Calcium and vitamin D to prevent fractures
Lancet. 2007 Aug 25;370(95880:657-66, Use of calcium or calcium in combination with vitamin D supplementation to prevent fractures and bone loss in people aged 50 years and older: a meta-analysis, Tang BM and others. PMID: 17720017. This study is a meta-analysis (a review of 29 trials that reported outcomes related to calcium or calcium plus vitamin D ingestion) for individuals older than 50 years that covered a 3 to 5 year period. There were 17 trials that reported fracture outcomes and 24 that reported bone mineral density (BMD) results, with some reporting both. There were 63,897 individuals in the combined studies, 92% were women with a mean age of 67.8 years. In 13 trials, participants received calcium and vitamin D, and in all others they received calcium-only supplementation. Of the trials reporting fracture outcome, calcium and calcium plus vitamin D were associated with a 12% risk reduction in all type fractures. Of the 24 trials reporting BMD, calcium and calcium plus vitamin D were reported to reduce bone loss by 0.54% at the hip and 1.19% in the spine. Trials with higher compliance showed a significantly greater risk reduction that did those with lower compliance rates. In trials with 80% or more compliance, there was a 24% risk reduction in fractures of all types. The addition of vitamin D to calcium did not change treatment significantly. People with low vitamin D serum concentration (< 25 nmol/L), had a greater risk reduction compared with those with normal serum vitamin D levels, but the result was not quite statistically significant (p=0.06). The treatment effect was greater for institutionalized individuals when compared to those living in the community (p=0.003). The treatment effect was also greater in participants whose daily calcium intake was low (< 700 mg/day). The treatment effect was also best with calcium doses of 1200 mg/day or more, or vitamin D doses of 800 IU or more, with the higher dose of calcium being more significant than the higher dose vitamin D. Only 14% of the participants had a greater than 1% increase in BMD. The effect of supplements on individuals aged 50-69 was only a 3% risk reduction, which increased to 11% in ages 70-79, and to 24% in ages greater than 80.
Here are some quotes from the authors: "Our meta-analysis has shown that calcium supplementation, alone or in combination with vitamin D, is effective in the preventive treatment of osteoporotic fracture. Over an average treatment duration of 3-5 years, the risk of fracture was reduced and was accompanied by a reduction of bone loss at the hip and spine." They also note, "The fracture risk reduction was greater in individuals who were elderly, lived in institutions, had a low body weight, had a low calcium intake, or were at high baseline risk than it was in others." They note, "However the treatment was less effective if compliance was poor. For calcium-only supplementation, a minimum dose of 1200 mg is needed for best therapeutic effect. For calcium in combination of vitamin D supplementation, a minimum dose of 800 IU of vitamin D is recommended." Here is a possibly important comment, "However, we would like to point out that our analysis was limited by the scarcity of data for vitamin D doses higher than 800 IU. It is possible that vitamin D does have a beneficial effect when the dose is large enough (ie, >800 IU)."
Editor's comments:
1. Compliance. In this study the best results were received when compliance rates for taking the supplements were 80% or greater. This is in agreement with recent studies that show similar results for bisphosphonate therapy, also requiring an 80% compliance rate. See a recent compliance Update on this site for details. Here is a recent study showing the effect of noncompliance on fracture rates which can be compared to the Lancet study above, Osteoporos Int. 2007 Sep 14; [Epub ahead of print], Loss of treatment benefit due to low compliance with bisphosphonate therapy, Penning-van Beest FJ and others. PMID: 17874028 In this study, less that 80% compliance resulted in a 45% increase in fracture rates for study participants. Here is another Update on this site relating the importance of compliance. In this study there was a 32% decrease in fractures for those patients who were compliant. Bottom line: clinicians need to monitor compliance with medications. If patients aren't taking them they are wasting their time and money, and, in many cases, the money of taxpayers or others in an insurance group.
2. Fracture rates. Here is an Update showing 51% to 83% reduction in fracture risk after taking teriparatide (Forteo). Here is a recent review in J Bone Miner Res. 2006 Feb;21(2):340-9, Anti-hip fracture efficacy of biophosphonates: a Bayesian analysis of clinical trials, Nguyen ND and others. PMID: 16526127. This Bayesian meta-analysis quantitatively reviewed data from 12 randomized clinical trials with 18,667 patients and found that bisphosphonate treatment was associated with a reduced risk for hip fracture by 42%. The absolute rate reduction was 52 hip fractures per 10,000 women (95% CrI, 4-110) for a period of 3-year treatment. The fracture rate reduction in the Lancet study above was 24% in the oldest, and best compliance group. It was near zero in the youngest or noncomplying groups. This information is for comparison purposes.
3. Calcium dose issues. Here is a quote from the 11th Newsletter, July 1999, regarding calcium absorption and dosage: "'Calcium absorption efficiency varies inversely as the logarithm of the size of the load.' Accordingly, if rather than taking a 1000-mg dose of calcium, it was divided into two doses of 500 mg each, 30% additional calcium would be absorbed. Or, if this 1000-mg dose was divided into four doses of 250 mg each, then 60% more calcium would be absorbed." All clinical trials mention only the total calcium dosage. If an individual takes the total 1,200 calcium supplement in one dose on an empty stomach, the absorbed dose might be half that of an individual who takes it in four small doses during the day with food. I recommend readers review this Newsletter for the valuable information there from Dr. Robert Heaney as he is one of the world's leading authorities on supplements and osteoporosis. Bottom line: Take calcium supplements with food in small doses several times daily--not all at once, or on an empty stomach. Note that a recent Update also mentions the importance of taking magnesium supplements along with calcium.
4. General comments on the Lancet study. The findings aren't new or earth shaking, but they reinforce what has been known regarding calcium and/or vitamin D supplements. They work best in older individuals, compliance with the dosing regimen is critically important, and the doses should be at least 1,200 mg/day for calcium and 800 IU/day for vitamin D. Best results with vitamin D supplements will be in individuals who have low serum vitamin D levels. The fracture risk reduction is not enough to justify taking only calcium and/or vitamin D for individuals with low BMD and great fracture risk, particularly younger people. Instead one of the approved osteoporosis medications should be taken. A very important issue is that for individuals in the 50-69 year-old group, there was essentially no benefit from the supplements. If you have osteoporosis and are in that age group you must use an approved osteoporosis medication to reduce your fracture risk. One other important issue that I don't see discussed in the paper, but that strikes me as significant, is that when discussing BMD, the authors only mention "reduction of bone loss" not "increase in bone density" when discussing the change in BMD in the treatment group. The goal with osteoporosis therapy is to increase bone density, not just to slow the loss of bone density. In all successful clinical trials of approved osteoporosis medications you will always note increased BMD, that is generally accompanied by loss of BMD in the control groups who are taking calcium and/or vitamin D supplements. In a normal clinical trial of, e.g., alendronate (Fosamax), one would expect about 4-5% increase in BMD per year. In the Lancet study only 14% of the participants had even a 1% or greater increase in BMD over the 3 to 5 year duration of the study.