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day) seemed to slightly reduce all-cause
mortality. The authors concluded that
the discrepancy between observational
and intervention studies suggests that
the serum 25-hydroxyvitamin D level is
a marker, rather than cause, of ill health.
Inflammatory processes involved in
disease occurrence and clinical course
would reduce serum 25-hydroxyvitamin D
levels, which would explain why low
vitamin D status is reported in a wide
range of disorders.
From a meta-analysis of
placebo-controlled randomised controlled
trials using multiple non-skeletal
and skeletal endpoints, Bolland and
colleagues found no significant effect
of vitamin D supplementation (with
or without calcium) on outcomes for
myocardial infarction, stroke, and cancer.
They also completed a trial sequential
analysis to assess both treatment effects
and the theoretical alteration on risk
estimates by future trials, and found
that vitamin D supplementation (with
or without calcium) on all of these
non-skeletal outcomes was below their
nominated futility boundary of 15%; for
mortality, whether there was an effect at
a boundary of 5% was unclear. The results
were not influenced by higher dose,
duration of treatment or lower baseline
25-hydroxyvitamin D concentrations. Their
analyses indicated that future studies are
not likely to change these pooled results;
the body of evidence is already sufficiently
large. Of skeletal endpoints, only a clear
reduction in the risk of hip fracture was
seen for the combination of calcium
and vitamin D in elderly nursing home
residents. Vitamin D supplementation
without the addition of calcium did not
reduce hip fracture or total fracture risk.
The same research group also recently
published a meta-analysis indicating
showing no major effect of vitamin D
supplementation on bone mineral
Based on these findings, NPS
MedicineWise has suggested the practical
implications summarised in Box 1.
According to Therapeutic Guidelines,
the serum 25-hydroxyvitamin D
concentration should be maintained
at 75 nmol/L (30 ng/mL) or more as
part of the prevention and treatment
of osteoporosis in older people.21
Vitamin D supplementation, in the form
of cholecalciferol 25 to 50 micrograms
(1,000 to 2,000 international units) daily, is
indicated in proven vitamin D deficiency,
in institutionalised or housebound
people, and in women who are veiled
for cultural reasons.
People who are
vitamin D-deficient require higher doses:
cholecalciferol 75 to 125 micrograms
(3,000 to 5,000 international units) daily
is required for at least 6–12 weeks to treat
moderate-to-severe deficiency; this will
usually return serum 25-hydroxyvitamin D
threshold levels to the normal range and
allow ongoing treatment with a lower dose
(e.g. 1,000 international units daily).22
The recent publications won’t be
the end of the debate on vitamin D.
Several large trials examining vitamin D
supplementation are ongoing.
1. Daly RM, Gagnon C, Lu ZX, Magliano DJ, Dunstan DW,
Sikaris KA, et al. Prevalence of vitamin D deficiency and its
determinants in Australian adults aged 25 years and older:
a national, population-based study. Clin Endocrinol (Oxf )
2. Nowson CA, Margerison C. Vitamin D intake and vitamin D
status of Australians. Med J Aust 2002;177(3):149–52 .
3. Zhang R, Naughton DP. Vitamin D in health and disease:
current perspectives. Nutr J 2010;9:65.
4. Nowson CA, McGrath JJ, Ebeling PR, Haikerwal A, Daly
RM, Sanders KM, et al. Vitamin D and health in adults in
Australia and New Zealand: a position statement. Med J Aust
5. Lips P. Vitamin D deficiency and secondary
hyperparathyroidism in the elderly: consequences for bone
loss and fractures and therapeutic implications. Endocr Rev
6. Mithal A, Wahl DA, Bonjour JP, Burckhardt P, Dawson-Hughes
B, Eisman JA, et al. Global vitamin D status and determinants
of hypovitaminosis D. Osteoporos Int 2009;20(11):1807–20.
7. Boyages S, Bilinski K. Seasonal reduction in vitamin D
level persists into spring in NSW Australia: implications for
monitoring and replacement therapy. Clin Endocrinol (Oxf )
8. Macdonald HM. Contributions of sunlight and diet to
vitamin D status. Calcif Tissue Int 2013;92(2):163–76.
9. Bogh MK. Vitamin D production after UVB: aspects of UV-
related and personal factors. Scand J Clin Lab Invest Suppl
10. Bhattoa HP, Nagy E, More C, Kappelmayer J, Balogh A, Kalina
E, et al. Prevalence and seasonal variation of hypovitaminosis
D and its relationship to bone metabolism in healthy
Hungarian men over 50 years of age: the HunMen Study.
Osteoporos Int 2013;24(1):179–86 .
11. Schwalfenberg G. Not enough vitamin D: health
consequences for Canadians. Can Fam Physician
12. Mosekilde L. Vitamin D and the elderly. Clin Endocrinol (Oxf ).
13. Malik R. Vitamin D and secondary hyperparathyroidism in
the institutionalized elderly: a literature review. J Nutr Elder
14. Sinha A, Cheetham TD, Pearce SH. Prevention and treatment
of vitamin D deficiency. Calcif Tissue Int 2013;92(2):207-15.
15. NPS Medicinewise. Vitamin D: cause or effect? 2014.
16. Michaëlsson K. The puzzling world of vitamin D insufficiency.
Lancet Diabetes Endocrinol 2014; published online Jan 24.
At: http://dx.doi.org/10.1016/S2213-8587(14)70008-7 .
17. Mannino DM. Is vitamin D’s ‘moment in the sun’ behind us?
Chest. 2014;145(1):5–6 .
18. Autier P, Boniol M, Pizot C, Mullie P. Vitamin D status and ill
health: a systematic review. Lancet Diabetes Endocrinol
19. Bolland MJ, Grey A, Gamble GD, Reid IR. The effect of
vitamin D supplementation on skeletal, vascular, or cancer
outcomes: a trial sequential meta-analysis. Lancet Diabetes
Endocrinol 2014; published online Jan 24. http://dx.doi.
20. Reid IR, Bolland MJ, Grey A. Effects of vitamin D supplements
on bone mineral density: a systematic review and meta-
analysis. Lancet 2014;383(9912):146–55 .
21. Prevention of osteoporosis [revised June 2009, amended
February 2011]. In: eTG complete [CD-ROM]. Melbourne:
Therapeutic Guidelines Limited; 2013 July, etg40.
22. Osteoporosis. Australian Medicines Handbook, Aged Care
Companion Online: Australian Medicines Handbook, 2012.
Figure. 1. Association of ageing with vitamin D deficiency and subsequent osteoporosis
to sunlight and ability
of skin to synthesise
dietary vitamin D
Low serum 1, 25
Other factors e.g.
Low serum calcium
Bone loss and
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