012). doi:10.1136/postgradmedj-2011-130243 1 of 6

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American adults under 70 years of age. The authors went on tosuggest that people over 70 years may require as much as 800 IUdaily because skin generates less vitamin D as it ages and theyalso set an upper daily dietary intake of 4000 IU for adults of allages.11 The authors of the UK consensus statement, whileconceding that supplements of 1120 IU and 1640 IU are likely tobe required in order to achieve levels >50 and >80 nmol/l,respectively, did not go so far as to recommend that they shouldbe given.12 They endorsed the Department of Health’s recom-mendation that supplements of 400 IU per day be considered forgroups at a high risk of vitamin D deficiency. Neither the US northe UK position statements addressed the question of ormade recommendations for treating patients with establishedvitamin D deficiency.

Against this background, we undertook a survey of vitamin Ddeficiency and choice of vitamin D replacement therapyprescribed for patients in southwest Scotland. Our objectiveswere twofold: first, to determine the prevalence and demo-graphics of patients with proven vitamin D deficiency in thispopulation over a 12-month period and, second, to assess theextent to which patients with vitamin D deficiency were beingtreated according to expert advice (table 1).

METHODSAll biochemistry requests by primary or secondary care insouthwest Scotland (population 147 000) are recorded on anelectronic laboratory results browser in Dumfries. Data storedon this database permit calculation of age, sex and date ofrequest for all patients. Using a search function, we identifiedthe results of all measurements of serum 25OHD over12 months from 2 September 2009 to 1 September 2010. Wedefined serum 25OHD $50 nmol/l as an adequate serum level,25e49 nmol/l as insufficient and <25 nmol/l as deficient.Within the subgroup of patients with vitamin D deficiency, wedocumented the reason for the request and the source of therequest (primary vs secondary care), together with both serumcreatinine and corrected calcium if these had been checkedwithin 3 months of the 25OHD measurement.

In the second part of our study we accessed the EmergencyCare Summaries (electronic records of current and prescribedmedication updated weekly by primary care) of all vitamin Ddeficient patients to determine whether they were receivingreplacement therapy and, if so, at what dose. Because we wereaware of difficulties experienced in obtaining high dose vitaminD on prescription in the UK, we sent an electronic questionnaireto all 33 general practices in southwest Scotland asking whether

they usually started replacement therapy with a loading dose,requesting details if they did. We also used this questionnaire toask the primary care team whether they always, sometimes,rarely or never advised their patients to buy vitamin D main-tenance therapy over-the-counter or online. Analysis of the datawas carried out using Microsoft Excel.

ETHICAL APPROVALThis study was conducted to define and measure current careand involved an assessment of practice already in use. We did notrandomise or allocate patients to treatment groups. Because ourstudy met the criteria for service evaluation, we did not seekapproval from our research ethics committee, in keeping withour Health Board policy. Permission to access the EmergencyCare Summary was granted by the Medical Director ofDumfries and Galloway Health Board.

RESULTSPrevalence and demographicsSerum 25OHD was measured 1330 times in 1162 patientsduring the 12-month period of the study. We excluded onepatient who was visiting Dumfries for whom no follow-up datawas available. Seven hundred and sixty-seven (66%) patientswere women and 395 (34%) were men. Their average age was60 years, range 3 months to 98 years. Vitamin D status wasjudged to be adequate or optimal in 355 (31%) patients withserum 25OHD levels $50 nmol/l, insufficient in 525 (45%)patients with serum levels 25e49 nmol/l and deficient in 282(24%) patients with serum levels <25 nmol/l. The proportion ofpatients with vitamin D deficiency showed seasonal variationand was highest in January and February as expected (figure 1).The mean age of the 282 patients found to be vitamin D

deficient was 62 (range 13e97 years). Women (n¼188, 24% withserum 25OHD <25 nmol/l) were no more likely to be vitamin Ddeficient than men (n¼94, 24% <25 nmol/l) in our survey.Ninety-six (34%) of the vitamin D deficient patients had theirserum 25OHD checked in primary care and 186 (66%) insecondary care. The most common reasons for assessing vitaminD status were musculoskeletal including myopathy, myalgia andfalls (31%), liver and gastrointestinal disorders (20%), andhypocalcaemia (6%). All other reasons or groups of reasonsaccounted for <5% of requests. Serum calcium was measured in191 of 282 vitamin D deficient patients. Median adjustedcalcium was 2.2 mmol/l (range 1.46e3.1 mmol/l). Of these 191patients, 41 (21%) had adjusted serum calcium below the lowerlimit of our normal range (2.12e2.62 mmol/l). A recent measure

Table 1 Treatment of vitamin D deficiency in adults

Source Target group Loading dose Maintenance therapy

SIGN Guideline 71. Management ofOsteoporosis 200313

‘Vitamin D deficiency confirmedor is likely’

No recommendation 800 IU daily

Australia and New Zealand PositionStatement 200514

Serum 25OHD <25 nmol/l 3000e5000 IU D2 daily for 6e12 weeksor 50 000 IU D3 once per month for 3e6 months

1000 IU D2 daily

Drug and Therapeutics Bulletin 200615 Serum 25OHD <25 nmol/l No recommendation ‘Minimum 800 IU daily. higher doses, toa maximum of 2200 IU may be needed’

Holick 20071 Serum 25OHD <50 nmol/l 50 000 IU D2 weekly for 8 weeks, repeatedfor another 8 weeks if 25OHD still <75 nmol/l

50 000 IU every 2e4 weeks

International Osteoporosis FoundationPosition Statement 201016

Serum 25OHD <75 nmol/l No recommendation ‘Up to 2000 IU daily may be required toreach 75 nmol/l’

Canadian Clinical Practice Guideline201017

‘Adults at moderate risk ofvitamin D deficiency’

No recommendation ‘1000e2000 IU daily may be required toachieve optimal vitamin D status’

Pearce and Cheetham 20104 Serum 25OHD <25 nmol/l 10 000 IU D3 daily or 60 000 IU weeklyfor 8e12 weeks

1000e2000 IU D3 daily or 10 000 IU weekly

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of renal function was available in 271 patients. Their medianserum creatinine was 74 mmol/l (mean 93.5 mmol/l, range29e1101 mmol/l). Serum creatinine was >200 mmol/l (equiva-lent to the estimated glomerular filtration rate <30 ml/min) in14 (5%) patients, 2 of whom were on dialysis and 1 of whomhad a functioning kidney transplant.

Preparations and dosesIn the second part of our study we accessed the Emergency CareSummary for all 282 vitamin D deficient patients. Only 119(42%) patients had been prescribed vitamin D replacementwithin 3 months of diagnosis. Prescriptions rose to 173 (61%)when we analysed our data at 3e15 months. Sixty-five of 96(68%) patients whose serum 25OHD had been checked byprimary care were prescribed vitamin D replacement therapycompared with 108/186 (58%) of those from secondary care.Only 2/33 practices had ever prescribed a loading dose. Twopatients managed by secondary care received a loading dose.Four practices ‘sometimes’ recommended over-the-counteror online purchases of vitamin D maintenance therapy.Twenty-nine practices rarely or never did.

One hundred and fifty-three (54%) vitamin D deficientpatients were treated with cholecalciferol or ergocalciferolusually in combination with calcium and 19 (7%) with one ofthe short-acting vitamin D analogues, alfacalcidol or calcitriol(figure 2). The median dose of cholecalciferol/ergocalciferol was

800 IU per day (range 200e1600) with only four patientsreceiving a maintenance dose of $1000 IU per day. The mediandose of alfacalcidol/calcitriol was 250 mg per day (range250e1000 mg). One patient received both cholecalciferol andalfacalcidol (1200 IU and 1000 mg, respectively) (figure 2). Thedecision to use short-acting vitamin D analogues rather thanstandard vitamin D preparations appeared to be influenced byserum creatinine which was lower in patients given cholecal-ciferol/ergocalciferol (mean 81 mmol/l, median 77 mmol/l, range31e349 mmol/l) than in the group given alfacalcidol/calcitriol(mean 217 mmol/l, median 103 mmol/l, range 41e1101 mmol/l).

DISCUSSIONThe main findings of our survey of serum 25OHD in southwestScotland are, first, that 69% of patients in whom the test wasrequested had vitamin D levels that were either insufficient(45%) or deficient (24%) and, second, that only 61% of deficientpatients were prescribed any form of vitamin D replacementtherapy. Moreover, those who were treated frequently receivedinadequate doses or inappropriate forms of therapy.Our results further suggest that many of the patients who

recorded adequate or optimal serum levels during summer andautumn are likely to become insufficient or frankly deficient inwinter and spring (figure 1).Neither a high prevalence of vitamin D deficiency nor seasonal

variation in serum 25OHD levels is a new finding.8 18 Of greaterinterest are our observations that 39% of patients were notprescribed any form of vitamin D replacement at all, and thatreplacement therapy when prescribed did not appear to beguided by expert advice. If we assume that measurement of25OHD had been prompted by suspicion of vitamin D defi-ciency in this patient population, then it would be illogical notto prescribe treatment. Vitamin D deficiency causes proximalmuscle weakness and predicts both falls and hip fractures,especially in older people.1 19 In patients whose serum 25OHD is<50 nmol/l, a replacement dose of at least 800 IU daily has beenshown in randomised trials to reduce falls and fracture risk.20 21

One meta-analysis has even suggested a reduction in totalmortality.22 One hundred and thirty-seven (49%) of our patientswith serum 25OHD <25 nmol/l were 65 years or older andshould certainly have received replacement therapy, but only 91(66%) did.We went on to consider two possibilities for the potentially

inadequate doses of vitamin D or inappropriate forms oftherapy. The first was that general practitioners may have givena loading dose of vitamin D but had not recorded this on theEmergency Care Summary, and the second that general practi-tioners had recommended an over-the-counter preparation orthat patients obtained vitamin D maintenance therapy online.Our results suggest that neither of these possibilities is correct orcould account for more than a small part of our findings,although we recognise that we cannot be certain on thesepoints. More likely explanations are conflicting advice ontreatment by health professionals and the lack of availability ofsuitable preparations.A difficulty here is the lack of expert agreement on which to

base firm recommendations. We summarise the currently avail-able advice on vitamin D replacement in adults in table 1.1 4 13e17

This table includes recommendations from one evidence-basedguideline on the treatment of osteoporosis,13 two personalopinions1 4 and three position statements from the workinggroups of specialist societies.14e17 There were differences in thedefinition of the target groups, whether or not to recommenda loading dose and in the amount of vitamin D required as

Figure 2 Pie chart showing maintenance therapies in 282 patientswith vitamin D deficiency (serum 25-hydroxyvitamin D <25 nmol/l).Chole/ergo ¼ cholecalciferol/ergocalciferol; short-acting analogue ¼alfacalcidol or calcitriol.

Figure 1 Bar chart showing seasonal variation in percentage ofpatients with deficient (<25 nmol/l) and adequate (at least 50 nmol/l)serum levels of 25-hydroxyvitamin D.

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maintenance therapy. At one end of the therapeutic spectrum,SIGN in their 2003 guideline on osteoporosis state that ‘Wherevitamin D deficiency has been confirmed or is likely, such as inthe case of housebound individuals, a vitamin D supplement of

20 mg (800 IU) is the recommended dose’.13 At the other extreme,Pearce and Cheetham in their 2010 BMJ review of vitamin Ddeficiency recommend a loading dose of 20 000 IU per week for8e12 weeks if serum 25OHD <25 nmol/l, followed by a main-tenance dose of 1000e2000 IU daily.4

A particular problem for clinicians is whether or not to starttreatment with a loading dose. The experts disagree (table 1). A

Table 2 Oral preparations for replacement of vitamin D

Preparations Availability Cost as of 12 December 2011 Status

Sunvite Vitamin D3 (cholecalciferol) 1000 IU caplets Pack of 100 caplets £7.65 (Holland & Barrett) Does not have UK marketing authorisation.Marketed as nutritional supplement

Boots Vitamin D3 (cholecalciferol) 1000 IU tablets Pack of 90 tabs £5.10 (Boots) Does not have UK marketing authorisation.Marketed as nutritional supplement

Vigatoletten (cholecalciferol) 1000 IU tablets Pack of 90 tabs £8.60 (IDIS) Does not have UK marketing authorisation

Vitamin D3 Valupak (cholecalciferol) 1000 IU Pack of 60 £0.59 (AAH) Does not have UK marketing authorisation.Marketed as nutritional supplement

Fultium D3 (cholecalciferol) 800 IU Pack of 30 capsules £3.63 (Available via normalwholesalers’ route).

Product has UK marketing authorisation

D3-50 (cholecalciferol) 50 000 IU capsules Pack of 100 capsules £19.32 (Mawdsleys) Does not have UK marketing authorisation

Dekristol (cholecalciferol) 20 000 IU capsules Pack of 50 capsules £12.24 (Durbin PLC) Does not have UK marketing authorisation

ProD3 (cholecalciferol) 1000 IU capsules Pack of 30 capsules £6.19 (AAH) Does not have UK marketing authorisation.Marketed as nutritional supplement

ProD3 (cholecalciferol) 10 000 IU capsules Pack of 30 capsules £13.27 (AAH) Does not have UK marketing authorisation.Marketed as nutritional supplement

ProD3 (cholecalciferol) 20, 000 IU capsules Pack of 30 capsules £17.69 (AAH) Does not have UK marketing authorisation.Marketed as nutritional supplement

Vitamin supplements can be bought over-the-counter or online. The ProD3 range is suitable for vegetarians and halal eaters. Unlicensed medicines cannot be prescribed without local riskassessment and Health Board or Health Authority approval. Prices are subject to variability but were correct as of 12 December 2011.

Box 1 Metabolism of vitamin D

Vitamin D has a complex metabolic pathway (figure 3). Chole-calciferol (vitamin D3) is predominantly manufactured in the skinby UVB radiation. Small amounts of cholecalciferol and ergo-calciferol (vitamin D2) are ingested in food. Both forms of vitaminD undergo 25 hydroxylation in the liver to 25-hydrox-ycholecalciferol (25OHD) in a process that has no feedbackcontrol. This common pathway produces the principal storageform of vitamin D, measurement of which gives the best indicatorof vitamin D status. From here there are two distinct pathways. Inthe endocrine pathway further hydroxylation takes place in thekidney to produce calcitriol (also called 1,25-dihydrox-ycholecalciferol or 1,25(OH)2D). The main action of calcitriol is toincrease intestinal calcium and phosphate absorption. It also self-regulates by inhibiting 1a-hydroxylase responsible for itsproduction and by stimulating the enzyme 24-hydroxylase, whichrenders it biologically inert. Only 5% of circulating 25OHD is usedby the endocrine pathway. The remainder is taken up by tissuesthat produce 1a-hydroxylase intracellularly and which cantherefore synthesise calcitriol locally. These tissues also possessthe enzyme 24 hydroxylase which ensures that no active vitaminD enters the circulation. Intracellular calcitriol is an importantchemical messenger in the signalling process that leads to theproduction of proteins responsible for cardiovascular, immuno-logical and oncological health. Cholecalciferol and ergocalciferolare necessary substrates for both the endocrine and cellularfunctions of vitamin D. The short-acting vitamin D analogues,calcitriol and alfacalcidol, can only be used to replace theendocrine function and should be reserved for patients withchronic kidney disease when the endocrine pathway fails. Itfollows that alfacalcidol and calcitriol should not be used to treatvitamin D deficiency in patients with normal renal function, andthat patients with chronic kidney disease may also need to takecalciferol in addition to alfacalcidol if their serum 25OHD levelsare low.

Figure 3 Metabolism of vitamin D showing both endocrine andautocrine pathways (see text for more details).

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pragmatic approach might be to recommend loading doses topatients who present with falls or fractures and are found tohave serum 25OHD <25 nmol/l, on the grounds that it willotherwise take months to restore 25OHD to adequate oroptimal levels by maintenance therapy alone.23 Unfortunately,the readily prescribable forms of vitamin D in the UK onlyprovide maintenance therapy and are combined with calcium.One or two tablets, sachets or caplets of these preparations willgive around 800 IU vitamin D with 1000e1200 mg calciumdaily. Pearce and Cheetham argue that the calcium component isunlikely to be necessary in most cases and may well be associ-ated with poor compliance.4 In any event, a daily dose of 800 IUper day will not load a patient with vitamin D deficiency and isunlikely to raise serum 25OHD to >50 nmol/l if the baselinevalue was <25 nmol/l7 (box 1).

In summary, we have shown as others have done that vitaminD deficiency and insufficiency are common in patients in whom

they are suspected. We have further shown a gap between expertadvice and clinical practice with up to 40% patients receiving notreatment at all, <2% being given a loading dose, 7% beingtreated inappropriately with alfacalcidol and the remainderreceiving a suboptimal maintenance dose of vitamin D withcalcium. Possible explanations are conflicting advice on treat-ment to health professionals and difficulties experienced inobtaining suitable vitamin D preparations, particularly high dosevitamin D and vitamin D without calcium, in the UK.This issue has recently been addressed in a paper summarising

the availability of vitamin D preparations, their potential usesand their costs, with information from importers and manu-facturers that was accurate as of November 2011.24 The authorsnote that licensed preparations are currently confined to oralvitamin drops for paediatric insufficiency and accept that, inmost instances, unlicensed products will be used. We reproducea representative sample of oral loading and maintenance thera-pies suitable for adults in table 2. Preparations such as the D3-50capsule containing 50 000 IU will, if given weekly for 10 weeksand then monthly thereafter, cost <£5 per patient per year. Sucha regimen is likely to be both safe23 25 and effective.26

AcknowledgementsWe acknowledge Mrs Josephine Campbell for her help in thepreparation of the manuscript.

Contributors CI and MF had the idea and wrote the first draft. JA extracted theresults from the biochemistry lab browser. SR is the guarantor of the pharmacy data.JA, SR and AA provided comments on the first draft and all five authors contributed tothe final draft.

Competing interests None.

Ethics approval Ethics approval was provided by the Medical Director.

Provenance and peer review Not commissioned; externally peer reviewed.

REFERENCES1. Holick MF. Vitamin D deficiency. N Engl J Med 2007;357:266e81.2. Rosen CJ. Vitamin D insufficiency. N Engl J Med 2011;364:248e54.3. Lewis PJ. Vitamin D deficiency: more on diagnosis and management. BMJ Rapid

Response to review by Pearce and Cheetham, 21 January 2010. Accessed onlineJanuary 2011 at www.BMJ.com

4. Pearce SH, Cheetham TD. Diagnosis and management of vitamin D deficiency. BMJ2010;340:142e7.

5. Malabanan A, Veronikis IE, Holick MF. Redefining vitamin D insufficiency. Lancet1998;351:805e6.

6. Dawson-Hughes B, Heaney RP, Holick MF, et al. Estimates of optimal vitamin Dstatus. Osteoporos Int 2005;16:713e16.

7. Heaney RP. Vitamin D in health and disease. Clin J Am Soc Nephrol2008;3:1535e41.

8. Hypponen E, Power C. Hypovitaminosis D in British adults at age 45 y: nationwidecohort study of dietary and lifestyle predictors. Am J Clin Nutr 2007;85:860e8.

9. Feelisch M, Kolb-Bachofen V, Liu D, et al. Is sunlight good for our heart? Eur Heart J2010;31:1041e5.

10. Department of Health. Nutrition and bone health: Report of the subgroup on bonehealth, working group on the Nutritional status of the population. Stationery Office.London: Stationery Office, 1998.

11. US Institute of Medicine Position Statement. Dietary reference intakes forcalcium and vitamin D 2010 (accessed 8 Jan 2011). http://www.iom.edu/Reports/2010/Dietary-Reference-Intakes-for-Calcium-and-Vitamin-D.aspx

12. The UK Consensus group position statement on vitamin D. Cancer research UK, Britishassociation of Dermatologists, diabetes UK, multiple sclerosis Society, National heartForum, National osteoporosis Society, primary care Dermatological Society 2010(accessed 8 Jan 2011). http://info.cancerresearchuk.org/prod_consump/groups/cr_common/@nre/@sun/documents/generalcontent/cr_052628.pdf

13. SIGN Guideline 71. Management of Osteoporosis. Edinburgh: Royal College ofPhysicians, 2003.

14. Working Group of the Australian and New Zealand Bone and MineralSociety, Endocrine Society of Australia, osteoporosis Australia. Vitamin D and adultbone health in Australia and New Zealand: a position statement. Med J Aust2005;182:281e5.

15. Anon. Primary vitamin D deficiency in adults. Drug Ther Bull 2006;44:25e9.16. Dawson-Hughes B, Mithal A, Bonjour JP, et al. International Osteoporosis

Foundation Position Statement: vitamin D recommendations for older adults.Osteoporos Int 2010;21:1151e4.

Main messages

< Vitamin D has important intracellular functions that extendbeyond its effect on bone metabolism.

< Vitamin D deficiency and insufficiency are common in patientsin whom they are suspected.

< There is a gap between clinical practice and expert advice onreplacement therapy.

< Possible explanations are conflicting advice on treatment anddifficulties experienced in obtaining suitable vitamin Dpreparations in the UK.

Current research questions

< More evidence is required on both the skeletal andextraskeletal benefits of vitamin D

< The need or otherwise for loading doses when initiatingvitamin D replacement therapy.

Key references

< Pearce SH, Cheetham TD. Diagnosis and management ofvitamin D deficiency. BMJ 2010;340:142e7.

< Heaney RP. Vitamin D in health and disease. Clin J Am SocNephrol 2008;3:1535e41.

< Hypponen E, Power C. Hypovitaminosis D in British adults atage 45 y: nationwide cohort study of dietary and lifestylepredictors. Am J Clin Nutr 2007;85:860e8.

< The UK Consensus group position statement on vitamin D.Cancer research UK, British association of Dermatologists,diabetes UK, multiple sclerosis Society, National heart Forum,National osteoporosis Society, primary care DermatologicalSociety (accessed 8 Jan 2011).

< East of England Specialist Pharmacy Services. Vitamin Ddeficiency and insufficiency: using appropriate availableproducts 2011. http://www.nelm.nhs.uk/en/NeLM/Vitamin-D-product-availability (accessed 14 Dec 2011).

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17. Papaionnou A, Morin S, Cheung AM, et al. For the Scientific Advisory Council ofosteoporosis Canada. 2010 clinical practice guidelines for diagnosis and managementof osteoporosis in Canada: summary. Can Med Assoc J 2010;182:1864e72.

18. Bolland MJ, Grey AB, Ames RW, et al. The effects of seasonal variation of 250HDand fat mass on diagnosis of vitamin D insufficiency. Am J Clin Nutr2007;86:959e64.

19. Cauley JA, Lacroix AZ, Wu L, et al. Serum 25 hydroxyvitamin D concentrations andrisk for hip fractures. Ann Intern Med 2008;149:242e50.

20. Bischoff-Ferrari HA, Willett WC, Wong JB, et al. Fracture prevention with vitaminD supplementation: a meta-analysis of randomised control trials. JAMA2005;293:2257e64.

21. BischoffeFerrari HA, Willett WC, Orav JE, et al. Falls prevention with vitamin D.BMJ 2011;342:d2608.

22. Autier P, Gandini S. Vitamin D supplementation and total mortality: a meta-analysisof the randomised controlled trials. Arch Int Med 2007;167:1730e7.

23. Bacon CJ, Gamble GD, Horne AM, et al. High dose oral vitamin D supplementationin the elderly. Osteoporos Int 2009;20:1407e15.

24. East of England Specialist Pharmacy Services. Vitamin D deficiency andinsufficiency: using appropriate available products. 2011. http://www.nelm.nhs.uk/en/NeLM/Vitamin-D-product-availability (accessed 14 Dec 2011).

25. Hathcock JN, Shao A, Vieth R, et al. Risk assessment for vitamin D. Am J Clin Nutr2007;85:6e19.

26. Trivedi D, Doll R, Khaw KT. Effect of four monthly oral vitamin D3(cholecalciferol) supplementation on fractures and mortality in men and womenliving in the community: randomised double blind controlled trial. BMJ2003;326:469e74.

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