Strontium Ranelate and Strontium Citrate Studies

Numerous studies on sr. ranelate found increasing BMD correlated with decreasing fracture risk (references #16 and #21-25 listed at the end of the Comb Study cited below). The French pharmaceutical company, Servier, funded the research on sr. ranelate to market the drug in Europe and elsewhere. Taking a drug through all the required clinical trials takes millions of dollars and the resources of a large company like Servier, which is present in 140 countries, with more than 20,000 employees, including close to 3000 in Research and Development (R&D).

Strontium citrate is not patentable and is sold as a supplement in the U.S. and Canada. There is no monetary incentive for a large pharmaceutical company to do research on strontium citrate. Any research on sr. citrate is most likely to come from universities that have obtained grants. We will continue to see small-scale strontium citrate studies that will add to our knowledge. I do not expect to see large-scale clinical trials involving thousands of subjects taking strontium citrate over a period of several years. Those are the types of trials needed to prove fracture-risk efficacy.  

The following is a review of some significant studies on strontium citrate:

In 2007, two American researchers with SDM College of Dental Sciences in Buffalo, NY, presented their work on osteoblasts at a dental conference. They wrote: “The data support the hypothesis that strontium citrate increases the proliferative/alkaline phosphatase activity of human osteoblastic cells from alveolar bone. The results validate previous research that has been done with other forms of strontium in clinical studies and rodent calvarial cells and indicates that strontium citrate could be a promising agent in treating oral as well as systemic bone disorders.”  The abstract of their paper is available here: http://iadr.confex.com/iadr/2007orleans/techprogram/abstract_89231.htm

 In 2012, two Canadian researchers, one with the University of Alberta, the other with the University of Calgary, published the results of a one-year study called the Combination of Micronutrients for Bone (COMB) Study. The daily protocol consisted of: docosahexanoic acid or DHA (from Purified Fish Oil) 250 mg, vitamin D3 2000 IU, vitamin K2 (non-synthetic MK7 form) 100 ug, Strontium citrate 680 mg elemental strontium, and elemental magnesium 25 mg/day. Dietary sources of calcium were recommended. Daily impact exercising was encouraged. The researchers concluded: “This combined micronutrient supplementation regimen appears to be at least as effective as bisphosphonates or strontium ranelate in raising BMD levels in hip, spine, and femoral neck sites. No fractures occurred in the group taking the micronutrient protocol. This micronutrient regimen also appears to show efficacy in individuals for whom bisphosphonate therapy was previously unsuccessful in maintaining or raising BMD. Prospective clinical trials are required to confirm efficacy.” The complete article is available here: http://www.hindawi.com/journals/jeph/2012/354151/

In July, 2012, four researchers at Ryerson University in Toronto, Canada, published a study in “Bone” entitled: “Monitoring bone strontium levels of an osteoporotic subject due to self-administration of strontium citrate with a novel diagnostic tool, in vivo XRF: a case study.” This study is significant because it used a non-invasive method (not an invasive method, such as bone biopsy) to analyze the strontium levels of bones in an osteoporotic patient who began taking strontium citrate for the study. Therefore, it was possible to obtain her baseline bone strontium levels prior to initiation of therapy with strontium citrate. The researchers wrote: “By 120 hours, the increase (in bone strontium level) was statistically significant at 0.68 ± 0.07 and 0.93 ± 0.05 (for the finger and ankle), respectively. Further increases occurred within an interval of 90-180 days, with the most recent, after 800 days, at the finger and ankle being 7 and 15 times higher than the initial baseline reading. The intriguing results show bone strontium incorporation and retention follow a pattern, suggesting strontium levels, at least in the ankle, do not plateau within two to three years and will continue to increase over time, as an individual takes strontium supplements. The ability of this IVXRF (in vivo X-ray fluorescence) system to monitor and measure bone strontium levels over time provides a useful diagnostic tool to help gain insight into strontium bone kinetics.” The abstract can be read here:  http://www.ncbi.nlm.nih.gov/pubmed/22549020

Does Strontium Change the Quality of Bone Apatite Crystals?

The potential effect of strontium (Sr) on bone apatite (bone mineral) crystals was investigated in paired biopsies of osteoporotic women treated with either strontium ranelate (SrRan) or a placebo for 36 months. In ten paired biopsies, crystallinity, apparent length and width/thickness of crystals, interplanar distances, and lattice parameters of unit cells were assessed by X-ray diffraction and selected area electron diffraction. None of these parameters, reflecting crystal and unit cell characteristics, was influenced by the presence of Sr. All of the parameters were similar in SrRan and placebo groups after 36 months of treatment. The mean rate of substitutions of calcium by Sr ions was 4.5 %. Overall, the quality of bone apatite crystals was maintained after 36 months of treatment with SrRan. Results of this study were published on March, 2013, in Osteoporosis International.

http://www.ncbi.nlm.nih.gov/pubmed/23108780

 

 

Protein Believed to Cause Postmenopausal Osteoporosis

Researchers have identified a protein that likely causes osteoporosis in women after menopause. In experiments on mice, the research team from Tokyo’s Keio University School of Medicine and other institutions found that a decrease in the secretion of estrogen enhances the function of HIF1 alpha protein. Once the amount of estrogen secreted by the ovaries begins to decline around the time of menopause, HIF1 alpha protein in osteoclasts increases.

Normal mice after menopause showed decreased femoral bone density compared with premenopausal levels, but mice whose genes were manipulated so as not to produce the HIF1 alpha protein did not show a decline of femoral bone density even after menopause. Moreover, a substance to inhibit the function of the HIF1 alpha protein that was given to postmenopausal mice led to an increase of bone density compared with premenopausal levels. The discovery is expected to lead to the development of an effective medicine to prevent osteoporosis.

The study is to be published in the online edition of the Proceedings of the U.S. National Academy of Science.

http://ajw.asahi.com/article/behind_news/social_affairs/AJ201309100058

 

 

From Osteoporosis to Osteopenia with Strontium Citrate

After five and a half years of taking strontium citrate (680 mg strontium daily), I went from osteoporosis to osteopenia. I was probably at the osteopenia stage much earlier, but I waited four years between my previous DEXA scan, which showed improvement at all sites but still left me with osteoporosis, and this one. My density increased 34% in the lumbar spine and 55% in the left hip! These numbers are phenomenal! Even if up to 50% of the change in BMD were attributed to the effect of strontium, which has a higher atomic number than calcium and will affect DEXA measurements, the numbers would still be great. My BMD is now 0.871 g/cm2 at the spine from L1- L4 (T-score -1.6), 0.692 g/cm2 at the left femoral neck (-1.4 T-score), and 0.775 g/cm2 at the left total hip (-1.4 T-score). Osteopenia is defined as T-scores < -1.0 and -2.5.

Non-Invasive Measurement of Bone Strontium Levels

Many of you have probably read that the only way to measure the amount of strontium in bone is to do a bone biopsy. That is no longer true, at least not in a research setting. A case study published last year in Bone used an in vivo X-ray fluorescence (IVXRF) I-125 based system to measure bone strontium levels non-invasively in an osteoporotic female volunteer before and after she began taking strontium citrate supplements (680 mg Sr/day).

Thirty-minute measurements were taken at the finger and ankle bone sites, representing primarily cortical and trabecular bone, respectively. Baseline natural strontium levels were obtained followed by a 24h measurement of first intake of strontium citrate supplements (680 mg Sr/day). The baseline levels of strontium (prior to supplementation) were 0.38 ± 0.05 and 0.39 ± 0.10 for the finger and ankle, respectively. After 24 hrs the levels were 0.62 ± 0.14 and 0.45 ± 0.12 for the finger and ankle, respectively. By 120 h, the increase was statistically significant at 0.68 ± 0.07 and 0.93 ± 0.05, respectively. Further increases occurred within an interval of 90-180 days, with the most recent, after 800 days, at the finger and ankle being 7 and 15 times higher than the initial baseline reading.

The results show bone strontium incorporation and retention follow a pattern and suggest strontium levels, at least in the ankle, do not plateau within two to three years and will continue to increase over time, as an individual takes strontium supplements. The ability of this IVXRF system to monitor and measure bone strontium levels over time provides a useful diagnostic tool to help gain insight into strontium bone kinetics.

 

 

Healing Fractures with Strontium Ranelate

Age and bone quality are the two most important factors influencing the fracture healing process. Cellular and molecular alterations in elderly patients may lead to pseudarthrosis (nonunion), i.e., a fracture that has not united in the stipulated time in which such fractures usually unite and has no chance of union without intervention. In the same way, in altered bone metabolism conditions, such as osteoporosis, physiological phases of fracture healing are impaired.

Two women with fractures that would not heal were started on strontium ranelate (2g/day), calcium (1200 mg/day), and vitamin D (800 IU/day). Patient B.G. was a 57-year-old Caucasian woman with osteopenia and a fracture of the right distal radius and ulna. Patient S.L. was a 59-year-old Caucasian woman with osteoporosis and a fracture of the base of the fifth metatarsal in the left foot. Their case studies showed healing of fractures in a short period of time after drug and supplement intervention.

Read more about these fascinating studies, which contain figures of several radiographs and a CT scan, at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2898010/

EMA Confirms Recommendations to Restrict Strontium Ranelate

The European Medicines Agency (EMA) has confirmed the recommendations to restrict the use of strontium ranelate (Protelos/Osseor, Servier) due to concerns about the risk of adverse cardiac events. The EMA's Pharmacovigilance Risk Assessment Committee (PRAC) recommended the restrictions earlier this month, and the Committee for Medicinal Products for Human Use (CHMP) has now endorsed these following its meeting of April 22-25, 2013. The CHMP opinion will be sent to the European Commission, the executive branch of the European Union, which will issue a legally binding decision.

 

Strontium and Your Heart

A committee of the European Medicines Agency (EMA) has recommended the following restrictions in the use of strontium ranelate (sold in the European Union under the brand names Protelos and Osseor) to reduce the risk of adverse cardiac events:

1a. Strontium ranelate should only be used for the treatment of severe osteoporosis in postmenopausal women at high risk for fracture and severe osteoporosis in men at increased risk for fracture.

2a.Strontium ranelate should not be used in patients with current or past history of ischemic heart disease (such as angina or MI), peripheral arterial disease (PAD), or cerebrovascular disease.

3a.Strontium ranelate should not be used in patients with hypertension that is not controlled by treatment.

http://www.ema.europa.eu/docs/en_GB/document_library/Medicine_QA/human/000560/WC500142021.pdf

What, if anything, should those of us taking strontium citrate do?

Here is what I think.

1b. Strontium citrate can be used as a supplement by men and women with osteopenia or osteoporosis. (I believe the first restriction on strontium ranelate is mostly for cost containment because bisphosphonates, especially the generic equivalents, are much cheaper than strontium ranelate.) 

2b. Strontium citrate can be used UNDER MEDICAL SUPERVISION in patients with current or past history of ischemic heart disease, PAD, or cerebrovascular disease.

    3b. Strontium citrate should not be used in patients with uncontrolled hypertension. Patients must get their hypertension under control by medication. Strontium citrate can be used UNDER MEDICAL SUPERVISION in patients with hypertension that is controlled by treatment.

Vitamin D Supplements and USP Verification

Vitamin D supplement potency varies widely, and the amount of vitamin D in over-the-counter and compounded supplements does not necessarily match the amount listed on the label, according to a research letter published February 11, 2013, in the journal JAMA Internal Medicine.

The analysis showed that the amount of vitamin D in these supplements ranged from 9 percent to 146 percent of the amount listed on the label. Not only was there variation among different brands and manufacturers, but also among different pills from the same bottle. The researchers were surprised by the variation in potency among these vitamin D pills. The greatest concern is that individuals with low levels of vitamin D in their blood and consistently taking a supplement with little vitamin D in it, could face health consequences.

The U.S. Food and Drug Administration (FDA) is considering new safety guidelines for some supplements, but, for the most part, the industry remains unregulated. Some manufacturers participate in a voluntary quality verification program operated by the U.S. Pharmacopeial Convention (USP) — an independent, nonprofit organization that sets public standards for the quality of dietary supplements. In order to receive the USP verification mark, manufacturers' facilities undergo annual good manufacturing-practice audits, and their products are tested for quality, potency and purity. Dr. LeBlanc and her colleagues included one supplement from a USP Verified manufacturer in their sample. They found the amount of vitamin D in pills from that bottle was generally more accurate than the other bottles tested.

"The USP verification mark may give consumers some reassurance that the amount of vitamin D in those pills is close to the amount listed on the label," said Erin S. LeBlanc, MD, MPH, lead author and investigator with the Kaiser Permanente Center for Health Research in Portland, Oregon. "There are not many manufacturers that have the USP mark, but it may be worth the extra effort to look for it."

The researchers tested 55 bottles of over-the-counter vitamin D from 12 different manufacturers. The over-the-counter vitamin D pills used in the analysis were purchased at five different stores in Portland, Oregon. The compounded vitamin D was made by a compounding pharmacy in Portland. The analysis was conducted by Eagle Analytical Services, an independent lab in Houston.

http://www.heraldonline.com/2013/02/11/4611392/vitamin-d-potency-varies-widely.html

USP Verified Dietary Supplements

Click on the brand names below to see a list of USP Verified products and a list of the retail stores where you can buy the products.

Berkley & Jensen		Equaline		Kirkland Signature
Nature Made		Sunmark		Safeway
TruNature

http://www.usp.org/usp-verification-services/usp-verified-dietary-supplements/verified-supplements

Note: I use Nature Made Multi For Her 50+, a multivitamin that contains 1000 IU vitamin D3. There are also several Nature Made vitamin D supplements: Vitamin D—400 IU, Vitamin D3 1000 IU Softgels, Vitamin D3 2000 IU Softgels, and Vitamin D3 5000 IU Softgels. This brand is carried at several brick-and-mortar stores. I buy mine online at www.iherb.com. If you use my code, KAP600, at checkout, you and I both get a discount.