Vitamin D matters variably?

[Guest guest]

Hi All,

The below paper seems to indicate that vitamin D matters more for some than for

others. It seemed that a conservative approach was recommended for not using

vitamin D in younger populations.

Theresa J. Allain

Age and Ageing 2005 34(6):542-544

Vitamin D and fracture prevention—treatment still indicated but clarification

needed

The publication of Chapuy’s 1992 paper, ‘Vitamin D3 and calcium to prevent hip

fractures in elderly women’, was a turning point in fracture prevention in older

adults. It was the first large-scale study to demonstrate that simple, oral,

daily

administration of calcium and vitamin D supplements could cause a substantial

reduction in hip fractures with a relative risk of 0.74 over 3 years [1]. The

mechanism for the reduction in fracture risk is probably a combination of

improved

bone health and neuromuscular changes. The latter may reduce falls risk or

improve

neuroprotective reflexes, so a fall is less likely to result in a serious

injury.

Chapuy’s study included 3,270 women aged over 70 years, living in residential

care.

This paper was followed by a number of others, which reinforced the view that

vitamin D alone, or with calcium, could reduce peripheral fractures in older

adults.

These studies extended the populations likely to benefit including men as well

as

women, those living in their own homes as well as in residential care and

slightly

younger adults, down to the age of 65 years [2–5]. The apparent benefits, cost

effectiveness (numbers needed to treat 17 to prevent one hip fracture of women

living in residential care) and relative safety have meant that many national

and

local guidelines advocate the widespread prescription of calcium and vitamin D

supplements to prevent fractures in adults aged 65 years and over.

However, not all studies of the effects of calcium and vitamin D supplementation

on

fracture rates in older people have had positive findings [6–8]. The publication

of

three high-profile, negative studies within the past year calls these

recommendations into doubt [9–11]. Two of these were primary prevention studies.

The

Wessex fracture prevention study was a population-based study of 9,440 men and

women, aged over 75, who received an annual injection of vitamin D

(ergocalciferol

300,000 IU) for 3 years [12]. The study by Porthouse and colleagues [9] looked

at

3,314 women aged over 70 years who were treated with calcium (1 g/day) and

vitamin D

(cholecalciferol 800 IU/day). The third study (RECORD) investigated secondary

prevention of fractures in 5,292 men and women, aged over 70 years, who had

suffered

a fragility fracture within the previous 10 years. In a factorial design, they

were

given calcium (1 g/day), vitamin D (cholecalciferol 800 IU/day), both or neither

[10]. It is unlikely that the conclusions of the studies demonstrating benefit

were

wrong, so what is it about the populations studied, the nature of the

interventions

or the ascertainment of outcomes that can explain these differences?

The variables that are likely to be significant in altering the outcome of such

studies are the likelihood of vitamin D deficiency or insufficiency in the

population being studied, the calcium intake of subjects, the rate of fracture

in

that population (in turn related to the duration of follow-up) and the dose and

type

of vitamin D administered. Furthermore, adherence to treatment may differ

depending

on the setting and the treatment regime, so that studies in care homes or those

using intermittent bolus vitamin D may have higher adherence rates and,

therefore,

be more likely to have positive results compared to population-based studies

such as

RECORD where compliance may have been as low as 45%. Finally, self-selection of

study subjects, particularly in population-based studies [9–11], may bias the

sample

towards fitter and more active older people, so the studies may be missing

frailer,

housebound people, the very group who are at higher risk of vitamin D

deficiency,

falls and fractures.

The likelihood of vitamin D deficiency in the populations studied and the dose

and

type of vitamin D supplements administered warrant further discussion.

Increasing age and housebound lifestyle are important determinants of vitamin D

status [13]. High rates of vitamin D deficiency have been demonstrated in

community-based samples of older people [14] and high-risk groups such as people

with falls [15] or fractures [16]. The majority of studies looking at the

efficacy

of vitamin D in fracture prevention, particularly those with a large sample

size,

have not ascertained vitamin D status in all subjects, presuming that the

population

under study will have a high prevalence of vitamin D deficiency. Vitamin D and

parathyroid hormone (PTH) levels (since PTH is an important mediator of bone

loss

and osteoporosis in later life), before and during supplementation, were either

measured in small subgroups [1, 4, 10, 12] or not measured at all [9]. Scrutiny

of

this data shows a wide range of levels of vitamin D with improvements with

treatment

which still leave many subjects in the deficient/insufficient range and modest

changes in PTH (if measured). Furthermore, the vitamin D status of the vast

majority

of subjects is unknown.

Since the publication of the papers by Chapuy [1] and then by Dawson- [3],

7–800 IU of cholecalciferol/day with or without calcium has been widely accepted

as

an appropriate dose of vitamin D for supplemental use; however, these doses may

not

be sufficient. Useful guidelines on interventional studies with vitamin D

suggest

that doses of 3,000–10,000 IU cholecalciferol/day are necessary [17, 18] and can

be

safely administered without toxicity. Ergocalciferol (vitamin D2) is at least

threefold less potent than cholecalciferol (vitamin D3) [19], which may account

for

the negative findings in the Wessex hip fracture prevention study [12] in which

an

ergocalciferol injection was used. Finally, it is not known whether activated

vitamin D would be a more effective supplement for widespread use in older

adults.

Calcitriol can reduce vertebral fractures in postmenopausal women with

osteoporosis

[20], and alpha-calcidol has been shown to reduce falls in frail older adults

with

low calcium intake or renal impairment [21]. Given that many older adults have

low

calcium intake and low glomerular filtration rate, activated vitamin D has

theoretical advantages in this respect, although the major disadvantage is the

risk

of hypercalcaemia. In contrast, supplementation with cholecalciferol and

ergocalciferol is unlikely to lead to hypercalcaemia due to homeostatic

regulation

of activation of vitamin D. If calcitriol were used on a routine ‘whole

population’

basis, the need for monitoring of calcium levels would lead to increased cost

and

inconvenience.

Where does the current body of literature leave us with regard to using calcium

and

vitamin D supplements for peripheral fracture prevention in older adults?

The situation is best summarised as follows:

i. For older women, aged over 70 years, living in residential or nursing care,

the

evidence for population-based supplements is good. This could still reasonably

be

extrapolated to frail, housebound adults of both genders. Oral supplements of

cholecalciferol 800 IU with calcium 1 g a day are preferable to an injection,

and

intermittent oral dosing of cholecalciferol may aid compliance.

ii. For secondary fracture prevention, since the publication of National

Institute

of Clinical Excellence (NICE) guidance on the secondary prevention of

osteoporotic

fracture [22], all women over 75 and postmenopausal women under 75 who meet

criteria

based on bone densitometry should now be treated with bone-strengthening drugs,

usually a bisphosphonate. The guidance specifically says that all patients

should

have adequate calcium and vitamin D levels before treatment, and it is important

that patients treated with bisphophonates are calcium and vitamin D replete, so

it

is good practice to co-prescribe calcium and vitamin D supplements to this group

too. Although NICE does not address osteoporosis treatment in men, this

recommendation also applies to men being treated for osteoporosis.

iii. In postmenopausal women under 75 who have fractured, but do not meet bone

densitometry criteria for specific treatment, there is no evidence at present to

give vitamin D supplements. However, between 20 and 50% will be vitamin D

deficient

and, given that they have already fractured, it would be good practice to check

vitamin D levels and replace if deficient or insufficient.

iv. For primary prevention of fractures in ‘younger’ older adults, there is

currently no evidence to support population-based administration of calcium and

vitamin D.

It is clear that there is a need for more research on this subject, particularly

using higher doses of vitamin D or activated vitamin D. Whether vitamin D needs

to

be combined with calcium supplements is also not clear. It should be remembered

that

vitamin D deficiency is common, and untreated vitamin D deficiency has adverse

effects throughout the body, including an increased risk of falls, increased

vascular risk and a higher incidence of cancer. So, reducing fracture rates is

not

the only desirable outcome of vitamin D supplementation in older adults.

Al Pater, PhD; email: old542000@...

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