Strontium Abstracts 2

©

Melatonin-micronutrients Osteopenia Treatment Study (MOTS): a translational study assessing melatonin, strontium (citrate), vitamin D3 and vitamin K2 (MK7) on bone density, bone marker turnover and health related quality of life in postmenopausal osteopenic women following a one-year double-blind RCT and on osteoblast-osteoclast co-cultures.
(Maria et al., 2017) Download
This one-year double blind randomized control trial assessed the effects of nightly melatonin, strontium (citrate), vitamin D3 and vitamin K2 (MK7; MSDK) on bone mineral density (BMD) and quality of life (QOL) in postmenopausal osteopenic women (ages 49-75). Compared to placebo, MSDK treatment increased BMD in lumbar spine (4.3%) and left femoral neck (2.2%), with an upward trend for total left hip (p=0.069). MSDK increased serum P1NP levels and reduced bone turnover (CTx:P1NP). Psychometric analyses indicated that mood and sleep quality improved for the MSDK group. MSDK-exposed human mesenchymal stem cells (hMSCs) and human peripheral blood monocytes (hPBMCs) plated in transwells or layered demonstrated increases in osteoblastogenesis, decreases in osteoclastogenesis, increases in OPG (TNFRSF11B) and decreases in RANKL (TNFSF11) levels. In transwell osteoblasts, MSDK increased pERK1/2 (MAPK1/MAPK3) and RUNX2 levels; decreased ERK5 (MAPK7); and did not affect the expression of NFκB (NFKB1) and β1integrin (ITGB1). In layered osteoblasts, MSDK also decreased expression of the metabolic proteins PPARγ (PPARG) and GLUT4 (SLC2A4). In adipose-derived human MSCs, MSDK induced osteoblastogenesis. These findings provide both clinical and mechanistic support for the use of MSDK for the prevention or treatment of osteopenia, osteoporosis or other bone-related diseases.

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.
            (Moise et al., 2012) Download
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.

Monitoring bone strontium intake in osteoporotic females self-supplementing with strontium citrate with a novel in-vivo X-ray fluorescence based diagnostic tool.
(Moise et al., 2014) Download
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.

 

Modeling elemental strontium in human bone based on in vivo x-ray fluorescence measurements in osteoporotic females self-supplementing with strontium citrate.
            (Moise et al., 2016) Download
An in-house custom I-125 excited in vivo x-ray fluorescence (IVXRF) system was used to perform bone strontium (Sr) measurements in individuals suffering from osteoporosis and/or osteopenia. These individuals, who were self-administering with Sr supplements of their choice, were measured frequently, ranging from weekly to biweekly to monthly, over four years, as part of the Ryerson and McMaster Sr in Bone Research Study. Based on these data collected, data from eight subjects were used to perform kinetic modeling of Sr in human bone. Power and exponential models were used to model the data based on one and two compartmental systems. Model parameters included: mean normalized baseline bone Sr signal, half-life and bone Sr uptake. A one compartmental exponential model applied to finger and ankle bone measurements gave half-lives of (508  ±  331) d and (232  ±  183) d, respectively, but did not show statistically significant differences (p  =  0.087 96). However, the values fall within literature estimates. When a two compartmental model was applied to finger bone measurements, half-lives of (300  ±  163) d and (2201  ±  1662) d were observed. Ankle bone data gave half-lives of (156  ±  117) d and (1681  ±  744) d. A two sample t-test, assuming unequal variances, showed these half-lives to be statistically different in both the finger and ankle bone measurements (p  =  0.0147 and p  =  0.00711, respectively). Common kinetic parameters amongst the different subjects could not be unambiguously identified due to the wide scatter of data, leading to an inconclusive kinetic model. The wide distribution of data is suggested to be physiological since technical and positioning factors were eliminated as possible causes. This outcome indicates the need for a more controlled study and further understanding of the physiological mechanism of Sr absorption.

 


References

Maria, S, et al. (2017), ‘Melatonin-micronutrients Osteopenia Treatment Study (MOTS): a translational study assessing melatonin, strontium (citrate), vitamin D3 and vitamin K2 (MK7) on bone density, bone marker turnover and health related quality of life in postmenopausal osteopenic women following a one-year double-blind RCT and on osteoblast-osteoclast co-cultures.’, Aging (Albany NY), 9 (1), 256-85. PubMed: 28130552
Moise, H, et al. (2012), ‘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, 51 (1), 93-97. PubMed: 22549020
Moise, H, DR Chettle, and A Pejović-Milić (2014), ‘Monitoring bone strontium intake in osteoporotic females self-supplementing with strontium citrate with a novel in-vivo X-ray fluorescence based diagnostic tool.’, Bone, 61 48-54. PubMed: 24434614
——— (2016), ‘Modeling elemental strontium in human bone based on in vivo x-ray fluorescence measurements in osteoporotic females self-supplementing with strontium citrate.’, Physiol Meas, 37 (3), 429-41. PubMed: 26910208