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Author: Patrick O'Mara

Long-Term Use Of Bisphosphonates Increases the Risk of Fractures in Older Women

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.

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How Does Calcium Affect Bone Health and Fracture Risk?

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

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Calcium and Cardiovascular Disease

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.

High Dose Vitamin D Supplementation Does Not Improve Muscle Function and May Increase the Risk of Falls

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.

Healthcare Professionals

Calcium Intake and Effect on Bone Health and Fracture Risk Reduction

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.

Healthcare Professionals

Swedish Milk Study

On Oct 28, 2014 a study on milk was published by Dr. Michaelsson of Uppsala University in Sweden. This study claims that high milk intake was associated with an increased rate of death.

In this study, over 61,000 women (ages 39-74) and over 45,000 men (ages 45-79) were followed for just over 11 years during which time they completed food questionnaires about their diet. After 20 years, it was observed that the death rate among the men and women appeared to be higher in those drinking three or more glasses of milk per day compared to those just drinking one glass per day. In addition, drinking more milk did not appear to reduce the risk of fractures (broken bones).

Although this study was published in The BMJ (originally called the British Medical Journal), its study design was not ideal for determining cause and effect between the high intake of milk and the increased risk of death. Other researchers have actually observed a lower rate of heart attacks in those with a diet rich in dietary sources of calcium. For example, in 2012 Li and colleagues evaluated a German cohort study of 23,980 people ages 35-64 who were followed over 11 years. This study found that a calcium enriched diet was associated with a lower rate of MI (heart attack) by 30%.

Clearly, further research is necessary before it can be concluded that a high intake of milk is harmful. In the meantime, Osteoporosis Canada still recommends that Canadians over age 50 consume 1200 mg of calcium daily through food and supplement, with food being the preferable source.

Healthcare Professionals

Swedish Milk Study

In a study published on Oct 28, 2014 by Dr. Michaelsson of Uppsala University, Sweden in the BMJ, high milk intake was associated with an increased rate of death in a large observational study completed in Sweden.

In this study 61,433 Women (39-74 years at baseline 1987-90) were followed for 20.1 years and 45,339 men (45-79 years at baseline 1997), were followed for 11.2 years. They completed food frequency questionnaires. During the follow-up of 20.1 years, 15,541 women died and 17,252 had a fracture, of whom 4259 had a hip fracture. Of the men being followed for an average of 11.2 years, 10,112 men died and 5,066 had a fracture, with 1,166 hip fracture cases. In women, the death rate was higher in those drinking three or more glasses of milk a day compared to those drinking just one glass a day (hazard ratio 1.93; 95% confidence interval 1.80 to 2.06). There did not appear to be a decrease in the risk of fracture with a higher intake of milk. Similar findings were seen in the men in this study. The researchers concluded that high milk intake was associated with a higher death rate and did not appear to protect from developing fractures.

This study design was not ideal however for determining cause and effect between the high intake of milk and the increased risk of death. Other researchers have actually observed a lower rate of heart attacks in those with a diet rich in dietary sources of calcium. In 2012, Li and colleagues evaluated a German cohort study of 23,980 people ages 35-64 followed over 11 years and found that a calcium enriched diet was associated with a lower rate of MI by 30%.

Clearly further research with well-designed studies is necessary before it can be concluded that high intake of milk is harmful. Osteoporosis Canada recommends that Canadians over 50 get 1200 mg of calcium daily through food and supplement, with food being the preferable source.

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Strontium Ranelate (Protelos) and Osteoporosis

Strontium ranelate (Protelos) is a drug approved for the treatment of osteoporosis in Europe, but not in Canada. It is effective in reducing fractures . Recently the European Medicines Agency has completed their review regarding the safety of this drug and recommend that strontium ranelate not be taken by patients with heart or circulatory problems. Individuals who have had a heart attack, angina, stroke or uncontrolled blood pressure should not take this medicine and should discuss their osteoporosis therapy with their physician.

The safety of strontium citrate commonly available at health food stores in Canada has not been evaluated and its effects on fracture risk reduction are not known.

Osteoporosis Canada recommends that all patients with osteoporosis or at an increased risk of fracture discuss their treatment options with their physician.

Healthcare Professionals

Vitamin D and Effects on BMD

In 15 of the studies the mean baseline vitamin D level was over 50 nmol/l which is higher than values seen in a significant number of Canadian men and women particularly during the winter months. In 1 study of adult Canadians who were not using vitamin D supplements, 34% had evidence of vitamin D insufficiency with vitamin D levels below 40 nmol/L.

The meta analysis completed by Reid and colleagues did not show an effect of vitamin D supplements on bone mineral density.

It is important to remember that vitamin D enables optimal calcium absorption from the bowel and inadequate vitamin D results in poor mineralization of the bone in addition to bone loss due to high levels of parathyroid hormone.

The majority of Canadians have inadequate vitamin D levels and do require approximately 400-2000 IU of vitamin D daily to reach a normal vitamin D level. Osteoporosis Canada’s guidelines for vitamin D are safe and are designed to prevent vitamin D deficiency, which is clearly harmful for bone health.

In those with osteoporosis it is necessary to take adequate calcium and vitamin D as well as drug therapy in order to significantly reduce fracture risk.

Healthcare Professionals

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