Advertisement
Journal of Prosthetic Dentistry

Efficacy of strontium supplementation on implant osseointegration under osteoporotic conditions: A systematic review

  • Wei Lu
    Affiliations
    MD of Dentistry candidate, Attending physician, Department of Periodontics, The Affiliated Hospital of Stomatology, School of Stomatology, Zhejiang University School of Medicine and Key Laboratory of Oral Biomedical Research of Zhejiang Province, Hangzhou, Zhejiang, PR China
    Search for articles by this author
  • Yi Zhou
    Affiliations
    Associate Chief Physician, Department of Implantology, The Affiliated Hospital of Stomatology, School of Stomatology, Zhejiang University School of Medicine, Hangzhou, Zhejiang, PR China
    Search for articles by this author
  • Hang Yang
    Affiliations
    Master of Dentistry candidate, Department of Prosthodontics, The Affiliated Hospital of Stomatology, School of Stomatology, Zhejiang University School of Medicine, Hangzhou, Zhejiang, PR China
    Search for articles by this author
  • Zijian Cheng
    Affiliations
    Resident Physician, Department of Periodontics, The Affiliated Hospital of Stomatology, School of Stomatology, Zhejiang University School of Medicine, Hangzhou, Zhejiang, PR China
    Search for articles by this author
  • Fuming He
    Correspondence
    Corresponding author: Dr Fuming He, Department of Prosthodontics and Implantology, The Affiliated Hospital of Stomatology, Zhejiang University School of Medicine, Key Laboratory of Oral Biomedical Research, No. 395 Yan’an Road, Hangzhou, Zhejiang 310006, PR CHINA
    Affiliations
    Chief Physician, Department of Prosthodontics and Implantology, The Affiliated Hospital of Stomatology, School of Stomatology, Zhejiang University School of Medicine, Hangzhou, Zhejiang, PR China
    Search for articles by this author
Published:February 12, 2021DOI:https://doi.org/10.1016/j.prosdent.2020.12.031

      Abstract

      Statement of problem

      Strontium has been validated for potent bone-seeking and antiosteoporotic properties and elicits a potentially beneficial impact on implant osseointegration in patients with osteoporosis. However, the efficacy of strontium supplementation on improving new bone formation and implant osseointegration in the presence of osteoporotic bone is still unclear.

      Purpose

      The purpose of this systematic review was to comprehensively assess the efficacy of strontium supplementation, encompassing oral intake and local delivery of strontium, on implant osseointegration in patients with osteoporosis.

      Material and methods

      Searches on electronic databases (MEDLINE or PubMed, Web of Science, EBSCO, Embase, and Clinicaltrials.gov) and manual searches were conducted to identify relevant preclinical animal trials up to June 2020. The primary outcomes were the percentage of bone-implant contact and bone area; the secondary outcomes were quantitative parameters of biomechanical tests and microcomputed tomography (μCT).

      Results

      Fourteen preclinical trials (1 rabbit, 1 sheep, and 12 rat), with a total of 404 ovariectomized animals and 798 implants, were eligible for analysis. The results revealed a significant 17.1% increase in bone-implant contact and 13.5% increase in bone area, favoring strontium supplementation despite considerable heterogeneity. Subgroup analyses of both bone-implant contact and bone area exhibited similar outcomes with low to moderate heterogeneity. Results of biomechanical and μCT tests showed that strontium-enriched implantation tended to optimize the mechanical strength and microarchitecture of newly formed bone despite moderate to generally high heterogeneity.

      Conclusions

      Based on the available preclinical evidence, strontium supplementation, including local and systemic delivery, showed promising results for enhancing implant osseointegration in the presence of osteoporosis during 4 to 12 weeks of healing. Future well-designed standardized studies are necessary to validate the efficacy and safety of strontium supplementation and to establish a standard methodology for incorporating Sr into implant surfaces in a clinical setting.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Journal of Prosthetic Dentistry
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Raisz L.G.
        Pathogenesis of osteoporosis: concepts, conflicts, and prospects.
        J Clin Investig. 2005; 115: 3318-3325
      1. NIH consensus development panel on osteoporosis prevention, diagnosis and therapy.
        J Am Med Assoc. 2001; 285: 785-795
        • Beppu K.
        • Kido H.
        • Watazu A.
        • Teraoka K.
        • Matsuura M.
        Peri-implant bone density in senile osteoporosis-changes from implant placement to osseointegration.
        Clin Implant Dent Relat Res. 2013; 15: 217-226
        • Temmerman A.
        • Rasmusson L.
        • Kübler A.
        • Thor A.
        • Merheb J.
        • Quirynen M.
        A prospective, controlled, multicenter study to evaluate the clinical outcome of implant treatment in women with osteoporosis/osteopenia: 5-year results.
        J Dent Res. 2019; 98: 84-90
        • Dahl S.
        • Allain P.
        • Marie P.
        • Mauras Y.
        • Boivin G.
        • Ammann P.
        • et al.
        Incorporation and distribution of strontium in bone.
        Bone. 2001; 28: 446-453
        • Bonnelye E.
        • Chabadel A.
        • Saltel F.
        • Jurdic P.
        Dual effect of strontium ranelate: stimulation of osteoblast differentiation and inhibition of osteoclast formation and resorption in vitro.
        Bone. 2008; 42: 129-138
        • Yang F.
        • Yang D.
        • Tu J.
        • Zheng Q.
        • Cai L.
        • Wang L.
        Strontium enhances osteogenic differentiation of mesenchymal stem cells and in vivo bone formation by activating Wnt/catenin signaling.
        Stem Cells. 2011; 29: 981-991
        • Peng S.
        • Liu X.S.
        • Huang S.
        • Li Z.
        • Pan H.
        • Zhen W.
        • et al.
        The cross-talk between osteoclasts and osteoblasts in response to strontium treatment: involvement of osteoprotegerin.
        Bone. 2011; 49: 1290-1298
        • McCaslin Jr., F.
        • Janes J.
        The effect of strontium lactate in the treatment of osteoporosis.
        Mayo Clin Proc. 1959; 34: 329-334
        • Marie P.J.
        • Felsenberg D.
        • Brandi M.L.
        How strontium ranelate, via opposite effects on bone resorption and formation, prevents osteoporosis.
        Osteoporos Int. 2011; 22: 1659-1667
        • Scardueli C.R.
        • Bizelli-Silveira C.
        • Marcantonio R.A.C.
        • Marcantonio E.
        • Stavropoulos A.
        • Spin-Neto R.
        Systemic administration of strontium ranelate to enhance the osseointegration of implants: systematic review of animal studies.
        Int J Implant Dent. 2018; 4: 21-29
        • Rizzoli R.
        • Laroche M.
        • Krieg M.A.
        • Frieling I.
        • Thomas T.
        • Delmas P.
        • et al.
        Strontium ranelate and alendronate have differing effects on distal tibia bone microstructure in women with osteoporosis.
        Rheumatol Int. 2010; 30: 1341-1348
        • Javed F.
        • Almas K.
        Osseointegration of dental implants in patients undergoing bisphosphonate treatment: a literature review.
        J Periodontol. 2010; 81: 479-484
        • Girotra M.
        • Rubin M.R.
        • Bilezikian J.P.
        The use of parathyroid hormone in the treatment of osteoporosis.
        Rev Endocr Metab Disord. 2007; 7: 113-121
        • Arcos D.
        • Boccaccini A.R.
        • Bohner M.
        • Diezperez A.
        • Epple M.
        • Gomezbarrena E.
        • et al.
        The relevance of biomaterials to the prevention and treatment of osteoporosis.
        Acta Biomater. 2014; 10: 1793-1805
        • Xin Y.
        • Jiang J.
        • Huo K.
        • Hu T.
        • Chu P.K.
        Bioactive SrTiO3 nanotube arrays: strontium delivery platform on Ti-based osteoporotic bone implants.
        Acs Nano. 2009; 3: 3228-3234
        • Li Y.
        • Luo E.
        • Zhu S.
        • Li J.
        • Zhang L.
        • Hu J.
        Cancellous bone response to strontium-doped hydroxyapatite in osteoporotic rats.
        J Appl Biomater Funct Mater. 2015; 13: 28-34
        • Wei L.
        • Ke J.
        • Prasadam I.
        • Miron R.J.
        • Lin S.
        • Xiao Y.
        • et al.
        A comparative study of Sr-incorporated mesoporous bioactive glass scaffolds for regeneration of osteopenic bone defects.
        Osteoporos Int. 2014; 25: 2089-2096
        • Zhao R.
        • Chen S.
        • Zhao W.
        • Yang L.
        • Yuan B.
        • Ioan V.S.
        • et al.
        A bioceramic scaffold composed of strontium-doped three-dimensional hydroxyapatite whiskers for enhanced bone regeneration in osteoporotic defects.
        Theranostics. 2020; 10: 1572-1589
        • Shi J.
        • Li Y.
        • Gu Y.
        • Qiao S.
        • Zhang X.
        • Lai H.
        Effect of titanium implants with strontium incorporation on bone apposition in animal models: a systematic review and meta-analysis.
        Sci Rep. 2017; 7: 1-10
        • Moher D.
        • Liberati A.
        • Tetzlaff J.
        • Altman D.G.
        The PRISMA group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement.
        Open Med. 2009; 3: e123-e130
        • Higgins J.P.
        • Thompson S.G.
        Quantifying heterogeneity in a meta-analysis.
        Stat Med. 2002; 21: 1539-1558
      2. Higgins JP, Green S, eds. Cochrane handbook for systematic reviews of interventions, Version 5.1.0 (updated March 2011). Available at: http://handbook-5-1.cochrane.org/. Accessed June 8, 2020.

        • Lin G.
        • Zhou C.
        • Lin M.
        • Xu A.
        • He F.
        Strontium-incorporated titanium implant surface treated by hydrothermal reactions promotes early bone osseointegration in osteoporotic rabbits.
        Clin Oral Implant Res. 2019; 30: 777-790
        • Liu F.
        • Li Y.
        • Liang J.
        • Sui W.
        • Bellare A.
        • Kong L.
        Effects of micro/nano strontium-loaded surface implants on osseointegration in ovariectomized sheep.
        Clin Implant Dent Relat Res. 2019; 21: 377-385
        • Offermanns V.
        • Andersen O.Z.
        • Riede G.
        • Andersen I.H.
        • Almtoft K.P.
        • Sørensen S.
        • et al.
        Bone regenerating effect of surface-functionalized titanium implants with sustained-release characteristics of strontium in ovariectomized rats.
        Int J Nanomedicine. 2016; 11: 2431-2442
        • Tao Z.S.
        • Bai B.L.
        • He X.W.
        • Liu W.
        • Li H.
        • Zhou Q.
        • et al.
        A comparative study of strontium-substituted hydroxyapatite coating on implant’s osseointegration for osteopenic rats.
        Med Biol Eng Comput. 2016; 54: 1959-1968
        • Tao Z.S.
        • Zhou W.S.
        • He X.W.
        • Liu W.
        • Bai B.L.
        • Zhou Q.
        • et al.
        A comparative study of zinc, magnesium, strontium-incorporated hydroxyapatite-coated titanium implants for osseointegration of osteopenic rats.
        Mater Sci Eng C. 2016; 62: 226-232
        • Zhang J.
        • Liu L.
        • Zhao S.
        • Wang H.
        • Yang G.
        Characterization and in vivo evaluation of trace element-loaded implant surfaces in ovariectomized rats.
        Int J Oral Maxillofac Implant. 2015; 30: 1105-1112
        • Li Y.
        • Li Q.
        • Zhu S.
        • Luo E.
        • Li J.
        • Feng G.
        • et al.
        The effect of strontium-substituted hydroxyapatite coating on implant fixation in ovariectomized rats.
        Biomaterials. 2010; 31: 9006-9014
        • Chen B.
        • Li Y.
        • Yang X.
        • Xu H.
        • Xie D.
        Zoledronic acid enhances bone-implant osseointegration more than alendronate and strontium ranelate in ovariectomized rats.
        Osteoporos Int. 2013; 24: 2115-2121
        • Li Y.
        • Li X.
        • Song G.
        • Chen K.
        • Yin G.
        • Hu J.
        Effects of strontium ranelate on osseointegration of titanium implant in osteoporotic rats.
        Clin Oral Implant Res. 2012; 23: 1038-1044
        • Li Y.
        • Feng G.
        • Gao Y.
        • Luo E.
        • Liu X.
        • Hu J.
        Strontium ranelate treatment enhances hydroxyapatite-coated titanium screws fixation in osteoporotic rats.
        J Orthop Res. 2009; 28: 578-582
        • Liang Y.
        • Li H.
        • Xu J.
        • Li X.
        • Li X.
        • Yan Y.
        • et al.
        Strontium coating by electrochemical deposition improves implant osseointegration in osteopenic models.
        Exp Ther Med. 2015; 9: 172-176
        • Zhou C.
        • Chen Y.Q.
        • Zhu Y.H.
        • Lin G.F.
        • Zhang L.
        • Liu X.
        • et al.
        Antiadipogenesis and osseointegration of strontium-doped implant surfaces.
        J Dent Res. 2019; 98: 795-802
        • Tao Z.S.
        • Zhou W.S.
        • Qiang Z.
        • Tu K.K.
        • Huang Z.L.
        • Xu H.M.
        • et al.
        Intermittent administration of human parathyroid hormone (1-34) increases fixation of strontium-doped hydroxyapatite coating titanium implants via electrochemical deposition in ovariectomized rat femur.
        J Biomater Appl. 2015; 30: 952-960
        • Abrahamsen B.
        • Grove E.
        • Vestergaard P.
        Nationwide registry-based analysis of cardiovascular risk factors and adverse outcomes in patients treated with strontium ranelate.
        Osteoporos Int. 2014; 25: 757-762
        • Musette P.
        • Kaufman J.
        • Rizzoli R.
        • Cacoub P.
        • Brandi M.L.
        • Reginster J.
        Cutaneous side effects of antiosteoporosis treatments.
        Ther Adv Musculoskelet Dis. 2011; 3: 31-41
        • Linderbäck P.
        • Agholme F.
        • Wermelin K.
        • Närhi T.
        • Tengvall P.
        • Aspenberg P.
        Weak effect of strontium on early implant fixation in rat tibia.
        Bone. 2012; 50: 350-356
        • Pearce A.I.
        • Richards R.G.
        • Milz S.
        • Schneider E.
        • Pearce S.G.
        Animal models for implant biomaterial research in bone: a review.
        Eur Cell Mater. 2007; 13: 1-10
        • Botticelli D.
        • Lang N.P.
        Dynamics of osseointegration in various human and animal models-a comparative analysis.
        Clin Oral Implants Res. 2017; 28: 742-748
        • Gittens R.A.
        • Olivares-Navarrete R.
        • Schwartz Z.
        • Boyan B.D.
        Implant osseointegration and the role of microroughness and nanostructures: lessons for spine implants.
        Acta Biomater. 2014; 10: 3363-3371