Vitamin D is a fat soluble vitamin that plays an essential role in maintaining calcium levels in the body, by increasing the absorption of calcium from the kidneys and the gut. In addition to its vital role in calcium homeostasis, latest research ascribes multiple benefits of reduced morbidity and mortality to maintenance of normal vitamin D levels.¹

Vitamin D is a unique hormone in that it can be synthesised in the skin from cholesterol precursors in the presence of sunlight. This de novo synthesis represents the primary source of vitamin D in the human body.² There are very limited natural food sources of the vitamin. Thus, the major cause of vitamin D deficiency is inadequate exposure to sunlight.³ The latest Endocrine Society guidelines⁴ define vitamin D deficiency as plasma levels of < 20ng/ml. As per this definition, 20-100% of Canadian, US and European elderly men and women currently living in the community are vitamin D deficient.²

Falls in elderly people

With advances in modern medicine, human beings today are living longer than ever before. As the geriatric population of the world rises, new health challenges are coming to the fore. One such challenge is falls in elderly people. People over 65 years of age represent only 12% of the population, but account for 75% of deaths from falls.⁵ Every year, 30-40% of elderly people living in the community and 60% living in nursing homes are affected by falls.⁶ Causes of falls in elderly people are outlined in Table 1.

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In addition to falls-associated mortality, elderly people who suffer from falls also suffer significant morbidity in terms of a decline in their level of physical activity, inability to maintain their independence for activities of daily living (ADLs) and an increased risk of requiring institutionalisation. 

Hospital stays have been recorded to be twice as long for falls-prone patients than age-matched controls who do not fall.⁵ The consequences of an older person falling can range from minor injury to major trauma. Hip fractures occur in 1-2% of all falls in elderly people.⁸ Head trauma, soft tissue injuries and dislocations are also commonly seen. An even heavier price to pay is the psychological fear of falling, which leads to self-restriction of activities.⁵ 

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Vitamin D deficiency in elderly people

Elderly people are a population that is more susceptible to vitamin D deficiency. In a study of 824 people above the age of 70 in 11 European countries, 36% of men and 47% of women were found to be vitamin D deficient.¹¹ Table 3 sets out causes of higher incidence of vitamin D deficiency in elderly people.

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This predisposition to vitamin D deficiency in the elderly population might have more far-reaching consequences than are generally ascribed to it. Mostly the role of vitamin D deficiency is only considered to be of relevance in this population with regard to osteoporosis. Recent studies have provided evidence of an association between muscle weakness and vitamin D deficiency. Muscle mass is already significantly reduced in the elderly population. Further compromise of the muscle function, especially in the proximal limb girdles, as would occur in vitamin D deficiency, can thus significantly increase the risk of falls. Also the morbidity of falls is significantly increased in patients who are vitamin D deficient, as such patients develop secondary hyperparathyroidism, leading to more mobilisation of calcium from the bones, a more rapid decline in bone mineral density (BMD) and thus an increased incidence of fractures.^11,12

So not only are the patients falling more when they are vitamin D deficient, but the falls have more serious consequences, in terms of long term morbidity and mortality. 

Benefit of vitamin D replacement in fall prevention

Thomas et al¹³ conducted a study on elderly residents  of nursing homes and established that those with a tendency to fall, on average, had lower vitamin D levels. This led to research on the hypothesis that vitamin D supplementation might decrease the incidence of falls.

Bischoff-Ferrari et al¹⁴ demonstrated a reduction in falls rate of up to 50% with calcium and vitamin D supplementation of 800IU per day. This finding was confirmed by a meta-analysis,¹⁵ which showed fall reduction rates of 22% with vitamin D supplementation alone, and even higher if calcium supplements were also given. The number needed to treat (NNT) to observe this beneficial effect was only 15.

Rothenbacker et al¹⁶ conducted a prospective population-based cohort study involving 1,385 institutionalised subjects aged 65 years and older, and found a significant association between serum25-hydroxyvitamin D (25-OHD) levels and the risk of first fall during a one-year follow-up. Subjects with serum calcium level above the median value and serum 25-OHD of 29ng/mL and below had a higher risk of first fall in comparison to the subjects with 25-OHD above 29ng/mL.

A meta-analysis by Murad et al¹⁷ involving 26 studies, including 45,782 subjects, demonstrated a significant reduction in fall risk in the group taking vitamin D. Furthermore, a greater reduction in fall risk was noted in subjects deficient in vitamin D at baseline and those who received combined treatment of vitamin D and calcium (compared to vitamin D only). In contrast to these findings, a randomised-controlled trial by Sanders et al¹⁸ found a 15% increase in falls and 26% rise in fractures in the subjects who received cholecalciferol compared to the placebo group. The study included 2,256 female volunteers ≥70 years of age who received a single dose of 500,000IU of cholecalciferol or a placebo every winter for three to five years. The results of this study provided a convincing argument for avoiding prescribing a single annual high dose of vitamin and preferring more ‘physiologic’ doses taken regularly (daily, monthly or quarterly).

The mechanisms postulated for the effect of vitamin D in decreasing falls incidence are based on its association with improved muscle strength and decreased body sway:

Effect on muscle strength: 

Mowe et al¹⁹ studied 349 elderly people and found that those with lower vitamin D levels had lower hand-grip strength, inability to climb stairs and had suffered more falls. However, when an attempt to reproduce their results was made in a double-blind RCT by Smedshaug et al,²⁰ they found no improvement in grip strength in the vitamin D supplemented population at the end of a year of supplementation. Most studies attempting to show improved muscle strength with vitamin D supplementation have had equivocal results. However, Pfeifer et al²¹ showed 8% improved quadriceps strength with vitamin D and calcium supplementation at 20 months as compared to calcium alone. Notable improvement in the strength of hip flexors and knee extensors as measured by a dynamometer was also noted by Moreira-Pfrimer et al.²² 

Effect on body sway: 

Body sway while walking provides an estimate of the balance and stability and can be used as a tool for falls risk assessment.²³ Pfeifer et al²⁴ showed significant reduction in body sway with vitamin D supplementation. Bunout et al²⁵ found an improvement in the timed up and go test and decreased body sway in patients on vitamin D supplementation. Dhesi et al²⁶ demonstrated a 13% improvement in postural stability with vitamin D supplementation. 

Vitamin D supplementation and fracture risk 

The anti-fracture benefits of vitamin D have been investigated in several clinical trials. Evidence on the role of vitamin D, either alone or in combination with calcium, in reducing fractures is conflicting. Some studies have shown a reduction in the risk of fractures, others have shown no effect, and a study by Sahota²⁷ found an increased risk of hip fracture. Furthermore, there is no consensus on:

• The optimal dosage of vitamin D for the purpose of supplementation 

• Which patients would benefit the most

• Fractures at which sites are most amenable to vitamin D treatment.

In 2007, two meta-analyses^28,29 concluded that vitamin D may not reduce fractures significantly or may do so only in combination with calcium, and primarily among institutionalised older individuals. A further meta-analysis in the same year³⁰ concluded that calcium with or without vitamin D may reduce total fracture risk by 12%. 

In 2005, Bischoff-Ferrari et al performed a meta-analysis of 12 double-blind trials, among individuals aged ≥65 years, and found that the anti-fracture efficacy of supplemental vitamin D increased significantly with higher received dose or higher achieved 25-OHD levels for any non-vertebral fractures and for hip fractures. No fracture reduction was observed for a received dose of 400IU/d or less, whereas a higher received dose of 482 to 770IU/d of supplemental vitamin D reduced non-vertebral fractures by 20% and hip fractures by 18%. Non-vertebral fracture reduction with the higher received dose was significant among all subgroups by age and dwelling, including younger individuals aged 65-74 years and those living in the community.³²

A couple of epidemiological studies have shown a dose-response relationship between vitamin D and fracture reduction.^14,33 This finding was supported by a meta-analysis of high-quality primary prevention trials with supplemental vitamin D showing greater anti-fracture efficacy with higher achieved 25-0HD levels.³²

More recently, Bischoff-Ferrari and colleagues³¹ conducted another analysis of 11 randomised controlled trials of supplementation with vitamin D (vitamin D2 or vitamin D3) with calcium or vitamin D alone. Their analysis included a total of 31,022 participants. They concluded that the significant reduction in the risk of fracture was observed only at the highest vitamin D intake level (800IU) with a 30% reduction in hip fracture risk and a 14% reduction in the risk of non-vertebral fracture. This analysis found no significant interaction between the highest actual intake of vitamin D and additional calcium intake. A recent literature review conducted by Marcelli et al³⁴ concluded that there is a moderate but significant reduction in osteoporotic fracture risk resulting from the action of vitamin D. They also suggested that the reduction in fracture risk seems to be more related to a reduction in fall risk that could be associated with the positive action of vitamin D on motor performance, and perhaps to a greater extent, with positive effect on cognitive performance, at least in elderly women.

Current guidelines for vitamin D supplementation in elderly people

The American Geriatric Society guidelines³⁵ recommend the use of 1,000IU of vitamin D along with calcium for all elderly patients (age >65 years) for the purpose of falls and fracture prevention. This recommendation is based on findings that doses <600IU per day do not seem to provide any benefit with regards to fall prevention and that most people assessed in this age group were found to be vitamin D deficient. It is recommended that an attempt should be made to individualise the vitamin D dose for the patient by taking into account factors such as dietary intake, sun exposure, skin tone and body weight. Routine checks of vitamin D levels are not required if supplementation is being provided at the aforementioned dose, but if the clinician is desirous of checking levels, then this should be done four months after starting treatment. Prescription of bolus doses of vitamin D (either D2 or D3) of > 300,000IU are not currently recommended. 

Conclusion

There are a wide range of conflicting results obtained from studies trying to establish a correlation between vitamin D levels in elderly people and the incidence of falls. The results range from startlingly encouraging to unequivocally disappointing. Researchers have postulated that the failure of some studies to demonstrate the benefits of vitamin D is related to inadequate dosing. However, the association of normal vitamin D levels and reduced incidence of fractures is undeniable. Additionally vitamin D supplementation has been ascribed a host of other beneficial effects including a role in prevention of dementia, anti-cancer benefits and immunity related benefits. For an inexpensive measure that provides beneficial health effects, the current consensus is to ensure appropriate vitamin D supplementation in all deficient individuals. 

References

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