What effect does strontium have in replacing so much calcium in bones? Does it only increase density and reduce fractures? Is it only being stored in bones or is it a beneficial part of bone structure? Does the different shape of the bone structure created by high strontium consumption have any negative consequences? The bone structure flattens out and thickens at the edges and does not keep it’s typical rod shape since strontium mostly attaches to bone surfaces. If bone flexiblity is hindered from increased density, could it make bones actually more brittle over time?
Since strontium acts like and replaces calcium in bone, how does it impact the normal calcium functions like activating calcium sensing receptors? How might this impact breast or prostate cancer cell lines? Does the body view strontium as if it was calcium in the blood and could it influence PTH levels? How does the increase in IGF-1 responsible for some of SR benefits influence cancer growth rates? Is the 50% increase observed in the risk of venous thromboembolism (clots in veins) a significant factor? While this is quite rare, if you have had VTE, you should not take strontium. Why does strontium ranelate cause the same type of adverse effects such as diarrhea, skin rashes, and gastrointestinal upsets similar to the other bone drugs in the first few months of usage? While adverse events are less than for the bone drugs, reactions in range of 6.5% are still significant. Plus, strontium is antagonistic to calcium assimilation and vice versa. It is suggested to take each at different times. Far to many questions still searching for answers.
Supplemental Strontium Forms need Safety Studies
Most likely, SR breaks apart during digestion leaving just the elemental strontium. Thus, nutritional supplements that are available of strontium citrate or other forms in dosages at about 300 mg. of strontium twice a day may have a similar effect on bone density and fracture prevention. Strontium gluconate at only 274 mg achieved the same plasma level as twice as much strontium carbonate since the gluconate is better absorbed. SR studies found benefits at 340 mg, but the most at 680. Animal studies over the last 25 years show most forms have bone density increasing benefits. NOTE: Animal studies have found adverse effects on bones using Strontium Carbonate. Some studies have found increased rickets even though calcium and vitamin D levels were normal. More research needed.
A lifetime of a proper diet with vegetables and whole grains should provide a continuous although small amount of strontium to maintain bone density if it has a role to play, but none discovered to date. Removing the bran to make white flour also removes the strontium.
One study did find a positive influence for SR on bone pain and density in cancers which had metastasized into bone.
If one has severe osteoporosis that places them in immediate danger from fractures, this high dose of strontium appears somewhat safer than other bone drugs, but a direct comparison has yet to studied. Nutritional and lifestyle changes take time to develop and not everyone is up to the task or able to carry out many of these factors, such as weight-bearing exercise. And SR is one of the only drugs shown to exhibit an increase in bone building instead of just preventing its tear down.
One point that needs further analysis is from animal studies that revealed SR may inhibit vitamin D activation. This could lower calcium absorption in addition to the calcium replacement process of strontium. Plus how might this affect vitamin D's activation and participation in lowering cancer and infection risks. Longer term studies are now ongoing and hopefully will settle many of these concerns.
Since strontium replaces calcium in bone crystals, might it also participate in this same process when it occurs in artery wall plaque. Animal studies show that strontium does enter into artery wall cells. Research has not clarified this aspect, or at least this author has not yet found this information. There is some discussion that since strontium is similar to both calcium and magnesium, if it took on a magnesium role instead of a calcium role in the blood, it might actually help prevent calcium's participation in calcification. This issue needs to be resolved immediatedly. Why not first increase magnesium intake to recommended amounts?
Another important point, adequate Calcium and vitamin D were given to both the placebo and the SR groups in the above studies. Vitamin K is necessary to activate the vitamin D produced osteocalcin protein which helps bind calcium into bone and also another protein, Matrix GLA, to keep calcium out of arteries, but vitamin K levels were not mentioned. Vitamin K2 as MK-7 maybe the preferred form. A synthetic vitamin K2 as MK-4 is not quite as effective and requires much higher dosages. People from 12 Countries participated in the studies for SR without any mention of dietary or activity level factors.
There are nutritional factors such as active silicon as orthosilicic acid included with calcium and vitamin D that also show positive improvement on bone density without any gastrointestinal upsets that both SR and the other osteoporosis drugs exhibit. Remember bone is both matrix structure and mineral density. The active from of silicon directs collagen formation by vitamin C and protein for new bone matrix. SR results are also showing a positive reduction in collagen breakdown markers.
What the Studies on SR Really Show
And one more point needs to be addressed. It is most revealing to understand the actual numbers that give the 40% reduction. The 40% sounds very impressive, but this is relative risk and does not mean that 40% of people were saved from a fracture. The actual number of people helped is called the absolute risk, usually a much smaller number. In the TROPOS study, 59 people have to take SR for 3 years to prevent one fracture. Or another way to present this fact: About 6 out of 59 people will sustain a fracture even while taking SR and the other 52 would not have fractured anyway. Just the 59th person was saved from having a fracture.
Here is where the 40% comes from in the SOTI study. In women already with a fracture, the SR taking group showed a 11.3% fracture rate compared to the placebo group at 17.4%, a difference in actual number of people of 6.1% which is 40% of 17.4%. A 40% reduction is a very positive result, but not equal to 40% of people taking SR. The much larger TROPOS study did not fair so well in the reductions. In 5091 women looking at the femur region at the top of the leg bone, only a reduction of fractures from 10.9% down to 9.1% in the SR group, this 1.8% difference would be called a 16.5% reduction. Barely significant. A subset did find a reduction of hip fractures in women over 74, which would be very welcome news as this age group is difficult to help due to slowing body processes and less weight bearing exercise ability.
You can go to www.ncbi.nlm.nih.gov/entrez/ and type strontium or strontium ranelate in the box to bring up a list of all these studies.
RIGHTWAY TAKE AWAY!
Strontium ranelate has drug effects beyond just nutritional aspects. While the adverse effects are somewhat rare, the benefits to risks have to be evaluated on an individual case basis with your health care provider. Beneficial for older folks, but for younger people, SR should be a last resort element before drugs since the very long term effects of structural changes caused by strontium replacing calcium in bone are at this time questionable.
The addition of strontium at SR drug amounts to Multiple vitamins with the current state of knowledge is ... borderline insanity.
Until independent scientific research studies the effects of nutritional forms of strontium, the prudent approach is one of upmost precaution. Check out the adverse effects below, especially ALP and osteomalacia.
Not Often Mentioned Possible Adverse Effects
Addendum: Side effects in the above studies and new animal research leads to the conclusion that high dose strontium should be a last resort before drugs. Plus, any person taking high dose strontium should be monitored by a health professional. Nutritional levels of about 50 milligrams for short time periods should not present any potential problems. Perhaps there is a reason that Nature does not make strontium available in foods at higher levels than about 5 or 10 mg.
While the fracture prevention percentages are impressive, they are greatest in the first year and then show a steady decline. Why? Could it be that the first year fracture prevention is only a result of increased density and that long term prevention is more a factor of bone structure and integrity which stontium may only slightly influence?
Check out these adverse effects % that are now showing up as the studies move past the 3 year results and go into the 3-5 year phases:
On the SPC  it says:
“In phase III studies, over 4 years, nervous system disorders were reported with higher frequency in patients treated with strontium ranelate, compared with placebo: disturbances in consciousness (2.5% vs. 2.0%), memory loss (2.4% vs. 1.9 %) and seizures (0.3% vs. 0.1%).”
We searched using TRIP, Medline and Cochrane for any more evidence about strontium ranelate and either memory loss or seizures, and found three reports:
A 2007 Health Technology Assessment report  states:
"Some nervous system disorders, including mental impairment, disturbed consciousness, memory loss and seizures, were also more common in patients randomised to strontium ranelate."
This report was similar to others mentioned in a 2008 Br J Clin Pharmacol article  and a Cochrane Review . In the case of the Cochrane review they reported that in trials memory loss occured in 2.4% of patients on strontium ranelate compared to 1.9% assigned to the placebo intervention.
A new warning is now required on SR labels to indicate possible adverse skin rashes called DRESS which have been respossible for 2 deaths, plus have the possibility for neurological symptoms.
1. eMC. SPC for Protelos, text last revised Sept 04.(http://emc.medicines.org.uk/emc/assets/c/html/displaydoc.asp?documentid=15410)
Below is the toxicolgy report for Strontium from the United States Center for Disease Control April 2004
This next study below reveals a possible connection of strontium to osteomalacia in rats (a mineralization dysfunction of bone observed at very high doses of strontium). This will of course have to be ruled out for humans or warnings are needed on supplements of high dose strontium. Dosages will vary widely in different people as to when this effect might occur, or if it will occur since this was just an animal study. The important aspect is that Strontium at higher dosages functions not as a nutritional nutrient BUT as a drug. There are conditions and situations where being monitored by a doctor is necessary. That supplements in forms without research are being offered at these drug levels for experimentation is a possible recipe for future disaster. Rightway's take: If the age of a person and bone health is such that an intervention is needed, Strontium under medical supervision might be the prudent action since any unknown long term effects might not become a factor. BUT, for younger people, a precautionary approach is still dictated.
NOTE: The enzyme, alkaline phosphatase, or ALP, increases when taking strontium. This enzyme is not only a marker for bone growth, as it is eleveated in young children and pregnancy, but it is also increased by vitamin D deficiency, liver disease, bone tumors, the bone disease osteomalacia, plus prostate cancer. Animal studies show that ALP reduces back to normal levels when strontium is stopped. But with so many adverse conditions also related to increases, it is important to be monitored by your medical team when taking higher doses of strontium. ref ref
Kidney Int. 2005 Mar;67(3):920-30.
Time-evolution and reversibility of strontium-induced osteomalacia in chronic renal failure rats.
Oste L, Bervoets AR, Behets GJ, Dams G, Marijnissen RL, Geryl H, Lamberts LV, Verberckmoes SC, Van Hoof VO, De Broe ME, D'Haese PC.
Department of Nephrology-Hypertension, University of Antwerp, Antwerp, Belgium.
BACKGROUND: Patients with impaired renal function can accumulate strontium in the bone, which has been associated with the development of osteomalacia. A causal role for strontium in the development of the disease was presented in chronic renal failure (CRF) rats. Strontium-ranelate has been put forward as a therapeutic agent in the treatment of osteoporosis. Since the target population for strontium treatment consists mainly in postmenopausal osteoporotic women, who may have a reduced renal function, the risk for osteomalacia should be considered.
METHODS: To determine the time evolution and reversibility of the strontium-induced mineralization defect, CRF rats were loaded with strontium (2 g/L) (+/- 200 mg/kg/day) during 2, 6, and 12 weeks, followed by a washout period of 0, 2, 4, or 8 weeks.
RESULTS: Histologic examination of the bone of the animals treated with strontium revealed signs of osteomalacia already after 2 weeks. Animals that received strontium during 6 and 12 weeks had a significantly higher osteoid perimeter, area and thickness as compared to CRF controls. After 12 weeks, the mineralization was significantly affected, as evidenced by a lower double-labeled surface, mineral apposition and bone formation rate in combination with an increased osteoid maturation time and mineralization lag time. The osteoblast perimeter was significantly lower in the strontium-treated animals. After the washout periods, these effects were reversed and the bone lesions evolved to the values of CRF controls. This went along with an 18% reduction of the bone strontium content. A significant rise in serum alkaline phosphatase (ALP) activity was apparent in the strontium-treated animals as compared to CRF controls. This was not only due to higher levels of the bone ALP but also to those of the liver and the intestinal isoenzymes. Serum parathyroid hormone (PTH) levels decreased during strontium treatment. After cessation of the treatment, the serum ALP activity and PTH concentration reversed to control levels.
CONCLUSION: In this study evidence is provided for the rapid development of a mineralization defect in strontium-loaded CRF rats, accompanied by a reduced osteoblast number, reduced PTH synthesis or secretion, and increased serum ALP levels. These effects can be rapidly reversed after withdrawal of the compound.
PMID: 15698431 [PubMed - indexed for MEDLINE]