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Researchers share insights into vitamin D, calcium for osteoporotic fracture prevention
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The general practice of taking vitamin D and calcium supplements to prevent osteoporosis and osteoporotic fractures is starting to be looked at more closely, and new evidence is coming to light that suggests taking these dietary supplements may not help the general population build better bone health. This practice may even increase the risks of cardiovascular disease and other health problems, according to physicians who spoke with Orthopaedics Today Europe.
Karl Michaëlsson, MD, who has researched the role that vitamin D and calcium may play in bone health, said new evidence has emerged that suggests that taking vitamin D and calcium supplements may have no effect on improving bone mineral density (BMD). In fact, it may actually increase the risk of some health complications.
“It is a rather frustrating field because it is complex. There are many diverse opinions in the field, and it makes it complicated. At present, do you have a benefit from vitamin D supplements alone for the prevention of fractures? I would say no,” Michaëlsson told Orthopaedics Today Europe. “The most convincing arguments are from studies done by a New Zealand study group. They did studies of randomized clinical trials that have evaluated the effect of vitamin D, for example, on BMD. Their conclusion was it had no effect in general on BMD,” he said.
Ian R. Reid, MD, of Auckland, New Zealand did those studies.
Effective in institutionalized elderly
However, there is evidence to support the practice of institutionalized elderly patients with low vitamin D and calcium levels taking additional supplements to increase their levels and prevent osteoporotic fractures. But, in terms of the general public, there is little to no benefit in taking these supplements, Michaëlsson said.
For example, most American women older than 40 years of age who take vitamin D and calcium supplements see no effect from the additional supplements. It is clear in some cases, the supplements can increase the risk for myocardial infarction and cardiovascular (CV) problems, he said.
“I know the majority of women in the United States do take calcium and vitamin D supplements if they are 40 [years] or older, and if they have benefits from the supplements, it is very unclear at the present. What we need to also know is that calcium supplements, with or without vitamin D, might have an impact on your CV risk and increase your risk of myocardial infarctions. It is a modest increase in risk, and it is much discussed, but I think again, Reid’s research group has done a good job. Because of this part, I would not recommend calcium and vitamin D supplementation for the general population if they have a normal, mixed diet,” Michaëlsson said.
Too much calcium increases risks
In a 2014 study, Michaëlsson and colleagues investigated the effect of milk intake on 61,433 women who were 39 years to 74 years old at baseline and 45,339 men who were 45 years to 79 years old at baseline. They concluded high milk intake led to higher mortality in one cohort of women and in another cohort of men. Furthermore, it led to a higher fracture incidence in the women studied.
Michaëlsson said a recommendation should not be made from this study alone, and this will lead to additional research.
Controversial field of research
The topic of what to tell patients about taking these supplements is controversial and the evidence is varied, according to Federica Rosso, MD, who noted that a systematic review of 53 studies focused on this area showed vitamin D alone is unlikely to prevent fractures in the elderly. However, she discussed a study by Kevin Zarca, MD, and colleagues from 2014 that involved a cost-effectiveness analysis of four vitamin D supplementation strategies for primary prevention of hip fracture.
“They concluded that population screening for vitamin D deficiency followed by vitamin D supplements is a cost-effective strategy for preventing hip fracture in elderly people. Some authors evaluated the relationship between vitamin D and BMD, concluding that higher calcium and vitamin D intakes were associated with higher total hip and femoral neck BMD in adults. I think people affected by vitamin D deficiency can benefit from supplementation,” she told Orthopaedics Today Europe.
Karsten Dreinhöfer, MD, an Orthopaedics Today Europe Editorial Board member, said vitamin D supplements alone can lessen the risk of some osteoporotic fractures, but this effect is clearer in some situations than others.
He said results several randomized, controlled trials indicate that supplementation with vitamin D reduces rates of bone loss in older women. In three recent systemic reviews and meta-analyses, supplementation with only vitamin D was associated with a reduction in non-vertebral fracture risk.
“For example, Bischoff-Ferrari et al found a reduction of 20% for non-vertebral fractures. The effects of vitamin D supplementation on hip fractures is less conclusive, probably related to lower incidence of hip fracture than of non-vertebral fractures. In some analyses, a hip fracture reduction was found, but not in other studies. Apart from that, lower 25-OH vitamin D levels were found in persons with a hip fracture, suggesting that an increase of 25-OH vitamin D levels in these persons might reduce hip fracture risk. In addition, a meta-analysis suggests that vitamin D supplementation of greater than 700 IU to 800 IU/day decreases falls incidents by 19% in older individuals with a history of vitamin D deficiency,” Dreinhöfer said.
Risk from excessive vitamin D
Vitamin D deficiency is recognized as a worldwide epidemic, according to Dreinhöfer. More than 60% of postmenopausal women have 25-OH vitamin D serum levels that are deficient, and that includes populations in sunny countries such as Spain, Australia and the Middle East region.
However, extra vitamin D intake, Dreinhöfer said, can have a negative impact on the health of a patient who consumes too much of the vitamin.
“Besides the reducing effects on fracture risk of calcium and vitamin D supplementation, [the supplements] also might create some side effects. Vitamin D, with or without calcium supplementation, increases the risk of hypercalcemia, gastrointestinal side-effects (obstipation), and increases the incidence of renal calculi or renal insufficiency,” he said.
“It is important for us to avoid the impression there is nothing you can do in preventing fractures, but only treating them. There is clear evidence that the adequate intake of calcium and vitamin D, as well as physical activities and avoidance of smoking and excess alcohol consumption can prevent fractures,” Dreinhöfer said. “We still believe in the German network of scientific osteology societies that vitamin D and calcium are important for bone health and it is critical to have an appropriate daily intake, either by diet or, if this not sufficient, by supplements.”
Calcium supplementation
The case for calcium supplementation is a little different. Although vitamin D supplements alone may not necessarily prevent fractures, when combined with calcium supplements they may be able to prevent fractures in postmenopausal women, Rosso said.
Like Michaëlsson, she said there have been recent correlations of high calcium levels to increased risk of heart attacks.
“I think adequate calcium levels are a fundamental aspect of any osteoporosis prevention or treatment program, and it is confirmed by the recent guidelines. The goal should be to achieve adequate calcium with diet alone, if possible. Physicians should avoid hypercalcemia because of its effect. Besides, some authors suggest that doses over of 1,000 mg to 1,300 mg daily for most adults might increase the chance of heart attack,” she said.
Calcium alone is not enough
Calcium supplements alone, Dreinhöfer said, have little evidence backing their effectiveness in increasing an individual’s BMD.
“While there is some evidence suggesting that calcium supplementation has beneficial effects on BMD, the influence of supplementation with calcium only on the reduction of vertebral and non-vertebral fractures is mostly non-significant. Calcium supplementation alone was even shown to increase the risk of hip fractures. In addition, calcium supplementation alone might increase the risk for cardiovascular events,” he said.
Calcium supplements may not be useful, as the excess calcium in our bodies is excreted through the kidneys, Huub J.L. van der Heide, MD, told Orthopaedics Today Europe.
The best way to avoid osteoporosis and osteoporotic fractures is to emphasize bone health and bone quality at a young age, not by taking supplements later on in life, he said.
“In the normal ageing skeleton, the BMD decreases and patients are at increased risk for fragility fractures. The best way to prevent fragility fractures is to acquire good bone quality at young age and prevent decline when getting older. As bone is the largest storage place for calcium in our body, calcium will be removed from the bone when the calcium levels in our blood decrease, so with a low calcium dietary intake, the calcium will be removed and the BMD will decrease.”
He noted the opposite is not true.
“Our dietary calcium intake is not completely stored in our bone. With a high calcium blood level, the uptake in the intestine will be decreased and the renal clearance will be increased, so when we take too much calcium, it will not help,” van der Heide said.
Because excess calcium is excreted through the kidneys, van der Heide said individuals with renal failure could be in danger if they take too much calcium.
Diet, not supplements
When it comes to bone homeostasis, vitamin D is important because it facilitates the calcium uptake in the bone and from the intestine. Among elderly patients who present with an osteoporotic fracture, van der Heide noted more than half of them have vitamin D levels that are too low.
“Vitamin D intake should be encouraged. As calcium and vitamin D are closely related in bone homeostasis, it is important to correct both deficiencies,” he said. “However, in my view, the focus should not be on supplements. But, the general tendency in our overdeveloped countries is to take a vitamin C tablet instead of an orange,” he said.
Orthopaedic surgeons and their patients need to know that supplements may not be the best route for someone with low calcium and vitamin D levels. There are other factors and approaches for patients to take to improve their bone quality, according to van der Heide.
“The most important factors for both a well-developed skeleton and prevention of decline are an active lifestyle, sufficient dietary intake of especially calcium and vitamin D, low alcohol intake and cessation of smoking. Furthermore, it is important to realize that an increase in BMD, or slowing down the decrease, does not necessarily mean that strength also increased. So, in my opinion, vitamin D and calcium supplements can help in the decline of our BMD, but other factors play an important role, such as prevention of falls, keeping mobility, preventing sarcopenia and so on,” he said.
Michaëlsson agreed there may be other more important factors for overall bone health and the prevention of osteoporotic fractures than taking supplements. Changes in lifestyle and health are some proven ways to prevent osteoporosis and osteoporotic fractures, he said.
“What is proven is you should stop smoking, for example, be physically active and do not lose too much weight. Do not get too thin. Regarding diet, have a normal mixed diet, and you will be fine for the primary prevention of fractures,” Michaëlsson said. – by Robert Linnehan
- References:
- Bischoff-Ferrari, et al. N Engl J Med. 2012;doi:10.1056/NEJMoa1109617.
- Michaëlsson K, et al. BMJ. 2014;doi:10.1136/bmj.g6015.
- Reid IR. Nutrients. 2013;doi:10.3390/nu5072522.
- Reid IR, et al. Lancet. 2014;doi:10.1016/S0140-6736(13)61647-5.
- Zarca K, et al. Osteoporos Int. 2014;doi:10.1007/s00198-014-2698-1.
- For more information:
- Karsten Dreinhöfer, MD, can be reached at Charité Universitätsmedizin and Medical Park Berlin Humboldtmühle, An der Mühle 2-9, 13507 Berlin, Germany; email: Karsten.Dreinhoefer@charite.de.
- Huub J.L. van der Heide, MD, can be reached at Leiden Universitair Medisch Centrum, Albinusdreef 2, 2333 ZA Leiden, Netherlands; email: H.J.L.van_der_Heide@lumc.nl.
- Karl Michaëlsson, MD, can be reached at Department of Surgical Sciences, Orthopaedics and Uppsala Clinical Research Center, Uppsala University, 751 85 Uppsala, Sweden; email: karl.michaelsson@surgsci.uu.se.
- Federica Rosso, MD, can be reached at AO Mauriziano Umberto I, Largo Turati 62, 10128 Torino, Italy; email: federica.rosso@yahoo.it.
Disclosures: Dreinhöfer, van der Heide and Rosso report no relevant financial disclosures. Michaëlsson reports he received research support from the Swedish Research Council.
Should orthopaedic surgeons be discussing vitamin D and calcium supplements with their patients?
Vitamin D insufficiency is widespread
A large body of randomized trial evidence exists on the use of calcium and/or vitamin D supplements for bone health. In community-dwelling adults, vitamin D alone does not reduce fracture risk. Calcium supplements of 1 g/day, with or without co-administered vitamin D, reduces the relative risk of fracture by about 10%, but also increases the relative risk of myocardial infarction by 24% and stroke by 15%, and almost doubles the risk of admission to hospital for gastrointestinal symptoms. In older adults treated with calcium supplements for 5 years, the number needed to treat to prevent a fracture (302) exceeds the number needed to harm in causing a vascular event (178). For generally healthy older adults, therefore, calcium and vitamin D supplements do not safely reduce fracture risk.
Recommendations to achieve threshold levels of dietary calcium intake for bone health (often 1,000 mg/day to 1,200 mg/day) are not supported by existing evidence, which is almost exclusively from observational studies.
Calcium and vitamin D supplements are recommended by some authorities as adjuncts to anti-resorptive agents, such as bisphosphonates, in patients with osteoporosis. However, no rigorous evidence exists that they act synergistically with such agents to reduce fracture risk.
Two randomized trials of combined calcium and vitamin D supplementation conducted in frail elderly institutionalized women reported 40% reductions in the relative risk of hip fracture. It is not known whether this effect is attributable to vitamin D, calcium or their combination. It is certainly reasonable to treat sunlight-deprived (housebound and/or institutionalized) elderly people with vitamin D supplements.
Andrew Grey, MBChB, MD, is an endocrinologist at the University of Auckland and Auckland District Health Board, in Auckland, New Zealand.
Disclosure: Grey reports no relevant financial disclosures.
Reduces fracture risk
Fractures in aging individuals may be the first step on a path leading to additional fractures, pain, disability and premature death. Among those who fracture their hip, about 10% to 15% will have a new hip fracture, and 20% to 25% will have a fracture of any type during the next 5 years. The excess mortality after a hip fracture is high, and this pertains particularly to the younger old, where more life-years could be saved by preventing this serious injury.
Ensuring an adequate supply of calcium and vitamin D is advocated in all secondary fracture prevention programs. Vitamin D insufficiency is widespread in the frail, elderly hip fracture patients, and nutritional status is likely to deteriorate further during immobilization after a fracture. Therefore, prevention should be initiated, and the sooner the better. Dairy products and oily fish constitute the major natural dietary sources of calcium and vitamin D, respectively. Dermal vitamin D synthesis depends on season, outdoor activity and clothing. Therefore, a few simple questions will help identify whether an insufficient supply of calcium or vitamin D may be suspected.
If not covered through the diet, supplements should be recommended — typically 800 IU of vitamin D and 1,000 mg of calcium, alternatively 500 mg if the patient reports a reasonable dairy intake. This level is regarded safe and practical and does not require determination of vitamin D in blood.
Kristin Holvik, PhD, RD, is a senior scientist at the Norwegian Institute of Public Health, Division of Epidemiology, in Oslo.
Disclosure: Holvik reports no relevant financial disclosures.