No evidence that vitamin D alone reduced older adults’ risk of fractures

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Taking calcium and vitamin D might help older adults curb the risk of a bone fracture, but vitamin D alone does not do the job, a new research review concludes.

The analysis of 28 past studies found that older adults with higher blood levels of vitamin D were less likely to suffer a broken hip or other fracture over five to 15 years.

But the picture was different in studies that actually tested the effects of using vitamin D supplements: They found no evidence that vitamin D alone reduced older adults’ risk of fractures.

In contrast, trials that tested a combination of calcium and vitamin D showed modest protective effects.

“Combined treatment with both calcium and vitamin D reduced the risk of hip fracture by one-sixth, and was more beneficial than taking standard doses of vitamin D alone,” said senior researcher Dr. Robert Clarke, a professor of epidemiology and public health medicine at the University of Oxford in England.

The findings, published online Dec. 20 in JAMA Network Open, are not the final word on vitamin D and fractures. Some ongoing trials are testing high-dose vitamin D in people who are at increased risk of bone breaks.

But for now, there’s no proof that it works, according to Clarke.

In the United States alone, about 54 million people have low bone mass or outright osteoporosis – the brittle-bone disease that can lead to fractures, according to the National Osteoporosis Foundation (NOF). It’s estimated that after age 50, half of women and one-quarter of men will break a bone due to osteoporosis.

Calcium is critical to building and maintaining strong bones, while vitamin D helps the body absorb calcium and supports the muscle function needed to avoid falls.

But when it comes to preventing fractures in people with osteoporosis, there’s only so much that supplements can do, said the NOF’s Beth Kitchin. She was not involved with the study.

“The expectation that vitamin D and calcium, alone, will prevent fractures is probably unrealistic,” said Kitchin, who is also an assistant professor of nutrition sciences at the University of Alabama at Birmingham.

To help preserve bone mass and keep muscles strong, people need regular exercise, according to Kitchin.

Exercise that makes the body move against gravity while staying upright – like jogging, jumping rope or dancing – can help maintain bone density.

And exercise that builds muscle strength or improves balance can help lower the risk of falls.

Avoiding smoking and excessive drinking is also critical to preventing bone loss, according to the NOF.

Once osteoporosis is diagnosed, medications – which either slow bone breakdown or boost bone formation – may be necessary, Kitchin said.

“Fall-proofing” your home is another important step. That means getting rid of tripping hazards inside and outside the house; installing grab bars in bathrooms; and keeping stairways well lit, among other measures.

Of the studies Clarke’s team analyzed, 11 were observational. They followed older adults in the “real world,” tracking fracture rates anywhere from five to 15 years. Overall, the higher a person’s blood levels of vitamin D were at the outset, the lower the risk of fracture.

“But that doesn’t prove cause and effect,” Kitchin stressed. “High vitamin D levels can be a marker of something else.”

Few foods contain vitamin D, she noted. Instead, the body synthesizes it when the skin is exposed to sunlight. So people with high vitamin D levels may spend a lot of time outdoors, for example.

The review also included 11 trials testing vitamin D alone, and six testing vitamin D and calcium. Study participants’ average age ranged from 62 to 85, and they were followed for up to five years.

Overall, people given calcium and vitamin D had a 16% lower risk of hip fracture than those given placebos or no treatment. Their risk of any bone break was 6% lower.

So how do you know if you should take supplements? You could ask your doctor to measure your blood level of vitamin D, to detect any deficiency, Kitchin said. As for calcium, she added, “take a look at your diet.”

If you’re not eating much dairy, green vegetables and foods fortified with calcium, you might need a supplement.

According to the NOF, adults younger than 51 should strive for 1,000 mg of calcium a day; after that, the recommendation goes up to 1,200 mg. As for vitamin D, people younger than 50 should get 400 to 800 international units (IU) per day, while older adults need 800 to 1,000 IU.

The advice on vitamin D does vary, however, with some groups recommending more. According to the Institute of Medicine, the safe upper limit of vitamin D is 4,000 IU per day for most adults.


Clinical fractures of the elderly represent a worldwide public health problem that leads to illness and social burden. The patients with osteoporosis in the European Union were estimated to be 27.5 million in 2010, and 3.5 million new fragility fractures were sustained.1 In Asia, the average cost of osteoporotic fractures accounted for 18.95% of the countries’ 2014 gross domestic product/capita and increased annually.2–4 

The overall prevalence of osteoporosis and low bone mass in non-institutional population over the age of 50 years in the USA was estimated at 10.3% and 43.9%, respectively, which means that 10.2 million elderly people had osteoporosis and 43.4 million people had low bone mass in 2010.5 

With the demographic trend of ageing and the predicted increase in life expectancy, the cost of fracture treatment is expected to rise.

Dietary allowances for calcium range from 700 to 1200 mg/day and vitamin D of 600–800 IU/day have long been recommended for the prevention of osteoporotic fractures in the elderly.6 7 The supplements of calcium and vitamin D are commonly taken to maintain bone health.

However, the previous randomised controlled trials (RCTs) and meta-analyses concerning vitamin D, calcium or their combination for fractures yielded different efficacy outcomes.

For instance, two meta-analyses demonstrated calcium or vitamin D supplementation alone has a small benefit on bone mineral density, but no clinically important to prevent fractures,8 9 while an updated meta-analysis and a pooled analysis found calcium plus vitamin D supplementation can significantly reduce hip fractures by 30% and total fractures by 15%.10 11 

Two RCTs reported that low dose of vitamin D supplementation (<800 IU/day) can reduce the incidence of falls12 and may prevent fractures without adverse effects,13 but other RCTs showed no significant reduction in the incidence of hip or other peripheral fractures,14 15 and its possible effects were seen only in patients with initial calcium insufficiency.

Based on the evidence from meta-analysis, Bischoff-Ferrari et al 16 illustrated that high-dose vitamin D supplementation (≥800 IU/day) not only reduced the risk of falls and hip fractures but also prevented non-vertebral fractures. In contrast, a study reported annual high-dose oral vitamin D resulted in an increased risk of falls and fractures.17 On the other hand, low-dose calcium supplementation (<800 mg/day) effectively led to a sustained reduction in the rate of bone loss18 and turnover. Although it was also reported that the high dose of calcium (≥800 mg/day) was associated with a lower risk of clinical fractures.19 

The high-dose calcium with high-dose vitamin D cannot prevent fractures according to the evidence from reported RCT,20 but a meta-analysis supported their combination can prevent bone loss and significantly reduce the risk of hip fractures and all osteoporotic fractures.21 Thus, it is challenging to conclude a dose-response relation between the intakes of vitamin D, calcium or their combination and the main outcomes in these heterogeneous literature.

Therefore, this study was designed to compare the fracture risk using different concentrations of vitamin D, calcium or their combination and comprehensively evaluate the optimal concentration to guide clinical practice and public prevention in community-dwelling older people.

Discussion

Vitamin D supplementation and calcium are suggested as interventions to treat and prevent fracture. We found the previous meta-analyses and RCTs are critically inconsistent in efficacy of different doses of vitamin D with calcium on fractures.

Results of this meta-analysis showed that calcium, calcium plus vitamin D and vitamin D supplementation alone were not significantly associated with a lower incidence of hip, vertebral or total fractures in community-dwelling older adults. Sensitivity analyses that excluded low-quality trials and studies that exclusively enrolled patients with particular medical conditions did not alter these results.

A meta-analysis conducted by Jia-Guo Zhao et al 46 showed that no significant difference was found in the incidence of hip or other fractures, which was similar to our result. However, the object of Zhao’s study was to investigate whether calcium, vitamin D or combined calcium and vitamin D supplement are associated with a lower fracture incidence, while our study was designed to evaluate the optimal concentration of them. Meanwhile, in Zhao’s meta-analysis, the participants of the included study reported by Massart47 were adult maintenance haemodialysis patients, which may result in the imbalance of calcium in the body. Patients on haemodialysis may also be receiving 1,25-dihydroxyvitamin D, which may affect their response to vitamin D supplementation.

So we did not include that trial in our network meta-analysis. What’s more, we didn’t include studies that lasted less than a year because we thought this time frame was too short to see antifracture efficacy. And we suspected that a network meta-analysis might be a more suitable choice concerning all these different interventions mixed.

Bischoff-Ferrari et al 48 reported that high-dose vitamin D supplementation (≥800 IU/day) played an important role in the reduction of the risk of falls and hip fractures as well as prevented non-vertebral fractures in adults aged 65 years or older.

However, their findings may have been influenced by the trial of Chapuy et al,49 which only enrolled participants living in an institution. What’s more, differences in conclusions of previous meta-analyses and the current meta-analysis were due to the recently published trials, which reported neutral or harmful associations of vitamin D supplementation and fracture incidence more and more. Study findings here indicated that vitamin D might result in a higher risk for hip fracture, but this conclusion did not reach statistical significance. This finding may be attributable to lack of statistical power in this meta-analysis.

Most recently, there was a meta-analysis published in the Lancet by Bolland et al,50 whose findings suggested that vitamin D supplementation does not prevent fractures or falls or has clinically meaningful effects on bone mineral density. Although it was similar to our study to some extent, they are really different.

First, we only included community-dwelling older people. We found that some meta-analyses equated community-dwelling older people with those in nursing institution. The lack of exercise, dietary intake and exposure to sunlight made people in nursing institution turned more susceptible to the use of supplements including vitamin D, calcium or their combination.

Although the studies involving participants living in nursing institution were only a small part, but it could change the whole outcomes and produce false-positive results. We found only Avenell’s study paid attention to this question when they conducted a subgroup analysis, but they did not discuss separately.

Meanwhile, we only enrolled adults aged older than 50 years and trial duration more than 1 year to reduce the statistical heterogeneity in network meta-analysis. Furthermore, the current analyses included calcium supplementation, where the Bolland’s study focused on vitamin D.

However, possible limitations of this study protocol include potential missing data and meta-biases, heterogeneity, which may limit the quality of evidence. Some RCTs were of poor quality and, for example, used unclear allocation concealment.

So we made a sensitivity analysis by excluding low-quality trials. Meanwhile, some study characteristics such as baseline serum 25-hydroxyvitamin D concentrations might be to contribute heterogeneity, so future analyses are still needed to explore this potential heterogeneity.

What’s more, we combined bolus dosing by injection with oral supplements taken daily/monthly/yearly, which might have different effects on vitamin D status in the body. In addition, the report ignored the effect of treatment with vitamin D on plasma 25-hydroxyvitamin D concentrations and subtypes of fracture, such as pathologic fractures; this work does not necessarily preclude any benefit of vitamin D and calcium supplementation in older, frail individuals.

Conclusions

In this meta-analysis of randomised clinical trials, we found that the use of different concentrations of vitamin D, calcium or their combination in community-dwelling older adults was not associated with a lower risk of fractures. Our findings may not support the routine use of these supplements in community-dwelling older people.


More information: The National Osteoporosis Foundation has more on calcium and vitamin D.

Pang Yao et al. Vitamin D and Calcium for the Prevention of Fracture, JAMA Network Open (2019). DOI: 10.1001/jamanetworkopen.2019.17789

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