Tag: Healthcare Professionals

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.

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.

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.

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.

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.

In 2008 the results of a small study were published reporting on the use of choline stabilized orthosilicic acid a form of silicon, or placebo in 184 women with low bone density. The women also received 1,000 mg of calcium in addition to vitamin D3 supplements. At 12 months 136 women had completed the study. There was wide variation in the markers of bone repair and renewal, a trend for higher markers of bone formation in the group receiving the orthosilicic acid. There was no significant change in the bone density at 12 months between the placebo group and the orthosilicic acid group.

There may be a potential benefit with this compound and it may warrant further research. However, at this time the research data available is extremely limited and has not confirmed that this product is of value in improving bone health and reducing the risk of fracture. Individuals with osteoporosis or low bone density should consult their physician regarding the best treatment options for them.

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.

Prepared and reviewed by members of the Scientific Advisory Council of Osteoporosis Canada – Updated August 6, 2013

Calcitonin is a hormone found naturally in our bodies. A synthetic form of calcitonin (Miacalcin NS® or generic calcitonin) is used in a nasal spray It decreases the function of the osteoclast (bone-eroding cells) and can decrease bone loss and the risk of spine fractures. It has also been found to be helpful in decreasing bone pain after a spine fracture. Calcitonin is also approved for the treatment of Pagets bone disease as well as for the treatment of high blood calcium in those with cancer. In 2012, the European Medicines Agency (EMA) reviewed the benefits and risks of taking this medication and noted that a small increased risk of cancer has been seen with long term use of calcitonin. The EMA reviewed all available information including safety data following release of the drug on the market as well as information from experimental cancer studies. A 2.4% increased rate of cancer was seen in those taking nasal calcitonin long term. The concern regarding cancer risk did not appear to be present with short term use (≤6 months). At this time the increased risk of cancer has not been confirmed to be caused by calcitonin and may simply be an association.

In July 2013, Health Canada decided to withdraw all nasal spray calcitonin products from the market following a review of the safety and effectiveness data for synthetic calcitonin. Calcitonin does not have a very potent anti-osteoporosis effect, and does not decrease the risk of hip or nonspine fractures. For this reason, Osteoporosis Canada has previously advised that it not be used as a first line treatment for osteoporosis. People taking nasal calcitonin for osteoporosis should speak to their physician regarding a switch to an alternative product.