Strontium enhances proliferation and osteogenic behavior of periodontal ligament cells in vitro.

BACKGROUND AND OBJECTIVE: Strontium (Sr) enhances osteogenic differentiation of certain multipotent cells. Periodontal ligament cells (PDLCs) are known to be multipotent, and Sr might be useful in periodontal bone tissue engineering. This study investigates the effect of high concentration of Sr on the proliferation and osteogenic behavior of PDLCs in vitro. MATERIAL AND METHODS: Primary human PDLCs were cultured in MEM + 10% FBS without (Ctrl) or with Sr in four diverse concentrations: Sr1, 11.3 × 10-3  mg/L, human serum physiological level; Sr2, 13 mg/L, typical human serum level after strontium ranelate treatment; Sr3, 130 mg/L, and Sr4, 360 mg/L. The spreading area (2, 4, 6, 24 hours), proliferation rate (1, 3, 7 days), osteogenic behavior (alkaline phosphatase - ALP activity, 7 and 14 days; expression of osteogenic genes, ALP, Runt-related transcription factor 2 - RUNX2, osteopontin - OPN, osteocalcin - OCN, and osteoprotegerin -OPG, 1, 3, 7, 14, 21 days), and formation of mineralized nodules (14 and 21 days) of the PDLCs were assessed. Data were compared group- and period-wise using ANOVA tests. RESULTS: Periodontal ligament cells cultured with Sr4 showed increased spreading area (after 4 hours), proliferation rate (from 3 days), and OCN and OPN (from 7 days) gene expression as compared to Ctrl, Sr1, Sr2, and Sr3. Sr4 also led to lower ALP activity (from 7 days), ALP (from 3 days), and RUNX2 (at 7 and 14 days) gene expression, together with more evident formation of mineralized nodules, compared to Ctrl, Sr1, Sr2, and Sr3. CONCLUSION: Periodontal ligament cells responded to Sr4 with increased cellular proliferation and osteogenic behavior in vitro.

Strontium enhances proliferation and osteogenic behavior of bone marrow stromal cells of mesenchymal and ectomesenchymal origins in vitro.

Obejective: To investigate the effect of increasing Strontium (Sr) concentrations on the growth and osteogenic behavior of human bone marrow stromal cells (BMSCs) from mesenchymal (i.e., fibula) and ectomesenchymal (i.e., mandible) embryonic origins. Materials and methods: Fibula and mandible BMSCs were cultured in media without (Ctrl) or with Sr in four diverse concentrations: Sr1, 11.3 × 10-3 mg/L, human seric physiological level; Sr2, 13 mg/L, human seric level after strontium ranelate treatment; Sr3, 130 mg/L, and Sr4, 360 mg/L. Proliferation rate (1, 3, and 7 days), osteogenic behavior (alkaline phosphatase [ALP] activity, 7 and 14 days; expression of osteogenic genes (ALP, osteopontin, and osteocalcin at 7, 14, and 21 days), and formation of mineralized nodules (14 and 21 days) of the BMSCs were assessed. Data was compared group- and period-wise using analysis of variance tests. Results: Fibula and mandible BMSCs cultured with Sr4 showed increased proliferation rate, and osteocalcin and osteopontin gene expression together with more evident formation of mineralized nodules, compared all other Sr concentrations. For both cell populations, Sr4 led to lower ALP activity, and ALP gene expression, compared with the other Sr concentrations. Conclusion: BMSCs from mesenchymal (i.e., fibula) and ectomesenchymal (i.e., mandible) embryonic origins showed increased cellular proliferation and osteogenic behavior when cultured with Sr4, in vitro.

Systemic administration of strontium ranelate to enhance the osseointegration of implants: systematic review of animal studies.

The literature states that Strontium (Sr) is able to simultaneously stimulate bone formation and suppress bone resorption. Recent animal studies suggest that the systemic administration of Sr, in the form of strontium ranelate (SRAN), would enhance the osseointegration of implants. The purpose of the present study was to undertake a systematic review on animal studies evaluating the systemic administration of Sr to enhance the osseointegration of titanium implants and the remodeling of bone grafts. The MEDLINE (PubMed) and Scopus bibliographic databases were searched from 1950 to October 2017 for reports on the use of systemic and non-radioactive Sr to enhance the osseointegration of titanium implants and the remodeling of bone grafts in animals. The search strategy was restricted to English language publications using the combined terms: "strontium" and "implant or graft or biomaterial or bone substitute". Five studies were included, all related to the systemic administration of Sr in the form SRAN, and its effects on osseointegration of titanium implants. No studies on the use of SRAN-based therapy to enhance the remodeling of bone grafts were found. The studies differed notably with respect to the study population (healthy female rats, healthy male rats, and female rats with induced osteoporosis) and SRAN dose (ranging from 500 to 1000 mg/kg/day). Results were diverse, but a tendency suggesting positive influence of systemic SRAN administration on the osseointegration of titanium implants was observed. No major side-effects due to strontium administration were reported. Systemic Sr administration, in the form of SRAN, seems to enhance peri-implant bone quality and implant osseointegration in animals, however, at a moderate extent. Further studies, evaluating both the effects of this drug on implant osseointegration and the risk/benefit of its use, are needed to provide a rationale of this therapeutic approach.