Osteoporosis Canada

POSITION STATEMENTS

COVID-19 Vaccination and Osteoporosis Drug Therapy

April 1, 2021

Dr. Aliya Khan, Dr. Heather Frame, Dr. Claudia Gagnon, Dr. Rowena Ridout, Dr. Lianne Tile and Dr. Sandra Kim

Recommendations from Osteoporosis Canada Rapid Response Team

Osteoporosis is a chronic condition which requires consistent pharmacologic intervention. There is currently no evidence that osteoporosis therapy increases the risk or the severity of COVID-19 infections. With the exception of bisphosphonates, which have long-term skeletal retention, cessation of osteoporosis drug therapy is associated with bone loss and an increased risk of fracture (1, 2). Thus it is important to not stop osteoporosis therapy or delay the dose of medication without consulting your physician.

The COVID -19 vaccine is given intramuscularly and may result in a mild flu like reaction as well as a local injection site reaction. This has been documented with both the adenovirus vector-based vaccine as well as the mRNA-based vaccine (3, 4). Since intravenous zoledronate or injected denosumab or romosozumab medications may also result in a flu like reaction or local injection site reaction, it is advisable that these medications not be administered at the same time as the COVID-19 vaccine. An interval of one week between infusion of the intravenous bisphosphonate zoledronate and COVID-19 vaccination is recommended. An interval of 4-7 days between subcutaneous administration of denosumab or romosozumab and the COVID-19 vaccination is recommended. As teriparatide is administered daily subcutaneously, it can be continued if it is well tolerated and has not resulted in any local injection site reactions. Osteoporosis Canada recommends administration of teriparatide in the abdominal wall or the thigh and not in the same location as the COVID-19 vaccine. Oral bisphosphonates and raloxifene can be continued without any delay in their administration. These recommendations are consistent with the joint recommendations made by the ASMBR, AACE, Endocrine Society, ECTS, IOF and NOF.

Osteoporosis Canada emphasizes the importance of close adherence to the dosing regimens of all osteoporosis medications to ensure optimal skeletal health.

References:

  1. Tsourdi E, Zillikens MC, Meier C, et al. Fracture risk and management of discontinuation of denosumab therapy: a systematic review and position statement by ECTS. J Clin Endocrinol Metab. 2020; doi: 10.1210/clinem/dgaa756 [Epub ahead of print)
  2. Napoli N, Elderkin AL, Kiel DP, Khosla S. Managing fragility fractures during the COVID-19 pandemic. Nat Rev Endocrinol. 2020;16(9):467-8.
  3. Zhu FC, Li YH, Guan XH, et al. Safety, tolerability, and immunogenicity of a recombinant adenovirus type-5 vectored COVID-19 vaccine: a dose-escalation, open-label, non-randomised, first-in-human trial. Lancet. 2020;395(10240):1845-54.
  4. Baden LR, El Sahly HM, Essink B, et al. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. N Engl J Med. 2021;384(5):403-16.

COVID-19 Vaccination and Osteoporosis Drug Therapy

April 1, 2021

Dr. Aliya Khan, Dr. Heather Frame, Dr. Claudia Gagnon, Dr. Rowena Ridout, Dr. Lianne Tile and Dr. Sandra Kim

Recommendations from Osteoporosis Canada Rapid Response Team

Osteoporosis is a chronic condition that, if you are at high risk of fracture, requires treatment with an osteoporosis medication. There is currently no evidence that osteoporosis medications increase the risk or the severity of COVID-19 infections. With the exception of bisphosphonates, which stay in your bones for a longer time after you stop taking them, stopping osteoporosis drug therapy is associated with bone loss and an increased risk of fracture. Thus it is important to not stop osteoporosis therapy or delay the dose of medication without consulting your physician.

The COVID-19 vaccine may result in a mild flu-like reaction as well as a reaction at the injection site. This is true of all the vaccines available at this time. Since intravenous zoledronate (Aclasta) or injected denosumab (Prolia) or romosozumab (Evenity) medications may also result in a flu-like reaction or local injection site reaction, it is advisable that these medications not be administered at the same time as the COVID-19 vaccine. Although the timing of denosumab (Prolia) can be adjusted to accommodate vaccine timing, it is important to make sure that the denosumab (Prolia) dose is not more than seven months after the previous dose. An interval of one week between infusion of the intravenous bisphosphonate zoledronate (Aclasta) and COVID-19 vaccination is recommended. An interval of 4-7 days between an injection of denosumab (Prolia) or romosozumab (Evenity) and the COVID-19 vaccination is recommended. As teriparatide (Forteo) is administered daily, it can be continued if it is well tolerated and has not resulted in any local injection site reactions. Osteoporosis Canada recommends administration of teriparatide (Forteo) in the abdominal wall or the thigh and not in the same location as the COVID-19 vaccine. Oral bisphosphonates (Actonel, Fosamax, Fosavance) and raloxifene (Evista) can be continued without any delay in their administration. These recommendations are consistent with the joint recommendations made by the American Society of Bone and Mineral Research, the International Osteoporosis Foundation, the National Osteoporosis Foundation and other international organizations.

Osteoporosis Canada emphasizes the importance of following the dosing regimens of all osteoporosis medications to keep your bones healthy. It is also important to keep up with good bone health habits: enough calcium ideally from food, vitamin D supplementation, a balanced diet and appropriate exercise, including weight-bearing and strength training.

Celiac Disease and Bone Health

October 7, 2020

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.

Vitamin D and Potential Impact on the Severity of COVID

May 16, 2020

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 and Potential Impact on the Severity of COVID-19

March 27, 2020

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.

Scientific Advisory Council

Osteoporosis Canada’s rapid response team, made up of members of the Scientific Advisory Council, creates position statements as news breaks regarding osteoporosis. The position statements are used to inform both the healthcare professional and the patient. The Scientific Advisory Council (SAC) is made up of experts in Osteoporosis and bone metabolism and is a volunteer membership.

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