More Fractures Seen When Vitamin D Is Consistently Low

Norra MacReady

April 15, 2014

Prolonged low levels of vitamin D increase long-term fracture risk in elderly women, a new study confirms.

Low serum vitamin D levels at baseline and at a 5-year follow-up examination were associated with a significantly increased incidence of hip fractures at a 10-year follow-up examination, lead author David Buchebner, PhD, and colleagues reported at the World Congress on Osteoporosis, Osteoarthritis and Musculoskeletal Diseases on April 4.

The findings suggest that "in the population sample of elderly women, vitamin D insufficiency sustained over 5 years was associated with increased 10-year risk of osteoporotic fracture," senior author Kristina Åkesson, MD, from the Clinical and Molecular Osteoporosis Research Unit at Lund University, Malmö, Sweden, said in a release about the study.

The results also "reinforce the importance of vitamin D deficiency and insufficiency in the setting of fracture risk," Andrea Singer, MD, clinical director of the National Osteoporosis Foundation and associate professor of medicine and obstetrics and gynecology, Georgetown University Medical Center, Washington, DC, told Medscape Medical News. She was not involved in the study.

Multiple Measurements of Vitamin D

Most previous research relied on a 1-time vitamin D measurement when determining the effects on bone health, Dr. Buchebner, also from the Clinical and Molecular Osteoporosis Research Unit, and colleagues state in the study abstract, published in Osteoporosis International. "However, in elderly women, relatively little is known about the effects of long-term hypovitaminosis D on bone health."

The study participants were 987 women enrolled in a prospective, Swedish population–based study of bone metabolism, bone mineral density, falling tendencies, and fracture incidence. All of the women were 75 years of age at baseline. Vitamin D status was determined by measuring serum 25-hydroxyvitamin D (25OHD).Levels greater than 75 nmol/L were considered high, those 50 to 75 nmol/L were intermediate, and those less than 50 nmol/L were low.

Of the original participants, 640 were available for the 5-year follow-up examination. Serum vitamin D levels were considered consistently low, intermediate, or high if they fell into the same category at both readings. Radiography was used to follow fracture incidence for 10 years starting from baseline. The researchers also gathered data using the Fracture Risk Assessment Tool (FRAX), which combines clinical risk factors with bone mineral density readings at the femoral neck to calculate a patient's 10-year risk for an osteoporotic fracture of the hip, spine, radius, or shoulder.

Among women with consistently low, intermediate, and high levels of 25OHD, 10-year hip fracture incidence rates were 20.6%, 9.9%, and 6.9%, respectively (P = 0.005 and P = 0.031). The proportions of women sustaining FRAX fractures were 26.2%, 30%, and 45.6% in the high, intermediate, and low 25OHD groups, respectively (P =.004 and P = .022).

Most of the fractures occurred between years 5 and 10 of the study (hip, 77%; FRAX, 64%). Time to first fracture did not differ among the groups, nor did the incidence of shoulder, radius, or vertebral fractures.

Can Vitamin D Supplementation Reduce Risk?

The findings did not surprise Dr. Singer. "Those of us who care for elderly women with osteoporotic fractures have long felt that vitamin D sufficiency is important for bone health, and that deficiency or insufficiency increases the risk of fracture," she told Medscape Medical News.

The real controversy lies in whether vitamin D supplementation can change fracture risk, Dr. Singers aid. "Adequate levels of vitamin D help increase calcium absorption from the gut, and both calcium and vitamin D are important in terms of bone health." Meta-analyses examining the effect of vitamin D supplementation on fracture and fall risk "depend on the amount of vitamin D that is given, so in most of the studies, patients needed at least 700 to 800 international units [IU] per day or more for us to see pooled results favoring supplementation compared to placebo." No changes were seen at lower doses in risk for hip fractures or falls.

The data also suggest that the combination of vitamin D and calcium is more effective "than just 1 nutrient alone," Dr. Singer said. The Institute of Medicine recommends 800 to 1000 IU of vitamin D daily for adults aged 50 years or older. The calcium recommendation is 1200 mg daily for women aged 51 years or older or men 71 years of age or older. For men younger than age 71, the recommendation is 1000 mg per day.

"There is not enough evidence for vitamin D without calcium," added James Judge, MD, clinical director of the American Geriatrics Society. "The evidence without calcium is not strong enough to omit it as part of your strategy."

Interpretation of the available data is difficult because the doses of vitamin D used in different studies range from 200 to more than 1000 IU per day, warned Dr. Singer. The patient's baseline vitamin D levels also may affect the findings."It's very difficult to look at the effect of single nutrients because there is so much interaction that occurs in the body, so creating a study to determine cause and effect with a single nutrient is very challenging. A lot of data suggest that while vitamin D and calcium clearly are important for bone health, they're not the only factors in play."

"This is a well-done, prospective study," said Dr. Judge, associate clinical professor of medicine at the University of Connecticut, Farmington, and senior medical director of Optum. "They had 2 measures and followed the patients prospectively for 10 years. Those are its strengths." When all the data are published, he believes "this will be a strong, epidemiological study that will support existing case-control studies that have shown a strong relationship between vitamin D and fractures." Dr. Judge was not involved in this research.

The remaining question, said Dr. Judge, is "Would intervening with the women with the lowest 25OHD levels decrease their risk of fractures?" He continued, "I believe the evidence suggests that the answer is yes. The working hypothesis is that vitamin D reduces fractures in elderly people by improving balance and reducing the risk of falls, rather than through its effect on bone density."

"Stay tuned for the evolving calcium recommendations," said Dr. Judge. "We know that at recommended blood levels, you absorb more calcium from the gut. And there is evolving work on how much calcium older people need when their vitamin D levels are in the recommended range."

The study authors and Dr. Judge have disclosed no relevant financial relationships. Dr. Singer consults, teaches for, or is on the advisory board or speakers' bureau of Actavis, Amgen, Eli Lilly, Mission Pharmacal, and Medtronic.

World Congress on Osteoporosis, Osteoarthritis and Musculoskeletal Diseases. Abstract OC19. Presented April 4, 2014.

Osteoporos Int. 2014;25(Suppl 2). Abstract OC19


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