Strontium

Supplementation of CaP-based bone graft substitutes with bioinorganics such as strontium, zinc or silicon is an interesting approach to increase the biological performance in terms of bone regenerative potential of calcium phosphate (CaP)-based bone substitutes. However, the in vivo efficacy of this approach has not been systematically analyzed, yet. Consequently, we performed a systematic review using the available literature regarding the effect of bioinorganic supplementation in CaP-based biomaterials on new bone formation and material degradation in preclinical animal bone defect models and studied this effect quantitatively by performing a meta-analysis. Additional subgroup analyses were used to study the effect of different bioinorganics, animal model, or phase category of CaP-based biomaterial on bone formation or material degradation. Results show that bioinorganic supplementation increases new bone formation (standardized mean difference [SMD]: 1.43 SD, confidence interval [CI]: 1.13-1.73). Additional subgroup analysis showed that strontium, magnesium and silica significantly enhanced bone formation, while zinc did not have any effect. This effect of bioinorganic supplementation on new bone formation was stronger for DCPD or β-TCP and biphasic CaPs than for HA or α-TCP (p < 0.001). In general, material degradation was slightly hindered by bioinorganic supplementation (mean difference [MD]: 0.84%, CI: 0.01-1.66), with the exception of strontium that significantly enhanced degradation. Overall, bioinorganic supplementation represents an effective approach to enhance the biological performance of CaP-based bone substitutes.

The study aimed to evaluate the remineralizing effect of hydroxyapatite and fluoride containing toothpastes (HAF's) on active caries lesions compared to a fluoridated standard toothpaste in pre/schoolchildren. A total of 610 children (4-5 and 6-7 years old) were enrolled. Four toothpastes, 2 containing fluoride-substituted hydroxyapatite (HAF) (1000 and 1450 ppmF) and magnesium-, strontium-, carbonate-substituted hydroxyapatite, in a chitosan matrix and 2 Mono fluoridated toothpastes (NaMFP) (1000 and 1450 ppmF), were randomly administered for 24 months. The children were instructed to brush for 2 minutes 3 times/day. Caries activities, by clinical surface features, were recorded at baseline and 12- and 24-month follow-ups. A per-protocol analysis was adopted, thus excluding children lost to follow-up. Overall, 518 children completed the trial. Baseline comparisons revealed no significant differences in primary teeth caries rates between HAF and NaMFP groups, both for enamel and dentinal lesions. By the end of the study, the HAF group exhibited a statistically significant reduction in enamel lesions compared to the NaMFP group (P < .01). Of the 40 partially active lesions at baseline in the HAF group, 13 were inactive at the 2-year follow-up. Of the active lesions in the HAF group (n = 78) at baseline, nearly 3-quarters (n = 58) were inactive at the follow-up. The difference between the 2 groups (HAF vs NaMFP) in terms of change of status in primary dentition (active at baseline and inactive at follow-up) was statistically significant (P = .04). Regarding dentinal lesions, both groups presented similar percentages of inactive lesions that were filled at the end of follow-up (P = .08). However, the HAF group demonstrated a higher number of inactivated lesions compared to the NaMFP group. The toothpaste containing biomimetic hydroxyapatite and fluoride may be better for children with active caries lesion in primary dentition.

OBJECTIVES: This randomised clinical trial was designed and carried out with the aim to evaluate the capacity of fluoride-substituted hydroxyapatite (HAF) toothpaste to modulate oral microflora composition and biofilm acidogenicity in schoolchildren. METHODS: In all, 610 children (4 to 5 and 6 to 7 years) were enrolled. Four toothpastes were randomly administered during 24 months: 2 contained fluoride-substituted hydroxyapatite (HAF1000 and HAF1450; 1000 and 1450 ppmF) and magnesium-, strontium-, and carbonate-substituted hydroxyapatite in a chitosan matrix, and 2 were monofluorophosphate fluoridated toothpastes (F1000 and F1450; 1000 and 1450 ppmF). Caries lesions were assessed by International Caries Detection and Assessment System scores, supragingival plaque was sampled from the approximal sites between primary molars using sterile Gracey curettes for microbiological analysis, and plaque pH curves after sucrose challenge were assessed at baseline and reevaluated after 1 year and after 2 years. The minimum and maximum pH decrease was calculated for caries-free patients and participants with a caries lesion(s) at baseline and at the end of the experimental period (24 months). Differences amongst measurements were analysed with 1-way analysis of variance. RESULTS: During the trial, the minimum pH value increased statistically significantly in all groups; in HAF1000 and HAF1450, the increase was greatest. At the end of trial, in the 2 HAF groups all primary cariogenic bacteria were statistically significantly lower with respect to F groups (P = .03 for Streptococcus mutans and sobrinus, for Lactobacillus casei, and for Lactobacillus fermentum). CONCLUSIONS: The trial provides robust but still inconclusive evidence on the efficacy of HAF toothpastes compared to traditional fluoridated toothpastes to reduce caries risk factors and to prevent caries lesions.

The 4-week double-blind clinical trial to manage dentin hypersensitivity (DH) using different desensitizing toothpastes was conducted. 53 participants with DH were enrolled in this trial. The participants were randomized into 3 groups: Group N; no active ingredient-containing toothpaste (Pleasia fluoride-free), Group SC; a toothpaste containing strontium chloride (Sensodyne Original), and Group TP; a toothpaste containing tricalcium phosphate (Vussen S). They were instructed to brush their teeth manually for 3 min, 3 times per day for 4 weeks with the allocated toothpastes, and were assessed at baseline (0), 2, and 4 weeks, respectively. Schiff sensitivity score was recorded to 3 different stimuli (air-blast, cold, and acid) at each assessment. Overall DH was also assessed using a visual analog scale (VAS). The longer participants used the toothpastes, the greater reduction in DH in all groups to the three stimuli. Group TP demonstrated significant reduction of DH compared to group N for air-blast and cold stimuli. Group TP showed significantly lower VAS than group N and SC. Tricalcium phosphate containing toothpaste used in this trial was most useful to reduce DH. It can be one of the treatment options that alleviate DH. © 2023. The Author(s).

INTRODUCTION: β-ray strontium-89 (Sr-89) intra-irradiation therapy has been approved and clinically used to reduce bone metastasis pain not alleviated by bone-modifying agents, external radiation, and analgesic agents. We examined the efficacy of zoledronic acid (ZOL) and Sr-89 combination therapy compared with ZOL alone in breast cancer patients with bone metastases. MATERIALS AND METHODS: A randomized controlled trial was conducted on breast cancer patients with bone metastasis to compare the efficacy between ZOL monotherapy and ZOL plus Sr-89 combination therapy. The primary endpoints were changes in urinary NTX levels at 13 weeks and brief pain inventory scores. The secondary endpoints were analgesic drug usages, response rates, changes in bone metabolism markers, quality of life, and adverse event rates. RESULTS: Thirty of the planned 60 cases were randomly assigned to ZOL alone or ZOL + Sr-89. There were no significant differences in the changes in urinary NTX levels between the 2 groups (P = 0.365). There was no consistent difference in the pain score changes between the 2 groups. Sr-89 addition to ZOL slightly reduced the white blood cell and platelet counts. However, all adverse events were Grade 1. Safety and analgesic drug dose reduction were more evident in ZOL + Sr-89. CONCLUSION: This trial showed the lack of benefits from Sr-89 addition to ZOL for breast cancer patients with painful bone metastases. However, safety and analgesic drug dose reduction were more evident in ZOL + Sr-89, indicating its potential for pain control. Sr-89 therapy is safe, thus more effective radiopharmaceuticals are anticipated. © 2022. The Japanese Society Bone and Mineral Research.

OBJECTIVES: The aim of this RCT was to compare the caries preventive efficacy and the slowing down of previous caries lesions of toothpastes containing fluoride biomimetic hydroxyapatite (HA) complex compared to sodium monofluorophosphate fluoridated toothpastes in Italian schoolchildren. To validate this hypothesis a triple-blind randomized clinical trial was designed. METHODS: In total 610 children (4-5 and 6-7 years) were enrolled. Four toothpastes, two containing fluoride-substituted hydroxyapatite (HAF) (1000 and 1450 ppmF) and magnesium-, strontium-, carbonate-substituted hydroxyapatite, in a chitosan matrix and two Mono fluoridated toothpastes (1000 and 1450 ppmF) were randomly administered during 24 months to two groups with younger children (Gyoung) and to two groups with older children (Gold), those containing 1450 ppmF. ICDAS was used to score lesions as initial (up to score 2), moderate (scores 3-4) and severe (scores 5-6). The children were instructed to brush for two minutes three times/day. Caries examination was repeated at 12 and 24 months. The efficacy of the treatment was assessed by calculating the reduction in Risk Ratio (RR) and the number needed to treat (NNT). Results; Overall, 518 patients (Gyoung = 268; Gold = 250) concluded the trial. The drop-rate was 11.84% for Gyoung and 17.22% for Gold. The caries increment at 24-month evaluation was statistically lower in the primary dentition in the HAF arms compared to the traditional fluoridated arms (0.18 vs 0.27 p = 0.04 in Gyoung and 0.16 vs 0.30 p = 0.01 in Gold for severe lesions). In the permanent dentition (Gold), caries increase was also statistically lower in the HAF arm, both for initial and severe lesions (0.09 vs 0.17 p = 0.02 and 0.18 vs 0.28 p = 0.01, respectively). In primary dentition, children receiving HAF Toothpaste had a RR of 39% (Gyoung) and 38% (Gold), compared to children receiving traditional Toothpastes. The RR in the permanent dentition was 29% in children treated with HAF toothpaste. Conclusions; The use of toothpastes containing biomimetic hydroxyapatite and fluoride reduces caries increment in children over a period of 2 years more than traditional fluoridated toot

BACKGROUND: Dentin hypersensitivity (DH) is a sharp toothache that influences a patients' oral health-related quality of life. Oral dentifrices have been marketed for pain relief within a minute for DH. The permanent management of DH is being investigated with the remineralisation potential of bioactive agents in dentinal tubules. This study investigated the relief from pain in DH in one minute after applying over the counter (OTC) dentifrices with Pro-Argin™ and strontium acetate and directly compared them with fluoro-calcium phospho-silicate (FCPS)-based dentifrices for immediate and sustained inhibition of painful stimulus provoking DH. METHODS: A randomised, controlled, triple-blinded clinical trial was conducted with 140 participants clinically diagnosed with DH and equally randomized into four groups with parallel treatment assignment of FCPS, Pro-Argin™, 8% strontium acetate, and sodium fluoride-based OTC dentifrices, and tested for DH with air blast, mechanical, and water jet stimuli on SCHIFF cold air sensitivity scale (SCASS) and visual analogue scale (VAS) at interim efficacy intervals of one minute, three days, two, four, and six weeks, subsequently. RESULTS: A total of 128 participants completed the trial. All the treatment groups showed statistically significant improvement in DH with p < 0.001 relative to baseline at all time points. Pro-Argin™ showed a greater reduction in DH with mean scores of (1.34 ± 0.68) (4.20 ± 1.70) (3.05 ± 2.17) followed by strontium acetate (1.57 ± 0.81) (4.65 ± 1.87) (3.75 ± 1.97) on SCASS and VAS for mechanical and water jet stimuli, one minute after application. There was no statistically significant treatment difference between the two (p = 0.499). FCPS showed the highest reduction in DH on SCASS and VAS for waterjet stimuli with mean scores of (0.97 ± 0.68) (1.80 ± 1.73) and Pro-Argin™ on VAS for mechanical stimuli with mean scores of (2.15 ± 1.92) in six weeks. CONCLUSION: OTC dentifrices with Pro-argin™ and strontium acetate are effective for immediate pain relief from DH, and FCPS could be the best possible treatment option for long term management of DH. TRIAL REGISTRATION: ID: NCT04249336 ( https://clinicaltria

OBJECTIVES: This study evaluated the effect of photobiomodulation (PBM) combined with 8% strontium acetate (SA8%) in the treatment of dentin hypersensitivity (DH) in non-carious lesions and analyzed the risk factors with the patient's quality of life. METHODS: Eighty teeth with DH were randomly allocated into four treatment groups (n = 20): G1, PBM imitation + toothpaste with no active ingredient; G2, PBM imitation + toothpaste with SA8%; G3, PBM + toothpaste without the active ingredient; and G4, PBM + toothpaste with SA8%. Participants were provided with a questionnaire on the experience of dentin hypersensitivity (QEDH) to assess the impact of desensitizing treatment on health-related quality of life (HRQL). Friedman and Kruskal-Wallis tests were used for intra- and intergroup comparisons, and Wilcoxon and Mann-Whitney tests were used to analyze HRQL. All analyses used significance levels of 5%. RESULTS: Intergroup comparisons revealed a significant difference (p < 0.05); G4 had the best response in terms of HD reduction in G4 compared to the other groups on the 7th day of assessment (T3). Only G4 showed a statistically significant difference (p < 0.05) in the reduction of EDH for intragroup analysis. CONCLUSION: The combination of therapies was more effective in reducing DH than the isolated use of these strategies. CLINICAL RELEVANCE: The combination of therapies is effective in the treatment of DH. © 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Strontium-substituted sub-micron bioactive glasses (Sr-SBG) have been reported to have enhanced osteogenic differentiation capacity compared to sub-micron bioactive glasses (SBG) in our previous study. However, the underlying molecular mechanisms of such beneficial effect of Sr-SBG are still not fully understood. In this study, we synthesized Sr-SBG, studied the effects of Sr-SBG on proliferation and osteogenic differentiation of mouse mesenchymal stem cells (mMSCs), and identified the molecular mechanisms of the enhancement effect of Sr-SBG on mMSCs. The results demonstrated that Sr-SBG had more profound promotion effect on proliferation and osteogenic differentiation of mMSCs than SBG and SrCl2 group which containing identical Sr concentration with Sr-SBG group. RT-qPCR and western blot analysis showed that the mRNA expressions and protein expressions involved in NFATc and Wnt/β-catenin signaling pathways were all upregulated mediated by Sr-SBG, while only Wnt/β-catenin signaling pathway related genes upregulated in SBG group and only NFATc signaling pathway activated in SrCl2 group, suggesting that NFATc and Wnt/β-catenin signaling pathways played important roles in osteogenesis enhancement induced by Sr-SBG. To conform the above conclusion, cyclosporin A (CSA) was applied to inhibit NFATc signaling pathway. It was found that the enhanced osteogenic differentiation of mMSCs induced by Sr-SBG was partially abrogated and the activated Wnt/β-catenin signaling pathway was also inhibited in part. However, the effects of SBG on proliferation and osteogenesis of mMSCs were unimpaired, yet the effects of SrCl2 were greatly suppressed. Taken together, these results indicated that strontium activated NFATc signaling pathway and silicate activated Wnt/β-catenin signaling pathway might synergistically mediated the enhanced osteogenesis induced by Sr-SBG.

BACKGROUND: Temporomandibular joint (TMJ) disorders show inflammatory components, heavily impacting on quality of life. Strontium ranelate has previously shown anti-inflammatory and antinociceptive effects on other experimental inflammatory pain models. Thus, we aim to investigate the strontium ranelate efficacy in reducing the zymosan-induced inflammatory hypernociception in the TMJ of rats by evaluating the TNF-α, IL-1β, and hemeoxygenase-1 (HO-1) involvement. METHODS: Wistar rats were treated with strontium ranelate (0.5, 5 or 50 mg/kg, per os) 1 h before zymosan injection (iart). Mechanical threshold was assessed by Von Frey test and synovial lavage was collected for leukocyte counting and myeloperoxidase measurement, joint tissue and trigeminal ganglion were excised for histopathological analysis (H&E) and TNF-α/IL-1β levels dosage (ELISA). Moreover, rats were pre-treated with ZnPP-IX (3 mg/kg, sc), a specific HO-1 inhibitor, before strontium ranelate administration (0.5 mg/kg, per os), and Evans Blue (5 mg/kg, iv) was administered to assess plasma extravasation. Pre-treatment with indomethacin (5 mg/kg, sc) was used as positive control while the sham group received 0.9% sterile saline (per os and iart). RESULTS: Strontium ranelate did not reduce leukocyte counting, myeloperoxidase activity, Evans Blue extravasation, IL-1β levels, and TNF-α/IL-1β immunolabeling; but it increased the nociceptive threshold and reduced TNF-α levels. Additionally, HO-1 inhibition did not change the strontium ranelate effects. CONCLUSION: Strontium ranelate may achieve its antinociceptive effects through the reduction of TNF-α levels in the trigeminal ganglion, but not suppressing IL-1β expression nor inducing the HO-1 pathway.

OBJECTIVE: The aim was to investigate the effects of fluoride, strontium, theobromine and their combinations on caries lesion rehardening and fluoridation (EFU) under pH cycling conditions. DESIGN: Human enamel specimens were demineralized at 37°C for 24h using a pH 5.0 solution containing 50mM lactic acid and 0.2% Carbopol 907 which was 50% saturated with respect to hydroxyapatite. Lesions were assigned to nine treatment groups (n=16) based on Knoop surface microhardness indentation length. TREATMENT: aqueous solutions were: placebo, 11.9mM sodium fluoride (F), 23.8mM sodium fluoride (2×F), 1.1mM strontium chloride hexahydrate (Sr), 1.1mM F theobromine, Sr+theobromine, F+Sr, F+theobromine, F+Sr+theobromine. Lesions were pH cycled for 5d (daily protocol: 3×1min-treatment; 2×60min-demineralization; 4×60min & overnight-artificial saliva). Knoop indentation length was measured again and%surface microhardness recovery (%SMHr) calculated. EFU was determined using the acid-etch technique. Data were analysed using ANOVA. RESULTS: Model showed fluoride dose-response for both variables (2×F>F>placebo). For%SMHr, F+Sr+/-theobromine resulted in more rehardening than F, however less than 2×F. F+theobromine was similar to F. For EFU, F+Sr was inferior to F, F+theobromine and F+Sr+theobromine which were similar and inferior to 2×F. In absence of fluoride, Sr, theobromine or Sr+theobromine were virtually indistinguishable from placebo and inferior to F. CONCLUSIONS: It can be concluded that a) strontium aids rehardening but not EFU and only in presence of fluoride; b) theobromine does not appear to offer any anti-caries benefits in this model; c) there are no synergistic effects between strontium and theobromine in the presence or absence of fluoride.

Summary Poor embryo quality is a major problem that contributes to the failure of pregnancy in somatic cell nuclear transfer (SCNT). The aims of this study were to improve the quality of ovine SCNT embryos by modifying the conventional activation protocol with the addition of SrCl2. In order to achieve this objective we conducted a series of experiments with in vitro-matured oocytes to optimize conditions for oocyte activation with strontium, and subsequently applied the protocol to SCNT embryos. The results showed that in vitro-matured oocytes could be activated effectively by 10 mM SrCl2 + 5 mg/ml cytochalasin B (CB) for 5 h in the absence of Ca2+ and that the blastocyst rate on day 7 (33.2%) was similar to that in the control group (31.0%) (5 M calcium ionophore [IP] A23187 for 5 min and cultured in CB/cycloheximide [CHX] for 5 h; P > 0.05). In SCNT experiments, the total cell number/blastocyst (104.12 ± 6.86) in the IP + SrCl2/CB-treatment group was, however, significantly higher than that in the control group (81.07 ± 3.39; P < 0.05). Apoptotic index (12.29 ± 1.22%) was significantly lower than the control (17.60 ± 1.39%; P < 0.05) when a combination of IP and SrCl2/CB was applied to SCNT embryos. In addition, karyotyping of the SCNT embryos showed that the percentage of diploid blastocysts in the IP + SrCl2/CB-treatment group was slightly higher than that in the control (P > 0.05). We conclude that the modified activation protocol with IP + SrCl2/CB can improve significantly the quality of ovine SCNT embryos in terms of total cell number, apoptosis and ploidy.

Osteoporosis is very common in elderly patients. Despite the severe health-related consequences for individual patients and the socioeconomic costs caused by osteoporotic fractures, treatment rates are still low. Due to drug interactions and patient compliance, polypharmacy is often mentioned as a reason for undertreatment. Several drugs have a direct or indirect effect on bone metabolism. The present paper discusses the risk of interactions of anti-osteoporotic drugs (oral and parenteral bisphosphonates, raloxifene, strontium ranelate, teriparatide, and denosumab) with other common medications in elderly patients and their impact on bone metabolism and fracture risk. In summary, the number and risk of drug interactions of all common anti-osteoporotic drugs are small and clinically rather irrelevant. However, patients with a polypharmacy are at a higher risk of fractures and should receive osteoporosis treatment, if indicated.

OBJECTIVE: To determine the effect of relatively low strontium concentrations on enamel remineralization and investigate the dose-response effects of strontium and fluoride combinations on the remineralization of artificial caries lesions in vitro. METHOD AND MATERIALS: Artificial caries lesions were created in 135 bovine enamel specimens. Lesion severity was analyzed using transverse microradiography (TMR) and quantitative light-induced fluorescence (QLF). The specimens were randomly assigned to nine treatment groups based on lesion volume after lesion creation, as measured by TMR. Treatment groups were based on a 3 x 3 factorial design (0/0.05/0.1 ppm fluoride and 0/10/15 ppm strontium). Lesions were remineralized at 37°C for 14 days in artificial saliva, which was supplemented or not with NaF and/or SrCl2 x 6H2O. Lesion remineralization was assessed using QLF and TMR. Data were analyzed using ANOVA. RESULTS: For the TMR data, lesion remineralization in the 10 ppm strontium + 0.05 ppm fluoride group was significantly higher than in all other groups (P < .05) except the 0 ppm strontium + 0.05 ppm fluoride group (P = .06). The 10 ppm strontium + 0 ppm fluoride group exhibited significantly less remineralization than the 0 ppm strontium + 0 ppm fluoride group (P = .048). For the QLF data, intergroup differences were not the same as for the TMR analysis. The QLF measurement was only moderately correlated with TMR mineral loss (r = -0.37). CONCLUSION: Strontium alone did not improve the remineralization of artificial caries lesions under the chosen in vitro conditions. However, a synergistic effect between the combination of fluoride and strontium was found at specific concentrations.

The purpose of this in vitro study was to evaluate the effect of aluminum and of combined strontium, aluminum, and fluoride treatments on enamel demineralization and remineralization. During a 6-day pH-cycling protocol, pre-softened bovine enamel slabs were immersed twice daily for 1 min in the following experimental solutions: (a) distilled water [W] (negative control); (b) 1,000 ppm F [F] (positive control); (c) 1,000 ppm Al [Al]; (d) 1,000 ppm Al,1,000 ppm F applied interchangeably [Al-F]; (e) 1,000 ppm Al, 1,000 ppm F, applied in sequential order [Al+F]; (f) combined 1,000 ppm Al and 150 ppm Sr [Al+Sr]; and (g) combined 150 ppm Sr and 1,000 ppm F [Sr+F]. Subsequently, the specimens were subjected to a 5-day acid resistance test. Lesions were evaluated quantitatively by performing surface microhardness and qualitatively by using polarized light microscopy. According to the results, solutions [Sr+F] and [Al-F] enhanced remineralization and inhibited demineralization as effectively as the [F] solution and significantly superiorly compared to [Al+Sr] and [Al] solutions. All tested solution groups, except for the [Al+Sr] group, presented significantly increased resistance to acidic attack, compared to [W]. PLM examination revealed that all solution groups, except for the [W] group, developed an acid-resistant zone at lesion surfaces. In conclusion, under the present experimental conditions, the combined strontium-fluoride and aluminum-fluoride treatments presented similar anti-caries efficacy compared to fluoride treatment alone, but they did not show evidence of synergistic activity on pre-softened enamel.

The pharmacological management of disease should involve consideration of the balance between the beneficial effects of treatment on outcome and the probability of adverse effects. The aim of this review is to explore the risk of adverse drug reactions and drug-drug interactions with treatments for postmenopausal osteoporosis. We reviewed evidence for adverse reactions from regulatory documents, randomized controlled trials, pharmacovigilance surveys, and case series. Bisphosphonates are associated with gastrointestinal effects, musculoskeletal pain, and acute-phase reactions, as well as, very rarely, atrial fibrillation, atypical fracture, delayed fracture healing, osteonecrosis of the jaw, hypersensitivity reactions, and renal impairment. Cutaneous effects and osteonecrosis of the jaw are of concern for denosumab (both very rare), though there are no pharmacovigilance data for this agent yet. The selective estrogen receptor modulators are associated with hot flushes, leg cramps, and, very rarely, venous thromboembolism and stroke. Strontium ranelate has been linked to hypersensitivity reactions and venous thromboembolism (both very rare) and teriparatide with headache, nausea, dizziness, and limb pain. The solidity of the evidence base depends on the frequency of the reaction, and causality is not always easy to establish for the very rare adverse reactions. Drug-drug interactions are rare. Osteoporosis treatments are generally safe and well tolerated, though they are associated with a few very rare serious adverse reactions. While these are a cause for concern, the risk should be weighed against the benefits of treatment itself, i.e., the prevention of osteoporotic fracture.

The commonest medical conditions following menopause are osteoporosis and atherosclerotic disease. This review considers the safety of pharmacotherapy of osteoporosis in cardiology patients. Drugs used for osteoporosis treatment may have adverse effects on the cardiovascular system. This article has detailed analysed of current drug classes, such as the bisphosphonates and strontium ranelate, as well as reviewed of the controversy surrounding hormone replacement therapy (HRT) and the selective estrogen receptor modulators (SERMs). Additionally, we discuss the adverse effects on the heart of calcium and drugs influencing calcium metabolism such as vitamin D, parathormone and calcitonin. We look at the interference between osteoporosis treatment and the drugs used for atherosclerosis. Moreover, the side effects on bones of cardiology drugs are analysed. Lastly, the possible advantages of selected drugs used for cardiovascular diseases in terms of osteoporosis prevention are evaluated.

Thalamocortical (TC) afferents relay sensory input to the cortex by making synapses onto both excitatory regular-spiking principal cells (RS cells) and inhibitory fast-spiking interneurons (FS cells). This divergence plays a crucial role in coordinating excitation with inhibition during the earliest steps of somatosensory processing in the cortex. Although the same TC afferents contact both FS and RS cells, FS cells receive larger and faster excitatory inputs from individual TC afferents. Here, we show that this larger thalamic excitation of FS cells occurs via GluR2-lacking AMPA receptors (AMPARs), and results from a fourfold larger quantal amplitude compared with the thalamic inputs onto RS cells. Thalamic afferents also activate NMDA receptors (NMDARs) at synapses onto both cells types, yet RS cell NMDAR currents are slower and pass more current at physiological membrane potentials. Because of these synaptic specializations, GluR2-lacking AMPARs selectively maintain feedforward inhibition of RS cells, whereas NMDARs contribute to the spiking of RS cells and hence to cortical recurrent excitation. Thus, thalamic afferent activity diverges into two routes that rely on unique complements of postsynaptic AMPARs and NMDARs to orchestrate the dynamic balance of excitation and inhibition as sensory input enters the cortex.

Pharmacokinetics of exogenous strontium (Sr) and bioequivalence of a new oral formulation of strontium ranelate compared with the brand-name drug in healthy Chinese subjects was evaluated. A balanced, randomized, single-dose, two-treatment parallel study was conducted in 36 healthy Chinese subjects. Subjects were randomly allocated into two groups of 18 to receive a single oral dose of test formulation and reference formulation under a fasting state, respectively. Blood samples were collected at 19 designated time points up to 240-h post-dose. Serum concentrations of Sr were quantified by ICP-MS. A total of 36 subjects were enrolled and completed the study. Nine mild adverse events in 6 subjects were reported. The Cmax, AUC0-72 h, AUC0-t, and AUC0-∞ of test and reference formulations shown as mean ± SD were 6.97 ± 1.78 and 6.78 ± 1.80 µg/mL, 199 ± 51 and 187 ± 38 µg·h/mL, 303 ± 89 and 278 ± 54 µg·h/mL, and 337 ± 109 and 305 ± 60 µg·h/mL, respectively. Two formulations were bioequivalent, and both were generally well tolerated.

A rapid, sensitive and accurate ICP-MS method using alternate analyte-free matrix for calibration standards preparation and a rapid direct dilution procedure for sample preparation was developed and validated for the quantification of exogenous strontium (Sr) from the drug in human serum. Serum was prepared by direct dilution (1:29, v/v) in an acidic solution consisting of nitric acid (0.1%) and germanium (Ge) added as internal standard (IS), to obtain simple and high-throughput preparation procedure with minimized matrix effect, and good repeatability. ICP-MS analysis was performed using collision cell technology (CCT) mode. Alternate matrix method by using distilled water as an alternate analyte-free matrix for the preparation of calibration standards (CS) was used to avoid the influence of endogenous Sr in serum on the quantification. The method was validated in terms of selectivity, carry-over, matrix effects, lower limit of quantification (LLOQ), linearity, precision and accuracy, and stability. Instrumental linearity was verified in the range of 1.00-500ng/mL, corresponding to a concentration range of 0.0300-15.0μg/mL in 50μL sample of serum matrix and alternate matrix. Intra- and inter-day precision as relative standard deviation (RSD) were less than 8.0% and accuracy as relative error (RE) was within ±3.0%. The method allowed a high sample throughput, and was sensitive and accurate enough for a pilot bioequivalence study in healthy male Chinese subjects following single oral administration of two strontium ranelate formulations containing 2g strontium ranelate.

In 2004, docetaxel was approved for the treatment of metastatic castration-resistant prostate cancer (mCRPC). For the next several years, there was a lull in drug approvals. However, from 2010 onwards, 5 additional therapies have been approved on the basis of showing a survival benefit in phase III studies. These agents include sipuleucel-T, cabazitaxel, abiraterone, enzalutamide and (most recently) radium-223. Amongst radiopharmaceuticals currently used for advanced prostate cancer (e.g. samarium-153 and strontium-89), radium-223 possesses several unique properties. As an alpha-emitting compound, the agent produces a high-energy output over a short range, facilitating selective destruction of tissue within the bone in the region of osteoblastic lesions while sparing surrounding normal tissue. The current review will outline biological rationale for radium-223 and also provide an overview of preclinical and clinical development of the agent. Rational sequencing of radium-223 and combinations, in the increasingly complex landscape of mCRPC will be discussed, along with factors influencing clinical implementation.

Strontium ranelate is a new effective anti-osteoporotic treatment having a unique mode of action, reducing bone resorption while promoting continued bone formation, with a broad range of anti-fracture efficacy at vertebral as well as peripheral sites. In Phase III studies, it has proven its early and sustained efficacy against vertebral fractures in Caucasians along with a significant increase in lumbar bone mineral density (BMD). The aim of this randomized double-blind study was to demonstrate the efficacy of strontium ranelate (2 g/day) on lumbar spine bone mineral density and the clinical and biological safety in Asian postmenopausal osteoporotic patients compared to placebo over 1 year. Three hundred and twenty-nine eligible women from mainland China, Hong Kong and Malaysia were randomized into the study. The baseline characteristics were similar in the treatment and placebo groups: mean age of 66.2+/-6.5 years, time since menopause 17.6+/-7.2 years. In the Full Analysis Set (FAS, N=302), the mean baseline lumbar L2-L4 BMD was 0.715+/-0.106 g/cm(2) in the strontium ranelate group and 0.708 +/- 0.109 g/cm2 in the placebo group. The mean baseline femoral neck BMD was 0.575+/-0.074 g/cm2 and 0.566+/-0.069 g/cm2 respectively and mean total hip BMD was 0.642+/-0.080 g/cm2 and 0.631 +/-0.088 g/cm2 respectively. The overall compliance was 91.4% in the study drug group, and 97.4% in the placebo group. After 1 year of treatment, the lumbar spine, femoral neck and total hip BMD in the treated group was significantly increased by 3-5% as compared to placebo. Strontium ranelate was well tolerated. The most frequently reported emergent adverse events were comparable in both groups (60.4% versus 60.0%), with majority of them being mild gastrointestinal disorders. There were no clinically relevant changes in laboratory tests, such as blood routine, hepatic and renal function. It is thus concluded that the effects of 2 g/day strontium ranelate on BMD and its safety profile in this cohort of postmenopausal osteoporotic Asian women were consistent with results obtained from Caucasian women in which the efficacy on the reduction in risk of fracture has been proven.

Erratum in Calcif Tissue Int. 2009 Apr;84(4):334. The aim of this study was to assess the efficacy and safety of strontium ranelate in the treatment of postmenopausal women with osteoporosis in Taiwan. In this 12-month multicenter, randomized, double-blind, placebo-controlled study, 125 women with osteoporosis were randomly given either strontium ranelate 2 g daily or placebo. Lumbar spine, femoral neck, and total-hip bone mineral density (BMD) and biochemical markers of bone turnover were measured; adverse events and tolerability were recorded and assessed. Subjects treated with strontium ranelate showed significant increases in BMD of 5.9% at the lumbar spine, 2.6% at the femoral neck, and 2.7% at the total hip, while the placebo group exhibited no significant change at 12 months. Serum level of a formation marker (bone-specific alkaline phosphatase) was also significantly increased at 6 and 12 months. Thus, although the sample size and the treatment duration of this study could not show its effect of reducing osteoprotic fractures, strontium ranelate showed bone protection effects by increasing BMD and concentrations of a bone formation marker. Safety assessment revealed adverse events were mild and not significantly different from placebo.

A novel approach to augmenting the osteogenic properties of nano-hydroxyapatite (nHA) is doping it with bioactive ions such as strontium (Sr) and zinc (Zn). The incorporation of Sr and Zn into the nano-hydroxyapatite structure enhances its bioactivity, providing a more favorable environment for osteogenesis. The aim of this review is to evaluate the osteogenic potential of Sr/Zn-doped nano-hydroxyapatite coatings on dental implants, focusing on their effects on osseointegration and bone regeneration. A comprehensive literature search was conducted to identify relevant studies. The following databases were systematically searched: PubMed, Scopus, Web of Science, Embase, and the Cochrane Library through September 2024. The search was designed to capture a wide range of studies from biomedical, clinical, and materials science. This systematic review initially identified 16 studies, with 6 excluded after screening for relevance. Of the 10 remaining, one was further excluded for not meeting criteria. Nine studies were included in the final analysis, out of which 4 were animal studies and 5 were in vitro studies but heterogeneity prevented a meta-analysis. Data extraction focused on study details, mechanisms, in vitro and in vivo results, and conclusions. Results indicated that Sr/ Zn-doped nHA plasma-sprayed coatings on titanium dental implants significantly enhance osteogenic potential. The collective evidence from the relevant studies shows that the benefits of Sr/Zn-doped HA materials for biomedical applications are multifaceted. They have demonstrated significant improvements in bioactivity, osseointegration, osteogenesis, antibacterial properties, and mechanical performance, making them promising candidates for a range of orthopedic, dental, and cranial implants.

BACKGROUND: The neonatal line (NNL) is an accentuated line visible in the enamel and dentine of primary teeth and in some of the cusps of the first permanent molars. It corresponds to the physiological stress associated with the event of birth. This study aimed to investigate the characteristics of the NNL, its relationship with prenatal and postnatal enamel, its correlation with health and life data of both contemporary and ancient individuals, and its potential to differentiate the prenatal from postnatal origin of enamel defects to better understand the life conditions of mother and child. MATERIALS AND METHODS: Following PRISMA guidelines and using the PICO framework, a systematic review was conducted across MEDLINE, Scopus, DOSS, and Google Scholar covering literature from 1937 to 2023. RESULTS: A total of 1420 references were identified, from which 32 studies met the inclusion criteria. The selected studies examined the impact of maternal factors, perinatal conditions and gestation on the NNL. The width of the NNL varied according to maternal health and birth conditions. The NNL was also a marker of birth viability, with its presence indicating a live birth. Lastly, dietary shifts around birth were observed through variations in the perinatal enamel strontium/calcium ratio. DISCUSSION AND CONCLUSION: This study highlights the value of the NNL in reconstructing early life history by linking maternal health, prenatal and postnatal stress, and enamel development. Further research on the relationship between hypomineralized lesions in pathological enamel and the NNL could help identifying early (i.e., in utero or perinatal) risk factors.

BACKGROUND AND AIMS: Reduced bone mineral density (BMD) and microarchitectural deterioration contribute to increased fracture risk. Although the effects of anti-fracture medications (AFMs) on BMD are well-documented, their impact on bone material properties (BMPs) remains poorly characterized. Accordingly, we conducted a systematic review and meta-analysis to evaluate the effects of AFMs on BMPs. Based on data availability, we further categorized AFMs into anti-resorptives, bisphosphonates alone, and strontium ranelate subgroups to perform additional analyses of BMPs in osteoporotic patients. METHODS: We did a comprehensive search of three databases, namely, PubMed, Web of Science, and Google Scholar, using various permutation combinations, and used Comprehensive Meta-Analysis software to analyze the extracted data. RESULTS: The 15 eligible studies (randomized and non-randomized) compared the following: (1) 301 AFM-treated patients with 225 on placebo; (2) 191 patients treated with anti-resorptives with 131 on placebo; (3) 86 bisphosphonate-treated patients with 66 on placebo; and (4) 84 strontium ranelate-treated patients with 70 on placebo. Pooled analysis showed that AFMs significantly decreased cortical bone crystallinity [standardized difference in means (SDM) -1.394] and collagen maturity [SDM -0.855], and collagen maturity in cancellous bone [SDM -0.631]. Additionally, anti-resorptives (bisphosphonates and denosumab) significantly increased crystallinity [SDM 0.387], mineral-matrix ratio [SDM 0.771], microhardness [SDM 0.858], and contact hardness [SDM 0.952] of cortical bone. Anti-resorptives increased mineral-matrix ratio [SDM 0.543] and microhardness [SDM 0.864] and decreased collagen maturity [SDM -0.539] in cancellous bone. Restricted analysis of only bisphosphonate-treated studies showed a significant decrease in collagen maturity [SDM -0.650] in cancellous bone and an increase in true hardness [SDM 1.277] in cortical bone. In strontium ranelate-treated patients, there was no difference in BMPs compared to placebo. CONCLUSION: Collectively, our study suggests that AFMs improve bone quality, which explains their anti-fracture ability that is not full

BACKGROUND: Environmental exposure to metal(loid)s has been associated with adverse effects on human health, but the systemic repercussion of these elements on the development of hypertensive disorders of pregnancy (HDP) is still poorly understood. OBJECTIVE: To summarize evidence published about the influence of environmental exposure to aluminum, arsenic, barium, cadmium, lead, strontium and mercury on the development of HDP. METHODS: We conducted a systematic literature review according to the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. The search strategy was validated by the Peer Review of Electronic Search Strategies. We searched for articles published up to February 2023 in seven databases without language restriction. Two researchers conducted the steps for selection, data extraction and evaluation of the methodological quality of the instruments for epidemiological studies of the Joanna Briggs Institute. Any disagreements were resolved by a third researcher. RESULTS: We obtained 5076 records, of which 37 articles met the inclusion criteria moderate to high methodological quality. Single exposure to metal(loid)s was predominant, and the leading biological matrix analyzed to detect the concentrations from exposure was maternal blood. Lead was the metal investigated the most, and had the largest number of studies showing positive association with HDP. In relation to the other metal(loid)s, higher levels were found in women with HDP in comparison with healthy women, but the finding of a cause-effect relationship was inconsistent. CONCLUSIONS: Although we found evidence of harmful effects of the metal(loid)s studied on human health, the results were inconclusive with regard to HDP. Longitudinal studies that consider prospective investigation, adjustment of confounding factors and the interference of other contaminants in the exacerbation of oxidative stress in women from the preconception phase to the puerperal period should be encouraged.

Hydroxyapatite [HA, Ca10(PO4)6(OH)2], with its robust biocompatibility and bioactivity, has found extensive utility in bone grafting, replacement therapies, and supplemental medical materials. HA is highly regarded for its osteoconductive properties because it boasts hydrophilicity, nontoxicity, non-allergenicity, and non-mutagenicity. Nevertheless, HA's intrinsic mechanical weakness has spurred efforts to enhance its properties. This enhancement is achieved through ion incorporation, with elements such as magnesium, zinc, lithium, strontium, boron, and others being integrated into the HA structure. In the domain of orthopedics, HA-based scaffolds have emerged as a solution for addressing prevalent issues like bone deformities and defects stemming from congenital anomalies, injuries, trauma, infections, or tumors. The fabrication of three-dimensional scaffolds (3D scaffolds) has enabled advancements in bone regeneration and replacement, with a focus on practical applications such as repairing calvarial, skull, and femoral defects. In vitro and in vivo assessments have substantiated the effectiveness of 3D scaffolds for bone defect repair, regeneration, and tissue engineering. Beyond bone-related applications, scaffolds demonstrate versatility in enhancing cartilage healing and serving as bioimplants. The wide array of scaffold applications underscores their ongoing potential for further development in the realm of medical science.

INTRODUCTION: Pharmacological strategies might influence bone healing in terms of time to union or quality of mature bone. This expert opinion discussed the current level I evidence on the experimental pharmacological agents used to favor bone fracture healing. AREAS COVERED: This study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses: the 2020 PRISMA statement. In April 2023, the following databases were accessed: PubMed, Web of Science, Google Scholar, Embase. All the randomized clinical trials investigating pharmacological agents for bone fracture healing were accessed. No time constraint was set for the search. The search was restricted to RCTs. No additional filters were used in the database search. Data from 19 RCTs (4067 patients) were collected. 78% (3160 of 4067) were women. The mean length of the follow-up was 9.3 months (range, 1-26 months). The mean age of the patients was 64.4 years (range, 8-84 years). EXPERT OPINION: Calcitonin could favor bone fracture healing. Bisphosphonates (alendronate, zoledronate, clodronate), monoclonal antibodies (denosumab, romosozumab), statins, vitamin D and calcium supplementation, strontium ranelate, and ibuprofen did not influence bony healing. Concerning the effect of parathormone, current level I evidence is controversial, and additional studies are required. LEVEL OF EVIDENCE: Level I, systematic review of RCTs.

BACKGROUND: Osteoporosis is characterized by low bone mass and micro-architectural deterioration of bone tissue leading to increased bone fragility. In people with beta-thalassaemia, osteoporosis represents an important cause of morbidity and is due to a number of factors. First, ineffective erythropoiesis causes bone marrow expansion, leading to reduced trabecular bone tissue with cortical thinning. Second, excessive iron loading causes endocrine dysfunction, leading to increased bone turnover. Lastly, disease complications can result in physical inactivity, with a subsequent reduction in optimal bone mineralization. Treatments for osteoporosis in people with beta-thalassaemia include bisphosphonates (e.g. clodronate, pamidronate, alendronate; with or without hormone replacement therapy (HRT)), calcitonin, calcium, zinc supplementation, hydroxyurea, and HRT alone (for preventing hypogonadism). Denosumab, a fully human monoclonal antibody, inhibits bone resorption and increases bone mineral density (BMD). Finally, strontium ranelate simultaneously promotes bone formation and inhibits bone resorption, thus contributing to a net gain in BMD, increased bone strength, and reduced fracture risk. This is an update of a previously published Cochrane Review. OBJECTIVES: To review the evidence on the efficacy and safety of treatment for osteoporosis in people with beta-thalassaemia. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register, which includes references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. We also searched online trial registries. Date of most recent search: 4 August 2022. SELECTION CRITERIA: Randomized controlled trials (RCTs) in people with beta-thalassaemia with: a BMD Z score below -2 standard deviations (SDs) for children aged under 15 years, adult males (aged 15 to 50 years) and premenopausal females aged over 15 years; or a BMD T score below -2.5 SDs for postmenopausal females and males aged over 50 years. DATA COLLECTION AND ANALYSIS: Two review authors assessed the eligibility and