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.

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.

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.

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.

Use of Strontium Chloride for the Treatment of Osteoporosis: A Case Report.

Context • Strontium ranelate is an approved prescription medication for the treatment of osteoporosis in Europe. In the United States, the only available forms of strontium are those that are nonprescription, dietary supplements. Some patients with osteoporosis use those products because they prefer an alternate treatment to conventional therapy. Currently, no controlled trials have been conducted on the effectiveness of the supplements for treating osteoporosis. Objective • The study intended to examine how one woman responded to the use of strontium chloride. Design • This was a retrospective case study. Setting • The woman in the case study was a patient in an academic urban women's health clinic in Minneapolis, MN, USA. Participant • The participant was a postmenopausal woman with a history of vertebral fracture. Intervention • The participant took 680 mg daily of strontium chloride for 2.5 y. Outcome Measures • The patient had begun receiving dual-energy X-ray absorptiometry (DXA) scans in 2004 and continued to receive follow-up scans every 2 y. After beginning strontium therapy in December 2011, she received DXA scans in March 2012 and May 2014. Results • During the study, the analysis of the patient's DXA scans showed a positive increase in the bone mineral density (BMD) of her vertebrae and her right hip and maintenance of her BMD in her left hip. Conclusions • Although the current case report does not provide enough evidence to conclude that US dietary supplements of strontium are effective in preventing fractures, it demonstrates a positive experience for one patient.

Short-term and long-term effects of osteoporosis therapies.

Progress continues to be made in the development of therapeutics for fracture prevention. Bisphosphonates are now available orally and intravenously, often as inexpensive generics, and remain the most widely used interventions for osteoporosis. The major safety concern associated with the use of bisphosphonates is the development of femoral shaft stress fractures and, although rare, this adverse event affords the principal rationale for restricting bisphosphonate therapy to those individuals with femoral T-scores <-2.5, and for providing drug holidays in those individuals requiring therapy for >5 years. Newer antiresorptive therapies, in the form of denosumab and cathepsin K inhibitors, might increase efficacy and possibly circumvent some of the safety concerns associated with bisphosphonate use (for example, gastrointestinal and renal complications). The combination of teriparatide with antiresorptives markedly increases effects on BMD; new anabolic agents are also very promising in this regard. However, whether or not these changes in BMD translate into improved efficacy of fracture prevention remains to be determined. Vitamin D is important for the prevention of osteomalacia, but does not influence BMD or fracture risk in patients not deficient in vitamin D. The balance of risks and benefits of calcium supplementation is contentious, but patients should be encouraged to adhere to a balanced diet aimed at maintaining a healthy body weight. Consideration of a patient's risk of falling, and its mitigation, are also important. In this Review, I summarize the short-term and long-term effects of osteoporosis therapies.

Effects of dentifrices on subsurface dentin tubule occlusion: an in situ study.

PURPOSE: To evaluate, in situ, the penetration of deposits formed within the subsurface of dentin samples treated with desensitizing dentifrices designed to occlude dentin tubules compared to two controls. MATERIALS AND METHODS: Twenty-eight healthy participants wore left and right intraoral appliances, each retaining four human dentin samples, for two periods of 4 days. Samples were power-brushed, outside the mouth, twice daily with test products (dentifrices containing 8% strontium or 8% arginine) or control (1,450 ppm NaF or water) and subjected to an agitated grapefruit juice acid challenge on days 3 and 4. Eighteen dentin samples were randomly selected from each treatment group and were dry fractured for scanning electron microscopy and energy-dispersive x-ray spectroscopy analysis. RESULTS: The proportion of cross-sectioned dentin tubules with subsurface occlusion (occluded to a mean of 5 ± 2 µm, range: 1 to 9 µm below the surface) for the 8% strontium group on days 1 and 2 (pre-acid) was 82% (SD: 9%, 95% confidence interval [CI] = 78% to 86%) and on days 3 and 4 (post-acid) was 88% (SD: 10%, CI = 83% to 93%). For 8% arginine on days 3 and 4 (post-acid), the proportion was 78% (SD: 8%, CI = 74% to 82%). These results were statistically significant compared to those for controls (P < .01). The 8% arginine on days 1 and 2 (pre-acid) and water and control paste on all days revealed no subsurface deposit. CONCLUSIONS: Within the limitations of this study, cross-sectional SEM analysis suggested strontium and arginine dentifrices occlude tubules subsurface in dentin compared to negative controls following acid challenge. The desensitizing dentifrices elicit subsurface changes that may potentiate their effects for the management of dentin hypersensitivity, particularly for patients who consume acidic beverages.

Short-term effect of strontium- and zinc-containing toothpastes and mouthrinses on volatile sulphur compounds in morning breath: a randomized, double-blind, cross-over clinical study.

Zinc (Zn) reduces the formation of volatile sulphur compounds (VSCs) associated with oral malodour. Although strontium (Sr) is included in some products for reducing dental hypersensitivity, it may also have anti-halitosis properties. This randomized, double-blind, cross-over clinical study compared the anti-VSC effect of brushing with commercial toothpastes and rinses containing Zn and Sr. The volunteers (n = 30) either brushed/rinsed with/without tongue brushing using Zn-containing toothpaste/rinse, Sr-containing toothpaste/rinse, or placebo (control). Volatile sulphur compounds [hydrogen sulphide (H2 S) and methyl mercaptan (CH3 SH)] were measured, in morning breath, using gas chromatography. The anti-VSC effects of the test toothpastes and test rinses were significantly better than the anti-VSC effects of the respective controls. Toothbrushing with test toothpastes gave median reductions, compared with the control, of 70% for H2 S and 55-57% for CH3 SH. Rinsing with the Sr- and Zn-containing solutions had the same anti-VSC effect as toothbrushing and tooth- and tongue brushing with the Sr- and Zn-containing toothpastes. Zinc-containing rinse resulted in a significantly higher median salivary level of Zn compared with brushing with Zn-containing toothpaste, although this effect did not correlate with the anti-VSC effect. It can be concluded that the Sr- and Zn-containing toothpastes and the Zn- and Sr-containing rinses, when used in the evening, are equally effective in reducing morning-breath VSCs the following day.

Monitoring bone strontium intake in osteoporotic females self-supplementing with strontium citrate with a novel in-vivo X-ray fluorescence based diagnostic tool.

Ten female volunteers were recruited as part of the Ryerson and McMaster University Strontium (Sr) in Bone Research Study to have their bone Sr levels measured as they self-supplemented with Sr supplements of their choice. Of the ten volunteers, nine were suffering from osteopenia and/or osteoporosis. Non-invasive bone Sr measurements were performed using an in vivo x-ray fluorescence (IVXRF) I-125 based system. Thirty minute measurements were taken at the finger and ankle, representing primarily cortical and trabecular bone, respectively. For analysis, the 14.2keV Sr K-alpha peak normalized to the Coherent peak at 35.5keV was used. Baseline readings, representing natural bone Sr levels were acquired since all volunteers had no previous intake of Sr based supplements or medications. Once Sr supplements were started, a 24h reading was taken, followed by frequent measurements ranging from weekly, biweekly to monthly. The longest volunteer participation was 1535days. The mean baseline Sr signal observed for the group was 0.42±0.13 and 0.39±0.07 for the finger and ankle, respectively. After 24h, the mean Sr signal rose to 1.43±1.12 and 1.17±0.51, for the finger and ankle, respectively, representing a statistically significant increase (p=0.0043 & p=0.000613). Bone Sr levels continued to increase throughout the length of the study. However the Sr signal varied widely between the individuals such that after three years, the highest Sr signal observed was 28.15±0.86 for the finger and 26.47±1.22 for the ankle in one volunteer compared to 3.15±0.15 and 4.46±0.36, for the finger and ankle, respectively in another. Furthermore, while it was previously reported by our group, that finger bone Sr levels may plateau within two years, these results suggest otherwise, indicating that bone Sr levels will continue to rise at both bone sites even after 4years of Sr intake.

A novel potassium oxalate-containing tooth-desensitising mouthrinse: a comparative in vitro study.

OBJECTIVE: To compare the efficacy of a new potassium oxalate (KO)-containing mouthrinse [Listerine® Advanced Defence Sensitive (LADS)] in reducing dentine permeability and occluding open dentinal tubules versus other desensitising products. METHODS: The permeability of acid-etched dentine disks was measured by hydraulic conductance; dentine surfaces were examined by scanning electron microscopy and energy-dispersive X-ray spectroscopy. The KO concentration was optimised for tubule occlusion by screening formulations containing 0.0-2.0% KO (n=5 disks per concentration). The optimal formulation was compared with five commercial products with non-oxalate occlusion technologies. After establishing the baseline permeability of acid-etched dentine disks, disks (n=6 per product) were randomly treated with the desensitising products (12 treatments, each 60 s, alternated with distilled-water rinses) and permeability was measured at intervals. Occluded disks were acid challenged. All experiments were conducted at room temperature. An unpooled, two-tailed t test was performed to assess between-treatment differences in relative residual permeability. RESULTS: The optimal concentration of KO in LADS was 1.4%, which provided ≈ 100% reduction in dentine permeability after nine treatments. Only LADS reduced permeability to zero and was significantly more effective in reducing dentine permeability than the other products (p ≤ 0.033 vs all other test products). All products partially occluded dentine. The occlusion associated with LADS was substantially more stable in resisting acid challenge versus Colgate® Sensitive Pro-Relief mouthrinse (p=0.054) and significantly more stable versus all other test products (p ≤ 0.045), as determined by dentine permeability. CONCLUSION: LADS was significantly more effective in occluding open dentinal tubules versus other desensitising products. CLINICAL SIGNIFICANCE: LADS provides fast, complete and stable intratubular occlusion of patent dentinal tubules.

Biological therapy of strontium-substituted bioglass for soft tissue wound-healing: responses to oxidative stress in ovariectomised rats.

New synthetic biomaterials are constantly being developed for wound repair and regeneration. Bioactive glasses (BG) containing strontium have shown successful applications in tissue engineering account of their biocompatibility and the positive biological effects after implantation. This study aimed to assess whether BG-Sr was accepted by the host tissue and to characterize oxidative stress biomarker and antioxidant enzyme profiles during muscle and skin healing. Wistar rats were divided into five groups (six animals per group): the group (I) was used as negative control (T), after ovariectomy, groups II, III, IV and V were used respectively as positive control (OVX), implanted tissue with BG (OVX-BG), BG-Sr (OVX-BG-Sr) and presented empty defects (OVX-NI). Soft tissues surrounding biomaterials were used to estimate superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and malondialdehyde (MDA) concentration. Our results show that 60 days after operation, treatment of rats with BG-Sr significantly increased MDA concentration and caused an increase of SOD, CAT and GPx activities in both skin and muscular tissues. BG-Sr revealed maturation of myotubes followed a normal appearance of muscle regenerated with high density and mature capillary vessels. High wound recovery with complete re-epithelialization and regeneration of skin was observed. The results demonstrate that the protective action against reactive oxygen species (ROS) was clearly observed in soft tissue surrounding BG-Sr. Moreover, the potential use of BG-Sr rapidly restores the wound skin and muscle structural and functional properties. The BG advantages such as ion release might make BG-Sr an effective biomaterial choice for antioxidative activity.

A 3-day randomized clinical trial to investigate the desensitizing properties of three dentifrices.

BACKGROUND: The aim of the present study is to evaluate the relative abilities of three desensitizing dentifrices to provide rapid relief of dentin hypersensitivity (DH). METHODS: Using a double-mask, randomized design, three dentifrices: 1) containing 8% arginine and 1,450 ppm sodium monofluorophosphate; 2) containing 8% strontium acetate and 1,040 ppm sodium fluoride; and 3) containing 30% microaggregation of zinc-carbonate hydroxyapatite nanocrystals were compared after 3-day treatment. Participant's DH was evaluated at baseline and after 3 days using air-blast, tactile, cold water, and subjective tests. RESULTS: The final sample consisted of 85 individuals: 29 received the arginine-based dentifrice (group 1), 27 the strontium acetate-based dentifrice (group 2), and 29 the dentifrice based on zinc-carbonate hydroxyapatite (group 3). All dentifrices were mostly effective to reduce DH: the percentage of score reduction from baseline to 3 days was >30% for all tests (except for subjective test of group 2). The comparison among the three dentifrices showed that, after 3 days, there was an improvement in air-blast (mean percentage of reduction, 39.2% in group 1, 42.0% in group 2, and 39.2% in group 3), cold water (41.5%, 51.8%, and 50%), tactile (50.3%, 40.1%, and 33.8%), and subjective (33.1%, 17.4%, and 31.4%) test scores, with differences being significant for cold water and subjective tests. For air-blast and tactile tests, there were no significant differences across groups at 3 days. Moreover, no significant differences at any test were observed in a subset of patients that were followed up to 8 weeks: all dentifrices were all highly efficacious. CONCLUSIONS: This study documents that the three tested dentifrices significantly reduced DH after 3-day treatment, supporting their use in clinical practice. To the best of the authors' knowledge, this is the first report documenting the rapid relief from DH of a zinc-carbonate hydroxyapatite dentifrice.

In situ randomised trial to investigate the occluding properties of two desensitising toothpastes on dentine after subsequent acid challenge.

OBJECTIVES: The aim of the study was to determine in situ the relative abilities of two desensitising toothpastes to occlude dentinal tubules with or without acid challenge. MATERIALS AND METHODS: The study design was a single centre, randomised, split mouth crossover model examining four treatments over two periods. The primary outcome was the degree of occlusion proffered by two desensitising toothpastes [Sensodyne® Rapid Relief (8% strontium acetate, 1040 ppm sodium fluoride) and Colgate® Sensitive Pro-ReliefTM daily (8% arginine, 1450 ppm sodium monofluorophosphate)], a standard toothpaste (1450 ppm sodium fluoride) and water, after acid challenge. Healthy adult volunteers wore bi-lateral lower buccal appliances each with two dentine sections, receiving two treatments per study period. Samples were brushed twice a day with treatment, with two additional 3-min extra-oral acidic challenges applied ex vivo on days 3 and 4. A secondary outcome was the degree of occlusion attained in the absence of acid challenge. Examiners blinded to the study assessed occlusion by visual score of post-treatment scanning electron microscope images. RESULTS: All 28 participants completed the study. In the absence of acid challenge, occlusion scores for both desensitising toothpastes were similar and significantly better than control scores (p < 0.02). After acid challenge both desensitising toothpastes occluded more effectively than controls; however, occlusion scores for the strontium acetate paste were significantly greater than those of the arginine paste (p < 0.02). CONCLUSIONS: The occluding properties of the strontium acetate toothpaste were significantly more robust after acid challenge than those of the arginine toothpaste. CLINICAL RELEVANCE: Patients with hypersensitivity, regularly imbibing dietary acidic drinks, should be advised that Sensodyne® Rapid Relief provides robust tubule occlusion despite repeated acidic challenges.

The effect of strontium and combinations of strontium and fluoride on the remineralization of artificial caries lesions in vitro.

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.

An in situ study investigating dentine tubule occlusion of dentifrices following acid challenge.

OBJECTIVES: To investigate the dentine occlusion and acid resistance of dentifrices developed to treat dentine hypersensitivity. METHODS: This was a single centre, single blind, randomised, split mouth, four treatments, two period crossover, in situ study in healthy subjects. Subjects wore buccal intra-oral appliances each fitted with four dentine samples over four consecutive days with one study product applied per appliance; 8% strontium acetate in silica base, 1040 ppm sodium fluoride (Sensodyne(®) Rapid Relief), 8% arginine, calcium carbonate, 1450 ppm sodium monofluorophosphate (Colgate Sensitive Pro-Relief(®)), 1450 ppm sodium fluoride (control paste) and water. On days 3 and 4, two agitated grapefruit juice challenges (ex vivo) occurred for 1 min. At the end of each treatment day 1 dentine sample was removed from each appliance for scanning electron microscopy (SEM). The extent of tubule occlusion was measured using an examiner-based visual scoring index (three trained examiners). RESULTS: In total, 28 subjects ((12 males and 16 females with a mean age of 34.7 years (SD 8.41 years)) completed the study. On day 2, both test dentifrices demonstrated significantly better dentine tubule occlusion than water (p < 0.0001) and control paste (8% strontium p = 0.0003 and 8% arginine p = 0.0019). After 3 and 4 days of twice daily brushing with acid challenges on days 3 and 4 the strontium-based dentifrice demonstrated significantly better dentine occlusion than all other treatments (p < 0.0001). CONCLUSIONS: Strontium acetate and arginine-based dentifrice result in statistically significant dentine tubular occlusion compared to controls, but the arginine-based dentifrice is more susceptible to acid challenge. CLINICAL SIGNIFICANCE: Erosive beverages are an important aetiology in DH by exposing dentine tubules. Their consumption has increased significantly over the past decade in the UK. This 4-day in situ study investigated the properties of commercially available dentifrices designed to occlude dentine tubules and their resistance to an agitated acid challenge.

A comparative effectiveness study of bone density changes in women over 40 following three bone health plans containing variations of the same novel plant-sourced calcium.

BACKGROUND: The US Surgeon General's Report on Bone Health suggests America's bone-health is in jeopardy and issued a "call to action" to develop bone-health plans incorporating components of (1) improved nutrition, (2) increased health literacy, and (3) increased physical activity. OBJECTIVE: To conduct a Comparative Effectiveness Research (CER) study comparing changes in bone mineral density in healthy women over-40 with above-average compliance when following one of three bone health Plans incorporating the SG's three components. METHODS: Using an open-label sequential design, 414 females over 40 years of age were tested, 176 of whom agreed to participate and follow one of three different bone-health programs. One Plan contained a bone-health supplement with 1,000 IUs of vitamin D(3 )and 750 mg of a plant-sourced form of calcium for one year. The other two Plans contained the same plant form of calcium, but with differing amounts of vitamin D(3) and other added bone health ingredients along with components designed to increase physical activity and health literacy. Each group completed the same baseline and ending DXA bone density scans, 43-chemistry blood test panels, and 84-item Quality of Life Inventory (QOL). Changes for all subjects were annualized as percent change in BMD from baseline. Using self-reports of adherence, subjects were rank-ordered and dichotomized as "compliant" or "partially compliant" based on the median rating. Comparisons were also made between the treatment groups and two theoretical age-adjusted expected groups: a non-intervention group and a group derived from a review of previously published studies on non-plant sources of calcium. RESULTS: There were no significant differences in baseline BMD between those who volunteered versus those who did not and between those who completed per protocol (PP) and those who were lost to attrition. Among subjects completing per protocol, there were no significant differences between the three groups on baseline measurements of BMD, weight, age, body fat and fat-free mass suggesting that the treatment groups were statistically similar at baseline. In all three treatment groups subjects with above average compliance had significantly greater increases in BMD as compared to the two expected-change reference groups. The group following the most nutritionally comprehensive Plan outperformed the other two groups. For all three groups, there were no statistically significant differences between baseline and ending blood chemistry tests or the QOL self-reports. CONCLUSIONS: The increases in BMD found in all three treatment groups in this CER stand in marked contrast to previous studies reporting that interventions with calcium and vitamin D(3) reduce age-related losses of BMD, but do not increase BMD. Increased compliance resulted in increased BMD levels. No adverse effects were found in the blood chemistry tests, self-reported quality of life and daily tracking reports. The Plans tested suggest a significant improvement over the traditional calcium and vitamin D(3) standard of care.

Development of an acid challenge-based in vitro dentin disc occlusion model.

OBJECTIVE: The objective of this study was to evaluate the utility of a novel acid challenge-based dentin disc occlusion model, and to compare the occluding effect and acid resistance exhibited by currently marketed occlusion dentifrices in vitro. METHODS: Ninety-six bovine dentin discs were polished and etched in citric acid (6% w/w) for two minutes to provide a smooth dentin surface with patent tubules. The discs were divided into three treatment groups. Each treatment group was brushed (Oral-B Vitality Precision Clean/EB 17 FlexiSoft head) twice a day, for up to four days, with either a strontium acetate dentifrice (Sensodyne Rapid Relief), an arginine-based dentifrice (Colgate Sensitive Pro-Relief), or water. Prior to and between treatments, the dentin samples were stored in human saliva. On days 3 and 4, following dentifrice treatment and incubation in saliva (60 minutes), the samples were subjected to a grapefruit juice challenge. Eight samples from each treatment group were removed from the study on each day and analyzed by scanning electron microscopy (SEM). The SEM images were graded according to a categorical occlusion scale, and the data were analyzed by ANOVA. RESULTS: The strontium acetate dentifrice occluded dentin tubules significantly better than the negative control (water) on days 1 through 4 (day 4 p < or = 0.0001). The marketed occlusion-based dentifrices demonstrated various degrees of dentin tubule occlusion over the four days. The strontium acetate dentifrice demonstrated significantly better occlusion than a currently marketed arginine-based occlusion dentifrice on day 1 (p = 0.0337), day 2 (p = 0.0021 ), and day 4 (p < or = 0.0001). CONCLUSION: An in vitro model has been developed that can differentiate the dentin tubular occlusive effects of currently marketed occlusion dentifrices. Surface analysis reveals that the occluding deposits vary according to product, and that some are more susceptible to acid mediated dissolution.

Recent advances in dentin hypersensitivity: clinically proven treatments for instant and lasting sensitivity relief.

PURPOSE: To provide a brief overview of the diagnosis, epidemiology, etiology and clinical management of dentin hypersensitivity, to discuss technical approaches to relieve sensitivity, with special emphasis on dentin tubule occlusion and the clinical evidence for efficacy of desensitizing toothpastes based upon this approach, and to summarize the science behind a new dentifrice technology, based upon arginine and calcium carbonate, and the clinical evidence which proves that it delivers both instant and lasting relief of dentin hypersensitivity. RESULTS: Clinical studies have shown that a new toothpaste, containing arginine and calcium carbonate (known as Pro-Argin technology) with 1450 ppm fluoride, offers clinically proven instant and lasting relief of dentin hypersensitivity. Three 8-week clinical studies have shown that this new toothpaste provides statistically significantly superior efficacy in reducing sensitivity to market leading desensitizing toothpastes containing 2% potassium ion. Importantly, three further clinical studies have shown that a single direct topical application of toothpaste to sensitive teeth, using a fingertip or cotton swab followed by 1 minute of massage, resulted in instant relief of dentin hypersensitivity and that the relief was maintained with subsequent twice-daily brushing. Mechanism of action studies have shown that this technology physically seals dentin tubules with a plug that contains arginine, calcium carbonate and phosphate. This plug, which is resistant to normal pulpal pressures and to acid challenge, effectively reduces dentin fluid flow and thereby relieves sensitivity. A new whitening variant of this desensitizing toothpaste, containing the Pro-Argin technology, fluoride and a high cleaning calcium carbonate system, has now been clinically and scientifically validated. This toothpaste works by the same mechanism of action as its non-whitening counterpart and is clinically proven to provide both instant and lasting relief of sensitivity, while providing proven efficacy in removal of extrinsic stains. No difference in desensitizing efficacy was observed between the whitening and non-whitening versions.

Preclinical assessment of gastrooesophageal tolerance of the new antiosteoporotic drug strontium ranelate: an endoscopic study in monkeys.

This study was aimed at evaluating the digestive tolerance of the new antiosteoporotic drug, strontium ranelate, and to compare it to that of another strontium salt, strontium chloride (SrCl2). Strontium ranelate, SrCl2, or placebo were administered orally (capsules) to 3 groups of 2 male and 2 female cynomolgus monkeys (Macaca fascicularis) once a day for 7 days at a dose of 2 g/day, which is the recommended therapeutic dose in man. Endoscopic examination of the oesophagus, the stomach and the first part of the duodenum was performed on fasted animals approximately 3 hr after the first (Day 1) and last dosing (Day 7), and, on Day 8 and Day 14 in case of lesions on Day 7. Strontium ranelate did not induce any acute or subchronic toxic effect on the gastric mucosa, the oesophagus and the first part of the duodenum. On the contrary, acute and superficial damages were noted on all animals receiving SrCl2 such as haemorrhagic and erosive lesions (formation of an ulcer in one male and a marked congestive antritis in one female). These effects were reversible after cessation of treatment. The microscopic examination of biopsies sampled at the site of gastric lesions revealed moderate granulocyte infiltration, indicating a local irritating origin of the lesions. Strontium ranelate by oral route is safe for the gastric mucosa while SrCl2 induced superficial and reversible lesions.

[Treatment of osteoporosis (with the exception of hormone replacement and its derivates]. / Les traitements de l'ostéoporose (à l'exception de la substitution hormonale et de ses dérivés).

Calcium and vitamin D supplementation are warranted for the treatment of osteoporosis, when other specific drugs are used. Vitamin D supplementation is necessary when the plasma level of 25-hydroxy-vitamin D is below 30 nmol/l (12 pg/l) in order to avoid any increase of the plasma parathyroid hormone level. Bisphosphonates are the most widely drugs used. Recent advances will provide patients with a more convenient therapeutically equivalent alternative: the once-weekly oral dosing regimen and probably the possibility to give infusions at intervals of up to one year. Parathyroid hormone administered subcutaneously daily produced a dramatic increase of trabecular and cortical bone mineral density, and an important decrease of vertebral and nonvertebral fracture risk. Strontium is a new original drug, which stimulates bone formation, and inhibits bone resorption. It significantly improves trabecular and cortical bone mass. Calcitonin not only prevents the recurrence of vertebral fractures, but possibly could decrease hip fractures risk. Hydrochlorothiazide preserves the bone mineral density, and decreases nonvertebral fracture risk, as showed in epidemiological studies. Large clinical trials with statins therapy in appropriate populations are required to find out whether these drugs have any role in preventing fractures.