Monitoring bone strontium intake in osteoporotic females self-supplementing with strontium citrate with a novel in-vivo X-ray fluorescence based diagnostic tool

Bone 2014
 
Moise H, Chettle DR, Pejović-Milić A

Ten female volunteers were recruited as part of the Ryerson and McMaster University Strontium (Sr) in Bone Research Study to have their bone Sr levels measured as they self-supplemented with Sr supplements of their choice. Of the ten volunteers, nine were suffering from osteopenia and/or osteoporosis. Non-invasive bone Sr measurements were performed using an in vivo x-ray fluorescence (IVXRF) I-125 based system. Thirty minute measurements were taken at the finger and ankle, representing primarily cortical and trabecular bone, respectively. For analysis, the 14.2keV Sr K-alpha peak normalized to the Coherent peak at 35.5keV was used.

Baseline readings, representing natural bone Sr levels were acquired since all volunteers had no previous intake of Sr based supplements or medications. Once Sr supplements were started, a 24h reading was taken, followed by frequent measurements ranging from weekly, biweekly to monthly. The longest volunteer participation was 1535days. The mean baseline Sr signal observed for the group was 0.42±0.13 and 0.39±0.07 for the finger and ankle, respectively. After 24h, the mean Sr signal rose to 1.43±1.12 and 1.17±0.51, for the finger and ankle, respectively, representing a statistically significant increase (p=0.0043 & p=0.000613).

Bone Sr levels continued to increase throughout the length of the study. However the Sr signal varied widely between the individuals such that after three years, the highest Sr signal observed was 28.15±0.86 for the finger and 26.47±1.22 for the ankle in one volunteer compared to 3.15±0.15 and 4.46±0.36, for the finger and ankle, respectively in another. Furthermore, while it was previously reported by our group, that finger bone Sr levels may plateau within two years, these results suggest otherwise, indicating that bone Sr levels will continue to rise at both bone sites even after 4years of Sr intake.

http://www.ncbi.nlm.nih.gov/pubmed/24434614

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

Bone 2012


Moise H, Adachi JD, Chettle DR, Pejović-Milić A

A previously developed in vivo X-ray fluorescence (IVXRF) I-125 based system was used to measure bone strontium levels non-invasively in an osteoporotic female volunteer. The volunteer was recruited in December 2008, as part of the Ryerson and McMaster University Strontium in Bone Research Study and measured at twice weekly, weekly and monthly intervals. Thirty minute measurements were taken at the finger and ankle bone sites, representing primarily cortical and trabecular bone, respectively and the strontium K-alpha X-ray peak at 14.16 keV was used in the analysis.

Since the volunteer had no prior history of strontium based medications or supplementation, baseline natural strontium levels were obtained followed by a 24h measurement of first intake of strontium citrate supplements (680 mg Sr/day). While the baseline levels of 0.38 ± 0.05 and 0.39 ± 0.10 for the finger and ankle, respectively, were on par with those previously reported in Caucasians among twenty-two healthy non-supplementing strontium individuals by our group, an increase began to be seen after 24 hrs of 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 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 system to monitor and measure bone strontium levels over time provides a useful diagnostic tool to help gain insight into strontium bone kinetics.

http://www.ncbi.nlm.nih.gov/pubmed/22549020

Monitoring Bone Strontium Intake in Females Taking Strontium Citrate

Ten female volunteers were recruited to have their bone strontium (Sr) levels measured as they self-supplemented with Sr supplements of their choice. Nine of the ten had been diagnosed with osteopenia and/or osteoporosis. Non-invasive bone Sr measurements were performed using an in vivo x-ray fluorescence (IVXRF) I-125 based system. Thirty minute measurements were taken at the finger and ankle, representing primarily cortical and trabecular bone, respectively.

Baseline readings, representing natural bone Sr levels were acquired since all volunteers had no previous intake of Sr based supplements or medications. Once Sr supplements were started, a 24 hour reading was taken, followed by frequent measurements ranging from weekly, biweekly to monthly. The longest volunteer participation was 1535 days (4.2 years).

The mean baseline Sr signal observed for the group was 0.42 ± 0.13 and 0.39 ± 0.07 for the finger and ankle, respectively. After 24 hours, the mean Sr signal rose to 1.43 ± 1.12 and 1.17 ± 0.51, for the finger and ankle, respectively, representing a statistically significant increase. Bone Sr levels continued to increase throughout the length of the study. However, the Sr signal varied widely between the individuals. After three years, the highest Sr signal observed was 28.15 ± 0.86 for the finger and 26.47 ± 1.22 for the ankle in one volunteer compared to 3.15 ± 0.15 and 4.46 ± 0.36, for the finger and ankle, respectively, in another. Furthermore, while it was previously reported by our group, that finger bone Sr levels may plateau within two years, these results suggest otherwise, indicating that bone Sr levels will continue to rise at both bone sites even after 4 years of Sr intake.

The most important points of this study are as follows:

• The bone Sr signal varies widely between subjects but follows a similar pattern.
• Results suggest bone Sr levels won't plateau as long as one supplements with Sr.
• This diagnostic tool is satisfactory for monitoring bone Sr levels over time.

 The original article was published online in “Bone” on February 08, 2014.

http://www.thebonejournal.com/article/S8756-3282%2814%2900004-0/abstract

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

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.