Recent developments in vitamin D deficiency and muscle weakness among elderly people
BMJ 2005; 330 doi: https://doi.org/10.1136/bmj.330.7490.524 (Published 03 March 2005) Cite this as: BMJ 2005;330:524All rapid responses
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I presume that
"A comprehensive review article of data on toxic hypocalcaemia during
vitamin D therapy for a variety of conditions found that the lowest level
at which an adverse effect was observed was a serum calcidiol
concentration of 200 nmol/l"
is meant to say "hypercalcaemia"
Competing interests:
None declared
Competing interests: No competing interests
Re: metabolism of vitamin D
It is hypothesized that Calcitriol
injection can be used as an emergency therapy in the encephalitis cases in the
normal VDR patients [1]
Kidney event might precede encephalitis
The prohormone vitamin D has virtually no biological
activity. However, they are hydroxylated in the liver at the carbon-25 (C-25)
position and subsequently at C-1 in the mitochondria of the cells of kidney
tubule to generate the active hormones calcitriol [2]. Renal 25-hydroxyvitamin D3 1alpha-hydroxylase is a member of the P450
family of enzymes [3].
Cisplatin impairs mitochondrial function of
calcitriol synthesis in proximal tubules in the kidney [4]. Antiinfective drugs sometimes show nephrotoxicity. Tubulotoxicity is a
well-known phenomenon, especially in connection with aminoglycosides and
amphotericin B as well as cephalosporins, pentamidine, foscarnet, and cidovir.
The tubulo-obstructive effect is caused by precipitation of the sulfadiazine,
cotrimoxazole, acyclovir and indinavir. Acute interstitial nephritis is the main
immunologic effect of antiinfective drugs (especially rifampicin but also
cephalosporins, quinolones, sulfonamides, and penicillins). Immune stimulation
by cytokine treatment (mainly interferon-alpha) involves several kinds of
autoimmune renal diseases like acute interstitial nephritis or
glomerulonephritis as well as interstitial and vascular rejection of renal
transplants [5].
Rifampicin and isoniazid, the drugs used in TB treatment
reduce circulating levels of 25-hydroxy vitamin D (25-OHD) and 1 alpha,
25-dihydroxy vitamin D (1,25(OH)2D) [6, I to IV]. Children patients with nephrotic syndrome (NS) and normal glomerular
filtration rate (GFR) treated with steroid frequently exhibit reduced
circulating vitamin D metabolites [7, I to V].
Antiepileptic drug-induced osteomalacia due to vitamin D deficiency is also
known to occur [8, I to III].
Herpes zoster associated encephalitis in dialysis
patients [9], acute renal failure with
neurological involvement in adults associated with measles virus isolation [10] and renal failure,
encephalitis and measles in a young woman [11] indicate that renal malfunctioning due to viral infection /
treatment to the disease could create deficiency of Calcitriol.
Hence it is hypothesized that tubular damage in the
kidney precedes encephalitis in some cases.
Liver event might also precede encephalitis in some
cases
Calcitriol synthesis in kidney depends on supply of
calcidiol (also known as calcifediol) from the liver. Calcidiol is produced from
cholecalciferol in the liver by hydroxylation. The cyclosporin A inhibits the
25-hydroxylase activities towards cholecalciferol [12]. Anticonvulsant drugs, phenytoin and sodium valproate inhibit the
25-hydroxylase activities on vitamin D3 in liver microsomes and mitochondria
[13]. The low circulating calcidiol in
alcoholics is associated with reduced hepatic 25-hydroxylase activities [14].
The role of liver function may not be as important as
kidney function but cannot be denied in some encephalitis cases.
References:
1. |
Deolankar RP, Calcitriol (1,25-dihydroxyvitamin D) |
2. |
Endocrinology, An Integrated Approach |
3. |
Takeyama K, Kitanaka S, Sato T, Kobori M, |
4. |
Gao Y, Shimizu M, Yamada S, Ozaki Y, Aso T. The |
5. |
Schwarz A, Perez-Canto A. Nephrotoxicity of antiinfective drugs. Int J Clin Pharmacol |
6.I |
Morcos MM, Gabr AA, Samuel S, Kamel M, el Baz M, el |
·6.II |
Kovacs CS, Jones G, Yendt ER. Primary |
·6.III |
Williams SE, Wardman AG, Taylor GA, Peacock M, |
·6.IV |
Brodie MJ, Boobis AR, Hillyard CJ, Abeyasekera G, |
7. I |
Freundlich M, Jofe M, Goodman WG, Salusky IB. Bone |
7.II |
Huang JP, Bai KM, Wang BL. Vitamin D and calcium |
·7.III · |
Freundlich M, Bourgoignie JJ, Zilleruelo G, Abitbol |
·7.IV |
Auwerx J, De Keyser L, Bouillon R, De Moor P. |
·7.V |
Freundlich M, Bourgoignie JJ, Zilleruelo G, Jacob |
8.I |
Kulak CA, Borba VZ, Bilezikian JP, Silvado CE, |
·8.II |
Mikati M, Wakim RH, Fayad M. Symptomatic |
·8.III |
Banakar MC, Paramasivan SK, Chattopadhyay MB, Datta |
9. |
Cheung WC, Yuen KY, Chang CM, Cheng KP. Herpes |
10. |
Wairagkar NS, Gandhi BV, Katrak SM, Shaikh NJ, |
11. |
Wairagkar NS, Kakrani AL, Shaikh NJ, Bapat VM, |
12. |
Dahlback-Sjoberg H, Bjorkhem I, Princen HM. |
13. |
Tomita S, Ohnishi J, Nakano M, Ichikawa Y. |
14. |
Pitts TO, Van Thiel DH. Disorders of divalent ions |
Competing interests:
None declared
Competing interests: In circulation calcitriol is bound to the globulin,transcalciferin (TC), with only a small fraction existing in free form. The freeform crosses the cell membrane and the nuclear membrane of target cells.
Calcitriol (1,25-dihydroxyvitamin D) for emergency encephalitis treatment in the normal VDR patients
Re: Vitamin D deficiency affects not just the
elderly
Several genes throughout the body are regulated by
calcitriol [1]. Calcitriol treatment decreased macrophage accumulation in the
CNS of mice with experimental autoimmune encephalomyelitis [2]. Calcitriol is
positive regulator for the two anti-encephalitogenic cytokines TGF-beta 1 and
IL-4 [3]. Calcitriol interacts with a calcitriol receptor (known as vitamin D
receptor, VDR) to induce dimerization with the retinoic acid receptor (RXR), DNA
binding and interaction of receptors with transcription factors resulting in
stimulation or inhibition of gene transcription [4]. The VDR and the enzyme
1alpha-hydroxylase that converts calcidiol to calcitriol are present both in
neurons and glial cells in a regional and layer-specific pattern. The VDR is
restricted to the nucleus whilst 1alpha-OHase is distributed throughout the
cytoplasm [5]. Calcitriol availability from brain cell cytoplasm to the nuclear-VDR
could be a limiting factor for the synthesis of protective anti-encephalitogenic
cytokines as kidney tubules are regarded as the major site of calcitriol
synthesis. Hence it is hypothesized that Calcitriol
injection can be used as an emergency therapy in the encephalitis cases. The
free form of calcitriol is expected to act fast. Exposure
of patients to artificial UVB light could also be beneficial. If this treatment
fails, malfunctioning of VDR could be indicated. Combination of Calcitriol with
retinoids [6] in the cancer treatment or with estrogen [7] in the treatment of
age related bone diseases are known. Estrogen modulates vitamin D hydroxylases
in the kidney [8].
Most cells of the immune system express the VDR,
including T cells and antigen-presenting cells, such as dendritic cells and
macrophages [9]. Calcitriol may not be effective if the VDR malfunctions.
Calcitriol may enhance innate immunity and inhibit the development of
autoimmunity [10]. Hence well thought calcitriol treatment could help
encephalitis cases.
References:
|
|
1. |
Guyton KZ, Kensler TW, Posner GH. Vitamin D and |
2. |
Nashold FE, Miller DJ, Hayes CE. |
3. |
Cantorna MT, Woodward WD, Hayes CE, DeLuca HF. |
4. |
Endocrinology, An Integrated Approach |
5. |
Eyles DW, Smith S, Kinobe R, Hewison M, McGrath JJ. |
6. |
Majewski S, Szmurlo A, Marczak M, |
7. |
Gallagher JC, Fowler SE, Detter JR, |
8. |
Caniggia A, Lore F, di Cairano G, Nuti R. |
9. |
Lin R, White JH. The pleiotropic actions of vitamin |
10. |
Griffin MD, Xing N, Kumar R. Vitamin D and its |
|
|
Competing interests:
None declared
Competing interests: Editor,
Sir,
The review by Venning highlights the prevalence of Vitamin D in the
elderly. A recent audit of vitamin D levels in patients with rheumatoid
arthritis carried out in our unit shows that this problem is not confined
to the elderly.
Recent guidelines (SIGN 71) recommend calcium and vitamin D
supplementation in all elderly housebound individuals. There is some
evidence that patients with rheumatoid arthritis (RA) have an increased
risk of vitamin D deficiency. We therefore aimed to establish the
prevalence of vitamin D deficiency and supplementation in patients with
RA attending a rheumatology follow up clinic, and to establish any
correlation with age, disability or disease activity.
266 patients attending the rheumatology follow up clinic were
studied. Blood was assayed for ESR, 25OH Vitamin D, Alkaline Phosphatase
and gamma GT. All patients completed a modified Stanford Health
Assessment Questionnaire (HAQ), and a drug history was recorded. 23 were
patients were taking Vitamin D supplements.
Vitamin levels were categorised as low (<20nmol/L), borderline (20
-40nmol/L) or normal (>40nmol/L). 38 patients had low levels (3
taking supplements), 135 had borderline levels (12 taking supplements) and
93 had normal levels (8 taking supplements).
When the low and normal groups were compared, there was a
statistically significant difference for ESR (P=0.02), Alk.Phos. (p=0.03)
and HAQ (p=0.01), but not age.
We have shown that Vitamin D deficiency is common in patients with
RA, independent of age. This may be an important additional risk factor
for falls and fractures in a group already at increased risk.
Competing interests:
None declared
Competing interests: No competing interests
EDITOR – Venning reviewed accumulating evidence of vitamin D to
prevent falls and fractures among nursing home residents.1 He pointed out
that vitamin D deficiency is particularly common among housebound aged
people and that deficiency is associated with muscle weakness, falls and
fractures. Furthermore, there is evidence that supplementation of 800 IU
but not with lower doses is associated with reduction of falls and
fractures.
It was early realized in Finland that vitamin D deficiency is a
special risk factor among old Finnish nursing home residents because of
their low exposure to sunlight.2 Finnish Current Care Guidelines for
osteoporosis recommended already year 2000 supplementation of 600 - 800 IU
of vitamin D for nursing home residents all year around.3 At that time two
randomized trials had already showed the effectiveness of high dose of
vitamin D in preventing falls and fractures among frail elderly people.4-5
We determined the vitamin D supplementation among long-term residents
in all nursing homes in Helsinki, in February 2003. Of all nursing home
residents, 87% (n=2 114) had available data on the use of vitamin D
supplementation. Their mean age was 83 years, and 80.7% were female. Of
these participants, 32.9% received vitamin D supplementation. However,
only 21.3% received vitamin D in the dose 400 IU or more and only 3.6% in
the dose 800 IU or more.
Regardless of the known benefit and guidelines of vitamin D
supplementation for the elderly residing mostly indoors, the proportion of
nursing home residents in Helsinki receiving vitamin D in 2003 was still
low. Current Care Guidelines for osteoporosis3 did consider and convince
the safety of vitamin D supplementation in higher doses. Our study shows
how slowly evidence and recommendations are implemented in practice.
Merja Suominen,
MSc, Project planner
The Central Union for the Welfare of the Aged,
Malmin kauppatie 26,
FIN-00700 Helsinki
Seija Muurinen,
PhD, Chief Development Consultant
City of Helsinki, Social Services Department, Elderly Services,
PO BOX 8555,
FIN-00099 City of Helsinki
Kaisu H. Pitkala,
MD, PhD, senior lecturer
Helsinki University Hospital,
Clinics of General Internal Medicine and Geriatrics,
PO BOX 340,
FIN-00029 HUS
email: kaisu.pitkala@hus.fi
Competing interests: None
References:
1 Venning G. Recent developments in vitamin D deficiency and muscle
weakness among elderly people. BMJ 2005;330:524-6.
2 Heikinheimo RJ, Inkovaara JA, Harju EJ, Haavisto MV, Kaarela RH,
Kataja JM, Kokko AM, Kolho LA, Rajala SA. Annual injection of vitamin D
and fractures of aged bones. Calcif Tissue Int 1992;51:105-10.
3 Finnish Endocrinological Society. Osteoporosis. Current Care
Guidelines 18.7.2000. (In Finnish). The Finnish Medical Society Duodecim
2000.At: http://www.kaypahoito.fi/
4 Chapuy MC, Arlot ME, Duboeuf F, Brun J, Crouzet B, Arnaud S, Delmas
PD, Meunier PJ. Vitamin D3 and calcium to prevent hip fractures in the
elderly women. N Engl J Med. 1992;327:1637-42.
5 Dawson-Hughes B, Harris SS, Krall EA, Dallal GE. Effect of calcium
and vitamin D supplementation on bone density in men and women 65 years of
age or older. N Engl J Med 1997;337:670-6.
Competing interests:
None declared
Competing interests: No competing interests
I thank the respondents for their rapid responses to my BMJ paper - Recent
developments in vitamin D deficiency and muscle weakness among elderly
people.
Re: 1998 and all that
My interest in Vitamin D arose after the Cambridge study in which I
was a guinea pig for 5 years. On completion I found that it is not
possible to buy Vitamin D in Boots or the other pharmacies in our town.
With my background in the drug industry I drafted an expert report
suitable for any company prepared to market a suitable dose with a claim
for preventing falls and fractures in the elderly. None of the companies I
approached were willing to do anything. All said the cost of marketing
would be prohibitive. I therefore re-wrote the paper for the BMJ. We now
need the government to produce a preparation, just as they produce flu
vaccines. The best preparation would be a tablet or capsule of 300,000
units of cholecalciferol (Vitamin D¬3) to be swallowed at the time of the
winter flu jab. The other action needed is for old people’s homes to make
sure their inmates get Vitamin D now. The best available preparation is
ergocalciferol, (Vitamin D2), 50,000 units (available from Celltech) and
the dose should be one tablet every 2 months. Sadly many old people’s
homes don’t even have a regular physician – they often expect each inmate
to be cared for by their previous GP.
Re: metabolism of vitamin D
I thank Dr Ballonoff for the correction to my paper.
Re: Vit D deficiency: product of decline in energy charge?
I am most interested in Dr Fiddian-Green's novel approach to the mechanism of action of Vitamin D and look forward to further work on this subject.
Re: Vitamin D deficiency: time for action long overdue
I did indeed define Vitamin D deficiency in the paper submitted to the BMJ but the editors omitted this when shortening the paper. I had written “Different authors have used different biochemical criteria of deficiency. 20ng/ml of 25(OH)D3 has been shown by Malabanan* to be the level below which parathyroid hormone levels rise and thus represents the threshold for maintenance of bone composition. Holick argues that 30ng/ml may be required for optimal health.” (I cited 10ng/ml as indicative of severe deficiency as used in WHAS study).
*Malabanan A et al Redefining Vitamin D deficiency, Lancet 1998;35:805-6
Regards, Geoff Venning
Competing interests:
None declared
Competing interests: No competing interests
Editor – Venning’s review (1) is a welcome reminder that vitamin D
deficiency in the elderly (and in fact the general population) is
certainly much more common than is generally recognised. However, a few
points need expansion and clarification.
Firstly, Venning fails to define vitamin D deficiency, or just how
common it is. Vitamin D status is most commonly assessed by measuring
serum levels of 25-hydroxyvitamin D (25(OH)D), the major circulating form.
Although published lower reference values for circulating 25(OH)D levels
are generally in the range 40-50 nmol/L, assessing ‘normal’ levels based
on a Gaussian distribution is now considered to be a grossly inaccurate
method of determining the normal range. Using functional indicators of
vitamin D status (such a intact parathyroid hormone, calcium absorption,
and bone mineral density), several studies have more accurately defined
vitamin D deficiency as circulating 25(OH)D levels </= 80 nmol/L (2);
Veith argues for a lower limit of 100 nmol/L (3).
The [British] National Diet & Nutrition Survey (4) found that the
mean 25(OH)D level for men was 48.3 nmol/L and for women 49.6 nmol/L; 91%
of men and 88% of women had 25(OH)D levels less than 80 nmol/L; 98% of men
and 97% of women had 25(OH)D levels less than 100 nmol/L. This suggests
that the majority of British adults are vitamin D deficient.
Vitamin D deficiency is an even greater problem amongst the elderly
(who may be house-bound or institutionalised) as a result of reduced
sunlight exposure, and also the age-related reduction in capacity to
produce previtamin D3 even when exposed to sunlight.
Secondly, Venning highlights the problem of inadequate vitamin D
doses, but is himself overcautious in dosage recommendations. Whilst 800
IU/day may indeed reduce the incidence of falls and fractures, it is
certainly quite inadequate to attain optimal vitamin D status. In cases of
established vitamin D deficiency, it is my experience that doses of
vitamin D3 (cholecalciferol) as high as 8,000-12,000 IU/day for 3 months
or longer are frequently required to ensure that 25(OH)D levels exceed 100
nmol/L. Thereafter, a maintenance dose of 4,000 IU/day is typically
required. It should also be emphasised that vitamin D2 (ergocalciferol) is
much less effective than vitamin D3 (5).
Furthermore, as well as contributing to falls, osteoporosis and
fractures, it is important to remember that vitamin D deficiency is also
associated with numerous other health problems, including rickets,
osteomalacia, non-specific musculoskeletal pain, back pain, ‘fibromyalgia’
(vitamin D deficiency is often misdiagnosed as fibromyalgia), fatigue,
osteoarthritis, periodontal disease, depression, seasonal affective
disorder, schizophrenia, insulin resistance, insulin deficiency, type 1
and type 2 diabetes, premenstrual syndrome, infertility, polycystic ovary
syndrome, auto-immune disorders, increased susceptibility to infection,
hypertension, myocardial infarction, congestive cardiac failure, multiple
sclerosis, Parkinson’s disease, Alzheimer’s disease, motor neurone
disease, migraine, multiple sclerosis, and increased risk of many cancers.
As vitamin D deficiency is so common (not only in the UK, but also in
sunnier climes, such as Australia), a high level of awareness of the
problem is called for, and annual screening should perhaps be considered.
In 1998 a BMJ editorial concluded that the evidence supported routine
vitamin D supplementation in the elderly and other high-risk populations
(6). It seems that the evidence is now even more compelling.
Treatment of vitamin D deficient individuals with high doses of
vitamin D3 (4,000-12,000 IU) is safe and likely to be a very cost-
effective intervention. However, it appears that the lessons of the past
have still not been learnt, and that the problems of under-diagnosis of
vitamin D deficiency, and under-dosing with vitamin D supplementation are
still prevalent.
Vitamin D deficiency is a major worldwide public health problem (7),
and the time for action is long overdue!
References
1.Venning G. Recent developments in vitamin D deficiency and muscle
weakness among elderly people. BMJ 2005;330:524-6.
2.Hollis BW. Circulating 25-hydroxyvitamin D levels indicative of
vitamin D sufficiency: implications for establishing a new effective
dietary intake recommendation for vitamin D. J Nutr 2005;135:317-322.
3.Veith R. Vitamin D supplementation, 25-hydroxyvitamin D
concentrations, and safety. Am J Clin Nutr 1999;69:482-56.
4.Rushton D, Hoare J, Henderson L, Gregory J. The National Diet &
Nutrition Survey: adults aged 19 to 64 years. Volume 4: Nutritional status
(anthropometry and blood analytes), blood pressure and physical activity
The Stationary Office, London, 2004.
5.Armas LAG, Hollis BW, Robert P Heaney RP. Vitamin D2 is much less
effective than vitamin D3 in humans. Journal of Clinical Endocrinology
& Metabolism 2004:89(11);5387-5391.
6. Compston JE. Vitamin D deficiency: time for action. BMJ
1998:317:1466-7.
7. Gannage-Yared MH, Tohme A, Halaby G. Hypovitaminosis D: a major
worldwide public health problem. [Article in French] Presse Med
2001;30(13)653-8.
Competing interests:
None declared
Competing interests: No competing interests
To what extent might vitamin D deficiency and the muscle weakness it
causes be due to a decline in Daniel Atkinson energy charge (1) in the
gut, liver and in the muscles themselves?
If a systemic decline in energy charge were a factor in causing
Vitamin D deficiency it is more likely to operate at the gut mucosal,
hepatic or renal levels. That would not seem to explain why higher plasma
concentrations of calcidiol are associated with muscle strength, physical
activity, and ability to climb stairs and lower concentrations with falls
among elderly people or why the effects can be reversed with supplements.
This raises the intriguing possibility that Vitamin D might have a direct
effect upon energy charge. A recent study suggests that it does.
Healthy volunteers were randomised to high dairy calcium (543 mg),
high vitamin D (349 IU) breakfast (HCB) or a low dairy calcium (248mg),
low vitamin D (12 IU) breakfast (LCB) (2). Non-esterified fatty acids were
less suppressed following HCD compared to LCD: -18.2 +/- 5.9% vs. -30.1 +/
- 4.7%; diet effect P<0.02). Diet induced thermogenesis (DIT) assessed
by indirect calorimetry was significantly higher on the HCD diet (6.8 +/-
0.42 % vs. 4.4 +/- 0.71%, diet effect P < 0.01). Fat oxidation was less
suppressed on the HCD diet (-1.6 +/- 1.49 g/4h vs. - 4.3 +/- 1.04 g/4h,
diet effect P < 0.05). Glucose and insulin responses were significantly
higher at lunch compared to breakfast. The authors concluded that higher
calcium and vitamin D acutely stimulated postprandial thermogenesis and
fat oxidation.
These data suggest to me that a diet high in dairy calcium and
vitamin D might stimulate lipolysis thereby releasing fatty acids which
are known to increase metabolic rate, accompanying oxygen consumption and
net ATP yield by uncoupling oxidative phosporylation and increasing
thermogenesis [Q10 effect]. They further suggest that the diet might have
caused the rise in blood glucose by shiftng substrate utilization from
glucose to fatty acids and some degree of insulin resistance. Hence the
accompanying post prandial rise in insulin. These changes have also been
interpreted as compensatory cytoprotective responses to acute reductive
stress such as those induced by exercise (3). As the tissue pH also falls
in acute reductive stress, and availability of ionized [Ca++] should rises
proprotionately, the inference being that the beneficial effects of the
supplements might be mediated by Ca++. Indeed calcium/calmodulin might
even be the default second messenger system operating in fight or flight
circumstances.
As a diet high in dairy calcium and vitamin D also appears to reduce
adiposity the inference is that the metabolic syndrome might either be the
product of a Vitamin D deficiency and/or of reductive stress as
previously proposed. A sustained demand for calcium induced by the
persistence of any reductive stress might even cause a deficiency in
Vitamin D by increasing the demand beypond the capicities for absorption,
metabolic transformations in liver and kidney and storage in gut mucosa
and other tissues. In which case muscle weakness in elderly patients might
indeed be the product of a decline in energy charge as mooted even if it
can be helped by a diet high in dairy calcium and/or vitamin D.
If so a more rational approach to managing the muscle weakness might
be to upregulate oxidative phosporylation and down regulate anaerobic
glycolyis. This might be accomplished either by decreasing the tissue pH
or by identifying and reversinga cause of reducutive stress such as
hypothyroidism or a pharmacological agent
1. Hardie DG, Hawley SA. AMP-activated protein kinase: the energy
charge hypothesis revisited.
Bioessays. 2001 Dec;23(12):1112-9
2. Soares MJ, Ping-Delfos WC, James AP, Cummings NK. Dairy calcium
and vitamin D stimulate postprandial thermogenesis: effect of sequential
meals. Asia Pac J Clin Nutr. 2004;13(Suppl):S56.
3. Richard G Fiddian-Green
SUD: product of an abnormally increased amplitude of synchronised
metabolic variations?
http://www.heartjnl.com/cgi/eletters/90/11/1263#525, 5 Nov 2004.
Competing interests:
Patents issued in my name
Competing interests: No competing interests
In the discussion of vitamin D metabolism the sites of conversion to
active 1,25 dihydroxy vitamin D were reversed. The liver attaches the
initial 25 hydroxy group and the kidney converts it to the active 1,25
metabolite. Most patients with liver disease can produce adequate 25
hydroxy vitamin D. Patients with kidney disease lose the ability to
produce the active metabolite early in their course and require calcitriol
and/or other treatments to control calcium and phosphorous levels. The
decreasing renal function with age can also play a part in decreased
levels of active vitamin D in the elderly.
Competing interests:
None declared
Competing interests: No competing interests
? for clarification
I emialed venning@hdd.co.uk. It was not deliverable. I would like him
or your editor to review the following:
Dear Sir,
Recently I came across your paper “Recent developments in vitamin D
deficiency and muscle weakness among elderly people” in BMJ 2005;330:524–6
I enjoy reading the article. It is informative. I am puzzled with
this statement just before the conclusion.
“The kidney is involved in the first step in metabolism of
cholecalciferol to calcidiol, the form in which it is stored, and the
liver in the final conversion to the active
hormone calcitriol.” I thought the liver is first site where
cholecalciferal is hydoxylased to 25 (OH)D which is then, in the kidney, 1
-apha-hydoxylased to active 1-alpha-25 (OH)2D that is the hormone
calcitriol. Am I not correct?
robert yong M.D.
Competing interests:
none
Competing interests: No competing interests