Vitamin D deficiency: time for action
BMJ 1998; 317 doi: https://doi.org/10.1136/bmj.317.7171.1466 (Published 28 November 1998) Cite this as: BMJ 1998;317:1466All rapid responses
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The recent article by Compston 1 has emphasised the importance of
Vitamin D supplementation for the elderly and others at risk.
Some Asians
in the UK are amongst the others particularly at high risk of Vitamin D
defiency. Lawson and Thomas2 very recently reported Vitamin D deficiency
in Asian children and Mughal3 et al reported rickets in breast fed infants
of mothers from the Middle East with similar cultural practises. Our local
experience very much supports this. Leicestershire has,
approximately, a domestic population of 866,000; 9% Asians, and Leicester
city a domestic population 266,000; 24% Asians. Almost exclusively in the
Asian subpopulation, we continue to see clinical Vitamin D deficiency in
the form of cases of rickets and osteomalacia presenting to hospitals.
There is likely to be a larger number of undiagnosed cases in the
community. Details of some of these cases have been published elsewhere.4
The problem of vitamin D deficiency in Asians was first described in
the 1960's following their migration to the UK. Studies from Glasgow5 have
been an exception in reporting some success followig a rickets prevention
campaign. However the recent reports and our own experience would suggest
that the problem is not resolved. This is inspite of the fact that
Leicester was one of the cities chosen for an Asian rickets campaign in
the early 1980's which may have had some impact initially but may have
lost impetus recently.
Clinical vitamin D defiency can cause significant morbidity4 and
should be simply preventable. Some decades have passed since the problem
of Vitamin D defiency in Asians was recognised; an effective, widely
applicable and sustained preventative policy in the form of
supplementation and or otherwise is long overdue.
Yours faithfully
Dr S J Iqbal
Consultant in Biochemical Medicine
P G Swift
Consultant Paediatrician
Leicester Royal Infirmary
Leicester
LE1 5WW
References
1. Compston JE. Vitamin D deficiency: time for action. Evidence
supports routines supplementation for elderly people and other as risk.
BMJ 1998; 317: 1466-1467
2. Lawson M, Thomas M, Vitamin D concentrations in Asian children
aged 2 years, living in England: population survey. BMJ. 1999; 318: 28
3. Mughal MZ, Salamar H, Greenway T, Laing I, Mawer EB, Florid
rickets associated with prolonged breast feeding without vitamin D
supplementation. BMJ 1999; 308: 39-40.
4. Iqbal SJ, Kaddam I, Wassif W, Nichol F, Walls J. Continuing
clinically severe
vitamin D deficiency in Asians in the UK (Leicester). Postgrad Med J
1994; 70; 708-714.
5. Dunnigan MG, Ghekins BM Henderson JB,McIntosh WB Saunders D,
Sutherland GR. Prevention of Rickets in Asian Children : Assessment of
the Glasgow Campaign. BMJ 1985; 291.239-42
Competing interests: No competing interests
EDITOR - I was heartened to read your editorial “Vitamin Deficiency: Time for
Action” (1). There are however further points that should be made to
encourage a more active role by the Health Service.
There is no tablet containing only Vitamin D in reasonable dose in
the British National Formulary. The prescriber can give a calcium/vitamin
D mixture which may be unpalatable and therefore impair compliance.
Alternatively a vitamin capsule can be prescribed involving many other
vitamins. If a dose greater than minimal daily requirements is needed
higher doses of unnecessary vitamins must also be given. Surely it should
be easy to prescribe 500 – 1000 units of Vitamin D daily without any other
addition?
Symptomatic osteomalacia in adult Asian women was recognised as long
ago as 1973 (2), and this situation still exists. The presence of limb or
skeletal pain in this group has become accepted as “normal”, both within
the Asian community and by some health professionals. Recognising and
treating this painful disability is both easy and rewarding.
Part of the reason for intrauterine growth retardation in infants of
mothers of Pakistani origin is poor bone mineralisation. Vitamin D
supplementation in pregnancy has been shown to increase both maternal and
foetal growth, and improve biochemical measures of bone metabolism (3).
We must continue to emphasise this point.
It is important to restate that the presence of Vitamin D deficiency
can only be proved by measuring Vitamin D blood levels. In particular
though alkaline phosphatase levels are often raised in rickets or
osteomalacia there is a strong overlap with many Vitamin D deficient
patients having normal alkaline phosphatase levels (4).
As your editorial states Vitamin D is a hormone formed in the skin as
a result of exposure to sunlight. It is not a normal dietary component.
The present increase in skin cancer relates to indiscriminate sun bathing
in warm climates. Moderate exposure to sunlight in temperate climates is
beneficial and we should continue to support this physiological mechanism
for maintaining normal bone mineralisation.
REFERENCES:
(1) Compston JE. Vitamin D deficiency: time for action BMJ 1998; 317: 1466
(2) Holmes AM, Enoch BA, Taylor JL, and Jones ME, Occult
Rickets and osteomalacia amongst the Asian immigrant population. Quart J
Med. 1973; 42: 125-149
(3) Brooke O.G. Brown I.R.F. Bone C.D.M. Carter N.D. Cleeve H.J.W.
Maxwell J.D. et al. Vitamin D supplements in pregnant Asian women: Effects on calcium
status and foetal growth BMJ 1980; 280: 751-754
(4) Thomas M K Lloyd-Jones D.M. Thadhani R.I. Shaw A.C. Deraska D.J.
Kitch B.T. et al
Hypovitaminosis D in medical inpatients. N Engl J. Med 1998; 338: 777-783
Competing interests: No competing interests
Editor,
In a recent editorial, Compston (1) serves a timely reminder that
hypovitaminosis D is a common neglected problem in susceptible populations
with adverse effects on bone mass and increased fracture risk.
Her article
raises as many questions as it answers. Whilst acknowledging uncertainty
over the best dose and administration route of vitamin D, and whether it
should be given with calcium, Compston appears to suggest that routine
supplementation (800 IU or 20 ug/day) should now begin in the elderly and
other high risk populations. In epilepsy, in addition to an increased risk
of bony injury due to seizures, the use of antiepileptic drugs (AED’s) is
known to be associated with disorders of bone metabolism resulting in
osteopaenia and,
occasionally, osteomalacia. This is attributed to vitamin D deficiency
consequent upon enzyme induction and increased vitamin D catabolism,
although AED’s have additional direct effects on bone metabolism(2).
Changes appear to be influenced by sex, duration of therapy, mono or
polytherapy and whether the drug is enzyme-inducing. While
Dr Comspton
includes patients with epilepsy among those at risk, she does not make it
clear whether all patients on AED’s or only specific groups should receive
supplementation. Is
the dose recommended intended as prophylaxis in patients commencing
medication or to correct established bone disease, where hypovitaminosis
has been shown to require far higher doses of vitamin D (3)? When should
assessment of bone metabolism and/or density be performed prior to
supplementation and how should treatment be monitored? Is supplementation
required in patients receiving new AED’s? Given that epilepsy is
common in children when maximum bone accretion occurs, how early in life
should supplementation start?
There are some 400,000 individuals with
epilepsy in the UK the majority of whom are taking AED’s without
supplementation. Blanket prescribing of
vitamin D has economic consequences. There is a danger that
supplementation may unmask undiagnosed primary hyperparathyroidism.
Furthermore, a distinction needs to be made between recommendations
regarding prophylaxis
in patients commencing treatment with AED’s and the identification and
treatment of osteopaenia/osteomalacia in patients already on long term
treatment, especially in the presence of other risk factors.
There is a
clear need for firm, evidence-based guidelines in this important clinical
setting: we would be grateful if Dr Compston could detail
recommendations for the investigation and treatment of disorders of bone
metabolism in those with epilepsy.
Lina Nashef, Consultant Neurologist
Edmund Lamb, Consultant Clinical Biochemist
Kent and Canterbury Hospital, Canterbury CT1 3NG
References
1. Compston JE. Vitamin D deficiency: time for action. BMJ
1998;317:1466-7.
2. Valimaki MJ, Tiihonen M, Latinen K, Tahtela R, Karkkainen M,
Lamberg-Allardt C, Makela P, Tunninen R. Bone mineral density measured by
dual-energy x-ray absorptiometry and novel markers of bone formation and
resorption in patients on antiepileptic drugs. J Bone Miner Res 1994; 9:
631-37.
3. Collins N, Maher J, Cole M, Baker M, Callaghan N. A prospective
study to evaluate the dose of vitamin D required to correct low 25-
hydroxyvitamin D levels, calcium, and alkaline phosphatase in patients at
risk of developing
antiepileptic drug-induced osteomalacia. Q J Med 1991; 78: 113-22.
Competing interests: No competing interests
I agree with Dr. Compston that hypovitamiosis D is common and
as a problem it has been neglected for long. Infants and pregnant and
lactating mothers are not routinely supplemented with vitamin D. Rickets
is still common in Pakistani infants and children.
We (1) reported vitamin
D deficiency rickets in breastfed infants and severe vitamin D deficiency
in all the mothers in whom serum 25(OH)D levels were measured,(15/15
mothers had levels Hypovitamonosi D is a serious nutritional problem which
has been neglected. Clearly there is urgent need for routine
supplementation both in infants and pregnant and lactating mothers albeit
in all. We agree with the recommendations of Dr. JE compston.
Yours
sincerely,
Iqbal Ahmed and Mehnaz Atiq
References
1. I. Ahmed, M Atiq, J Iqbal, M Khurshid,and P Whittaker. Vitamin D
deficiency rickets in breastfed infants presenting wiith hypocalcemic
seizures.Acta Paediatr 1995;84:941-942
2. M Atiq,A Suria, SQ Nizami,Ahmed I. VitaminD status of breastfed
Pakistani infants. Acta Paediatr 1998;87:737-40
Competing interests: No competing interests
EDITOR-Dr. Compston's editorial 1 well indicated how widespread is
vitamin D deficiency and how advisable is its correction, despite the
contradictory evidence for its efficacy in preventing proximal femoral
fracture, the most
fearful of the skeletal complications in old age.
The editorial mentioned two methods of supplementation, either an
annual injection of a massive dose of the vitamin, or small-dose daily
oral supplements. For many years my (adopted) method has been one
somewhere in between-the six-monthly administration of 60,000 IU (10ml) of
either
cholecalciferol or ergocalciferol in one supervised swallow 2,3. This has
ensured, in the elderly, compliance and safety, vitamin D adequacy, and
has even healed severe biopsy-proved osteomalacia.
MARK N. LOWENTHAL
Division of Medicine
Ben Gurion University of the Negev
P.O. Box 151
Beer Sheva 84101
Israel
1. Compston JE. Vitamin D deficiency: time for action. BMJ
1998;317:1466-7 (28 November.)
2. Davies M, Mawer EB, Hann JJ, et al. Vitamin D prophylaxis in the
elderly: a simple effective method suitable for large populations. Age and
Ageing 1985;14:349-54.
3. Weisman Y, Schen RJ, Eisenberg Z, et al. JAGS 1986;34:515-8.
Competing interests: No competing interests
Vitamin D deficiency with AED treatment - guidelines still needed
Dear Editor,
Vitamin D deficiency with AED treatment – guidelines still needed
In a BMJ editorial in 1998, Compston [1] called for action citing evidence in support of routine supplementation for the prevention of vitamin D deficiency for elderly people and others at risk, including patients on long-term enzyme-inducing antiepileptic drugs (AEDs). At the time, we highlighted areas of uncertainty and the need for clear management pathways in patients with epilepsy [2]. Vitamin D deficiency causes secondary hyperparathyroidism, bone loss, osteopenia, osteoporosis and increases fracture risk [3]. Nevertheless guidelines for the prevention and treatment of hypovitaminosis D in patients on long-term AEDs are still to be established. Neither determining vitamin D status nor vitamin D supplementation are part of routine practice in neurology and epilepsy clinics in the UK.
Vitamin D (25-hydroxy) concentrations measured last year among 50 Caucasian outpatients considered at potential risk of vitamin D insufficiency (e.g. on long-term enzyme-inducing AEDs) were surveyed. Nineteen were found to have vitamin D deficiency with concentrations of less than 10 ug/L (laboratory reference range 10-50 ug/L). Thirty-six patients had concentrations below 17 ug/L, known to be associated with raised parathyroid hormone levels [4]. All patients had concentrations below 40 ug/L: it has been suggested that reduced fracture risk is associated with concentrations above this threshold [5]. Medical notes were reviewed in relation to AEDs used and duration of treatment as well as the presence of other risk factors, including age above 65 years, menopausal status, limited mobility, gastro-intestinal disease and other relevant drugs (table).
The findings clearly demonstrate vitamin D insufficiency among this, albeit selected, patient group, This data emphasizes the need for clear guidelines on appropriate monitoring and replacement regimens in this context. Given that no patients maintained concentrations in excess of 40 ug/L, it may be appropriate to supplement all patients at risk.
Andreas Kirschke, final year medical student, Heidelberg University, Germany
Lina Nashef, Consultant Neurologist, Kent and Canterbury Hospital, Canterbury, CT1 3NG
Edmund J Lamb, Consultant Clinical Biochemist, Kent and Canterbury Hospital, Canterbury, CT1 3NG, Edmund.Lamb@ekht.nhs.uk
References:
1. Compston JE. Vitamin D deficiency: time for action. Evidence supports routine supplementation for elderly people and others at risk. BMJ 1998; 317:1466-7.
2. Nashef L, Lamb E. Vitamin D deficiency. Guidelines are needed for treating diseases of bone metabolism in epilepsy. BMJ 1999; 318:1285.
3. Lips P. Vitamin D deficiency and secondary hyperparathyroidism in the elderly: consequences for bone loss and fractures and therapeutic implications. Endocr Rev 2001; 22:477-501.
4. Dhesi JK, Bearne LM, Moniz C, Hurley MV, Jackson SH, Swift CG, Allain TJ. Neuromuscular and psychomotor function in elderly subjects who fall and the relationship with vitamin D status. J Bone Miner Res 2002; 17:891-7.
5. McKenna MJ, Freaney R. Secondary hyperparathyroidism in the elderly: means to defining hypovitaminosis D. Osteoporos Int 1998; 8(Suppl 2):S3-6.
vitamin D concentration
< 10 ug/L, (n=19/50)
vitamin D concentration
< 17 ug/L, (n=36/50)
Age (median, range) [years]
44, 30-70
44, 19-77
Female patients [n], postmenopausal [%]
10 (60)
16 (56)
No. of other risk factorsa (median, range)
1, 0-2
1, 0-2
Single drug therapy [n]
6
13b
- phenytoin [n]
4
7
- carbamazepine [n]
2
4
- valproate [n]
0
1
- ethosuximide [n]
0
1
Multiple drug therapy [n]
13
23c
a see text
b duration of treatment: median, range [years]: phenytoin 6.3, 0.6-30.9; carbamazepine 3.5, 1.2-21.5; valproate 31.6; ethosuximide 16.5
c drugs used: (n), (median duration of treatment, range [years]): phenytoin (14/23), (3.2, 0.6-54.9); carbamazepine (11/23), (2.7, 0.6-6.9); valproate (8/23), (2.8, 0.6-12.3); topiramate (6/23), (1.0, 0.6-3.6); lamotrigine (6/23), (2.1, 0.6-4.1); phenobarbitone (5/23), (7.7, 0.7-34.8); primidone (5/23), (1.4, 0.6-4.7); levetiracetam (2/23), (0.8, 0.7-0.9); gabapentin (1/23, 4.9)
Competing interests: vitamin D concentration