Tag: Healthcare Professionals

Updated: November 25 2024

Update Authors: Dr. Adrian Lau, Dr. Rowena Ridout, Dr. Laetitia Michou, Dr. Claudia Gagnon, Dr. Vithika Sivabalasundaram, Dr. Emma Billington, Dr. Zahra Bardai

“Dairy, soy, and risk of breast cancer: those confounded milks”

This title from a 2020 study suggests that 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 is part of the Adventist Health Study, by Synnove Knutsen et al, from Loma Linda University and published in the International Journal of Epidemiology (1). The study evaluated associations between intakes of soy milk, other soy products, dairy milk and other dairy foods with risk of breast cancer.

This study followed nearly 53,000 Adventist women for 7.9 years focusing on the relative risk of a rare outcome. The authors concluded that as cow’s milk intake increased, regardless of fat level, so did the risk of breast cancer. No clear associations were found between consumption of soy products and breast cancer.

Weaknesses of this study are its observational design (cause and effect cannot be established) and possible residual confounding between dairy and unmeasured factors, despite extensive covariate adjustment (1).  Diet was measured only once at study baseline leaving room for error and omissions. Whether these results can be applied to other populations is unknown and therefore difficult to draw conclusions.  Adventist lifestyle may differ considerably from the general population as many follow a plant-based diet and exclude processed foods, alcohol and caffeine.

The authors do note that cow’s milk has many positive nutritional qualities and suggest more research is needed to understand if there is a 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.

In addition to this study, there are many reviews and studies looking at the association of dairy and cancer risk in other organ sites. The pooled results from several large population-based epidemiological studies have found dairy consumption to be beneficial in reducing the risk of colorectal cancer (2). However, for prostate cancer, many studies do suggest a higher risk of prostate cancer, with greater amounts of dairy intake (3).

Further studies looking at breast cancer risk from dairy show mixed results, with some studies showing a protective effect of dairy, and some showing possible harms from dairy. One systematic review and meta-analysis found no association between breast cancer and dairy intake < 450 g per day, and also found a protective effect of cheese on breast cancer risk (4). However, an intake >450 g per day did correlate to a higher risk of breast cancer by approximately 30%.  Another study which pooled the results of 21 cohort studies (5) found a protective effect of yogurt, ricotta cheese and cottage cheese against the risk of estrogen-receptor positive breast cancer.

Many of the studies have similar limitations that often many different types of foods and beverages are grouped together as one larger category labelled as dairy. For example, this group can include cow’s milk, as well as goat’s milk or sheep milk and other dairy-containing foods such as ice cream, butter, cheese, yogurt, kefir, etc. Some questions for future research include whether differences in cancer risk exist between cultured versus uncultured dairy, organic versus conventional dairy, the addition of sugar, preservatives, colorants and whether fat content has an effect.

1. Fraser GE, Jaceldo-Siegl K, Orlich M, Mashchak A, Sirirat R, Knutsen S. Dairy, soy, and risk of breast cancer: those confounded milks. Int J Epidemiol. 2020;49(5):1526-1537. doi:10.1093/ije/dyaa007
2. Barrubés L, Babio N, Becerra-Tomás N, Rosique-Esteban N, Salas-Salvadó J. Association Between Dairy Product Consumption and Colorectal Cancer Risk in Adults: A Systematic Review and Meta-Analysis of Epidemiologic Studies [published correction appears in Adv Nutr. 2020 Jul 1;11(4):1055-1057. doi: 10.1093/advances/nmaa071]. Adv Nutr. 2019;10(suppl_2):S190-S211. doi:10.1093/advances/nmy114
3. López-Plaza B, Bermejo LM, Santurino C, Cavero-Redondo I, Álvarez-Bueno C, Gómez-Candela C. Milk and Dairy Product Consumption and Prostate Cancer Risk and Mortality: An Overview of Systematic Reviews and Meta-analyses. Adv Nutr. 2019;10(suppl_2):S212-S223. doi:10.1093/advances/nmz014
4. Kazemi A, Barati-Boldaji R, Soltani S, et al. Intake of Various Food Groups and Risk of Breast Cancer: A Systematic Review and Dose-Response Meta-Analysis of Prospective Studies. Adv Nutr. 2021;12(3):809-849. doi:10.1093/advances/nmaa147
5. Wu Y, Huang R, Wang M, et al. Dairy foods, calcium, and risk of breast cancer overall and for subtypes defined by estrogen receptor status: a pooled analysis of 21 cohort studies. Am J Clin Nutr. 2021;114(2):450-461. doi:10.1093/ajcn/nqab097

Updated: November 25 2024

Update Authors: Dr. Adrian Lau, Dr. Rowena Ridout, Dr. Laetitia Michou, Dr. Claudia Gagnon, Dr. Vithika Sivabalasundaram, Dr. Emma Billington, Dr. Zahra Bardai

Denosumab (Prolia) has been shown to reduce the risk of fracture in postmenopausal women and men ≥50 years old 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 reduction in bone mineral density (BMD) and an increase in the risk of fracture (1).

Analysis of the data from the FREEDOM study as well as the Extension trial of denosumab up to a total of 10 years, confirmed that stopping denosumab was associated with an increase in rate of bone loss as measured by bone turnover markers, which rose 3 months after missing a scheduled dose. BMD decreased back to the baseline level 12 months after missing a scheduled dose of denosumab (2).

Individuals who had received ≥ 2 doses of denosumab or placebo, and stopped treatment but remained in the study for ≥ 7 months after the last dose, were reviewed. In the 1001 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. Multiple (>1) vertebral 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 (>1) vertebral fractures after stopping denosumab was higher in those people who had already experienced a prior 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) (2).

Due to the risk of rapid bone loss and vertebral fractures associated with denosumab discontinuation, the injection schedule of every 6 months should not be delayed by more than one month once treatment has started. Patients need to be advised of the increased risk of bone loss and vertebral fracture when therapy is stopped. 

Osteoporosis Canada advises individuals on denosumab therapy to discuss their treatment with their physician prior to stopping therapy or missing a scheduled dose. If denosumab needs to be stopped after 4 or fewer doses, transitioning with a bisphosphonate is suggested 6 months after the last dose of denosumab for a duration of one year, and then reassessed for ongoing therapy, to help prevent rapid bone loss and risk of fractures (3). For individuals discontinuing denosumab after 5 or more doses, it is good practice to seek advice from a consultant with expertise in osteoporosis.

1. Bone HG, Bolognese MA, Yuen CA, et al. Effects of denosumab treatment and discontinuation on bone mineral density and bone turnover markers in postmenopausal women with low bone mass. J Clin Endocrinol Metab. 2011 Apr; 96(4):972-980.
2. Cummings SR, Ferrari S, Eastell R, et al. Vertebral fractures after discontinuation of denosumab: A post hoc analysis of the randomized placebo-controlled FREEDOM trial and its extension. J Bone Miner Res. 2018 Feb; 33(2): 190-198.
3. Morin SN, Feldman S, Funnell L et. al. Clinical practice guideline for management of osteoporosis and fracture prevention in Canada: 2023 update. CMAJ. 2023 Oct;195:E1333-48. 

Prepared by Aliya Khan, Sandra Kim, Rowena Ridout and Lianne Tile, on behalf of the Scientific Advisory Council of Osteoporosis Canada, Rapid Response Committee.

The recent study by Bolland and colleagues published in the Lancet Diabetes Endocrinology (Oct 4, 2018) is an updated meta-analysis that evaluated the effects of vitamin D supplementation on fractures, falls and bone mineral density (BMD) in adults. This study analyzed the pooled findings of 81 randomized control trials, collectively involving more than 50,000 participants.

The majority of the trials included in this analysis were of vitamin D alone, with daily doses of more than 800 IU daily, vs. untreated controls, in community-dwelling women age 65-years or older. Trials of high-dose vs. low-dose vitamin D, as well as co-administration of calcium with vitamin D were also included. Study duration was 1 year or less. The primary outcomes were fractures and falls; and the secondary outcome was change in BMD from baseline at the lumbar spine, total hip, femoral neck, total body, and forearm (1).

This meta-analysis found that vitamin D supplementation did not have an effect on the risk of fractures or falls, and there were no meaningful effects on BMD. The authors also concluded that there were no differences between the effects of higher and lower doses of vitamin D (1).

In more than half of the trials, subjects had a baseline vitamin D level (25OHD) of <50 nmol/L (a cutoff considered by many including the Endocrine Society (2) to indicate vitamin D insufficiency), and almost all had a baseline 25OHD <75 nmol/L. Only four trials (6%) studied people with vitamin D deficiency (25OHD <25 nmol/L), in whom vitamin D supplementation may produce different results. Since there is large variability in how vitamin D levels respond to fixed doses of vitamin D (most studies used 1000 IU per day or less), 25OHD levels may not have reached the target range of interest in these studies. The finding that vitamin D alone may not prevent fractures, falls or improve BMD is consistent with prior published studies. While studies have shown little impact on outcomes when vitamin D or calcium are used separately, a review of trials of calcium and vitamin D used together in individuals living in long-term care showed benefit (3). The current meta-analysis by Bolland included only 20 trials (25%) of vitamin D taken with calcium vs. calcium alone, and did not include studies that compared vitamin D used together with calcium vs. no treatment. Although the major strength of the current study lies in the large number of studies included in the analysis, it is important to recognize potential limitations including the heterogeneity of populations, study designs and results of the studies in the meta-analysis. Importantly, 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. It is important to remember that vitamin D is needed for optimal 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. Although this study 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. Osteoporosis Canada recommends that individuals with osteoporosis or with risk factors for fractures receive adequate vitamin D, as recommended at 800-2000 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. 7. Manson JE et al. Vitamin D supplements and prevention of cancer and cardiovascular disease. N Engl J Med 2018 Nov 10; [e-pub]. (https://doi.org/10.1056/NEJMoa1809944) Prepared by Aliya Khan, Sandra Kim, Rowena Ridout and Lianne Tile, on behalf of the Scientific Advisory Council of Osteoporosis Canada, Rapid Response Committee.

Updated: November 25 2024

Update Authors: Dr. Adrian Lau, Dr. Rowena Ridout, Dr. Laetitia Michou, Dr. Claudia Gagnon, Dr. Vithika Sivabalasundaram, Dr. Emma Billington, Dr. Zahra Bardai

A study published by Drieling and colleagues 2017 (1) described the results of a cohort study of 5120 older women with an average age of 80 years and at high fracture risk. This observational study from the Women’s Health Initiative included 5120 women who had been using oral bisphosphonates for at least 2 years and had a 5-year hip fracture risk of 1.5% or higher. Women who had been on parathyroid analogues, calcitonin or aromatase inhibitors were excluded. The average follow-up data was available for 4 years.

10-13 years of oral bisphosphonate use was associated with a higher risk of any clinical fracture than 2 years 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 bisphosphonates have been shown to significantly reduce the risk of vertebral and nonvertebral fracture in randomized controlled trials. Among patients with osteoporosis (defined as T-score < -2.5, or prior fragility fracture), bisphosphonate therapy provides a risk reduction of about 50% for vertebral, 30% for hip, and 20% for nonvertebral fractures after 3 years of treatment. The extension studies of these fracture trials unfortunately were not powered to evaluate impact on fracture risk.  Currently we do not have data consistently demonstrating reductions in nonvertebral fracture risk with long-term bisphosphonate use.

It appears that the optimal period of use for oral or IV bisphosphonates is 3-6 yrs with published randomized controlled trial data confirming reductions in fracture risk for vertebral, nonvertebral and hip fracture with use for this time period.

Osteoporosis Canada advises that all patients should have their fracture risk and treatment strategy reviewed by their physicians after 3-6 years of bisphosphonate use, as long-term use may not have the same risk-benefit ratio as seen with shorter term use.

1. Drieling RL, LaCroix AZ, Beresford SAA, Boudreau DM, Kooperberg C, Chlebowski RT, Ko MG, Heckbert SR. Long-Term Oral Bisphosphonate Therapy and Fractures in Older Women: The Women’s Health Initiative. J Am Geriatr Soc. 2017 Sep;65(9):1924-1931. doi: 10.1111/jgs.14911. Epub 2017 May 29. PMID: 28555811; PMCID: PMC5603349.

Updated: November 25 2024

Update Authors: Dr. Adrian Lau, Dr. Rowena Ridout, Dr. Laetitia Michou, Dr. Claudia Gagnon, Dr. Vithika Sivabalasundaram, Dr. Emma Billington, Dr. Zahra Bardai

Vitamin D supplementation has recently been evaluated in Switzerland in a small one-year randomized clinical trial by Bischoff-Ferrari and colleagues (1). 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 years. 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. A recent systematic review and meta-analysis of 15 randomized controlled trials also showed that intermittent or single high-dose vitamin D supplementation has no preventive effect on the risk of falls and may even increase the risk of falls (2).  

Patients should discuss their vitamin D requirements with their health care professionals before making any changes to their routines. We encourage patients with osteoporosis to continue with their current vitamin D supplementation, as per the current Osteoporosis Canada Guideline (3), and according to their personal clinical needs. 

As few foods contain vitamin D, Health Canada recommends that all Canadians over age 50 years take 400 IU of vitamin D per day (4).  

1. Bischoff-Ferrari HA, Dawson-Hughes B, Orav EJ et al. Monthly high-dose vitamin D treatment for the prevention of functional decline: A randomized clinical trial. JAMA Intern Med. 2016 Feb; 176(2): 175-83. doi: 10.1001/jamainternmed.2015.7148.
2. Myung S-K, Cho E. Effects of intermittent or single high-dose vitamin D supplementation on risk of falls and fractures: a systematic review and meta-analysis. Osteoporosis Int. 2023 Aug; 34(8): 1355-67. doi: 10.1007/s00198-023-06761-3.
3. Morin SN, Feldman S, Funnell L et. al. Clinical practice guideline for management of osteoporosis and fracture prevention in Canada: 2023 update. CMAJ 2023 October 10;195:E1333-48. doi: 10.1503/cmaj.221647.
4. https://www.canada.ca/en/health-canada/services/nutrients/vitamin-d.html. 

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.

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.