0
We're unable to sign you in at this time. Please try again in a few minutes.
Retry
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
Retry
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Original Investigation |

Treatment of Vitamin D Insufficiency in Postmenopausal Women A Randomized Clinical Trial

Karen E. Hansen, MD, MS1; R. Erin Johnson, BS1,2; Kaitlin R. Chambers, BS1; Michael G. Johnson, MS1; Christina C. Lemon, MS, RD, CD1; Tien Nguyen Thuy Vo, MS3; Sheeva Marvdashti, BS1
[+] Author Affiliations
1Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison
2Quality and Patient Safety Analysis, Saint Luke’s Health System, Kansas City, Missouri
3Department of Computing and Biometry, University of Wisconsin College of Agriculture and Life Sciences, Madison
JAMA Intern Med. 2015;175(10):1612-1621. doi:10.1001/jamainternmed.2015.3874.
Text Size: A A A
Published online

Importance  Experts debate optimal 25-hydroxyvitamin D (25[OH]D) levels for musculoskeletal health.

Objective  To compare the effects of placebo, low-dose cholecalciferol, and high-dose cholecalciferol on 1-year changes in total fractional calcium absorption, bone mineral density, Timed Up and Go and five sit-to-stand tests, and muscle mass in postmenopausal women with vitamin D insufficiency.

Design, Setting, and Participants  This randomized, double-blind, placebo-controlled clinical trial was conducted at a single center in Madison, Wisconsin, from May 1, 2010, through July 31, 2013, and the final visit was completed on August 8, 2014. A total of 230 postmenopausal women 75 years or younger with baseline 25(OH)D levels of 14 through 27 ng/mL and no osteoporosis were studied.

Interventions  Three arms included daily white and twice monthly yellow placebo (n=76), daily 800 IU vitamin D3 and twice monthly yellow placebo (n=75), and daily white placebo and twice monthly 50,000 IU vitamin D3 (n=79). The high-dose vitamin D regimen achieved and maintained 25(OH)D levels ≥30 ng/mL.

Main Outcomes and Measures  Outcome measures were 1-year change in total fractional calcium absorption using 2 stable isotopes, bone mineral density and muscle mass using dual energy x-ray absorptiometry, Timed Up and Go and five sit-to-stand tests, functional status (Health Assessment Questionnaire), and physical activity (Physical Activity Scale for the Elderly), with Benjamini-Hochberg correction of P values to control for the false discovery rate.

Results  After baseline absorption was controlled for, calcium absorption increased 1% (10 mg/d) in the high-dose arm but decreased 2% in the low-dose arm (P = .005 vs high-dose arm) and 1.3% in the placebo arm (P = .03 vs high-dose arm). We found no between-arm changes in spine, mean total-hip, mean femoral neck, or total-body bone mineral density, trabecular bone score, muscle mass, and Timed Up and Go or five sit-to-stand test scores. Likewise, we found no between-arm differences for numbers of falls, number of fallers, physical activity, or functional status.

Conclusions and Relevance  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. We found no data to support experts’ recommendations to maintain serum 25(OH)D levels of 30 ng/mL or higher in postmenopausal women. Instead, we found that 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.

Trial Registration  clinicaltrials.gov Identifier: NCT00933244

Figures in this Article

Sign in

Purchase Options

• Buy this article
• Subscribe to the journal
• Rent this article ?

Figures

Place holder to copy figure label and caption
Figure 1.
Participant Flow Diagram

The calcium isotope doses were not recorded in 2 individuals, and a urine sample was mishandled in 1 individual. Muscle tests were not performed in 4 individuals because of pain and/or an injury. 25(OH)D indicates 25-hydroxyvitamin D; TFCA, total fractional calcium absorption; BMD, bone mineral density.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 2.
Serum 25-Hydroxyvitamin D (25[OH]D) Levels by Treatment Assignment

Serum 25(OH)D levels were summarized using mean (SD) and compared across treatment arms by analysis of variance, with correction of P values to control for the false discovery rate using the Benjamini and Hochberg method.21 The 25(OH)D levels were not significantly different across treatment groups at the screening (P = .89) and randomization (P = .89) visits. At all subsequent visits, serum 25(OH)D levels were significantly different (P < .001) across all 3 treatment arms. Pairwise comparisons likewise had P < .001. To convert 25(OH)D to nanomoles per liter, multiply by 2.496.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 3.
Annualized Percent Change in Bone Mineral Density by Treatment Assignment

We found no significant between-arm differences for the change in spine, mean total-hip, mean femoral neck, or total-body bone mineral density. Kruskal-Wallis tests were used to calculate the overall P value, with correction of P values to control for the false discovery rate using the Benjamini and Hochberg method.21

Graphic Jump Location

Tables

References

Correspondence

CME


You need to register in order to view this quiz.
Submit a Comment
Primary Results Not Included in Manuscript
Posted on September 2, 2015
Michael P. Carson MD, Nishita Parikh MD
Jersey Shore University Medical Center
Conflict of Interest: None Declared
Dr. Parikh and I decided to review this article for our residency's journal club using the Critical Appraisal tool from the Oxford Center for Evidence Based Medicine (www.cebm.net). We were frustrated that the results for the primary endpoint of Fractional Calcium Absorption were not included in the primary document, to which we have access via our hospital library, but in \"Supplement 2\" that must be obtained via an interlibrary loan. We are confused why the authors, editors and/or reviewers would make it difficult for a clinician to critically review this article in an efficient manner. However, it was an interesting lesson for our residents as the first question I ask in our journal club is \"Was it easy to read and interpret?\".
Submit a Comment

Multimedia

Some tools below are only available to our subscribers or users with an online account.

12,200 Views
9 Citations
×

Sign in

Purchase Options

• Buy this article
• Subscribe to the journal
• Rent this article ?

Related Content

Customize your page view by dragging & repositioning the boxes below.

See Also...
Articles Related By Topic
Related Collections
PubMed Articles
Jobs
brightcove.createExperiences();