Tag: Public

A recent study from the US suggests women who drink as little as one cup /250 ml of cow’s milk per day could be increasing their risk of developing breast cancer by up to 50%. This study from Knutsen and colleagues is part of the Adventist Health Study-2, a large population-based study of Adventists from the US and Canada. The study assessed the relationship between risk of breast cancer and the intake of soy milk, other soy products, dairy milk, and other dairy foods.

This study followed nearly 53,000 women who were members of the Seventh Day Adventist Church for almost 8 years. The authors concluded that as dairy milk intake increased (regardless of fat content) so did the risk of breast cancer. No clear association was found between consumption of soy products and breast cancer.

It should be noted that this was an observational study. In this type of study, researchers observe what effect a risk factor (e.g., soy and dairy) has on health outcomes (e.g., breast cancer) over time. While this type of study can suggest a link (correlation or association) between a risk factor and an outcome, it cannot establish that the risk factor CAUSED the health outcome. In this study, dietary intake of soy and dairy was self-reported, leaving room for errors and omissions. In addition, diet was only assessed once, at the beginning of the study, meaning that possible changes in diet over the 8 years were not taken into account. The study also does not take into account other potential risk factors that could affect the outcome, such as quality of diet (fruit and vegetable intake was not measured); amount or intensity of physical activity; quantity of alcohol consumed; or amount smoked. Furthermore, Adventists diet may differ considerably from the general population as many follow a plant-based diet and exclude processed foods, alcohol, and caffeine, so it is difficult to know if these results can be applied to the general population.

The authors note that dairy milk has many positive nutritional qualities and suggest more research is needed to understand if there is a causal link between dairy intake or other closely related unidentified factors and breast cancer risk. Until then, a balanced and a varied diet including sources of calcium, regular physical activity, and avoiding smoking and excess alcohol make for a healthy lifestyle.

Osteoporosis Canada recommends that men and women over the age of 50 get 1000-1200 mg of calcium through all sources (diet and supplements). Information on non-dairy sources of calcium is available from the Calcium Calculator on the OC website.

https://osteoporosis.ca/bone-health-osteoporosis/calcium-calculator/#page-1

1. Dairy, soy, and risk of breast cancer: those confounded milks. Fraser GE, Jaceldo-Siegl K, Orlich M, Mashchak A, Sirirat R, Knutsen S. Int J Epidemiol. 2020 Feb 25. pii: dyaa007. doi: 10.1093/ije/dyaa007.

Osteoporosis Canada advises individuals on denosumab therapy to discuss their treatment with their physician prior to delaying therapy, stopping therapy or missing a scheduled dose.  

Denosumab (Prolia) has been shown to reduce the risk of fractures in postmenopausal women and men aged 50 years or older with osteoporosis.  It has also been approved for steroid induced bone loss.

Individuals who were in the FREEDOM study, which evaluated denosumab in comparison to placebo, were followed, and those who stopped denosumab had a subsequent loss of bone mineral density (BMD) and an increase in the risk of fracture (Bone JCEM 2011).

Analysis of the data from the FREEDOM study as well as the Extension trial of denosumab (where treatment was continued up to a total of 10 years) confirmed that stopping denosumab was associated with an increase in the rate of bone loss, as measured by bone turnover markers, which rose 3 months after missing a scheduled dose. 12 months after missing a scheduled dose of denosumab, BMD decreased back to the baseline (pre-treatment) level (Cummings JBMR 2017).

Individuals who had received at least 2 doses of denosumab or placebo, and stopped treatment but remained in the study for at least 7 months after the last dose, were reviewed.  In the 1,001 patients who stopped denosumab, the rate of spine fractures increased from 1.2/100 patient-years (while on treatment) to 7.1/100 patient-years, a similar rate to the placebo group. Patient years is a statistical measure used to express the time at risk. 7.1 spine fractures/100 patient-years means that if you followed 100 people for 1 year, on average you would see 7.1 spine fractures. Multiple (more than 1) spine fractures appeared to be more common in the group stopping denosumab than the group stopping placebo (3.4% vs 2.2%). The risk of having multiple (more than 1) spine fractures after stopping denosumab was higher in those people who had already experienced a spine fracture, and also in those who had rapid rates of bone loss. The rates of non-spine fractures were similar in those stopping denosumab and those stopping placebo (2.8% denosumab, 3.8% placebo) (Cummings et al JBMR 2017).

Due to the risk of BMD loss and spine fractures associated with denosumab discontinuation, it is important not to miss scheduled doses of denosumab once treatment has started. Patients need to be advised of the increased risk of bone loss and vertebral fracture when therapy is stopped.  If denosumab needs to be stopped, it should be replaced by an alternative osteoporosis medication to help prevent rapid bone loss and risk of fractures (Symonds CMAJ April 2018).

Osteoporosis Canada advises individuals on denosumab therapy to discuss their treatment with their physician prior to delaying therapy, stopping therapy or missing a scheduled dose.

1. Bone HG et al JCEM 2011:96:972-980
2. Cummings et al JBMR vol 33, No2, Feb 2018 pp 190-198
3. Symonds C, Kline G CMAJ 2018 April 23:190 pp E485-486

Osteoporosis Canada’s overall position statement in response to this study:

This study did not specifically address the vitamin D requirements of individuals with osteoporosis, those with risk factors for osteoporotic fractures, or those with risk factors for vitamin D deficiency. Vitamin D is needed for optimal calcium absorption from the gut, and plays an important role in calcium balance and bone mineralization. Osteoporosis Canada recommends that individuals with osteoporosis or with risk factors for fractures receive adequate vitamin D, as recommended at 800-2,000 IU per day.

A recent article on the effect of vitamin D supplementation on fractures, falls and bone mineral density was published in the journal Lancet Diabetes Endocrinology by Bolland and colleagues (October 4, 2018). This research reviewed the available literature as part of a systematic review and meta-analysis. A systematic review is a research method used to thoroughly locate and synthesize all the information (evidence) related to a specific topic. A meta-analysis uses statistical tools to combine data from the studies included in the review to provide an overall finding. During the systematic review process, it is important that the researchers combine studies that are clinically and statistically similar. This research summarized and combined the results of 81 randomized controlled trials, in which more than 50,000 people were enrolled.

There are some noteworthy characteristics of the included 81 studies. For example, the majority of studies were done in community-dwelling women age 65 years or older, and the only “intervention” was vitamin D in doses of more than 800 IU/day. There were also studies of higher dose vs. lower dose vitamin D, as well as studies that included calcium and vitamin D given together. The studies in the review were based on participants taking vitamin D for one year, or less. The main focus of the systematic review was to look at the effect of vitamin D on fractures and falls. However, there was also a summary of the effect of vitamin D on the change in bone mineral density [from the start of the study (baseline) to the final assessment] (1).

Based on the results of the meta-analysis, the authors reported that vitamin D supplementation did not have an effect on the risk of fractures or falls, and that there were no meaningful effects on participants’ bone mineral density. The authors also concluded that there were no differences between the effects of taking higher and lower doses of vitamin D (1) for these health outcomes.

There are several factors that should be considered when reviewing these results. First, in more than half of the studies, participants had a baseline vitamin D level (25OHD – the blood test used to measure Vitamin D levels in the blood) of less than 50 nmol/L (a cutoff considered by many (2) to indicate a low level of vitamin D). Almost all of the participants had a baseline 25OHD that was less than 75 nmol/L, which is considered an adequate level. Only four trials (6%) studied people with vitamin D deficiency (25OHD <25 nmol/L), in whom vitamin D supplementation may produce different results. In addition, there can be individual differences in how the body’s level of vitamin D responds to the administration of a fixed dose of Vitamin D. Most studies used 1,000 IU per day or less, and so the 25OHD levels after treatment (used as the intervention) may not have been high enough to make a difference in the health outcomes studied (fractures and falls).

Second, the finding that vitamin D alone (without calcium) may not prevent fractures, falls or improve bone mineral density is consistent with other published reviews. However, a review of studies of calcium and vitamin D for people living in long-term care showed benefit (3) but the current meta-analysis by Bolland and colleagues included only 20 trials (25%) that compared vitamin D and calcium to calcium alone. They also did not include studies that compared vitamin D and calcium with no treatment.

Third, although the major strength of the current review lies in the large number of studies included in the analysis, it is important to recognize there are potential limitations. For example, there were differences in the participants enrolled between studies, the study designs, and the results of the studies in the meta-analysis. Importantly, this review did not specifically address the vitamin D requirements of people with osteoporosis, those with risk factors for low trauma fractures, or those with risk factors for vitamin D deficiency. Although this systematic review suggests that routine vitamin D supplementation, in particular, high dose vitamin D, may not be necessary for healthy individuals in the general population, these findings cannot be applied to people with osteoporosis, or to those with risk factors for fractures or vitamin D deficiency.

Fourth, it must be highlighted that falls have many causes. Even specific fall prevention exercise programs are not always effective, and the relative benefit of any intervention on falls is individual.

It is important to remember that vitamin D is needed to optimize calcium absorption from the gut, and plays an important role in calcium balance and bone mineralization. Inadequate vitamin D can result in poor bone mineralization, as well as bone loss due to a rise in parathyroid hormone levels.

Osteoporosis Canada recommends that individuals with osteoporosis or with risk factors for fractures receive adequate vitamin D, as recommended at 800-2,000 IU per day (4); however, vitamin D dosing may require adjustment in order to achieve the adequate 25OHD level needed for optimal calcium homeostasis. Further studies are needed to clarify the optimal 25OHD level for those with osteoporosis or with risk factors for fracture. High dose vitamin D supplementation should be avoided due to potential harms (5). There are large randomized trials currently ongoing to help answer questions about effects of vitamin D supplementation on other aspects of health (6).

Appropriate osteoporosis medication may be required for those at high fracture risk. It is important to note that clinical trials showing the effectiveness of osteoporosis medications all included vitamin D and calcium as part of the treatment regimen.

References:

1. Bolland et al. Lancet Diabetes Endocrinol Oct 2018

2. Evaluation, Treatment, and Prevention of Vitamin D Deficiency: an Endocrine Society Clinical Practice Guideline. Michael F. Holick et al. The Journal of Clinical Endocrinology & Metabolism, 2011 96 (7): 1911-1930.

3. Papaioannou et al. CMAJ 2015 187: 1-11.

4. Vitamin D in adult health and disease: a review and guideline statement from Osteoporosis Canada by David A. Hanley MD et al CMAJ 2010

5. Smith et al. 2017 J Steroid Biochem Mol Biol173:317-22

6. Pradhan AD, Manson JE Update on the Vitamin D and OmegA-3 trial (VITAL). Study J Steroid Biochem Mol Biol. 2016 Jan;155(Pt B):252-6.

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

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.

A recent report by the US Preventive Services Task Force (USPSTF) suggests that low doses of vitamin D up to 400 IU daily and calcium supplements up to 1000 mg daily are not effective in reducing the risk of fracture in healthy people (that is, people without osteoporosis or fractures).

The report expresses concerns that the use of calcium and vitamin D supplements may increase the risk of kidney stones in certain individuals and that for some, the potential benefit may not justify the potential harm.

Further research is needed to better determine the benefits and risks of calcium and vitamin D supplementation in healthy low risk adults. Based on all research to date, Osteoporosis Canada still recommends that those who are 50 years of age or more take 1200 mg of elemental calcium daily, preferably from dietary sources, and 800-2000 IU of a vitamin D supplement daily. Those who are under 50 and at high risk (with osteoporosis, multiple fractures, or conditions affecting vitamin D absorption) also require 800 – 2000 IU of a vitamin D supplement daily.

Along with exercise, good nutrition, and in some cases medication (for those who have an increased risk of fracture), dietary calcium and vitamin D supplementation are important components of a comprehensive plan to maintain your bone health.

Osteoporosis Canada urges all individuals to get the recommended amounts of calcium and vitamin D to protect their bone health.

It is important to talk to and work with your doctor to determine your fracture risk and to ensure that you have the bone health plan that is right for you.