Comparative evaluation of remineralisation potential of bioactive glass, casein phosphopeptide-amorphous calcium phosphate and novel strontium-doped nanohydroxyapatite paste: An In-Vitro study.

Background: Many studies explained the importance of remineralisation of early carious lesions with various remineralising agents. In the present study, we incorporated the remineralising agents in a dentifrice, applied that in artificial enamel caries and evaluated their remineralising potential and compared the efficacy among the three. Aim: To evaluate and compare the remineralisation potential of a dentifrice containing bioactive glass, casein phosphopeptide-amorphous calcium phosphate and novel laboratory synthesised strontiumdoped nanohydroxyapatite paste in artificial enamel caries. Methods and Materials: 120 enamel specimens were divided into 4 groups of 30 specimens each, based on the type of dentifrice applied: GI - conventional toothpaste (control group), GII - calcium sodium phosphosilicate (Novamin), GIII - casein phosphopeptide-amorphous calcium phosphate (GC tooth mousse) and GIV- Novel strontiumdoped nanohydroxyapatite paste (SrnHAp paste). Specimens in all the groups were subjected to demineralisation, and calcium/phosphorous ratio was analysed followed by remineralisation and the mean calcium-phosphorus ratio was assessed using a scanning electron microscope and energy dispersing X-ray analysis. Statistical Analysis: Data were analysed using IBM SPSS Statistics for Windows Software, version 22 (IBM Corp., Armonk, NY, USA). Descriptive statistics were used to calculate the mean and standard deviation. Kruskal-Wallis, ANOVA and Mann-Whitney tests were used. The level of significance was set at 5%. Results and Conclusion: All except the control group showed a net increase in calcium and phosphorous values after application of the respective remineralising agents in respective groups. Inter-group comparison revealed that Group IV - SrnHAp paste yields higher net calcium and phosphorous values than other groups. Hence, novel SrnHAp can be considered as the material of choice in remineralising early enamel carious lesions.

Effect of strontium-doped bioactive glass-ceramic containing toothpaste on prevention of artificial dentine caries formation: an in vitro study.

BACKGROUD: Root caries in aging population was prevalent worldwide. Due to the absence of enamel and specific structure of dentine, bacteria are able to penetrate further into dentine at an earlier stage of lesion development. The aim of this study was to investigate the effect of adding of a strontium-doped bioactive glass-ceramic (HX-BGC) to a fluoride-free toothpaste on prevention of formation of artificial dentine caries. METHODS: Thirty-six human tooth specimens were allocated to three groups (n = 12 per group). Group 1 treated with slurry containing a fluoride-free toothpaste and 5% HX-BGC, Group 2 was treated with fluoride-free toothpaste slurry, and Group 3 received deionized water as a negative control. The specimens were subjected to four cycles (15 h demineralization and 8 h remineralization for one cycle) of biochemical cycling. A mixed suspension of five bacteria species (Streptococcus mutans, Streptococcus sobrinus, Lactobacillus acidophilus, Lactobacillus rhamnosus, and Actinomyces naeslundii) were prepared in brain heart infusion broth with 5% sucrose and used as acidic challenge in biochemical cycling. Subsequently, surface morphology of the dentine lesion was assessed by scanning electron microscopy, while the lesion depths and mineral loss were assessed by micro-computed tomography. RESULTS: The mean lesion depths in dentine in Groups 1 to 3 were 87.79 ± 16.99 µm, 101.06 ± 10.04 µm and 113.60 ± 16.36 µm, respectively (p = 0.002). The mean amounts of mineral loss in Groups 1 to 3 were 0.82 ± 0.10 g/cm3, 0.89 ± 0.09 g/cm3 and 0.96 ± 0.11 g/cm3, respectively (p = 0.016). No obvious differences in the surface morphology were seen among the groups. CONCLUSION: Addition of strontium-doped bioactive glass-ceramic to fluoride-free toothpaste has potential to reduce formation of dentine lesions.

Does the incorporation of strontium into calcium phosphate improve bone repair? A meta-analysis.

BACKGROUND: The application of calcium phosphate (CaP)-based bone substitutes plays an important role in periodontal regeneration, implant dentistry and alveolar bone reconstruction. The incorporation of strontium (Sr) into CaP-based bone substitutes appears to improve their biological properties, but the reported in vivo bone repair performance is inconsistent among studies. Herein, we conducted a systematic review and meta-analysis to investigate the in vivo performance of Sr-doped materials. METHODS: We searched PubMed, EMBASE (via OVIDSP), and reference lists to identify relevant animal studies. The search, study selection, and data extraction were performed independently by two investigators. Meta-analyses and sub-group analyses were conducted using Revman version 5.4.1. The heterogeneity between studies were assessed by I2. Publication bias was investigated through a funnel plot. RESULTS: Thirty-five studies were finally enrolled, of which 16 articles that reported on new bone formation (NBF) were included in the meta-analysis, covering 31 comparisons and 445 defects. The overall effect for NBF was 2.25 (95% CI 1.61-2.90, p < 0.00001, I2 = 80%). Eight comparisons from 6 studies reported the outcomes of bone volume/tissue volume (BV/TV), with an overall effect of 1.42 (95% CI 0.65-2.18, p = 0.0003, I2 = 75%). Fourteen comparisons reported on the material remaining (RM), with the overall effect being -2.26 (95% CI - 4.02 to - 0.50, p = 0.0009, I2 = 86%). CONCLUSIONS: Our study revealed that Sr-doped calcium phosphate bone substitutes improved in vivo performance of bone repair. However, more studies are also recommended to further verify this conclusion.

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

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.

The Influence of Strontium on Bone Tissue Metabolism and Its Application in Osteoporosis Treatment.

Osteoporosis is a chronic disease characterized by low bone mass caused by increased bone turnover and impaired bone microarchitecture. In treatment, we use antiresorptive or anabolic drugs, which usually have a unidirectional effect, i.e., they inhibit the activity of osteoclasts or stimulate the effect of osteoblasts. Strontium ranelate is an anti-osteoporosis drug with a unique mechanism of action (used primarily in postmenopausal women). Unlike other medicines, it has a multidirectional effect on bone tissue, intensifying osteoblastogenesis while inhibiting osteoclastogenesis. It turns out that this effect is demonstrated by strontium ions, an element showing physical and chemical similarity to calcium, the basic element that builds the mineral fraction of bone. As a result, strontium acts through the calcium-sensing receptor (CaSR) receptor in bone tissue cells. In recent years, there has been a significant increase in interest in the introduction of strontium ions in place of calcium ions in ceramics used as bone replacement materials for the treatment of bone fractures and defects caused by osteoporosis. The aim of this study was to summarize current knowledge about the role of strontium in the treatment of osteoporosis, its effects (in various forms), and the ways in which it is administered.

Synthesis of carboxymethyl chitosan-strontium complex and its therapeutic effects on relieving osteoarthritis.

Osteoarthritis (OA) is an age-related joint disorder and one of the leading causes of physical disability. In this study, we designed and synthesized a new polysaccharide complex, carboxymethyl chitosan strontium (CMCS-Sr), which is believed to have positive effects on relieving OA. The synthesized CMCS-Sr was structurally verified by SEM, EDS, FTIR, etc. The therapeutic effects of CMCS-Sr were evaluated using various biological experiments. The cell viability and apoptosis results reveal that CMCS-Sr can significantly promote the proliferation and suppress OA chondrocytes apoptosis in vitro. The immunofluorescence staining results suggest that CMCS-Sr facilitates the promotion of the secretion of Type II collagen (Col-II). The transcriptomic results support the observed positive effects of CMCS-Sr on inhibiting chondrocytes apoptosis and alleviating inflammatory reactions. Moreover, animal study demonstrates that CMCS-Sr effectively reduced articular cartilage damage and subchondral bone degradation. Therefore, we propose the use of CMCS-Sr as a promising candidate for relieving OA.

The Translation from In Vitro Bioactive Ion Concentration Screening to In Vivo Application for Preventing Peri-implantitis.

Peri-implantitis is a typical pathological condition characterized by the destructive inflammation in the soft tissue and the progressive loss of supporting bones. As the current effective treatments and preventive measures are inconsistent and unpredictable, the use of biomaterials as carriers of bioactive ion coatings is a promising approach. However, the translation from lab to large-scale production and clinical applications is difficult due to a technology barrier. Determining the effective dosage of each ion to achieve an in vivo application of the in vitro screening is challenging. Here, we selected zinc and strontium ions to provide multiple effects on antibacterial activity and osteogenesis. The optimal coating with effective release concentrations of the two ions was obtained after the two-step screening from in vitro testing. The results showed that this type of in vivo bioactive ion usage leads to an enhanced osseointegration during the immediate implantation in a periodontitis-affected environment and prevents soft tissue inflammation and bone resorption in an inflammatory environment. The new biologically active ion screening method could verify the effectiveness of this clinical translation and its potential for large-scale production and could determine the effective dosage of each ion for a specific application.

Monitoring and Handing of 89Sr Injection Site Extravasation in a Patient With Breast Cancer.

Extravasation of various imaging tracers during administration was not a rare complication during nuclear medicine practice. However, the occurrence of extravasation of therapeutic radiopharmaceutical was rarely reported. Here we reported a 60-year-old woman with breast cancer and diffuse painful bone metastases who received strontium chloride (SrCl2) therapy to palliate her bone pain. Accidental subcutaneous extravasation in the injection site occurred. The extravasated Sr was absorbed rapidly by arm elevation, squeezing a stress ball, local warming, and gently massaging. Follow-up results showed the patient's bone pain significantly relieved and her right arm remained normal.

Strontium­containing α­calcium sulfate hemihydrate promotes bone repair via the TGF­ß/Smad signaling pathway.

Calcium phosphate­based bone substitutes have been widely used for bone repair, augmentation and reconstruction in bone implant surgery. While some of these substitutes have shown excellent biological efficacy, there remains a need to improve the performance of the current calcium phosphate­based bone substitutes. Strontium ions (Sr) can promote new osteogenesis, inhibit osteoclast formation and increase osteoconductivity. However, the therapeutic effect and mechanism of strontium­containing α­calcium sulfate hemihydrate (Sr­CaS) remains unclear. The present study created bone injuries in rats and treated the injuries with Sr­CaS. Then Cell Counting Kit­8, soft agar colony formation, flow cytometry, Transwell and Alizarin Red staining assays were performed to assess the bone cells for their proliferation, growth, apoptosis, invasion, and osteogenic differentiation abilities. The bone reconstructive states were measured by the microCT method, hematoxylin and eosin staining and Masson staining. Bone­related factors were analyzed by the reverse transcription­quantitative PCR assay; transforming growth factor (TGF)­ß, mothers against decapentaplegic homolog (Smad)2/3 and ß­catenin expression was measured by western blot analysis and osteocalcin (OCN) expression was assessed by immunohistochemistry. Sr­CaS did not significantly affect the proliferation and apoptosis of bone marrow stem cells (BMSCs), but did accelerate the migration and osteogenic differentiation of BMSCs in vitro. Sr­CaS promoted bone repair and significantly increased the values for bone mineral density, bone volume fraction, and trabecular thickness, but decreased trabecular spacing in vivo in a concentration­-dependent manner. In addition, Sr­CaS dramatically upregulated the expression levels of genes associated with osteogenic differentiation (Runt­related transcription factor 2, Osterix, ALP, OCN and bone sialoprotein) both in vitro and in vivo. Sr­CaS also increased Smad2/3, TGF­ß and phosphorylated­ß­catenin protein expression in vitro and in vivo. These results indicated that materials that contain 5 or 10% Sr can improve bone defects by regulating the TGF­ß/Smad signaling pathway.

Bibliographic review on the state of the art of strontium and zinc based regenerative therapies. Recent developments and clinical applications.

Musculoskeletal disorders such as osteoporosis and rheumatoid arthritis are responsible for more than 25k deaths every year in the European Union and constitute a chronic burden on the individuals who suffer from this condition. There is no medical cure for these diseases and there are many therapies applied which have limited effectiveness and severe side effects over time. Regenerative therapies are being studied as a potential treatment for musculoskeletal diseases and are known for their upgrading effects of the natural healing processes carried out in the human body. It is believed that both strontium and zinc play an essential role in bone and cartilage tissue formation, which has led many scientists to study the effect of including these elements to promote tissue formation and inhibit its resorption. In this review, a deep analysis is undertaken of the most relevant developments in strontium and zinc based regenerative therapies that have occurred in the last five years, taking into consideration only those studies reporting significant progress towards real clinical applications. This review brings up to date the state of the art of strontium and zinc based regenerative therapies as it is believed that both have a promoting effect on tissue formation and have an essential role inhibiting resorption in musculoskeletal disorders.

Tumoricidal effect and pain relief after concurrent therapy by strontium-89 chloride and zoledronic acid for bone metastases.

OBJECTIVE: The purpose of this study was to investigate the palliative and tumoricidal effects of concurrent therapy of strontium-89 chloride (89SrCl2) and zoledronic acid (ZA) for painful bone metastases. SUBJECTS AND METHODS: Fifty-one patients with painful bone metastases prostate cancer (n=17), lung cancer (n=13), breast cancer (n=12), other cancers (n=9) were treated. Bone metastases was confirmed in all patients by technetium-99m hydroxymethylene diphosphonate (99mTc-HMDP) bone scintigraphy. The numeric rating scale (NRS) and performance status (PS) were used to assess the degree of pain and patients' physical condition. The extent of bone metastases was assessed with imaging modalities including CT, MRI and/or 99mTc bone scintigraphy before treatment and 2 or 3 months after. RESULTS: The pain relief response of 89SrCl2 with ZA for bone metastases was 94% (48/51) from 1 to 3 months after treatment. The tumoricidal effect of concurrent therapy by 89SrCl2 with ZA for painful bone metastases was 8/22 as shown by imaging modalities and the rate of non-progressive disease (non-PD) was 19/22. Pain due to bone metastases assessed with the NRS was significantly improved (P<0.001) in many types of primary cancer, including prostate, breast and lung cancers. CONCLUSION: Concurrent therapy of 89SrCl2 with ZA may offer not only pain relief, but also a tumoricidal effect for painful bone metastases.

Comparison of the efficacy of strontium-89 chloride in treating bone metastasis of lung, breast, and prostate cancers.

OBJECTIVE: The aim of this study was to comparatively evaluate the efficacy of strontium-89 chloride (89 SrCl2) in treating bone metastasis-associated pain in patients with lung, breast, or prostate cancer. MATERIALS AND METHODS: The 126 patients with lung cancer included 88, 16, 15, 4, and 3 patients with adenocarcinoma, squamous cell carcinoma, nonsmall cell carcinoma, mixed carcinoma, and small cell carcinoma, respectively, and the control group consisted of patients with breast (71 patients) or prostate cancer (49 patients) who underwent 89 SrCl2 treatment during the same period. The treatment dose of 89 SrCl2 was 2.22 MBq/kg. RESULTS: The efficacy rate of treatment in the lung cancer group was 75.4%, compared to 95.0% in the control group. Approximately 67% of patients with lung cancer and bone metastases and 47% of control patients exhibited mild-to-moderate reductions of leukocyte and platelet counts 4 weeks after 89 SrCl2 treatment. CONCLUSIONS: 89 SrCl2 can safely and effectively relieve bone pain caused by bone metastasis from lung cancer. However, its efficacy was lower in patients with lung cancer with bone metastasis than in those with breast or prostate cancer with bone metastasis, and its effects on the peripheral hemogram were also significantly stronger in the lung cancer group.

Injectable simvastatin gel for minimally invasive periosteal distraction: In vitro and in vivo studies in rat.

OBJECTIVES: To evaluate whether the subperiosteal injection of simvastatin (SIM) with a novel in situ gel-forming system, SrHA/Alg (strontium hydroxyapatite/alginate), can stimulate vertical bone augmentation in a rat calvarial model. MATERIAL AND METHODS: The SrHA/Alg solution was synthesized and combined with different doses of SIM (0.01, 0.02, 0.1, and 0.2 mg) to form the following groups: (1) SrHA/Alg only, (2) SrHA/Alg/0.01, (3) SrHA/Alg/0.02, (4) SrHA/Alg/0.1, and (5) SrHA/Alg/0.2. The SIM release pattern was analyzed, and rat primary periosteum-derived cell (PDC) responses were investigated. Twenty male Wistar rats were enrolled in the calvarial subperiosteal injection experiment with each animal receiving a 200-µl single subperiosteal injection of SrHA/Alg with different amounts of SIM (0, 0.01, 0.02, and 0.1 mg) incorporated (n = 5). The 0.2 mg dose group was not tested in vivo due to the severe toxicity found in vitro. The new bone formation was assessed histologically and radiologically at 8 weeks. RESULTS: The slow release of SIM was confirmed, and PDC viability decreased in the SrHA/Alg/0.2 group. Alkaline phosphatase positive areas and mineralization areas were significantly greater in the SrHA/Alg/0.01 and SrHA/Alg/0.02 groups (p < .05). The mRNA expression level of Runx2 significantly increased in the SrHA/Alg/SIM-0.02 group by day 7 (p < .05) and significantly higher levels of VEGF were found in the SrHA/Alg/0.01 and SrHA/Alg/0.02 groups at different time points (p < .05). In vivo, no prominent clinical sign of inflammation was observed, and the most significant bone gain was shown in the SrHA/Alg/0.02 group (p < .05). The osteoclast formation within the newly formed bone area was reduced in the SrHA/Alg/0.1 group (p < .05). CONCLUSIONS: When combined with SrHA/Alg system, the 0.02 mg SIM seemed to be the optimal dose to stimulate subperiosteal bone formation without inducing inflammation. This combination may hold potential therapeutic benefits for clinical bone augmentation in a minimally invasive manner.

Low-dose strontium stimulates osteogenesis but high-dose doses cause apoptosis in human adipose-derived stem cells via regulation of the ERK1/2 signaling pathway.

BACKGROUND: Strontium is a widely used anti-osteoporotic agent due to its dual effects on inhibiting bone resorption and stimulating bone formation. Thus, we studied the dose response of strontium on osteo-inductive efficiency in human adipose-derived stem cells (hASCs). METHOD: Qualitative alkaline phosphatase (ALP) staining, quantitative ALP activity, Alizarin Red staining, real-time polymerase chain reaction and Western blot were used to investigate the in vitro effects of a range of strontium concentrations on hASC osteogenesis and associated signaling pathways. RESULTS: In vitro work revealed that strontium (25-500 µM) promoted osteogenic differentiation of hASCs according to ALP activity, extracellular calcium deposition, and expression of osteogenic genes such as runt-related transcription factor 2, ALP, collagen-1, and osteocalcin. However, osteogenic differentiation of hASCs was significantly inhibited with higher doses of strontium (1000-3000 µM). These latter doses of strontium promoted apoptosis, and phosphorylation of ERK1/2 signaling was increased and accompanied by the downregulation of Bcl-2 and increased phosphorylation of BAX. The inhibition of ERK1/2 decreased apoptosis in hASCs. CONCLUSION: Lower concentrations of strontium facilitate osteogenic differentiation of hASCs up to a point; higher doses cause apoptosis of hASCs, with activation of the ERK1/2 signaling pathway contributing to this process.

The Incorporation of Strontium in a Sodium Alginate Coating on Titanium Surfaces for Improved Biological Properties.

Orthopedic implant failure is mainly attributed to the poor bonding of the implant to bone tissue. An effective approach to minimize the implant failure would be modifying the surface of the implant. Strontium (Sr) can stimulate the proliferation and differentiation of osteoblasts and reduce the activity of osteoclasts. In this study, a titanium (Ti) surface was successively functionalized by covalently grafting dopamine, sodium alginate (SA), and Sr2+ via the electrostatic immobilization method. The as-prepared coatings on the Ti surface were characterized by using scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FT-IR), and contact angle. The results indicated that the Sr-incorporated coatings were successfully prepared and that Sr distributed uniformly on the surface. A long-lasting and sustained Sr release had been observed in Sr2+ release studies. The Ti/DOPA/SA/Sr exhibited little cytotoxicity and a robust effect of Sr incorporation on the adhesion and spreading of MG63 cells. The proliferation and alkaline phosphatase (ALP) activity of MG63 cells were enhanced by immobilizing Sr2+ on the SA-grafted Ti. The Sr-containing coatings, which displayed excellent biocompatibility and osteogenic activity, may provide a promising solution for promoting the tissue integration of implants.

Effect of titanium implants with strontium incorporation on bone apposition in animal models: A systematic review and meta-analysis.

This systematic review aims to assess the efficacy of titanium (Ti) implant surfaces with or without strontium (Sr) incorporation on osseointegration in animal experimental studies. An electronic search was conducted using databases of PubMed and EMBASE up to November 2016 to identify studies focusing on osseointegration of strontium-modified titanium implants following PRISMA criteria. The primary outcome was the percentage of bone-to-implant contact (BIC) around the implants with or without strontium-modified surface. Of the 1320 studies, 17 studies fulfilling the inclusion criteria were finally included. A random effect meta-analysis was conducted based on BIC in 17 studies, and the results demonstrated considerable heterogeneity (I² = 79%). A sensitivity analysis found that three studies using the same surface modification method were the major source of the heterogeneity. Therefore, exploratory subgroup analysis was performed. Subgroup one including 14 studies showed a standard mean differences (SMD) of 1.42 (95% CI, 1.13-1.71) with no heterogeneity (I² = 0.0%), while subgroup two including the other three studies showed a SMD of 9.49.95% CI, 7.51-11.47) with low heterogeneity (I² = 0.1%). Sr-modified implants in both subgroups showed significantly higher BIC than unmodified implants (P < 0.01). The results showed a statistically significant effect of Sr-modified titanium implant surfaces on osseointegration and bone apposition in animal models.

Osteoporose: seleção de medicamentos e avanços no manejo clínico / Osteoporosis: medication selection and advances in the clinical management

Osteoporose é um problema de saúde pública importante que acomete mais de metade das mulheres com idade superior a 50 anos. Doença com um enorme impacto sobre a saúde pública, através da morbidade e mortalidade aumentadas, com custos econômicos associados resultantes das fraturas. O objetivo é avaliar e identificar as pessoas de risco para desenvolver fraturas osteoporóticas de fragilidade que necessitam ser tratadas. A abordagem de mulheres com baixa massa óssea e aumento do risco de fraturas deve ser multidisciplinar. A farmacoterapia é apenas uma Steiner ML, Strufaldi R, Fernandes CE das possíveis intervenções. Aspectos como a nutrição orientada, fortalecimento muscular, prevenção de quedas, suplementos vitamínicos e minerais devem ser considerados. O tratamento farmacológico permite a prevenção da perda óssea, a prevenção primária e secundária de fragilidade óssea e deve ser baseado na avaliação do risco de fratura do indivíduo e na relação custo-benefício do medicamento escolhido.

Osteoporosis is a significant public health problem that affects more than half of women aged over 50. This disease has a huge impact on public health through morbidity and increased mortality, and economic costs associated with the resulting fractures. The goal is to assess and identify risk people to develop osteoporotic fragility fractures that need to be addressed. The approach of women with low bone mass and increased risk of fractures should be multidisciplinary. Pharmacotherapy is just one of the possible interventions. Aspects such as the guidance nutrition, muscle strengthening, prevention of falls, mineral and vitamin supplements should be considered. Pharmacological treatment allows preventing bone loss and primary and secondary prevention of osteoporosis and should be based on risk factors and pharmaceutical cost benefit analysis.

Strontium-loaded titania nanotube arrays repress osteoclast differentiation through multiple signalling pathways: In vitro and in vivo studies.

The loosening of implants is an important clinical issue, particularly for patients with osteoporosis. In these patients, an implant should preferably both promote osteoblast differentiation and repress osteoclastic resorption. In the present study, we fabricated coatings containing TiO2 nanotubes (NTs) incorporated with strontium (Sr) on titanium (Ti) surfaces through hydrothermal treatment. The amount of loaded Sr was controlled by hydrothermally treating the samples in a Sr(OH)2 solution for 1 and 3 h (samples NT-Sr1h and NT-Sr3h, respectively) and found that both types of NT-Sr samples inhibited osteoclast differentiation by reducing the expression of osteoclast marker genes. Additionally, this inhibitory effect was mainly attributed to suppression of RANKL-induced activation of nuclear factor-κB (NF-κB). Moreover, NT-Sr also inhibited the Akt and nuclear factor of activated T-cell cytoplasmic 1 (NFATc1) signalling pathways. Interestingly, we also found that NT-Sr promoted RANKL-induced extracellular signal-regulated kinase (ERK) phosphorylation. Using ovariectomised rats as a model, we observed that NT-Sr prevented bone loss in vivo. In conclusion, our findings demonstrate that NT-Sr might effectively inhibit osteoclast differentiation by repressing the NF-κB and Akt/NFATc1 pathways and by negatively regulating the ERK pathway in vitro and in vivo.

Evaluación de la respuesta densitométrica en pacientes con osteoporosis posmenopáusica tratadas con ranelato de estroncio o denosumab / Densitometric response in postmenopausal osteoporosis treated with strontium ranelate or denosumab

Tanto el ranelato de estroncio (RSr) como el denosumab (Dmab) son eficaces en el tratamiento de la osteoporosis (OP) posmenopáusica (PM). El efecto de cada fármaco por separado sobre la densidad mineral ósea (DMO) ha sido estudiado recientemente. Con ambas drogas se observó, al año de tratamiento, un aumento significativo de la DMO en columna lumbar (CL), cuello femoral (CF) y cadera total (CT). En este trabajo comparamos la respuesta densitométrica al año de tratamiento con una y otra droga. Utilizamos los registros de 425 pacientes PMOP tratadas con Dmab y 441 tratadas con RSr. En cada paciente analizamos el porcentaje de cambio; se clasificaron como respondedoras aquellas que mostraron un cambio ≥3%. Adicionalmente se comparó la respuesta en pacientes no previamente tratadas con bifosfonatos (BF-naïve) en comparación con pacientes que habían recibido previamente un BF. Al analizar el grupo completo para Dmab, el porcentaje de pacientes respondedoras fue de 68,4% en CL, 63,3% en CF y 49,3% en CT. Por otro lado, en el grupo de pacientes tratadas con RSr, el porcentaje de respondedoras (53,8% en CL, 40,0% en CF y 35,6% en CT) fue estadísticamente menor. Cuando comparamos la respuesta entre las pacientes BF-naïve que recibieron RSr o Dmab, el Dmab indujo mayor respuesta en CL y CF que el grupo RSr, sin diferencias en CT. Cuando se analizaron los subgrupos BF-previo, las tratadas con Dmab mostraron mayor respuesta en todas las regiones. Conclusión: en pacientes con OP-PM, el tratamiento con Dmab produjo mayores incrementos densitométricos que el RSr, siendo el porcentaje de pacientes respondedoras mayor con Dmab que con RSr. (AU)

Both strontium ranelate (SrR) and denosumab (Dmab) are effective in the treatment of postmenopausal osteoporosis (PMOP). The effect of each drug on bone mineral density (BMD) has been studied separately by us. With both treatments, there was a significant increase after one year of treatment at the lumbar spine (LS) and hip. In this paper we compared the densitometric response after one year of treatment with both drugs used separately. We used the clinical records of 425 PM patients treated with Dmab and 441 treated with SrR. For each patient we analyzed the percentage of change; those who showed a change ≥3% were classified as responders. Additionally, the response was compared in patients not previously treated with bisphosphonates (BP-naïve) compared to patients who had previously received a BP. When analyzing the complete group for Dmab, the percentage of "responders" was 65.2% at the LS, 62.9% at the femoral neck (FN) and 47.4% at the total hip (TH). On the other hand, in the group of patients treated with SrR the percentage of responders (53.8% at the LS, 40.0% at the FN and 35.6% at the TH) was statistically lower. When comparing the response between in BF-naïve patients receiving RSr or Dmab, Dmab induced a greater response at the LS and FN than the RSr group, with no statistical differences at the TH. When the subgroups with prior BP treatment were analyzed, those treated with Dmab showed greater response in all regions. Conclusion: in patients with PMOP treatment with Dmab produced greater densitometric increments than SrR, and the percentage of responders was higher with Dmab than with SrR. (AU)