The number of treatments formulated each year has increased dramatically over the last 10 years due to technological advancements within the biomedical field. However, formulation and development does not necessarily equate to launch on the market, as many treatments are deemed ineffective, inferior to those already on the market, or unsafe. Therefore, all treatments produced by pharmaceuticals must undergo rigorous testing before being launched on the market. It would of course be premature and dangerous to immediately commence the testing of a new treatment in human subjects. As such, scientists take to studying the effects in models, which can include
Introduction to Strontium
In 2002, AOR introduced the world’s first strontium citrate as a dietary supplement for bone health. There have been some recent concerns about strontium’s safety as well as a lack of information regarding strontium citrate. The goal of this article is to discuss the foundations of such concerns and to increase awareness about new research on the safety and effectiveness of strontium citrate.
Strontium is a natural element. In nature, it is found in highest amounts in the ocean and consequently in certain bony fish. 99% of the strontium found in the human body is in the bone. Because strontium and calcium have very similar molecular structures, the body treats them much the same.
Although much of the clinical research on strontium has been done recently on a compound called strontium ranelate, which is a patented pharmaceutical drug used in Europe (but not in Canada or the USA), it boasts a rich history of use prior to being known as strontium ranelate.
Strontium was discovered in ore in the late 1700s and isolated in the early 1800s, but its medicinal effects were first identified in the late 1800s. Strontium was introduced into various medical pharmacopoeias around the world after first appearing in Squire’s Companion to the British Pharmacopoeia in 1884.
Which Form of Strontium?
Since then, strontium has been combined with various compounds to form strontium salts such as strontium salicylate, strontium cinnamate, strontium chloride, strontium lactate and strontium gluconate, all of which have been used for medical purposes. Ranelic acid is a synthetic compound not found in nature and is the most recently studied partner for strontium. However, it is the elemental strontium that is important. Early studies demonstrated this fact by basing their doses, evaluations and conclusions on the amount of elemental strontium given and not those of the entire compound.
In these early studies, up to 1750 mg/day of the strontium ion from strontium gluconate and strontium lactate were found to be safely tolerated in patients with bone cancer or postmenopausal osteoporosis receiving strontium from three months to three years. In bone cancer patients, remineralization was seen in areas where bone had become weak, and patients reported less pain and feeling better overall.
Although strontium citrate has not been well studied, we can imagine that the strontium from ranelate is absorbed into the bone at a similar rate as strontium from citrate. A recent study in rats administered either strontium ranelate or strontium citrate providing the same amounts of elemental strontium per day. They found that the amount of strontium accumulated in the bone from either source was the same. At last, at least two studies have been completed in humans using strontium citrate. However, the strontium was given in combination with other nutrients known to benefit bone health.
The First Study
In the first study, subjects were given an algae-derived mineral supplement providing calcium, magnesium and trace minerals (including strontium) along with additional nutrients known to benefit bone health such as additional strontium citrate, vitamin D3, boron, vitamin C and vitamin K2 as either MK-4 or MK-7. A third group did not receive extra strontium, vitamin K, vitamin C or activity and lifestyle advice like the first two groups. While all three groups experienced increases in bone density (even the group that did not receive extra strontium), the group that received strontium at 680 mg per day and 1.5 mg of MK-4 performed better than the group receiving more vitamins and minerals but only 100 mcg of MK-7.
The Second Study
The second study out of Edmonton, Alberta administered the same amount of strontium from citrate, vitamin K2 in the form of MK-7, 2000 IU of vitamin D3, 25 mg of magnesium, and 250 mg of DHA omega-3 fatty acids from fish oils. The subjects were advised to get their calcium from foods rich in calcium rather than take a calcium supplement. They were also advised to engage in impact physical activity. Over the course of one year, bone mineral density increased the most at the spine and at certain points in the hip. The most exciting thing is that the increases in bone mineral density were twice as good as the results that some of the subjects had previously seen with bisphosphonate treatment for one year, and at least equal to and even greater in some cases than strontium ranelate treatment for one year! Equally important, the subjects who did not take the supplements every day for the whole year were evaluated separately, and no significant differences were found in their bone density scores after the study.
What About the Adverse Effects of Strontium?
Strontium ranelate has been associated with, but not necessarily the cause of, rare cases of gastrointestinal disturbances, minor skin rashes, blood clots and memory loss, in descending order. Two other studies pooled information obtained from physicians working with patients in their practices and found that people who had osteoporosis appeared to have a higher risk of blood clots regardless of whether or not they had been treated with strontium ranelate, bisphosphonates or other post-menopausal osteoporosis treatment. For strontium ranelate, the blood clot effects were measured within the first year of use. In the two recent studies using strontium citrate for one year, there were no adverse effects of any kind either self-reported or from blood samples.
Strontium and Bone Fragility Rumours
There has been some concern in the past few years that strontium may eventually increase the risk of fractures by reducing
Let’s start logically by saying that of the various forces on bone that cause fractures, tension forces are the least common culprits.
A review of strontium’s effects on bone architectural structure found that overall, strontium works.8 Several studies found that blood indicators of bone formation increased by about 8% while markers of bone deterioration decreased by about 12%, and that these markers were sustained from three months to three years with strontium ranelate use. One of these studies took bone samples after treating subjects with strontium ranelate for up to five years. The bone samples showed a 14% increase in trabeculae number, a 16% decrease in trabecular separation (these are measures of the quality of the cancellous bone) and an 18% increase in cortical thickness. This shows that strontium positively affects both the inner and outer bone structure. These same studies also found that for every 1% increase in bone density of the femoral neck (the thin part of the thigh bone which insets into the hip socket), there was a 3% reduced risk of a fracture of the spine. These results counter the argument that bone mineral density scans show inflated readings only because strontium is a denser mineral than calcium. While this is true, increases in bone mineral density as measured by scans do indeed equal a reduced incidence of fractures and improvements in bone formation markers.
Several more recent studies have found that strontium is only present in bone formed during strontium treatment, that bone formation is actually higher in cancellous bone than cortical bone during the three years of treatment with strontium, and that even with the replacement of up to 4.5% of calcium ions by strontium, bone mineral quality is maintained even up to three years of treatment with strontium. An extension of these trials found that five years of treatment with strontium ranelate with calcium and vitamin D in women over 80 years increased quality of life, number of years, and was actually cost saving due to reducing the risk of fracture.
The longest study to date examined the effect of strontium ranelate when used continuously for 10 years. This is a very long time for a substance used
So while the reduced tensile strength argument seems possible in theory, clinical human studies have clearly shown otherwise!
Strontium as a Treatment for the Treatment
Bisphosphonates are a group of osteoporosis drugs known to work well for the short term but can have devastating opposite effects after several years of use. In this case, bone fragility increasing as a result of the treatment is proven to be true in numerous clinical studies. Several studies have suggested that strontium ranelate is a possible solution for those who have experienced excessive bone deterioration after taking bisphosphonates. They found that subjects who had been treated with bisphosphonates actually had a delayed response to strontium ranelate for the first six months, where not many changes in the bone were seen. Between six to 12 months, the bone growth occurred at a similar rate to those who had never taken bisphosphonates. Strontium may therefore help restore bone health for victims of failed bisphosphonate treatment, albeit a slower recovery.
Research on Strontium Continues and Expands
Strontium’s mechanisms of action are beginning to be understood. It is thought that strontium activates calcium-sensing receptors and also influences the expression of genes that control bone formation and bone breakdown. One study has also caught a glimpse of how strontium is lost from the bone after stopping treatment with strontium ranelate. Bone strontium content declined by about 27% after three months of stopping use and by about 33% after six months of stopping use. This is a small amount considering they found that bone strontium content is about 1% on average after three to eight years of use. Bone strontium loss is suggested to be less marked over time, and strontium may remain in bone for years after treatment. According to this study, the longer strontium is taken, the longer it takes for the bone to lose strontium after stopping treatment. Some of the newest research has shown that strontium benefits men with osteoporosis the same as it does women. Strontium has also been shown to be a potential treatment for knee osteoarthritis, providing some structural support, reducing pain symptoms and improving physical function of the knee joint in osteoarthritis patients. The use of strontium in bone and heart implants may even be on the horizon since new research shows that it is degraded slower than other materials like magnesium typically used in implants.
The Final Word
Since its discovery until today, strontium’s popularity has risen and fallen on waves of
What You Need to Know
Strontium is strontium, and it is treated the same way by the body no matter what salt form it is in. Several human studies on strontium citrate have emerged, producing the same positive results as other forms of strontium in combination with other important bone health nutrients and a healthy lifestyle. However, inconsistently or sporadically taking strontium may not produce positive results. Strontium citrate has not produced the same adverse effects as strontium ranelate during the first year of use. The claim that strontium negatively impacts the quality of bone structure and integrity is unfounded and false; in fact, it has an overwhelmingly positive effect on the quality of bone mineral, it increases bone density and bone formation, and it reduces the risk of bone fractures. Improvements in bone density scans really do correlate with increases in bone formation and reduced fractures. Strontium has indeed been safely and effectively used with relatively few adverse effects for periods of up to 10 years. We have even seen that strontium is a potential treatment for failed conventional treatment with bisphosphonates, as well as for other types of people and health concerns. Finally, Health Canada has granted AOR’s Strontium Support II containing strontium citrate an NPN based on the evidence presented here, approving of its safety and effectiveness.