Tag: Healthcare Professionals

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.

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.

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.

Prepared and reviewed by members of the Scientific Advisory Council of Osteoporosis Canada

Calcium is essential for the achievement and maintenance of normal bone health. The current daily requirements for elemental calcium are approximately 1200 mg daily preferably from dietary sources and if this is not possible then supplements are recommended ideally in the form of calcium carbonate or calcium citrate. Recently concern has been raised regarding potential increased risk of coronary events in association with calcium supplements.

Research from New Zealand evaluated the results of 11 randomized controlled trials of calcium supplementation involving more than 12,000 patients. Ian Reid and his colleagues found an increase in the risk of heart attacks by 31% in the groups receiving calcium in comparison to placebo with 143 women experiencing a heart attack in the calcium groups and 111 women experiencing a heart attack in the placebo groups. This analysis however included studies in which women reported the presence of a heart attack based on their own opinion and the facts were not confirmed by medical records. In the review of the Women’s Health Initiative women who were taking calcium and vitamin D in addition to their own personal use of calcium did not have an increased risk of heart attacks or stroke. There was also no relationship between daily dose of personal calcium supplements and the risk of a heart attack or stroke

Li and colleagues evaluated 23,980 men and women from the European Prospective Investigation into Cancer and Nutrition cohort study (EPIC study). Participants completed questionnaires providing information on dietary calcium intake and the use of supplements. Those people with an increased intake of dietary calcium had a lower risk of heart attacks by approximately 31%. People using calcium supplements actually had an almost 2 fold increased risk of heart attacks. This study also has been criticized as the questionnaire simply asked the people if they took “vitamins” but did not ask which ones and the amounts taken. The presence of heart attacks was however confirmed by following medical records or reviewing the death certificates.

In summary the research studies which have been completed have been relatively small and have been of less than ideal design. Further research with large well designed studies is needed.

Osteoporosis Canada recommends that daily intake of calcium be obtained largely from dietary sources. If this is not possible then supplements may be used preferably calcium carbonate or calcium citrate following discussion with your doctor regarding the safe dose for each individual.

An atypical femoral fracture is an uncommon type of hip fracture which has been associated with long term use of certain osteoporosis medications. This type of hip fracture affects the shaft of the femur bone and is often preceded by thigh or groin pain which may occur for several weeks or months before the fracture. If you are taking osteoporosis medications and you are experiencing thigh or groin pain you should discuss this with your physician. The fracture is confirmed on xray; it may however require additional imaging to identify the fracture in the early stages and a bone scan or an MRI may be required. Atypical femoral fractures have been seen in people taking bisphosphonates or denosumab for several years. They have also been reported to occur without the use of osteoporosis therapy and a causal relationship between the use of osteoporosis medications and these fractures has not yet been confirmed.

Related Links:

Prolia (denosumab) product monograph: http://www.amgen.ca/Prolia_PM.pdf

We are aware of recent media reports that long-term use of bisphosphonates for osteoporosis (sold under the names of Fosamax [alendronate] and Actonel [risedronate]) may be associated with the occurrence of unusual fractures, most commonly reported to affect the thigh bone.

It is a fact that all medications have risks associated with them. Osteoporosis medications are no exception. Every time a m edication is recommended or prescribed, a car eful weighing of the risks and benefits associated with taking that medication is included.

The concern raised in some recent press reports relates, in part, to two studies presented at the annual meeting of the American Academy of Orthopaedic Surgeons in March 2010. 1 One study, from Columbia University, evaluated bone structure in 111 women, half of whom had been taking bisphosphonates for a minimum of 4 years. Using a research technique called Hip Structural Analysis, the study found that in the early treatment period bisphosphonates improved the structural integrity of bone, but that the effects were diminished with long term use. The second study examined bone biopsies from 12 patients treated with bisphosphonates for an average of 8 years and 9 without bisphosphonate therapy. They found no differences in the architecture between the groups, but the group treated with bisphosphonates had less microscopic variability in bone tissue. Other reports have not seen a definite link between prolonged bisphosphonate use and atypical femoral fractures. Using national observational register-based data from Denmark, the ratio b etween h ip an d s ubtrochanteric/diaphyseal femur f ractures w as i dentical i n alendronate-treated patients and the control cohort even in the limited number of patients who received long-term treatment.2 The other study reviewed data from three large randomized trials and concluded t hat s ubtrochanteric/diaphyseal femur fractures w ere v ery r are, even among women w ho ha d be en treated with bisphosphonates a s long a s 10 y ears, without a significant increase in risk associated with bisphosphonate use. 3

This data prompted the Food and Drug Administration (FDA) to state that they were going to undertake a thorough review of possible association between bisphosphonate use and thigh bone fractures. Specifically, the FDA worked with outside experts, including members of the recently convened American Society for Bone and Mineral Research Subtrochanteric Femoral Fracture Task Force to gather additional information that might provide more insight into this issue. It is important to note that the FDA did review the data concerning the link between oral bisphosphonates and thigh bone fractures in 2008 and concluded t hat t here w as no clear association be tween bisphosphonate use and these fractures.

The ASBMR Subtrochanteric Femoral Fracture Task Force report has now been published in the Journal of Bone and Mineral Research (JBMR). As mentioned in the task force report, atypical fractures are very rare, but one should be aware of warning signs and symptoms in someone on long t erm bi sphosphonate t herapy ( new groin or thigh pa in): “ we know t hat bi sphosphonates prevent many, many common fractures. F or t his r eason, w e w ant t o e mphasize t hat pa tients should not stop taking these drugs because they are afraid of the much more uncommon femur fractures. They should talk to their health professionals about their concerns and should let them know if they experience any new groin or thigh pain.”4 The exact cause for these unusual atypical fractures is still uncertain and more research is needed to identify who is at risk and why these fractures occur.

Other studies, evidence and data support the notion that thigh fractures associated with bisphosphonate use are extremely rare with less than 1% of femur fractures being atypical. The risk of other osteoporotic fractures is significantly reduced with bisphosphonate therapy and the benefits far exceed the risks. Nonetheless, if groin or thigh pain is present, this should be further evaluated with bone scans or MRI and if necessary a change in therapy may be required.

References: 1. http://www6.aaos.org/news/pemr/releases/release.cfm?releasenum=877

2. Abrahamsen B, Eiken P, Eastell R. Subtrochanteric and diaphyseal femur fractures in patients treated with alendronate: a register-based national cohort study. J Bone Miner Res. 2009;24:1095-102.

3. Black DM et al N Engl J Med 2010; 362: 1761-71

4. http://www.asbmr.org/About/PressReleases/Detail.aspx?cid=a68f2b70-a117-4094-9f6fb5993c6a6149

Related Links:

1. For more information on the ASBMR task force report and to access the press release, please visit: http://www.asbmr.org/About/PressReleases/Detail.aspx?cid=a68f2b70-a117-4094-9f6fb5993c6a6149

2. Journal of Bone and Mineral Research: http://www.jbmr.org

3. National Osteoporosis Foundation press release

4. American Academy of Orthopaedic Surgeons : http://www6.aaos.org/news/pemr/releases/release.cfm?releasenum=877

A recently released Canadian research study confirms what has been shown in past preliminary studies; – inflammation of the eye as a possible side effect of bisphosphonate therapy is very rare. Bisphosphonates include Alendronate (Fosamax), Risedronate (Actonel), Etidronate (Didrocal) and Zoledronic Acid (Aclasta).

In this new study to evaluate the risk of inflammation of the eye while taking bisphosphonates, Dr Etminan and his colleagues reviewed the electronic medical records for specific diagnoses and medications in all British Columbia residents seen by an eye doctor from 2000 to 2007. They found that uveitis (inflammation of the uvea or middle layer of the eye) occurred in 0.29% of people using bisphosphonates for the first time. Uveitis also occurred in 0.20% of people not taking bisphosphonates. Uveitis can cause blurred vision, eye pain and redness. The researchers also found that episcleritis (inflammation of the sclera or white part of the eye) occurred in 0.63% of bisphosphonates users and in 0.36% of non-users. Episcleritis can cause eye pain, redness, tearing and light sensitivity.

To be clear, this study does not prove that bisphosphonates cause these types of eye problems. In addition, these eye conditions are quite rare and the number of people that are affected is very small. The overall risk of eye inflammation in people taking bisphosphonates is very low compared to the much larger risk of a fracture (broken bone) in people with osteoporosis who do not take bisphosphonates.

If you are taking a bisphosphonate and do not have any eye symptoms continue to take your bisphosphonate as you normally would. However, if you are taking a bisphosphonate and you do develop any symptoms of eye inflammation report these to your doctor as soon as possible. Your doctor will make sure that you get the proper treatment for your eyes and will advise you whether to continue with bisphosphonate therapy or to switch to a different type of therapy for your Osteoporosis.

No link between the use of bisphosphonates and the risk of cancer of the esophagus or stomach has also been noted in a recent large study from the UK. This study evaluated the risk of cancer in 41,826 people using bisphosphonates and a similar number not on therapy. An increase in the risk of cancer was not seen with bisphosphonates.

We are also aware of previous reports on the association between oral bisphosphonate use and esophageal cancer1,2 .

We recognize that you might find these reports concerning. Osteoporosis Canada takes your concerns seriously and we will continue to be vigilant in order to inform you about the latest research. The publication has been reviewed by experts from the Scientific Advisory Council at Osteoporosis Canada and their response is below

It is a fact – all medications have risks associated with them. Osteoporosis medications are no exception. Every time a physician recommends and prescribes a medication, it includes carefully weighing the risks and benefits of taking a medication.

A letter sent to the editor of the New England Journal of Medicine from a member of the Food and Drug Administration (FDA) in the United States, reported that from October 1995 to mid May 2008 the FDA received reports of 23 patients who were diagnosed with esophageal cancer while taking the oral bisphosphonate medication, alendronate. There have been no reports of esophageal cancer associated with other oral bisphosphonates such as risedronate or etidronate in the United States. However, in Europe and Japan, there have been up to 10 cases of cancer of the esophagus with the other bisphosphonate medications. The author concludes that further studies are required to establish whether a clear association exists.

The major limitation of this report, (also highlighted by the author) is the fact that this was not a prospective randomized clinical trial – therefore it is not possible to state that bisphosphonates cause esophageal cancer. Indeed, it is possible that the patients who developed cancer had conditions that put them at risk for this type of cancer unrelated to the use of bisphosphonate medications.

That said inflammation of the esophagus (esophagitis) can occur with the use of bisphosphonates, usually when these medications are not taken according to directions. As a result, it is important to ensure you are taking your medication properly. You may wish to review this information with your health care professional to ensure that you are taking your medication properly.

It is important to remember that esophageal cancer is a rare condition. Fractures (broken bones) due to osteoporosis, on the other hand, are extremely common. Osteoporotic fractures are linked to additional fractures, altered quality of life, worsening of other health conditions and in some cases – death. Bisphosphonate medications provide protection from osteoporotic fractures. It is important to remember that your physician carefully weighs the risks and benefits of taking a medication for your unique situation every time he or she recommends and prescribes a medication. Your healthcare team is available to review any concerns or questions you may have about this issue.

1. Wysowski DK, Reports of Esophageal Cancer with Oral Bisphosphonate Use. N Engl J Med 2009;360;1:89-90.

2. Green, J et al, Oral bisphosphonates and risk of cancer of oesophagus, stomach, and colorectum: case-control analysis within a UK primary care cohort. BMJ 2010; 341:c4444.