One year of high-dose vitamin D treatment results in no clinically meaningful benefit for postmenopausal women with vitamin D insufficiency, according to a randomized controlled clinical trial published in the October issue of JAMA Internal Medicine.
“In postmenopausal women with vitamin D insufficiency, defined as a serum 25(OH)D level < 30 ng/mL…we found no musculoskeletal benefits of raising serum vitamin D levels over 30 ng for 1 year,” commented first author Karen Hansen, MD, an associate professor at the University of Wisconsin in Madison.
“Our study does not support the widely held opinion that vitamin D levels must be > 30 ng/mL for optimal musculoskeletal health,” she noted.
Simply taking vitamin D “at doses recommended by the Institute of Medicine will prevent vitamin D deficiency,” she advised.
Vitamin D insufficiency can contribute to osteoporosis by decreasing calcium absorption, leading to hyperparathyroidism, increased bone resorption, and decreased bone-mineral density.
Controversy reigns among experts, however, about the optimal level of vitamin D for musculoskeletal health. Some assert that 25(OH)D levels should be ≥ 30 ng/mL and that levels below this cutoff constitute vitamin D insufficiency. The US Institute of Medicine, on the other hand, advises that 25(OH)D levels should be ≥ 20 ng/mL.
However, even the lower-dose vitamin D group in this study did not experience appreciable benefits, notes Deborah Grady, MD, MPH, a professor at the University of California, San Francisco, in an accompanying editor’s note.
“Neither dose of cholecalciferol improved bone density, strength, muscle mass, functional status, or fall rate,” she concluded, “It is possible that treatment beyond 1 year would result in better outcomes, but these data provide no support for use of higher-dose cholecalciferol-replacement therapy or indeed any dose of cholecalciferol compared with placebo.”
No Clinically Meaningful Differences
Dr Hansen and colleagues say they designed a clinical trial to directly address the ongoing controversy about optimal vitamin D levels for musculoskeletal health.
The randomized double-blind placebo controlled study took place at a single center in Madison, Wisconsin from May 2010 to July 2013. Participants included 230 postmenopausal women aged ≤ 75 years. Women did not have osteoporosis and had baseline 25(OH)D levels measuring 14 to 27 ng/mL. The study excluded women who had used bone-active medications in the past 6 months and who had comorbid conditions that could affect calcium absorption or skeletal health, including diabetes.
Researchers randomized women to one of three treatment arms:
- Placebo: Daily white placebo and twice-monthly yellow placebo pills (n = 76).
- Low-dose vitamin D: Daily 800 IU vitamin D3 and twice-monthly yellow placebo pills (n = 75).
- High-dose vitamin D: Daily white placebo and twice-monthly 50,000 IU vitamin D3 pills (n = 79).
Researchers measured total fractional calcium absorption using the gold standard dual stable calcium isotopes method and 25 (OH)D levels with high-performance liquid mass spectrometry.
They assessed mobility and muscle strength using the Timed Up and Go (TUG) tests and sit-to-stand assessments and functional status using the modified Stanford Health Assessment Questionnaire and Physical Activity for the Elderly Scale. Women self-reported pain and adverse events like falls, fractures, and hospitalizations. Participants also received sunscreen to minimize increases in vitamin D levels due to sun exposure.
Adherence to therapy was about 100% in all participants, and all women in the high-dose arm maintained 25(OH)D levels ≥ 30 ng/mL.
Controlling for baseline calcium absorption, results at 1 year showed that absorption increased by 1% in the high-dose group and decreased by 2% in the low-dose group and by 1.3% in the placebo group (P = .005 and .03, respectively, vs high-dose arm).
Results showed no differences between the three groups concerning bone-mineral density in the spine, hip, femoral neck, and total body. Likewise, all three groups had similar trabecular bone scores, muscle mass, Timed Up and Go scores, sit-to-stand test scores, number of falls, number of women who fell, physical activity, and functional status.
In a subset of women, measurements of bone turnover were also comparable for the three groups.
Ninety percent of participants were white, which could limit the generalizability of the study’s results, say the researchers. In addition, the study lasted only 1 year.
Longer exposure to high-dose vitamin D could have had a larger effect on bone-mineral density, the authors point out.
Nevertheless they conclude, “High-dose cholecalciferol therapy increased calcium absorption, but the effect was small and did not translate into beneficial effects on bone-mineral density, muscle function, muscle mass, or falls,” adding that the study results “do not justify the common and frequently touted practice of administering high-dose cholecalciferol to older adults to maintain serum 25(OH)D levels of 30 ng/mL or greater.”
And in fact, they add, low- and high-dose cholecalciferol were equivalent to placebo in their effects on bone and muscle outcomes in this cohort of postmenopausal women with 25(OH)D levels less than 30 ng/mL.
In her editor’s note, Dr Grady agreed that although the trial is “informative,” the results didn’t show any “clinically meaningful” differences after 1 year of either therapy, compared with placebo.
Dr Hansen reports working as a local principal investigator for a clinical trial sponsored by Takeda. Disclosures for the coauthors are listed in the paper. Dr Grady reports no relevant financial relationships.