Aliya Khan, Heather Frame,  Claudia Gagnon,  Rowena Ridout , Lianne Tile,  Wendy Ward, Sandra Kim

Recently Duerksen and colleagues published on fracture risk assessment in celiac disease – a registry-based cohort study (1).  This study evaluated the incidence of major osteoporotic fractures (hip, spine, forearm and humerus) in patients with celiac disease confirmed by a positive celiac profile on blood testing, and compared the risk of fracture with those who did not have celiac disease. Individuals with celiac disease had more fractures in comparison to those who did not have celiac disease (HR 1.43 (95% CI 1.11-1.86)) (1).

This study confirms that celiac disease is associated with an increased risk of fracture. This registry-based study supports previous research (2) indicating that celiac disease appeared to be associated with an increased risk of fracture, however previous research was not conclusive as it was not clear if the increased fracture risk was due to the presence of celiac disease. Also, the impact of the gluten-free diet on fracture risk is still not well understood. People with celiac disease benefit from an assessment of bone health and fracture risk.

1. What is celiac disease and how does it affect bone health?

Celiac disease results from an immune reaction to the gluten present in wheat and other foods – ingestion of these foods results in the small bowel lining becoming flat, and affects absorption of nutrients including calcium, phosphate and vitamin D which are essential for bone mineralization and bone health. Also, celiac disease is associated with the release of inflammatory cytokines or proteins which increase the rate of bone loss, and may negatively affect bone formation. 

2. How does FRAX calculate fracture risk in celiac disease?

The FRAX calculation incorporates multiple risk factors for fracture and provides a prediction of future fracture risk over the next 10 years. If the bone mineral density data is entered into the calculator, it does not incorporate the presence of another cause for the osteoporosis (such as celiac disease) in determining the fracture risk. However, if BMD is not provided, it includes the presence of a secondary cause for the osteoporosis in determining fracture risk. This study showed that people with celiac disease had more fractures than expected if the celiac disease had not been present. The FRAX calculation appropriately predicted a higher fracture risk if the presence of celiac disease was considered as a secondary cause, or if BMD data was entered (1).

3. Are there any limitations of this study?

This data may not apply to men  or younger  individuals as the majority of the patients were women and the mean age was 60yrs. . It was also not possible to evaluate the patient’s ability to follow a gluten-free diet – some but not all patients may have followed the diet, and this may have affected the results of the study. Finally, the study was relatively small, with 693 patients with celiac disease and 68,037 patients in the general population.  

4.  How should this information be applied to people with celiac disease? 

People with celiac disease benefit from an assessment of bone health and fracture risk. It is important to ensure that adequate calcium, phosphate and vitamin D are being ingested and absorbed, as malabsorption of these essential nutrients can impair bone quality and strength. (3).  The importance of strict adherence to the gluten-free diet needs to be emphasized  to enhance absorption of key nutrients for optimal  bone quality and strength in those with celiac disease.

References

1. Duerksen DR, Lix LM, Johansson H, McCloskey EV, Harvey NC, Kanis JA and Leslie WD. Fracture risk assessment in celiac disease: a registry-based cohort study. Osteoporosis International. August 3, 2020
2. Heikkilä K, Pearce J, Mäki M and Kaukinen K. Celiac disease and bone fractures: A systematic review and meta-analysis. Journal of Clinical Endocrinology & Metabolism, 2015;100(1):25-34.
3. Fouda MA, Khan AA, Sultan M, Rios LP, McAssey K and Armstrong D. Canadian evaluation and management of skeletal health in celiac disease: Position statement. Canadian Journal of Gastroenterology. 2012;26(11):819-29.

By Aliya Khan MD, FRCPC, FACP, FACE, Rowena Ridout MD FRCPC, Heather Frame MD FCFP, Claudia Gagnon MD, Lianne Tile MD MEd FRCPC, Wendy Ward M.Sc., Ph.D., David A. Hanley, MD, FRCPC, Sandra Kim MD, FRCPC

Previously we have described the role of vitamin D in optimizing bone health and treatment strategies for osteoporosis. In light of the current COVID-19 pandemic, the effects of vitamin D on modulating the immune system are being reviewed.

Two recent studies have suggested that low levels of vitamin D may be associated with an increased risk of severe COVID-19 infections.

Ilie and colleagues from the UK noted that countries with low levels of vitamin D had a higher number of COVID cases, as well as the highest mortality rates from COVID (1)). Similarly, Daneshkhah and colleagues from Northwestern University(2) also found that severe COVID-19 infections appeared to be more common in countries where vitamin D deficiency is more common. We recognize that the number of cases of COVID identified in each country will clearly be affected by the number of tests completed, as well as preventive measures taken by the various countries which were not accounted for in these studies. In addition, linking an observation of low vitamin D levels in a population with an illness needs to be interpreted with caution due to the limitation of confounding factors. At this time it is not known if low vitamin D levels are causally associated with a higher number and severity of COVID infections. Keeping that caution in mind, the possible link between vitamin D deficiency and an impaired immune response to COVID-19 infections may have some support from earlier studies of vitamin D effects on the immune system.

Vitamin D deficiency reduces the ability of white cells to mature and to produce antigens necessary to prevent infections (3) Vitamin D may prevent macrophages from releasing excessive inflammatory cytokines and chemokines (4)). Vitamin D may also enhance expression of ACE2 (Angiotensin converting enzyme 2), which has been associated with improved outcomes with COVID-19 infections (5, 6 )

These early observations may suggest that adequate vitamin D levels are of value in the immune response to infections such as from COVID-19. This would be of particular importance in patient populations vulnerable to low vitamin D levels. These include those who are obese, have malabsorption or short gut syndrome, long term anticonvulsant use as well as the elderly. However, further research is needed to determine if low vitamin D levels are causally associated with a higher number and severity of COVID-19 infections.

While the relationship between vitamin D and COVID-19 is unclear, we know that vitamin D is critical for bone health. 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. This would also be important for those at higher risk of developing vitamin D deficiency. High dose vitamin D supplementation should be avoided due to potential harms..

References

1. Ilie et al Aging Clinical and Experimental Research May 6, 2020
2. Daneshkhah et al Northwestern University May 2020
3. Abu-Amer et al 1993 Cell Immunol 151: 356-368
4. Helming et al Blood 106: 4351-4358
5. Kuka et al 2006 Curr Opin Pharmacol 6: 271-276
6. Cui et al 2019 Redox Biol 26: 101295

Vitamin D plays a significant role in building and maintaining healthy bones. In light of the current COVID-19 pandemic, the effects of vitamin D on the immune system are being reviewed.

Two recent studies have suggested that low levels of vitamin D may be associated with an increased risk of severe COVID-19 infections.

One study noted that countries with low levels of vitamin D had a higher number of COVID cases, as well as the highest mortality rates from COVID. Another study found that severe COVID-19 infections appeared to be more common in countries where vitamin D deficiency is more common. Many different factors may contribute to the number of COVID-19 cases identified in a particular country. These may include the number of tests performed to identify COVID cases, and public health measures taken to prevent the spread of disease, which were not accounted for in these studies.  The severity of disease can also be affected by many different factors, including age, underlying health conditions, and accessibility to health care. Hence, we need to be cautious in linking low vitamin D levels to COVID cases or severity, when other important factors have not been taken into account. At this time it is not known if low vitamin D levels are the cause of the higher number and severity of COVID infections.

Keeping that caution in mind, the possible link between vitamin D deficiency and an impaired immune response to COVID-19 infections may have some support in earlier studies of vitamin D effects on the immune system. These early studies may suggest that adequate vitamin D levels are of value in the immune response to infections such as from COVID-19. This would be of particular importance in patient populations vulnerable to low vitamin D levels. This includes those who are obese, have a malabsorption syndrome or who have been treated with long-term anticonvulsant therapy as well as the elderly. However, further research is needed to determine if low vitamin D levels are a cause of a higher number and severity of COVID-19 infections.

While the relationship between vitamin D and COVID-19 is unclear, we know that vitamin D is critical for bone health. 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. This would also be important for those at higher risk of developing vitamin D deficiency. Taking more than 2000 IU per day should only be done after consultation with your healthcare provider.

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.

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