Study Title:

Vitamin D, Calcium, and Bone Health

Study Abstract

Objectives To identify participants’ characteristics that influence the anti-fracture efficacy of vitamin D or vitamin D plus calcium with respect to any fracture, hip fracture, and clinical vertebral fracture and to assess the influence of dosing regimens and co-administration of calcium.
Design Individual patient data analysis using pooled data from randomised trials.

Data sources Seven major randomised trials of vitamin D with calcium or vitamin D alone, yielding a total of 68 517 participants (mean age 69.9 years, range 47-107 years, 14.7% men).

Study selection Studies included were randomised studies with at least one intervention arm in which vitamin D was given, fracture as an outcome, and at least 1000 participants.

Data synthesis Logistic regression analysis was used to identify significant interaction terms, followed by Cox’s proportional hazards models incorporating age, sex, fracture history, and hormone therapy and bisphosphonate use.

Results Trials using vitamin D with calcium showed a reduced overall risk of fracture (hazard ratio 0.92, 95% confidence interval 0.86 to 0.99, P=0.025) and hip fracture (all studies: 0.84, 0.70 to 1.01, P=0.07; studies using 10 µg of vitamin D given with calcium: 0.74, 0.60 to 0.91, P=0.005). For vitamin D alone in daily doses of 10 µg or 20 µg, no significant effects were found. No interaction was found between fracture history and treatment response, nor any interaction with age, sex, or hormone replacement therapy.

Conclusion This individual patient data analysis indicates that vitamin D given alone in doses of 10-20 µg is not effective in preventing fractures. By contrast, calcium and vitamin D given together reduce hip fractures and total fractures, and probably vertebral fractures, irrespective of age, sex, or previous fractures

From press release:

Taking both calcium and vitamin D supplements on a daily basis reduces the risk of bone fractures, regardless of whether a person is young or old, male or female, or has had fractures in the past, a large study of nearly 70,000 patients from throughout the United States and Europe has found.

The study included data published in 2006 from clinical trials conducted at UC Davis in Sacramento as part of the Women's Health Initiative (WHI). It appears online in this week's edition of the British Medical Journal.

"What is important about this very large study is that goes a long way toward resolving conflicting evidence about the role of vitamin D, either alone or in combination with calcium, in reducing fractures," said John Robbins, professor of internal medicine at UC Davis and a co-author of the journal article. "Our WHI research in Sacramento included more than 1,000 healthy, postmenopausal women and concluded that taking calcium and vitamin D together helped them preserve bone health and prevent fractures. This latest analysis, because it incorporates so many more people, really confirms our earlier conclusions."

Led by researchers at Copenhagen University in Denmark, Robbins and an international team of colleagues analyzed the results of seven large clinical trials from around the world to assess the effectiveness of vitamin D alone or with calcium in reducing fractures among people averaging 70 years or older. The researchers could not identify any significant effects for people who only take vitamin D supplements.

Among the clinical trial results analyzed was Robbins' WHI research, which was part of a 15-year, national program to address the most common causes of death, disability and poor quality of life in postmenopausal women such as cardiovascular disease, cancer and osteoporosis. Those trials were primarily designed to study the effect of calcium and vitamin D supplementation in preventing hip fractures, with a secondary objective of testing the supplements on spine and other types of fractures, as well as on colorectal cancer. The results were published in the Feb. 16, 2006 edition of the New England Journal of Medicine.

Fractures are a major cause of disability, loss of independence and death for older people. The injuries are often the result of osteoporosis, or porous bone, a disease characterized by low bone mass and bone fragility. The National Osteoporosis Foundation estimates that about 10 million Americans have osteoporosis; 80 percent of them are women. Four of 10 women over age 50 will experience a fracture of the hip, spine or wrist in their lifetime, and osteoporosis-related fractures were responsible for an estimated $19 billion in health-related costs in 2005.

"This study supports a growing consensus that combined calcium and vitamin D is more effective than vitamin D alone in reducing a variety of fractures," said Robbins. "Interestingly, this combination of supplements benefits both women and men of all ages, which is not something we fully expected to find. We now need to investigate the best dosage, duration and optimal way for people to take it."

Study Information

The DIPART (vitamin D Individual Patient Analysis of Randomized Trials) Group
Patient level pooled analysis of 68 500 patients from seven major vitamin D fracture trials in US and Europe
BMJ
2010 January

Full Study

http://www.bmj.com/cgi/content/full/340/jan12_1/b5463