Influence of Various Strontium Formulations (Ranelate, Citrate, and Chloride) on Bone Mineral Density, Morphology, and Microarchitecture: A Comparative Study in an Ovariectomized Female Mouse Model of Osteoporosis.

Osteoporosis stands out as a prevalent skeletal ailment, prompting exploration into potential treatments, including dietary strontium ion supplements. This study assessed the efficacy of supplementation of three strontium forms-strontium citrate (SrC), strontium ranelate (SrR), and strontium chloride (SrCl)-for enhancing bone structure in 50 female SWISS mice, aged seven weeks. In total, 40 mice underwent ovariectomy, while 10 underwent sham ovariectomy. Ovariectomized (OVX) mice were randomly assigned to the following groups: OVX (no supplementation), OVX + SrR, OVX + SrC, and OVX + SrCl, at concentrations equivalent to the molar amount of strontium. After 16 weeks, micro-CT examined trabeculae and cortical bones, and whole-bone strontium content was determined. Results confirm strontium administration increased bone tissue mineral density (TMD) and Sr content, with SrC exhibiting the weakest effect. Femur morphometry showed limited Sr impact, especially in the OVX + SrC group. This research highlights strontium's potential in bone health, emphasizing variations in efficacy among its forms.

Strontium Ranelate and Strontium Chloride Supplementation Influence on Bone Microarchitecture and Bone Turnover Markers-A Preliminary Study.

Despite strontium ranelate use in osteoporosis management being one of the promising concepts in disease treatment, there is no clear evidence that strontium organic compounds are more effective than inorganic ones. The aim of this study was to compare strontium chlorate and strontium ranelate influence on the mice bone microarchitecture. We investigated whether strontium chlorate (7.532 mmol/L) and strontium ranelate (7.78 mmol/L) solutions fed to healthy SWISS growing mice (n = 42) had an influence on the percent of bone volume (BV/TV), trabecular thickness (Tb.Th), number of trabeculae (Tb.N), and separation between each trabecula (Tb.Sp) in the chosen ROI (region of interest) in the distal metaphysis of the left femurs. The cortical bone surface was examined close to the ROI proximal scan. There was an increase in each examined parameter compared with the control group. There were no statistical differences between strontium ranelate and strontium chlorate parameters. Our study indicates that organic and inorganic strontium compounds similarly affect the bone microarchitecture and strength.

Strontium ranelate-laden near-infrared photothermal-inspired methylcellulose hydrogel for arthritis treatment.

Rheumatoid arthritis (RA) is of foremost concern among long-term autoimmune disorders, as it leads to inflammation, exudates, chondral degeneration, and painful joints. Because RA severity often fluctuates over time, a local drug delivery method that titrates release of therapeutics to arthritis bioactivity should represent a promising paradigm of RA therapy. Given the local nature of RA chronic illnesses, polysaccharide-drug delivering systems have the promise to augment therapeutic outcomes by offering controlled release of bioactive materials, diminishing the required frequency of administration, and preserving therapeutic levels in affected pathological regions. Herein, an intra-articular photothermal-laden injectable methylcellulose (MC) polymeric hydrogel carrier incorporating strontium ranelate (SrR) and sodium chloride was investigated to resolve these issues. Physicochemical and cellular characteristics of the MC carrier system were thoroughly evaluated. The slow release of SrR, enhancement of the material mechanical strength, and the potential of the non-invasive near-infrared photothermal gel to improve blood circulation and suppress inflammation in a mini-surgical model of RA were examined. Biocompatibility and suppression of intracellular ROS-induced inflammation were observed. This multifunctional photothermal MC hydrogel carrier is anticipated to be an alternative approach for future orthopedic disease treatment.

Chinese topical herbal medicine gives additive effect on pharmaceutical agent on fracture healing.

OBJECTIVE: To investigate the efficacy on the combination of oral strontium ranelate (SrR) with a topical Chinese herbal paste on facilitation of fracture healing. METHODS: An open fracture was created at the mid-shaft of the right tibia of rat. A herbal paste called CDR containing Honghua (Flos Carthami), Chuanxuduan (Radix Dipsaci Asperoidis) and Dahuang (Radix Et Rhizoma Rhei Palmati) was prepared. The rats were treated with either CDR topically on the fracture site, or SrR orally, or their combinations. Bone turnover biochemical markers in serum were measured. Microarchitecture of the fracture was analyzed using micro-CT after 14 and 28 d, followed by histomorphometrical analysis. RESULTS: Micro-computed tomography analysis revealed that the combined treatment of CDR with 600 mg/g SrR significantly increased the total callus density, mineralized callus volume fraction, mineralized callus mineral content and mineralized callus density of the callus after 28 d of treatment. This result was consistent with the histomorphometrical analysis on the osteoid volume. Analysis of biochemical markers showed that the combined treatments reduced the bone resorption that occurs temporarily after fracture. CONCLUSION: This study demonstrated that the combined treatment of oral SrR and topical CDR is effective to promote fracture healing by their additive effect on promoting bone formation and retarding bone resorption.

Strontium ranelate stimulates trabecular bone formation in a rat tibial bone defect healing process.

Strontium ranelate treatment is known to prevent fractures. Here, we showed that strontium ranelate treatment enhances bone healing and affects bone cellular activities differently in intact and healing bone compartments: Bone formation was increased only in healing compartment, while resorption was reduced in healing and normal bone compartments. INTRODUCTION: Systemic administration of strontium ranelate (SrRan) accelerates the healing of bone defects; however, controversy about its action on bone formation remains. We hypothesize that SrRan could affect bone formation differently in normal mature bone or in the bone healing process. METHODS: Proximal tibia bone defects were created in 6-month-old female rats, which orally received SrRan (625 mg/kg/day, 5/7 days) or vehicle (control groups) for 4, 8, or 12 weeks. Bone samples were analyzed by micro-computed tomography and histomorphometry in various regions, i.e., metaphyseal 2nd spongiosa, a region close to the defect, within the healing defect and in cortical defect bridging region. Additionally, we evaluated the quality of the new bone formed by quantitative backscattered electron imaging and by red picosirius histology. RESULTS: Healing of the bone defect was characterized by a rapid onset of bone formation without cartilage formation. Cortical defect bridging was detected earlier compared with healing of trabecular defect. In the healing zone, SrRan stimulated bone formation early and laterly decreased bone resorption improving the healing of the cortical and trabecular compartment without deleterious effects on bone quality. By contrast, in the metaphyseal compartment, SrRan only decreased bone resorption from week 8 without any change in bone formation, leading to little progressive increase of the metaphyseal trabecular bone volume. CONCLUSIONS: SrRan affects bone formation differently in normal mature bone or in the bone healing process. Despite this selective action, this led to similar increased bone volume in both compartments without deleterious effects on the newly bone-formed quality.

Comparison of parathyroid hormone and strontium ranelate in combination with whole-body vibration in a rat model of osteoporosis.

We investigated the combinatorial effects of whole-body vertical vibration (WBVV) with the primarily osteoanabolic parathyroid hormone (PTH) and the mainly antiresorptive strontium ranelate (SR) in a rat model of osteoporosis. Ovariectomies were performed on 76 three-month-old Sprague-Dawley rats (OVX, n = 76; NON-OVX, n = 12). After 8 weeks, the ovariectomized rats were divided into 6 groups. One group (OVX + PTH) received daily injections of PTH (40 µg/kg body weight/day) for 6 weeks. Another group (OVX + SR) was fed SR-supplemented chow (600 mg/kg body weight/day). Three groups (OVX + VIB, OVX + PTH + VIB, and OVX + SR + VIB) were treated with WBVV twice a day at 70 Hz for 15 min. Two groups (OVX + PTH + VIB, OVX + SR + VIB) were treated additionally with PTH and SR, respectively. The rats were killed at 14 weeks post-ovariectomy. The lumbar vertebrae and femora were removed for biomechanical and morphological assessment. PTH produced statistically significant improvements in biomechanical and structural properties, including bone mineral density (BMD) and trabecular bone quality. In contrast, SR treatment exerted mild effects, with significant effects in cortical thickness only. SR produced no significant improvement in biomechanical properties. WBVV as a single or an adjunctive therapy produced no significant improvements. In conclusion, vibration therapy administered as a single or dual treatment had no significant impact on bones affected by osteoporosis. PTH considerably improved bone quality in osteoporosis cases and is superior to treatment with SR.

Assessment of OPG, RANKL, bone turnover markers serum levels and BMD after treatment with strontium ranelate and ibandronate in patients with postmenopausal osteoporosis.

INTRODUCTION: The aim of this study was to evaluate quantitative changes in OPG and RANKL proteins after treatment with strontium ranelate (SR) and ibandronate in patients with postmenopausal osteoporosis. MATERIAL AND METHODS: A total of 89 women with postmenopausal osteoporosis (PO), aged 51-85 years, patients of the Outpatient Clinic of Osteoporosis of the Military Teaching Hospital in Lodz, were enrolled in the study. The patients were randomly assigned to different therapies: ibandronate and (SR). Patients of the control group received only calcium and vitamin D3 supplements. The patients' visits were repeated after three and six months. Measurements of beta-CTX (C-terminal Telopeptide of type 1 collagen), osteocalcin, RANKL, osteoprotegerin (OPG), alkaline phosphatase concentrations in serum, as well as of total 24-hour calcium and phosphate levels in serum and urine, were carried out in material collected at baseline and after three and six months of therapy. Left hip and lumbar spine densitometry was done twice (at baseline visit and after six months). RESULTS: In all three groups there were no significant differences noted in the concentrations of OPG and RANKL serum protein levels during the study period. Both negative and positive correlations or tendencies of correlations were found between OPG serum concentrations and BMD changes in the SR group. CONCLUSIONS: Both ibandronate and SR do not seem to cause any significant changes in OPG and RANKL protein serum levels during the first six months of treatment. OPG may play a role in osteoclast activity suppression in the course of treatment with ibandronate in patients with PO. OPG may play an important role in the mechanism of SR therapy and may be viewed as a potentially valuable parameter for monitoring and predicting the course of treatment with SR in PO.

Strontium ranelate as an adjuvant for fracture healing: clinical, radiological, and ultrasound findings in a randomized controlled study on wrist fractures.

UNLABELLED: This randomized and controlled study evaluated the effect of therapy with strontium ranelate on callus formation in wrist fractures and its incidence in wrist recovery. Radiographic healing, progression of clinical recovery, and callus quality with ultrasound were evaluated. No statistically significant benefit of therapy was found. INTRODUCTION: Fracture prevention is the main goal of any therapy for osteoporosis. Various drugs used in osteoporosis treatment have the theoretical premises to promote fracture healing and osseointegration. In this study, the effect of strontium ranelate on callus formation in wrist fractures was evaluated and whether it could lead to clinically relevant modification of wrist recovery; having strontium ranelate osteoinductive properties, it could be used, if effective, as an adjunct in fracture healing for a faster and functionally better recovery and, at the same time, in starting proper therapy in osteoporotic patients with fragility fractures. METHODS: We considered only patients older than 60 years who had suffered wrist fracture and received nonoperative treatment with manual reduction of the fracture and cast for 35 days. Forty patients were included and randomly assigned to one of two groups: group A [patients treated with calcium (1200 mg/day) and vitamin D (800 IU/day)] and group B [patients treated with calcium (1200 mg/day) and vitamin D (800 IU/day) associated with strontium ranelate 2 g daily]. Radiographic healing was evaluated through the bone callus formation, cortical continuity, and density of the callus. A clinical evaluation using Castaing's criteria was carried out 2 and 3 months following the fracture together with an ultrasound study of callus density and vessels. RESULTS: A parametric analysis of the X-ray data, clinical evaluation, and ultrasonography results showed that there were no statistically significant differences in the two groups (p > 0.05 for all data). CONCLUSION: In analyzing the data obtained, we concluded that strontium ranelate administered in acute phase did not improve nor accelerate wrist fracture healing in our population.

New strategies for osteoporosis patients previously managed with strontium ranelate.

The aim of this article is to describe potential alternatives to patients no longer eligible for management with strontium ranelate for osteoporosis according to the recommendations by the European Medicines Agency. A systematic search of Pubmed was done for papers on fracture efficacy of various treatments for osteoporosis, and potential harms especially in terms of cardiovascular events and stroke. The results showed that drugs more efficacious in terms of relative risk reduction of fractures than strontium ranelate were alendronate, risedronate, zoledronate, and denosumab. Raloxifene, as for strontium, may be associated with an increased risk of deep venous thromboembolism and fatal stroke. In terms of cardiovascular events special attention may be given to calcium supplements. Thus, patients at risk of stroke and ischemic cardiac events such as acute myocardial infarction should not use strontium ranelate. Ideally more efficacious drugs in terms of fracture reduction should be used such as alendronate, risedronate, zoledronate or denosumab. Raloxifene may pose a special problem as this too may be associated with an increased risk of fatal strokes. Other less-potent drugs in terms of fracture reduction should only be used if no alternatives are available (ibandronate, pamidronate, clodronate). Parathyroid hormone or analogs may be used for a limited time interval in specially selected patients and needs to be followed up with antiresorptive treatment to prevent loss of the bone gained. However, it should be remembered that no head-to-head comparison studies exist.

Pregnancy-associated osteoporosis with seven vertebral compression fractures, a case treated with strontium ranelate.

This paper shows a case of pregnancy-associated osteoporosis (PAO) with seven vertebral compression fractures treated with strontium ranelate and supplementation of calcium and cholecalciferol. Clinical evaluation, laboratory and radiological results are analyzed in the case-report to demonstrate that strontium ranelate is a good option to restore quickly the value of bone mineral density in the treatment of a case of PAO.