Bisphosphonate therapy – long term use

Recently a study published by Drieling et al in JAGS 2017 described the results of a cohort study of 5120 older women with an average age of 80 yrs and at high fracture risk . This observational study from the Womens Health Initiative included 5120 women who had been using oral BP for at least 2 years and had a FRAX score of 1.5% or higher for 5 yrs. Women who had been on PTH , calcitonin or aromatase inhibitors were excluded. The average follow up data was available for 4 yrs.

10-13 yrs of oral bisphosphonate use was associated with higher risk of any clinical fracture then 2 yrs of use HR =1.29 , 95% CI 1.07-1.57.

There was no association between intermediate use and fracture risk. There are a number of limitations to this observational data including the fact that this study did not include a group without bisphosphonate use also compliance was not evaluated.

Oral BPs have been shown to significantly reduce the risk of vertebral and non vertebral fracture in randomized controlled trials. The extension studies of these fracture trials unfortunately were not powered to evaluate impact on fracture risk and currently we do not have long term data consistently demonstrating reductions in non vertebral fracture risk with long term BP use.

It appears that the optimal period of use for oral or IV bisphosphonates is 3-5 yrs with published randomized controlled trial data confirming reductions in fracture risk for vertebral , non vertebral and hip fracture with use for this time period. After the first 5 years of bisphosphonate use the fracture risk should be re-evaluated and bisphosphonate therapy should also be re-evaluated.

Osteoporosis Canada advises that all patients should have their treatment strategy reviewed by their physicians particularly after 5 years of use as long term use of bisphosphonates may not have the same risk benefit ratio as seen with short term use of up to 5 yrs.

On September 29, 2015, two research articles were published online in the British Medical Journal (BMJ) concerning the effect of calcium intake on bone mineral density (BMD) and fracture reduction. These have been widely reported in the media.

The full text of the Osteoporosis Canada response can be found on the website at http://www.osteoporosis.ca/calcium-intake-and-effect-on-bone-health-and-fracture-risk-reduction/

The following is a summary of the OC response.

The first study published in the BMJ summarizes the results of 59 earlier studies to evaluate the effects of calcium intake on BMD in people over the age of 50. According to this study, both extra dietary calcium intake and the use of calcium supplements were associated with small increases in BMD. A small reduction in fractures was observed with calcium supplementation. The authors concluded that calcium intake from dietary sources and supplements increase BMD similarly, but that this is unlikely to reduce fractures.

The second study explored whether calcium could reduce fractures. This study did not show a significant reduction in fracture risk in the large randomized trials with calcium supplementation.

The two studies significantly differed in both the numbers of people evaluated and in the quality of the assessments. They also differed in how fractures were identified. As a result, in order to better determine the effects of calcium supplementation on bone health, additional research is needed using well-designed, large, controlled studies.

Every cell in our body requires calcium in order to function normally. Inadequate calcium intake results in the release of calcium from our bones in order to meet our daily requirements. Because of this, Osteoporosis Canada continues to recommend 1000-1200 mg of calcium daily, preferably from dietary sources, and to use supplements only if this is not possible (in the form of calcium carbonate or calcium citrate).

Click here for more detailed information on Osteoporosis Canada’s nutritional recommendations

However, in individuals with osteoporosis or high fracture risk, there is no research evidence supporting the use of calcium supplements alone as a treatment to prevent fractures. Such individuals may require medication in addition to adequate calcium intake and vitamin D supplementation in order to reduce their fracture risk.

Click here for more information on drug treatments for osteoporosis

The National Osteoporosis Foundation and the American Society for Preventive Cardiology formed an expert panel and completed a detailed review of all published research evaluating the effects of calcium intake from food sources and or supplements with or without vitamin D on the risk of heart attacks, strokes and death.

The results of that review were published in the Annals of Internal Medicine by Kopecky and colleagues on October 25, 2016. The review confirms that there does not appear to be any harmful or beneficial effects of calcium and or vitamin D on the risk of heart disease or stroke or on the likelihood of death in healthy adults. The expert panel recommended that calcium intake from food and or be not greater than supplements 2000 mg or 2500 mg on a daily basis.

This position taken by the National Osteoporosis Foundation and the American Society for Preventive Cardiology supports the position of Osteoporosis Canada which advises Canadians to take in 1000 mg to 1200 mg of calcium daily from food sources. If this is not possible then Osteoporosis Canada advises that calcium supplements may be used to meet the daily calcium requirements. Osteoporosis Canada recommends discussing the need for additional calcium or vitamin D supplements with your physician as both nutrients are essential for achieving and maintaining optimal bone health.

Vitamin D supplementation has recently been evaluated in Switzerland in a small 1 year randomized clinical trial by Bischoff-Ferrari and colleagues. This study compared the effects of two “high” doses of vitamin D (60,000 IU of vitamin D3 per month or 24,000 IU vitamin D3 plus 300 mg of calcifediol per month) to a standard dose of 24000 IU per month (equivalent to 800 IU per day). The study did not include a control group receiving zero vitamin D supplementation. The study was completed in 200 men and women over the age of 70 yrs. The people enrolled in the study had at least 1 fall before entering the study.

High dose vitamin D did not result in improvements in strength in the lower limbs. In fact there were actually more falls in the high dose vitamin D groups in comparison to the standard dose 24,000 IU Vitamin D monthly. Therefore, increasing vitamin D intake above standard recommended intake levels provided no benefit with respect to muscle strength, and was actually associated with an increased risk of falling.

Although vitamin D is present in a few food groups, including fatty fish, eggs and D fortified milk and cereal, it is difficult to meet daily requirements with diet alone. Vitamin D in doses of 800-1000 IU daily will prevent vitamin D deficiency in most people.

Osteoporosis Canada recommends routine vitamin D supplementation for all Canadian adults year round. Healthy adults between19-50 years of age, including pregnant or breast feeding women, require 400 – 1,000 IU daily. Those over 50 or those younger adults at high risk (with osteoporosis, multiple fractures, or conditions affecting vitamin D absorption) should receive 800 – 2,000 IU daily.

Osteoporosis Canada advises Canadians to discuss their vitamin D requirements with their physician.

Osteoporosis Canada continues to advise Canadians to meet the Institute of Medicine established daily calcium requirement of 1000 -1200 mg, from dietary sources preferably, and to use supplements if this is not possible (in the form of calcium carbonate or calcium citrate). Every cell in our body requires calcium in order to function normally and inadequate calcium intake results in the release of calcium from the skeleton in order to meet daily requirements.

On the 29 of September 2015,Tai and colleagues published an article in the BMJ summarizing the careful assessment of 59 studies collectively evaluating the effects of calcium intake on bone mineral density in people over the age of 50 years . Small increases in bone mineral density (BMD) were noted with extra dietary calcium intake by 0.6 -1.8% over 1-2 years. Calcium supplements also were associated with increased BMD by 0.7-1.8%. Small decreases in total and spinal fractures were observed with calcium supplementation. The authors concluded that calcium intake from dietary sources and from supplements increase BMD similarly, however, the small effect on BMD is unlikely to reduce fractures.

Whether calcium could reduce fractures was explored in a second study by Bolland and colleagues, in the same issue of the BMJ. However, it did not demonstrate a significant reduction in fracture risk in the large randomized trials with calcium supplementation.

The studies which were evaluated did have significant variability with differences in the numbers of people evaluated as well as the quality of the assessments. In addition there were differences in how fractures were identified in the studies being evaluated.

Large well-designed controlled studies are required to determine the effects of calcium supplementation on skeletal health. There is no data supporting the use of calcium supplements alone as a treatment to prevent fracture in individuals with osteoporosis.

Individuals who have osteoporosis and are at increased risk for fractures may require medication, in addition to adequate calcium and vitamin D intake, in order to reduce their risk for fractures.