Component

Strontium ion / Sr2+

Context-specific entity; species, compartment and exposure are stated on each claim.

35 recorded relationships. Experimental role, claim status and evidence remain attached to each record.

Read recorded mechanisms Open recursive mind map

How nutrients influence it

Every nutrient with a recorded effect on this component, credited to the nutrient that acted rather than the chapter that recorded it. Open a nutrient to see the findings and the conditions they were measured under.

How nutrients reach it in more than one step

Chains of two or more recorded steps that end here, grouped by the nutrient they start from. Each step is a separate finding, so a chain is a route a mechanism could take, not proof that it does.

Tracing routes…

What it does

Every recorded relationship this component is part of, grouped by its role. Plain wording comes first; the technical statement follows.

Recorded relationships

What it acts on

  1. In 17 patients with osteoporosis or chronic renal failure, mean six-hour fractional absorption was 20.2% for stable strontium versus 37.8% for calcium, despite correlated time courses.

    Strontium ion / Sr2+ → Calcium ion source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Consecutive-day dual-tracer tests with standardized meals; ten osteoporosis and seven renal-failure patients.
    limitations
    Small selected sample; nonlinear relationship and meal/carrier doses matter. Accessed abstract is explicitly truncated.
    nutrient_topic
    Strontium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Strontium
    plain_language
    Strontium can be a calcium tracer surrogate without behaving identically.
    primary_references
    Stable strontium absorption as a measure of intestinal calcium absorption: comparison with the double-radiotracer calcium absorption test. · 1994 · https://pubmed.ncbi.nlm.nih.gov/7955914/ · DOI 10.1042/cs0870363

    Strontium: calcium interactions, cellular mechanisms and mineralization (2026-09-19) · lines 46–52

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Consecutive-day dual-tracer tests with standardized meals; ten osteoporosis and seven renal-failure patients. · source_derived_draft · unverified_draft

    ## strontium-absorption-not-identical Strontium can be a calcium tracer surrogate without behaving identically. In 17 patients with osteoporosis or chronic renal failure, mean six-hour fractional absorption was 20.2% for stable strontium versus 37.8% for calcium, despite correlated time courses. Model: Consecutive-day dual-tracer tests with standardized meals; ten osteoporosis and seven renal-failure patients. Limitations: Small selected sample; nonlinear relationship and meal/carrier doses matter. Accessed abstract is explicitly truncated. Evidence access: Primary abstract Stable strontium absorption as a measure of intestinal calcium absorption: comparison with the double-radiotracer calcium absorption test. · 1994 · https://pubmed.ncbi.nlm.nih.gov/7955914/ · DOI 10.1042/cs0870363
    Complete structured claim and evidence

  2. Strontium stimulated calcitonin secretion with higher potency than calcium in the rat 6-23 cell study despite differing signaling bias.

    Strontium ion / Sr2+ → Calcitonin secretion by rat thyroid 6-23 cells source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Rat medullary thyroid carcinoma cell concentration-response assays.
    limitations
    Calcitonin is not T3/T4, and this does not establish the net human calcium response.
    nutrient_topic
    Strontium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Strontium
    plain_language
    A calcium-like ion can affect a hormone involved in calcium regulation.
    primary_references
    Strontium is a biased agonist of the calcium-sensing receptor in rat medullary thyroid carcinoma 6-23 cells. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22942242/ · DOI 10.1124/jpet.112.197210

    Strontium: calcium interactions, cellular mechanisms and mineralization (2026-09-19) · lines 350–356

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Rat medullary thyroid carcinoma cell concentration-response assays. · source_derived_draft · unverified_draft

    ## strontium-calcitonin-secretion A calcium-like ion can affect a hormone involved in calcium regulation. Strontium stimulated calcitonin secretion with higher potency than calcium in the rat 6-23 cell study despite differing signaling bias. Model: Rat medullary thyroid carcinoma cell concentration-response assays. Limitations: Calcitonin is not T3/T4, and this does not establish the net human calcium response. Evidence access: Primary abstract Strontium is a biased agonist of the calcium-sensing receptor in rat medullary thyroid carcinoma 6-23 cells. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22942242/ · DOI 10.1124/jpet.112.197210
    Complete structured claim and evidence

  3. Combining extracellular strontium and calcium produced greater apoptosis of mature rabbit osteoclasts than either ion alone.

    Strontium ion / Sr2+ → Apoptosis of mature rabbit osteoclasts source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Primary rabbit osteoclast combination experiment.
    limitations
    Greater combined effect is not proof of clinical synergy, an optimal ratio or a supplement recommendation.
    nutrient_topic
    Strontium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Strontium
    plain_language
    A measured interaction between the two ions is preserved as its own finding.
    primary_references
    The calcium-sensing receptor is involved in strontium ranelate-induced osteoclast apoptosis. New insights into the associated signaling pathways. · 2009 · https://pubmed.ncbi.nlm.nih.gov/18927086/ · DOI 10.1074/jbc.M801668200

    Strontium: calcium interactions, cellular mechanisms and mineralization (2026-09-19) · lines 238–244

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Primary rabbit osteoclast combination experiment. · source_derived_draft · unverified_draft

    ## strontium-calcium-combination A measured interaction between the two ions is preserved as its own finding. Combining extracellular strontium and calcium produced greater apoptosis of mature rabbit osteoclasts than either ion alone. Model: Primary rabbit osteoclast combination experiment. Limitations: Greater combined effect is not proof of clinical synergy, an optimal ratio or a supplement recommendation. Evidence access: Primary abstract The calcium-sensing receptor is involved in strontium ranelate-induced osteoclast apoptosis. New insights into the associated signaling pathways. · 2009 · https://pubmed.ncbi.nlm.nih.gov/18927086/ · DOI 10.1074/jbc.M801668200
    Complete structured claim and evidence

  4. Strontium increased replication in both wild-type and Casr-knockout mouse osteoblasts despite loss of the rapid ERK response in knockout cells.

    Strontium ion / Sr2+ → Replication of Casr-knockout mouse osteoblasts source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract and accessible full-text Methods
    experimental_model
    Same primary mouse-cell study and defined SrCl2/ranelate mixture.
    limitations
    Does not identify the alternative sensor or establish universal CaSR independence.
    nutrient_topic
    Strontium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Strontium
    plain_language
    Losing one receptor branch did not remove every growth response.
    primary_references
    Calcium sensing receptor-dependent and receptor-independent activation of osteoblast replication and survival by strontium ranelate. · 2009 · https://pubmed.ncbi.nlm.nih.gov/20141614/ · DOI 10.1111/j.1582-4934.2009.00673.x

    Strontium: calcium interactions, cellular mechanisms and mineralization (2026-09-19) · lines 94–100

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Same primary mouse-cell study and defined SrCl2/ranelate mixture. · source_derived_draft · unverified_draft

    ## strontium-casr-independent-growth Losing one receptor branch did not remove every growth response. Strontium increased replication in both wild-type and Casr-knockout mouse osteoblasts despite loss of the rapid ERK response in knockout cells. Model: Same primary mouse-cell study and defined SrCl2/ranelate mixture. Limitations: Does not identify the alternative sensor or establish universal CaSR independence. Evidence access: Primary abstract and accessible full-text Methods Calcium sensing receptor-dependent and receptor-independent activation of osteoblast replication and survival by strontium ranelate. · 2009 · https://pubmed.ncbi.nlm.nih.gov/20141614/ · DOI 10.1111/j.1582-4934.2009.00673.x
    Complete structured claim and evidence

  5. Theoretical attenuation calculations predicted strontium overestimation factors around 9–10.8 for the tested DXA systems, with different factors for single-energy CT.

    Strontium ion / Sr2+ → Strontium-associated DXA bone-density overestimation source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    biomarker_context Imported condition classification; unverified.
    evidence_access
    Primary abstract
    experimental_model
    Physical modeling using X-ray attenuation coefficients.
    limitations
    Historical device calculations, not universal current scanner calibration; bone retention also matters after treatment stops.
    nutrient_topic
    Strontium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Strontium
    plain_language
    The size of the measurement effect depends partly on the method.
    primary_references
    Effect of bone strontium on BMD measurements. · 2007 · https://pubmed.ncbi.nlm.nih.gov/17289524/ · DOI 10.1016/j.jocd.2006.10.004
    trigger_kind
    biomarker_context Imported condition classification; unverified.

    Strontium: calcium interactions, cellular mechanisms and mineralization (2026-09-19) · lines 318–324

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Physical modeling using X-ray attenuation coefficients. · source_derived_draft · unverified_draft

    ## strontium-dxa-device-dependence The size of the measurement effect depends partly on the method. Theoretical attenuation calculations predicted strontium overestimation factors around 9–10.8 for the tested DXA systems, with different factors for single-energy CT. Model: Physical modeling using X-ray attenuation coefficients. Limitations: Historical device calculations, not universal current scanner calibration; bone retention also matters after treatment stops. Evidence access: Primary abstract Effect of bone strontium on BMD measurements. · 2007 · https://pubmed.ncbi.nlm.nih.gov/17289524/ · DOI 10.1016/j.jocd.2006.10.004
    Complete structured claim and evidence

  6. In calcium/strontium hydroxyapatite mixtures, approximately 1 mol% strontium caused about 10% overestimation of DXA bone mineral density/content across the tested instruments.

    Strontium ion / Sr2+ → Strontium-associated DXA bone-density overestimation source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    biomarker_context Imported condition classification; unverified.
    evidence_access
    Primary abstract
    experimental_model
    Physical phantom experiments with 0–3.5 mol% strontium.
    limitations
    Mixture calibration is not a patient-specific correction; bone strontium content at the scanned site is required.
    nutrient_topic
    Strontium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Strontium
    plain_language
    Strontium can make a scan read denser without an equivalent increase in calcium mineral.
    primary_references
    Influence of strontium on bone mineral density and bone mineral content measurements by dual X-ray absorptiometry. · 1999 · https://pubmed.ncbi.nlm.nih.gov/10677790/ · DOI 10.1016/s1094-6950(06)60402-2
    trigger_kind
    biomarker_context Imported condition classification; unverified.

    Strontium: calcium interactions, cellular mechanisms and mineralization (2026-09-19) · lines 310–316

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Physical phantom experiments with 0–3.5 mol% strontium. · source_derived_draft · unverified_draft

    ## strontium-dxa-physics Strontium can make a scan read denser without an equivalent increase in calcium mineral. In calcium/strontium hydroxyapatite mixtures, approximately 1 mol% strontium caused about 10% overestimation of DXA bone mineral density/content across the tested instruments. Model: Physical phantom experiments with 0–3.5 mol% strontium. Limitations: Mixture calibration is not a patient-specific correction; bone strontium content at the scanned site is required. Evidence access: Primary abstract Influence of strontium on bone mineral density and bone mineral content measurements by dual X-ray absorptiometry. · 1999 · https://pubmed.ncbi.nlm.nih.gov/10677790/ · DOI 10.1016/s1094-6950(06)60402-2
    Complete structured claim and evidence

  7. An Akt-dependent signaling cascade through CaSR promoted beta-catenin nuclear translocation in strontium-treated primary human osteoblasts.

    Strontium ion / Sr2+ → Human beta-catenin / CTNNB1 source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Human primary osteoblast signaling experiments.
    limitations
    Does not prove direct binding to Akt or beta-catenin; Akt isoform not resolved here.
    nutrient_topic
    Strontium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Strontium
    plain_language
    A receptor signal can reach a transcriptional regulator through Akt.
    primary_references
    An Akt-dependent increase in canonical Wnt signaling and a decrease in sclerostin protein levels are involved in strontium ranelate-induced osteogenic effects in human osteoblasts. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21566129/ · DOI 10.1074/jbc.M111.251116

    Strontium: calcium interactions, cellular mechanisms and mineralization (2026-09-19) · lines 182–188

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human primary osteoblast signaling experiments. · source_derived_draft · unverified_draft

    ## strontium-human-beta-catenin A receptor signal can reach a transcriptional regulator through Akt. An Akt-dependent signaling cascade through CaSR promoted beta-catenin nuclear translocation in strontium-treated primary human osteoblasts. Model: Human primary osteoblast signaling experiments. Limitations: Does not prove direct binding to Akt or beta-catenin; Akt isoform not resolved here. Evidence access: Primary abstract An Akt-dependent increase in canonical Wnt signaling and a decrease in sclerostin protein levels are involved in strontium ranelate-induced osteogenic effects in human osteoblasts. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21566129/ · DOI 10.1074/jbc.M111.251116
    Complete structured claim and evidence

  8. Strontium chloride and the ranelate preparation stimulated ERK phosphorylation in HEK293 cells transfected with human CaSR.

    Strontium ion / Sr2+ → Calcium-sensing receptor / CaSR source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Human receptor transfection and dose-response signaling assays.
    limitations
    Receptor signaling is not itself proof of stronger bone or a nutritional requirement.
    nutrient_topic
    Strontium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Strontium
    plain_language
    Strontium can engage a receptor normally used to sense extracellular calcium.
    primary_references
    The Calcium-sensing Receptor (CaR) is involved in strontium ranelate-induced osteoblast differentiation and mineralization. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20560105/ · DOI 10.1055/s-0030-1255091

    Strontium: calcium interactions, cellular mechanisms and mineralization (2026-09-19) · lines 70–76

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human receptor transfection and dose-response signaling assays. · source_derived_draft · unverified_draft

    ## strontium-human-casr Strontium can engage a receptor normally used to sense extracellular calcium. Strontium chloride and the ranelate preparation stimulated ERK phosphorylation in HEK293 cells transfected with human CaSR. Model: Human receptor transfection and dose-response signaling assays. Limitations: Receptor signaling is not itself proof of stronger bone or a nutritional requirement. Evidence access: Primary abstract The Calcium-sensing Receptor (CaR) is involved in strontium ranelate-induced osteoblast differentiation and mineralization. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20560105/ · DOI 10.1055/s-0030-1255091
    Complete structured claim and evidence

  9. At 10 mM, strontium did not produce calcium oscillations or activation in the tested human oocytes, although TRPV3 expression and responses to TRPV3 agonists were detected.

    Strontium ion / Sr2+ → Human oocyte activation after strontium exposure source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary full text
    experimental_model
    Small human oocyte study, largely in-vitro matured material, with mouse comparisons.
    limitations
    Limited fresh in-vivo-matured human oocytes and no human knockout; channel presence is not proof of strontium permeability.
    nutrient_topic
    Strontium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Strontium
    plain_language
    The mouse result did not transfer to these human eggs.
    primary_references
    Strontium fails to induce Ca2+ release and activation in human oocytes despite the presence of functional TRPV3 channels. · 2018 · https://pubmed.ncbi.nlm.nih.gov/30895246/ · DOI 10.1093/hropen/hoy005

    Strontium: calcium interactions, cellular mechanisms and mineralization (2026-09-19) · lines 398–404

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Small human oocyte study, largely in-vitro matured material, with mouse comparisons. · source_derived_draft · unverified_draft

    ## strontium-human-egg-null The mouse result did not transfer to these human eggs. At 10 mM, strontium did not produce calcium oscillations or activation in the tested human oocytes, although TRPV3 expression and responses to TRPV3 agonists were detected. Model: Small human oocyte study, largely in-vitro matured material, with mouse comparisons. Limitations: Limited fresh in-vivo-matured human oocytes and no human knockout; channel presence is not proof of strontium permeability. Evidence access: Primary full text Strontium fails to induce Ca2+ release and activation in human oocytes despite the presence of functional TRPV3 channels. · 2018 · https://pubmed.ncbi.nlm.nih.gov/30895246/ · DOI 10.1093/hropen/hoy005
    Complete structured claim and evidence

  10. Strontium increased mineralization in primary human osteoblast cultures in the 2011 study.

    Strontium ion / Sr2+ → Mineralization in strontium-treated human osteoblast cultures source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Primary human osteoblast mineralization assay.
    limitations
    Later rat primary-culture work directly challenged a general mineralization-promoting interpretation; matched exposure and culture comparisons remain necessary.
    nutrient_topic
    Strontium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Strontium
    plain_language
    This study found more mineral deposition in its culture system.
    primary_references
    An Akt-dependent increase in canonical Wnt signaling and a decrease in sclerostin protein levels are involved in strontium ranelate-induced osteogenic effects in human osteoblasts. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21566129/ · DOI 10.1074/jbc.M111.251116

    Strontium: calcium interactions, cellular mechanisms and mineralization (2026-09-19) · lines 190–196

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Primary human osteoblast mineralization assay. · source_derived_draft · unverified_draft

    ## strontium-human-mineralization-positive This study found more mineral deposition in its culture system. Strontium increased mineralization in primary human osteoblast cultures in the 2011 study. Model: Primary human osteoblast mineralization assay. Limitations: Later rat primary-culture work directly challenged a general mineralization-promoting interpretation; matched exposure and culture comparisons remain necessary. Evidence access: Primary abstract An Akt-dependent increase in canonical Wnt signaling and a decrease in sclerostin protein levels are involved in strontium ranelate-induced osteogenic effects in human osteoblasts. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21566129/ · DOI 10.1074/jbc.M111.251116
    Complete structured claim and evidence

  11. Strontium inhibited maturation, TRAP expression and hydroxyapatite resorption in human blood-derived osteoclast cultures.

    Strontium ion / Sr2+ → Maturation, TRAP activity and resorption in human osteoclast cultures source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Human blood-derived osteoclast assays paired with HEK293 receptor signaling.
    limitations
    Cell-culture effects do not independently establish fracture reduction.
    nutrient_topic
    Strontium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Strontium
    plain_language
    The human-cell study measured function as well as a marker.
    primary_references
    Divergent effects of strontium and calcium-sensing receptor positive allosteric modulators (calcimimetics) on human osteoclast activity. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29714810/ · DOI 10.1111/bph.14344

    Strontium: calcium interactions, cellular mechanisms and mineralization (2026-09-19) · lines 254–260

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human blood-derived osteoclast assays paired with HEK293 receptor signaling. · source_derived_draft · unverified_draft

    ## strontium-human-osteoclast The human-cell study measured function as well as a marker. Strontium inhibited maturation, TRAP expression and hydroxyapatite resorption in human blood-derived osteoclast cultures. Model: Human blood-derived osteoclast assays paired with HEK293 receptor signaling. Limitations: Cell-culture effects do not independently establish fracture reduction. Evidence access: Primary abstract Divergent effects of strontium and calcium-sensing receptor positive allosteric modulators (calcimimetics) on human osteoclast activity. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29714810/ · DOI 10.1111/bph.14344
    Complete structured claim and evidence

  12. Strontium exposure decreased sclerostin protein expression in primary human osteoblast cultures in the 2011 study.

    Strontium ion / Sr2+ → Human sclerostin / SOST source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Human primary osteoblast culture.
    limitations
    Separate from the Akt branch; an earlier long-term culture report found increased SOST mRNA with an osteocyte-like phenotype. Protein, RNA, stage and time are not interchangeable.
    nutrient_topic
    Strontium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Strontium
    plain_language
    Removing a Wnt inhibitor can favor a bone-cell response.
    primary_references
    An Akt-dependent increase in canonical Wnt signaling and a decrease in sclerostin protein levels are involved in strontium ranelate-induced osteogenic effects in human osteoblasts. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21566129/ · DOI 10.1074/jbc.M111.251116

    Strontium: calcium interactions, cellular mechanisms and mineralization (2026-09-19) · lines 174–180

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human primary osteoblast culture. · source_derived_draft · unverified_draft

    ## strontium-human-sclerostin Removing a Wnt inhibitor can favor a bone-cell response. Strontium exposure decreased sclerostin protein expression in primary human osteoblast cultures in the 2011 study. Model: Human primary osteoblast culture. Limitations: Separate from the Akt branch; an earlier long-term culture report found increased SOST mRNA with an osteocyte-like phenotype. Protein, RNA, stage and time are not interchangeable. Evidence access: Primary abstract An Akt-dependent increase in canonical Wnt signaling and a decrease in sclerostin protein levels are involved in strontium ranelate-induced osteogenic effects in human osteoblasts. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21566129/ · DOI 10.1074/jbc.M111.251116
    Complete structured claim and evidence

  13. Strontium strongly inhibited mineral deposition while collagenous matrix structures remained apparent and osteoblast numbers were unchanged; ionized calcium remained in the medium.

    Strontium ion / Sr2+ → Mineralization in strontium-treated rat calvarial osteoblast cultures source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary full text
    experimental_model
    Same rat primary osteoblast cultures.
    limitations
    Does not establish that all bone effects are physicochemical, nor deny fracture outcomes in a clinical trial.
    nutrient_topic
    Strontium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Strontium
    plain_language
    Making a scaffold and depositing calcium mineral are different steps.
    primary_references
    Strontium potently inhibits mineralisation in bone-forming primary rat osteoblast cultures and reduces numbers of osteoclasts in mouse marrow cultures. · 2014 · https://pubmed.ncbi.nlm.nih.gov/25048011/ · DOI 10.1007/s00198-014-2791-5

    Strontium: calcium interactions, cellular mechanisms and mineralization (2026-09-19) · lines 278–284

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Same rat primary osteoblast cultures. · source_derived_draft · unverified_draft

    ## strontium-matrix-versus-mineral Making a scaffold and depositing calcium mineral are different steps. Strontium strongly inhibited mineral deposition while collagenous matrix structures remained apparent and osteoblast numbers were unchanged; ionized calcium remained in the medium. Model: Same rat primary osteoblast cultures. Limitations: Does not establish that all bone effects are physicochemical, nor deny fracture outcomes in a clinical trial. Evidence access: Primary full text Strontium potently inhibits mineralisation in bone-forming primary rat osteoblast cultures and reduces numbers of osteoclasts in mouse marrow cultures. · 2014 · https://pubmed.ncbi.nlm.nih.gov/25048011/ · DOI 10.1007/s00198-014-2791-5
    Complete structured claim and evidence

  14. Strontium salts reduced osteoclast formation and total resorption pits in mouse marrow cultures; the study attributed much of the lower total resorption to fewer osteoclasts.

    Strontium ion / Sr2+ → Osteoclast numbers in strontium-treated mouse marrow culture source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary full text
    experimental_model
    Eight-day mouse marrow cultures on dentine with M-CSF and RANKL.
    limitations
    Different assay from the murine sealing-zone study; total versus per-cell measures should not be collapsed.
    nutrient_topic
    Strontium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Strontium
    plain_language
    Total resorption can fall because there are fewer cells, not necessarily because each cell works less.
    primary_references
    Strontium potently inhibits mineralisation in bone-forming primary rat osteoblast cultures and reduces numbers of osteoclasts in mouse marrow cultures. · 2014 · https://pubmed.ncbi.nlm.nih.gov/25048011/ · DOI 10.1007/s00198-014-2791-5

    Strontium: calcium interactions, cellular mechanisms and mineralization (2026-09-19) · lines 286–292

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Eight-day mouse marrow cultures on dentine with M-CSF and RANKL. · source_derived_draft · unverified_draft

    ## strontium-osteoclast-number-versus-function Total resorption can fall because there are fewer cells, not necessarily because each cell works less. Strontium salts reduced osteoclast formation and total resorption pits in mouse marrow cultures; the study attributed much of the lower total resorption to fewer osteoclasts. Model: Eight-day mouse marrow cultures on dentine with M-CSF and RANKL. Limitations: Different assay from the murine sealing-zone study; total versus per-cell measures should not be collapsed. Evidence access: Primary full text Strontium potently inhibits mineralisation in bone-forming primary rat osteoblast cultures and reduces numbers of osteoclasts in mouse marrow cultures. · 2014 · https://pubmed.ncbi.nlm.nih.gov/25048011/ · DOI 10.1007/s00198-014-2791-5
    Complete structured claim and evidence

  15. Strontium dose-dependently induced apoptosis of primary mature rabbit osteoclasts through a CaSR-linked pathway.

    Strontium ion / Sr2+ → Apoptosis of mature rabbit osteoclasts source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Primary mature rabbit osteoclast study.
    limitations
    Species and high experimental exposures limit translation to human dietary intake.
    nutrient_topic
    Strontium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Strontium
    plain_language
    In this model, the ion can promote death of bone-resorbing cells.
    primary_references
    The calcium-sensing receptor is involved in strontium ranelate-induced osteoclast apoptosis. New insights into the associated signaling pathways. · 2009 · https://pubmed.ncbi.nlm.nih.gov/18927086/ · DOI 10.1074/jbc.M801668200

    Strontium: calcium interactions, cellular mechanisms and mineralization (2026-09-19) · lines 214–220

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Primary mature rabbit osteoclast study. · source_derived_draft · unverified_draft

    ## strontium-rabbit-apoptosis In this model, the ion can promote death of bone-resorbing cells. Strontium dose-dependently induced apoptosis of primary mature rabbit osteoclasts through a CaSR-linked pathway. Model: Primary mature rabbit osteoclast study. Limitations: Species and high experimental exposures limit translation to human dietary intake. Evidence access: Primary abstract The calcium-sensing receptor is involved in strontium ranelate-induced osteoclast apoptosis. New insights into the associated signaling pathways. · 2009 · https://pubmed.ncbi.nlm.nih.gov/18927086/ · DOI 10.1074/jbc.M801668200
    Complete structured claim and evidence

  16. Unlike calcium in the same experimental program, strontium-associated osteoclast apoptosis was independent of inositol 1,4,5-trisphosphate action.

    Strontium ion / Sr2+ → Apoptosis of mature rabbit osteoclasts source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Rabbit osteoclast pathway perturbations.
    limitations
    Absence of IP3 dependence here is not absence of calcium signaling in every strontium response.
    nutrient_topic
    Strontium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Strontium
    plain_language
    Similar ions need not use identical intracellular messengers.
    primary_references
    The calcium-sensing receptor is involved in strontium ranelate-induced osteoclast apoptosis. New insights into the associated signaling pathways. · 2009 · https://pubmed.ncbi.nlm.nih.gov/18927086/ · DOI 10.1074/jbc.M801668200

    Strontium: calcium interactions, cellular mechanisms and mineralization (2026-09-19) · lines 230–236

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Rabbit osteoclast pathway perturbations. · source_derived_draft · unverified_draft

    ## strontium-rabbit-ip3-difference Similar ions need not use identical intracellular messengers. Unlike calcium in the same experimental program, strontium-associated osteoclast apoptosis was independent of inositol 1,4,5-trisphosphate action. Model: Rabbit osteoclast pathway perturbations. Limitations: Absence of IP3 dependence here is not absence of calcium signaling in every strontium response. Evidence access: Primary abstract The calcium-sensing receptor is involved in strontium ranelate-induced osteoclast apoptosis. New insights into the associated signaling pathways. · 2009 · https://pubmed.ncbi.nlm.nih.gov/18927086/ · DOI 10.1074/jbc.M801668200
    Complete structured claim and evidence

  17. Strontium-induced rabbit osteoclast apoptosis required PLC-dependent signaling and PKC beta II activation, with nuclear NF-kappaB translocation.

    Strontium ion / Sr2+ → Rabbit protein kinase C beta II source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Rabbit mature-osteoclast signaling and inhibitor experiments.
    limitations
    Accessed abstract does not resolve PLC or NF-kappaB subunits; do not assign human proteins.
    nutrient_topic
    Strontium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Strontium
    plain_language
    The shared calcium sensor can use a distinct downstream pathway.
    primary_references
    The calcium-sensing receptor is involved in strontium ranelate-induced osteoclast apoptosis. New insights into the associated signaling pathways. · 2009 · https://pubmed.ncbi.nlm.nih.gov/18927086/ · DOI 10.1074/jbc.M801668200

    Strontium: calcium interactions, cellular mechanisms and mineralization (2026-09-19) · lines 222–228

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Rabbit mature-osteoclast signaling and inhibitor experiments. · source_derived_draft · unverified_draft

    ## strontium-rabbit-plc-pkc The shared calcium sensor can use a distinct downstream pathway. Strontium-induced rabbit osteoclast apoptosis required PLC-dependent signaling and PKC beta II activation, with nuclear NF-kappaB translocation. Model: Rabbit mature-osteoclast signaling and inhibitor experiments. Limitations: Accessed abstract does not resolve PLC or NF-kappaB subunits; do not assign human proteins. Evidence access: Primary abstract The calcium-sensing receptor is involved in strontium ranelate-induced osteoclast apoptosis. New insights into the associated signaling pathways. · 2009 · https://pubmed.ncbi.nlm.nih.gov/18927086/ · DOI 10.1074/jbc.M801668200
    Complete structured claim and evidence

  18. Calcium and strontium each competitively inhibited uptake of the other in the renal-vesicle assay, increasing apparent half-saturation concentration without changing maximum velocity.

    Strontium ion / Sr2+ → Calcium uptake by renal basolateral membrane vesicles source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary full text
    experimental_model
    Radiotracer uptake in isolated renal basolateral membranes.
    limitations
    Shared-site kinetics do not establish a dietary calcium-loss threshold or quantify whole-kidney excretion.
    nutrient_topic
    Strontium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Strontium
    plain_language
    The two ions compete for access to the same transport machinery.
    primary_references
    A Comparison Between Calcium and Strontium Transport by the (Ca2+ + Mg2+)ATPase of the Basolateral Plasma Membrane of Renal Proximal Convoluted Tubules. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40277992/ · DOI 10.3390/membranes15040122

    Strontium: calcium interactions, cellular mechanisms and mineralization (2026-09-19) · lines 22–28

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Radiotracer uptake in isolated renal basolateral membranes. · source_derived_draft · unverified_draft

    ## strontium-renal-competition The two ions compete for access to the same transport machinery. Calcium and strontium each competitively inhibited uptake of the other in the renal-vesicle assay, increasing apparent half-saturation concentration without changing maximum velocity. Model: Radiotracer uptake in isolated renal basolateral membranes. Limitations: Shared-site kinetics do not establish a dietary calcium-loss threshold or quantify whole-kidney excretion. Evidence access: Primary full text A Comparison Between Calcium and Strontium Transport by the (Ca2+ + Mg2+)ATPase of the Basolateral Plasma Membrane of Renal Proximal Convoluted Tubules. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40277992/ · DOI 10.3390/membranes15040122
    Complete structured claim and evidence

  19. Strontium-loaded drinking water at approximately 200 mg/kg/day caused growth-plate expansion, increased osteoid and reduced bone formation in rats with mild chronic renal failure.

    Strontium ion / Sr2+ → Rickets during strontium loading in rats with chronic renal failure source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Growing renal-failure rats; 2, 6 or 12 weeks of loading.
    limitations
    High animal exposure and disease context; not a human intake threshold or strontium deficiency.
    nutrient_topic
    Strontium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Strontium
    plain_language
    High exposure with impaired renal function can disrupt growing-bone mineralization.
    primary_references
    Moderate strontium loading induces rickets in rats with mild chronic renal failure. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21654178/ · DOI 10.1159/000328329

    Strontium: calcium interactions, cellular mechanisms and mineralization (2026-09-19) · lines 326–332

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Growing renal-failure rats; 2, 6 or 12 weeks of loading. · source_derived_draft · unverified_draft

    ## strontium-renal-loading-rickets High exposure with impaired renal function can disrupt growing-bone mineralization. Strontium-loaded drinking water at approximately 200 mg/kg/day caused growth-plate expansion, increased osteoid and reduced bone formation in rats with mild chronic renal failure. Model: Growing renal-failure rats; 2, 6 or 12 weeks of loading. Limitations: High animal exposure and disease context; not a human intake threshold or strontium deficiency. Evidence access: Primary abstract Moderate strontium loading induces rickets in rats with mild chronic renal failure. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21654178/ · DOI 10.1159/000328329
    Complete structured claim and evidence

  20. In the synaptotagmin-1 domain assays, strontium supported C2B/phospholipid complexes but not C2A/phospholipid complexes, whereas calcium supported both.

    Strontium ion / Sr2+ → Synaptotagmin-1 C2B domain in the strontium-binding assay source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Biochemical domain/phospholipid binding accompanying mouse neuronal experiments.
    limitations
    Accessed abstract does not identify the species of recombinant domain constructs; that identity remains unresolved.
    nutrient_topic
    Strontium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Strontium
    plain_language
    Different domains of a calcium sensor discriminate between the ions.
    primary_references
    Sr2+ binding to the Ca2+ binding site of the synaptotagmin 1 C2B domain triggers fast exocytosis without stimulating SNARE interactions. · 2003 · https://pubmed.ncbi.nlm.nih.gov/12526776/ · DOI 10.1016/s0896-6273(02)01145-5

    Strontium: calcium interactions, cellular mechanisms and mineralization (2026-09-19) · lines 358–364

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Biochemical domain/phospholipid binding accompanying mouse neuronal experiments. · source_derived_draft · unverified_draft

    ## strontium-syt-binding Different domains of a calcium sensor discriminate between the ions. In the synaptotagmin-1 domain assays, strontium supported C2B/phospholipid complexes but not C2A/phospholipid complexes, whereas calcium supported both. Model: Biochemical domain/phospholipid binding accompanying mouse neuronal experiments. Limitations: Accessed abstract does not identify the species of recombinant domain constructs; that identity remains unresolved. Evidence access: Primary abstract Sr2+ binding to the Ca2+ binding site of the synaptotagmin 1 C2B domain triggers fast exocytosis without stimulating SNARE interactions. · 2003 · https://pubmed.ncbi.nlm.nih.gov/12526776/ · DOI 10.1016/s0896-6273(02)01145-5
    Complete structured claim and evidence

  21. Unlike calcium, strontium did not stimulate synaptotagmin C2-domain binding to SNARE proteins even at high tested concentrations.

    Strontium ion / Sr2+ → Strontium-stimulated synaptotagmin/SNARE binding source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Biochemical protein-binding assays.
    limitations
    Negative result is specific to the stimulated-binding assay, not absence of SNARE machinery from exocytosis.
    nutrient_topic
    Strontium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Strontium
    plain_language
    Triggering release did not require every interaction induced by calcium.
    primary_references
    Sr2+ binding to the Ca2+ binding site of the synaptotagmin 1 C2B domain triggers fast exocytosis without stimulating SNARE interactions. · 2003 · https://pubmed.ncbi.nlm.nih.gov/12526776/ · DOI 10.1016/s0896-6273(02)01145-5

    Strontium: calcium interactions, cellular mechanisms and mineralization (2026-09-19) · lines 366–372

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Biochemical protein-binding assays. · source_derived_draft · unverified_draft

    ## strontium-syt-no-snare-stimulation Triggering release did not require every interaction induced by calcium. Unlike calcium, strontium did not stimulate synaptotagmin C2-domain binding to SNARE proteins even at high tested concentrations. Model: Biochemical protein-binding assays. Limitations: Negative result is specific to the stimulated-binding assay, not absence of SNARE machinery from exocytosis. Evidence access: Primary abstract Sr2+ binding to the Ca2+ binding site of the synaptotagmin 1 C2B domain triggers fast exocytosis without stimulating SNARE interactions. · 2003 · https://pubmed.ncbi.nlm.nih.gov/12526776/ · DOI 10.1016/s0896-6273(02)01145-5
    Complete structured claim and evidence

  22. In rat medullary thyroid carcinoma 6-23 cells, strontium biased CaSR signaling toward ERK1/2 relative to Gq/11 and intracellular-calcium mobilization compared with calcium.

    Strontium ion / Sr2+ → Rat calcium-sensing receptor / Casr source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Rat C-cell model; concentration-response measurements across six signaling outputs.
    limitations
    Biased agonism is model- and assay-dependent; not a direct human thyroid-hormone effect.
    nutrient_topic
    Strontium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Strontium
    plain_language
    The same receptor can send different relative signals depending on the ion.
    primary_references
    Strontium is a biased agonist of the calcium-sensing receptor in rat medullary thyroid carcinoma 6-23 cells. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22942242/ · DOI 10.1124/jpet.112.197210

    Strontium: calcium interactions, cellular mechanisms and mineralization (2026-09-19) · lines 342–348

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Rat C-cell model; concentration-response measurements across six signaling outputs. · source_derived_draft · unverified_draft

    ## strontium-thyroid-bias The same receptor can send different relative signals depending on the ion. In rat medullary thyroid carcinoma 6-23 cells, strontium biased CaSR signaling toward ERK1/2 relative to Gq/11 and intracellular-calcium mobilization compared with calcium. Model: Rat C-cell model; concentration-response measurements across six signaling outputs. Limitations: Biased agonism is model- and assay-dependent; not a direct human thyroid-hormone effect. Evidence access: Primary abstract Strontium is a biased agonist of the calcium-sensing receptor in rat medullary thyroid carcinoma 6-23 cells. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22942242/ · DOI 10.1124/jpet.112.197210
    Complete structured claim and evidence

What acts on it

  1. TRPV3 mediated strontium influx into mouse eggs in the reported channel and activation experiments.

    Mouse TRPV3 → Strontium ion / Sr2+ source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary full text
    experimental_model
    Mouse egg electrophysiology and genetic experiments.
    limitations
    Laboratory artificial activation; no claim about dietary strontium or human fertility.
    nutrient_topic
    Strontium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Strontium
    plain_language
    A calcium-permeable channel can also admit strontium in mouse eggs.
    primary_references
    TRPV3 channels mediate strontium-induced mouse-egg activation. · 2013 · https://pubmed.ncbi.nlm.nih.gov/24316078/ · DOI 10.1016/j.celrep.2013.11.007

    Strontium: calcium interactions, cellular mechanisms and mineralization (2026-09-19) · lines 382–388

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse egg electrophysiology and genetic experiments. · source_derived_draft · unverified_draft

    ## strontium-mouse-egg-entry A calcium-permeable channel can also admit strontium in mouse eggs. TRPV3 mediated strontium influx into mouse eggs in the reported channel and activation experiments. Model: Mouse egg electrophysiology and genetic experiments. Limitations: Laboratory artificial activation; no claim about dietary strontium or human fertility. Evidence access: Primary full text TRPV3 channels mediate strontium-induced mouse-egg activation. · 2013 · https://pubmed.ncbi.nlm.nih.gov/24316078/ · DOI 10.1016/j.celrep.2013.11.007
    Complete structured claim and evidence

  2. The reported uptake half-saturation concentrations were about 13.4 micromolar for Sr2+ and 0.28 micromolar for Ca2+, consistent with lower affinity for strontium.

    Renal proximal-tubule basolateral calcium/magnesium ATPase assay preparation → Strontium ion / Sr2+ source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary full text
    experimental_model
    Renal-vesicle uptake kinetics.
    limitations
    Assay-specific apparent affinities; do not assign them to every calcium channel or human compartment.
    nutrient_topic
    Strontium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Strontium
    plain_language
    Using the same pump does not mean being transported equally efficiently.
    primary_references
    A Comparison Between Calcium and Strontium Transport by the (Ca2+ + Mg2+)ATPase of the Basolateral Plasma Membrane of Renal Proximal Convoluted Tubules. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40277992/ · DOI 10.3390/membranes15040122

    Strontium: calcium interactions, cellular mechanisms and mineralization (2026-09-19) · lines 30–36

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Renal-vesicle uptake kinetics. · source_derived_draft · unverified_draft

    ## strontium-renal-affinity Using the same pump does not mean being transported equally efficiently. The reported uptake half-saturation concentrations were about 13.4 micromolar for Sr2+ and 0.28 micromolar for Ca2+, consistent with lower affinity for strontium. Model: Renal-vesicle uptake kinetics. Limitations: Assay-specific apparent affinities; do not assign them to every calcium channel or human compartment. Evidence access: Primary full text A Comparison Between Calcium and Strontium Transport by the (Ca2+ + Mg2+)ATPase of the Basolateral Plasma Membrane of Renal Proximal Convoluted Tubules. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40277992/ · DOI 10.3390/membranes15040122
    Complete structured claim and evidence

  3. Basolateral proximal-tubule membrane vesicles accumulated radiolabeled strontium in an ATP- and Mg2+-dependent transport assay.

    Renal proximal-tubule basolateral calcium/magnesium ATPase assay preparation → Strontium ion / Sr2+ source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary full text
    experimental_model
    Isolated renal membrane vesicles; 90Sr and 45Ca tracers; ATP/Mg uptake assays.
    limitations
    Accessed methods refer to a prior preparation protocol without resolving species or ATP2B isoform. The assay measures ion transport, not radiation injury or net human renal clearance.
    nutrient_topic
    Strontium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Strontium
    plain_language
    A calcium-handling membrane preparation can also pump strontium.
    primary_references
    A Comparison Between Calcium and Strontium Transport by the (Ca2+ + Mg2+)ATPase of the Basolateral Plasma Membrane of Renal Proximal Convoluted Tubules. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40277992/ · DOI 10.3390/membranes15040122
    transport_effect
    depends Membrane vesicles accumulated strontium in the assay, while the basolateral pump's role in the intact cell is extrusion toward blood; the two pools move opposite ways.
    transport_pool
    the proximal-tubule cell interior Membrane vesicles accumulated strontium in the assay, while the basolateral pump's role in the intact cell is extrusion toward blood; the two pools move opposite ways.

    Strontium: calcium interactions, cellular mechanisms and mineralization (2026-09-19) · lines 14–20

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Isolated renal membrane vesicles; 90Sr and 45Ca tracers; ATP/Mg uptake assays. · source_derived_draft · unverified_draft

    ## strontium-renal-uptake A calcium-handling membrane preparation can also pump strontium. Basolateral proximal-tubule membrane vesicles accumulated radiolabeled strontium in an ATP- and Mg2+-dependent transport assay. Model: Isolated renal membrane vesicles; 90Sr and 45Ca tracers; ATP/Mg uptake assays. Limitations: Accessed methods refer to a prior preparation protocol without resolving species or ATP2B isoform. The assay measures ion transport, not radiation injury or net human renal clearance. Evidence access: Primary full text A Comparison Between Calcium and Strontium Transport by the (Ca2+ + Mg2+)ATPase of the Basolateral Plasma Membrane of Renal Proximal Convoluted Tubules. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40277992/ · DOI 10.3390/membranes15040122
    Complete structured claim and evidence

Where it participates (unsigned role)

  1. Pharmacological Akt inhibition abolished strontium protection against osteoblast apoptosis in the tested wild-type and Casr-knockout mouse cultures.

    Mouse Akt protein family (isoform unresolved) → Strontium-associated survival of mouse osteoblasts source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_access
    Primary abstract
    experimental_model
    Serum deprivation or IL-1beta/TNF-alpha challenge in mouse osteoblasts.
    limitations
    Pharmacological evidence; Akt isoform unresolved.
    nutrient_topic
    Strontium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Strontium
    plain_language
    A downstream survival pathway remained necessary even when the receptor was absent.
    primary_references
    Calcium sensing receptor-dependent and receptor-independent activation of osteoblast replication and survival by strontium ranelate. · 2009 · https://pubmed.ncbi.nlm.nih.gov/20141614/ · DOI 10.1111/j.1582-4934.2009.00673.x
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Strontium: calcium interactions, cellular mechanisms and mineralization (2026-09-19) · lines 102–108

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Serum deprivation or IL-1beta/TNF-alpha challenge in mouse osteoblasts. · source_derived_draft · unverified_draft

    ## strontium-akt-survival A downstream survival pathway remained necessary even when the receptor was absent. Pharmacological Akt inhibition abolished strontium protection against osteoblast apoptosis in the tested wild-type and Casr-knockout mouse cultures. Model: Serum deprivation or IL-1beta/TNF-alpha challenge in mouse osteoblasts. Limitations: Pharmacological evidence; Akt isoform unresolved. Evidence access: Primary abstract Calcium sensing receptor-dependent and receptor-independent activation of osteoblast replication and survival by strontium ranelate. · 2009 · https://pubmed.ncbi.nlm.nih.gov/20141614/ · DOI 10.1111/j.1582-4934.2009.00673.x
    Complete structured claim and evidence

  2. Across 34 iliac biopsies after 2–60 months of ranelate treatment, secondary mineralization remained at a normal level while the bone area containing strontium increased.

    Strontium ranelate → Degree of mineralization in human ranelate-treatment biopsies source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Human iliac-bone microradiography and microanalysis.
    limitations
    Related clinical research program; not independent randomized proof of every cellular mechanism or absence of all adverse effects.
    nutrient_topic
    Strontium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Strontium
    plain_language
    A human biopsy series did not reproduce generalized mineralization failure.
    primary_references
    Distribution of strontium and mineralization in iliac bone biopsies from osteoporotic women treated long-term with strontium ranelate. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21690207/ · DOI 10.1530/EJE-11-0415

    Strontium: calcium interactions, cellular mechanisms and mineralization (2026-09-19) · lines 302–308

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human iliac-bone microradiography and microanalysis. · source_derived_draft · unverified_draft

    ## strontium-biopsy-mineralization A human biopsy series did not reproduce generalized mineralization failure. Across 34 iliac biopsies after 2–60 months of ranelate treatment, secondary mineralization remained at a normal level while the bone area containing strontium increased. Model: Human iliac-bone microradiography and microanalysis. Limitations: Related clinical research program; not independent randomized proof of every cellular mechanism or absence of all adverse effects. Evidence access: Primary abstract Distribution of strontium and mineralization in iliac bone biopsies from osteoporotic women treated long-term with strontium ranelate. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21690207/ · DOI 10.1530/EJE-11-0415
    Complete structured claim and evidence

  3. Biopsies from ranelate-treated osteoporotic women localized strontium mainly to bone structural units formed during treatment, with old units reported devoid of strontium in the analyzed samples.

    Strontium ranelate → Strontium deposition in newly formed human bone source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Human treatment biopsies; X-ray microanalysis and cartography, up to three years for these analyses.
    limitations
    Sampled iliac bone does not define uptake or release kinetics for the entire skeleton.
    nutrient_topic
    Strontium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Strontium
    plain_language
    Bone turnover determines where the element is incorporated.
    primary_references
    In osteoporotic women treated with strontium ranelate, strontium is located in bone formed during treatment with a maintained degree of mineralization. · 2010 · https://pubmed.ncbi.nlm.nih.gov/19597910/ · DOI 10.1007/s00198-009-1005-z

    Strontium: calcium interactions, cellular mechanisms and mineralization (2026-09-19) · lines 294–300

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human treatment biopsies; X-ray microanalysis and cartography, up to three years for these analyses. · source_derived_draft · unverified_draft

    ## strontium-bone-localization Bone turnover determines where the element is incorporated. Biopsies from ranelate-treated osteoporotic women localized strontium mainly to bone structural units formed during treatment, with old units reported devoid of strontium in the analyzed samples. Model: Human treatment biopsies; X-ray microanalysis and cartography, up to three years for these analyses. Limitations: Sampled iliac bone does not define uptake or release kinetics for the entire skeleton. Evidence access: Primary abstract In osteoporotic women treated with strontium ranelate, strontium is located in bone formed during treatment with a maintained degree of mineralization. · 2010 · https://pubmed.ncbi.nlm.nih.gov/19597910/ · DOI 10.1007/s00198-009-1005-z
    Complete structured claim and evidence

  4. AC-265347 and BTU-compound 13 potentiated calcium/strontium CaSR signaling in HEK293 cells but neither replicated nor potentiated strontium inhibition of human osteoclast function.

    AC-265347 and BTU-compound 13 CaSR modulators → Maturation, TRAP activity and resorption in human osteoclast cultures source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Paired receptor and human osteoclast experiments; cinacalcet behaved differently.
    limitations
    Distinct ligand and cell contexts; no claim that CaSR alone fully explains osteoclast effects.
    nutrient_topic
    Strontium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Strontium
    plain_language
    A stronger receptor assay signal did not guarantee the same cell-level outcome.
    primary_references
    Divergent effects of strontium and calcium-sensing receptor positive allosteric modulators (calcimimetics) on human osteoclast activity. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29714810/ · DOI 10.1111/bph.14344

    Strontium: calcium interactions, cellular mechanisms and mineralization (2026-09-19) · lines 262–268

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Paired receptor and human osteoclast experiments; cinacalcet behaved differently. · source_derived_draft · unverified_draft

    ## strontium-calcimimetic-dissociation A stronger receptor assay signal did not guarantee the same cell-level outcome. AC-265347 and BTU-compound 13 potentiated calcium/strontium CaSR signaling in HEK293 cells but neither replicated nor potentiated strontium inhibition of human osteoclast function. Model: Paired receptor and human osteoclast experiments; cinacalcet behaved differently. Limitations: Distinct ligand and cell contexts; no claim that CaSR alone fully explains osteoclast effects. Evidence access: Primary abstract Divergent effects of strontium and calcium-sensing receptor positive allosteric modulators (calcimimetics) on human osteoclast activity. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29714810/ · DOI 10.1111/bph.14344
    Complete structured claim and evidence

  5. The reported Casr knockout abolished rapid strontium-associated ERK1/2 phosphorylation in primary mouse osteoblasts.

    Mouse calcium-sensing receptor / Casr → Rapid ERK phosphorylation after strontium in mouse osteoblasts source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_access
    Primary full text, publicly accessible Methods and results
    experimental_model
    Mouse calvarial cells; exon-4-disrupted Casr model; SrCl2/sodium-ranelate mixture at 100:1, expressed as Sr2+ concentration.
    limitations
    Genotype and assay-specific finding; other response branches persisted.
    nutrient_topic
    Strontium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Strontium
    plain_language
    One signaling branch requires the receptor in this model.
    primary_references
    Calcium sensing receptor-dependent and receptor-independent activation of osteoblast replication and survival by strontium ranelate. · 2009 · https://pubmed.ncbi.nlm.nih.gov/20141614/ · DOI 10.1111/j.1582-4934.2009.00673.x
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Strontium: calcium interactions, cellular mechanisms and mineralization (2026-09-19) · lines 86–92

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse calvarial cells; exon-4-disrupted Casr model; SrCl2/sodium-ranelate mixture at 100:1, expressed as Sr2+ concentration. · source_derived_draft · unverified_draft

    ## strontium-casr-knockout-erk One signaling branch requires the receptor in this model. The reported Casr knockout abolished rapid strontium-associated ERK1/2 phosphorylation in primary mouse osteoblasts. Model: Mouse calvarial cells; exon-4-disrupted Casr model; SrCl2/sodium-ranelate mixture at 100:1, expressed as Sr2+ concentration. Limitations: Genotype and assay-specific finding; other response branches persisted. Evidence access: Primary full text, publicly accessible Methods and results Calcium sensing receptor-dependent and receptor-independent activation of osteoblast replication and survival by strontium ranelate. · 2009 · https://pubmed.ncbi.nlm.nih.gov/20141614/ · DOI 10.1111/j.1582-4934.2009.00673.x
    Complete structured claim and evidence

  6. Selective COX-2 inhibition abolished the proliferative and anti-apoptotic strontium responses in wild-type and Casr-knockout osteoblasts.

    Mouse cyclooxygenase-2 / Ptgs2 → Growth and survival responses to strontium in mouse osteoblasts source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_access
    Primary abstract
    experimental_model
    Mouse bone-cell inhibitor experiments; the paper also reports PGE2 production.
    limitations
    Not proof that dietary arachidonic acid or a COX-2 drug changes fracture benefit in humans.
    nutrient_topic
    Strontium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Strontium
    plain_language
    Prostaglandin-producing machinery links the response to lipid signaling.
    primary_references
    Calcium sensing receptor-dependent and receptor-independent activation of osteoblast replication and survival by strontium ranelate. · 2009 · https://pubmed.ncbi.nlm.nih.gov/20141614/ · DOI 10.1111/j.1582-4934.2009.00673.x
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Strontium: calcium interactions, cellular mechanisms and mineralization (2026-09-19) · lines 110–116

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse bone-cell inhibitor experiments; the paper also reports PGE2 production. · source_derived_draft · unverified_draft

    ## strontium-cox2-dependence Prostaglandin-producing machinery links the response to lipid signaling. Selective COX-2 inhibition abolished the proliferative and anti-apoptotic strontium responses in wild-type and Casr-knockout osteoblasts. Model: Mouse bone-cell inhibitor experiments; the paper also reports PGE2 production. Limitations: Not proof that dietary arachidonic acid or a COX-2 drug changes fracture benefit in humans. Evidence access: Primary abstract Calcium sensing receptor-dependent and receptor-independent activation of osteoblast replication and survival by strontium ranelate. · 2009 · https://pubmed.ncbi.nlm.nih.gov/20141614/ · DOI 10.1111/j.1582-4934.2009.00673.x
    Complete structured claim and evidence

  7. Trpv3-knockout mouse eggs failed to conduct Sr2+ or undergo strontium-induced activation.

    Mouse TRPV3 → Strontium-induced mouse egg activation source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_access
    Primary full text
    experimental_model
    Mouse Trpv3 genetic knockout.
    limitations
    Does not establish that channel expression alone is sufficient in other species.
    nutrient_topic
    Strontium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Strontium
    plain_language
    Removing the channel removes the experimental response.
    primary_references
    TRPV3 channels mediate strontium-induced mouse-egg activation. · 2013 · https://pubmed.ncbi.nlm.nih.gov/24316078/ · DOI 10.1016/j.celrep.2013.11.007
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Strontium: calcium interactions, cellular mechanisms and mineralization (2026-09-19) · lines 390–396

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse Trpv3 genetic knockout. · source_derived_draft · unverified_draft

    ## strontium-mouse-trpv3-loss Removing the channel removes the experimental response. Trpv3-knockout mouse eggs failed to conduct Sr2+ or undergo strontium-induced activation. Model: Mouse Trpv3 genetic knockout. Limitations: Does not establish that channel expression alone is sufficient in other species. Evidence access: Primary full text TRPV3 channels mediate strontium-induced mouse-egg activation. · 2013 · https://pubmed.ncbi.nlm.nih.gov/24316078/ · DOI 10.1016/j.celrep.2013.11.007
    Complete structured claim and evidence

  8. The strontium-ranelate study found NFATc1 nuclear translocation and increased transcriptional activity in murine MC3T3-E1 and primary osteoblasts.

    Strontium ranelate → Mouse NFATc1 source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Murine osteoblast nuclear-localization and reporter assays.
    limitations
    Cell-culture preparation and model; not direct human target engagement.
    nutrient_topic
    Strontium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Strontium
    plain_language
    A calcium-responsive transcription factor connects exposure to gene regulation.
    primary_references
    Essential role of nuclear factor of activated T cells (NFAT)-mediated Wnt signaling in osteoblast differentiation induced by strontium ranelate. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20554534/ · DOI 10.1074/jbc.M110.110502

    Strontium: calcium interactions, cellular mechanisms and mineralization (2026-09-19) · lines 118–124

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Murine osteoblast nuclear-localization and reporter assays. · source_derived_draft · unverified_draft

    ## strontium-nfat-activation A calcium-responsive transcription factor connects exposure to gene regulation. The strontium-ranelate study found NFATc1 nuclear translocation and increased transcriptional activity in murine MC3T3-E1 and primary osteoblasts. Model: Murine osteoblast nuclear-localization and reporter assays. Limitations: Cell-culture preparation and model; not direct human target engagement. Evidence access: Primary abstract Essential role of nuclear factor of activated T cells (NFAT)-mediated Wnt signaling in osteoblast differentiation induced by strontium ranelate. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20554534/ · DOI 10.1074/jbc.M110.110502
    Complete structured claim and evidence

  9. Omission of ATP or magnesium prevented strontium uptake in the tested renal membrane preparation; other tested nucleotides did not substitute for ATP.

    Mg2+ → Strontium uptake by renal membrane vesicles source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_access
    Primary full text
    experimental_model
    Isolated membrane-vesicle cofactor-dependence experiments.
    limitations
    Cofactor removal is experimental machinery impairment, not proof that dietary magnesium deficiency changes human strontium retention by a specified amount.
    nutrient_topic
    Strontium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Strontium
    plain_language
    The pump needs both its energy source and magnesium.
    primary_references
    A Comparison Between Calcium and Strontium Transport by the (Ca2+ + Mg2+)ATPase of the Basolateral Plasma Membrane of Renal Proximal Convoluted Tubules. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40277992/ · DOI 10.3390/membranes15040122
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Strontium: calcium interactions, cellular mechanisms and mineralization (2026-09-19) · lines 38–44

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Isolated membrane-vesicle cofactor-dependence experiments. · source_derived_draft · unverified_draft

    ## strontium-renal-cofactor-loss The pump needs both its energy source and magnesium. Omission of ATP or magnesium prevented strontium uptake in the tested renal membrane preparation; other tested nucleotides did not substitute for ATP. Model: Isolated membrane-vesicle cofactor-dependence experiments. Limitations: Cofactor removal is experimental machinery impairment, not proof that dietary magnesium deficiency changes human strontium retention by a specified amount. Evidence access: Primary full text A Comparison Between Calcium and Strontium Transport by the (Ca2+ + Mg2+)ATPase of the Basolateral Plasma Membrane of Renal Proximal Convoluted Tubules. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40277992/ · DOI 10.3390/membranes15040122
    Complete structured claim and evidence

  10. Synaptotagmin-1 knockout selectively impaired the fast component of both calcium- and strontium-induced neurotransmitter release in mouse neurons.

    Mouse synaptotagmin 1 / Syt1 → Fast strontium-triggered release at mouse synapses source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_access
    Primary abstract
    experimental_model
    Mouse synaptotagmin-1 knockout synaptic recordings.
    limitations
    Ion substitution in neuronal experiments is not evidence that oral strontium reaches or improves this pathway.
    nutrient_topic
    Strontium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Strontium
    plain_language
    Fast release needs this sensor even when strontium replaces calcium experimentally.
    primary_references
    Sr2+ binding to the Ca2+ binding site of the synaptotagmin 1 C2B domain triggers fast exocytosis without stimulating SNARE interactions. · 2003 · https://pubmed.ncbi.nlm.nih.gov/12526776/ · DOI 10.1016/s0896-6273(02)01145-5
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Strontium: calcium interactions, cellular mechanisms and mineralization (2026-09-19) · lines 374–380

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse synaptotagmin-1 knockout synaptic recordings. · source_derived_draft · unverified_draft

    ## strontium-syt-knockout Fast release needs this sensor even when strontium replaces calcium experimentally. Synaptotagmin-1 knockout selectively impaired the fast component of both calcium- and strontium-induced neurotransmitter release in mouse neurons. Model: Mouse synaptotagmin-1 knockout synaptic recordings. Limitations: Ion substitution in neuronal experiments is not evidence that oral strontium reaches or improves this pathway. Evidence access: Primary abstract Sr2+ binding to the Ca2+ binding site of the synaptotagmin 1 C2B domain triggers fast exocytosis without stimulating SNARE interactions. · 2003 · https://pubmed.ncbi.nlm.nih.gov/12526776/ · DOI 10.1016/s0896-6273(02)01145-5
    Complete structured claim and evidence

In the sources

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    This is a research prototype built from draft material. It is not medical advice, and its statements still await verification against the original studies.

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