Administration Of Alendronate Research Articles

Poloxamer 407 modified collagen/β-tricalcium phosphate scaffold for localized delivery of alendronate.

Systemic administration of alendronate is associated with various adverse reactions in clinical settings. To mitigate these side effects, poloxamer 407 (P-407) modified with cellulose was chosen to encapsulate alendronate. This drug-loaded system was then incorporated into a collagen/β-tricalcium phosphate (β-TCP) scaffold to create a localized drug delivery system. Nuclear magnetic resonance spectrum and rheological studies revealed hydrogen bonding between P-407 and cellulose as well as a competitive interaction with water that contributed to the delayed release of alendronate (ALN). Analysis of the degradation kinetics of P-407 and release kinetics of ALN indicated zero-order kinetics for the former and Fickian or quasi-Fickian diffusion for the latter. The addition of cellulose, particularly carboxymethyl cellulose (CMC), inhibited the degradation of P-407 and prolonged the release of ALN. The scaffold's structure increased the contact area of P-407 with the PBS buffer, thereby, influencing the release rate of ALN. Finally, biocompatibility testing demonstrated that the drug delivery system exhibited favorable cytocompatibility and hemocompatibility. Collectively, these findings suggest that the drug delivery system holds promise for implantation and bone healing applications.

Effect of alendronate and platelet-rich plasma in tendon-bones integration in sheep anterior cruciate ligament surgery

Context: Anterior cruciate ligament (ACL) reconstruction often faces challenges due to poor integration of the tendon with bone. Aims: To evaluate the potential benefits of alendronate and platelet-rich plasma (PRP) in enhancing tendon-to-bone osteointegration in ACL surgery. Methods: This was a post-test only control group experimental study with Ovis aries Linnaeus sheep as experimental animals. The sample was divided into four groups: the control group ACL reconstruction with calcaneal tendons given NaCl, the group given PRP, alendronate, and PRP and alendronate. Bone healing biomarkers (NF-B, TNF-α, MMP-9, TGF-β1, and COL1A1) were examined through immunohistochemical analysis and histological studies to assess osteoblast counts and inflammatory tissue. Results: There was a statistically significant (p<0.05) increase in MMP-9 and osteoblast count after alendronate and PRP administration. Administration of alendronate and PRP also increased other variables, namely TNF-α, COL1A1, and the level of inflammation, although not statistically significant (p>0.05). The intervention did not affect NF-B and TGF-β1 (p> 0.05). Conclusions: These results show that the administration of alendronate and PRP improves the healing of tendon-calcaneal ACL reconstruction surgery in sheep.

Bone quality in zebrafish vertebrae improves after alendronate administration in a glucocorticoid-induced osteoporosis model

Glucocorticoid-induced osteoporosis (GIOP) changes the microarchitecture of bones and often leads to the reduction of bone-mineral density (BMD) and increased fracture rates. Zebrafish has been used as an alternative model for GIOP, however, the interaction of GIOP, and its treatment, with zebrafish bone morphometrics and mechanical properties, remains a challenge. Thus, this study aimed to evaluate the effects of prednisolone and alendronate on the properties of zebrafish vertebrae. Adult 7-month-old zebrafish were distributed into four groups: control (CTRL), prednisolone-only (PN), alendronate-only (ALN), and the sequential use of both medicines (PN + ALN). Fish skeletons were scanned via micro-tomography (n = 3) to obtain vertebra morphometrics (e.g., BMD). Bone morphology was assessed using scanning electron microscopy (n = 4) and the biomechanical behaviour with nanoindentation technique (n = 3). The BMD decreased in PN (426.08 ± 18.58 mg/cm3) and ALN (398.23 ± 10.20 mg/cm3) groups compared to the CTRL (490.43 ± 41.96 mg/cm3) (p < 0.001); however, administering the medicines in sequence recovered the values to healthy levels (495.43 ± 22.06 mg/cm3) (p > 0.05). The bone layered structures remain preserved in all groups. The vertebrae of the groups that received ALN and PN + ALN, displayed higher modulus of elasticity (27.27 ± 1.59 GPa and 25.68 ± 2.07 GPa, respectively) than the CTRL (22.74 ± 1.60 GP) (p < 0.001). ALN alone increased the hardness of zebrafish vertebrae to the highest value among the treatments (1.32 ± 0.13 GPa) (p < 0.001). Conversely, PN + ALN (1.25 ± 0.11 GPa) showed unaltered hardness from the CTRL (1.18 ± 0.13 GPa), but significantly higher than the PN group (1.08 ± 0.12 GPa) (p < 0.001). ALN administered after GIOP development, rescued osteoporotic condition by recovering the BMD and bone hardness in zebrafish vertebrae.

Improvement of osteoblast adhesion, viability, and mineralization by restoring the cell cytoskeleton after bisphosphonate discontinuation in vitro.

Bisphosphonates are prescribed to treat excessive bone resorption in patients with osteoporosis. However, its use is associated with potential adverse effects such as medication-related osteonecrosis of the jaw, prompting the introduction of the drug holiday concept in patients prior to dentoalveolar surgery. Furthermore, bisphosphonate discontinuation has been studied in vivo, in humans, and in animal models. However, it is not known whether this approach could affect bone cells in vitro. Therefore, the objective of this study was to investigate the potential effects of bisphosphonate discontinuation on pre-osteoblast and osteoblast activities in vitro. Pre-osteoblasts (MC3T3) and osteoblasts were treated with bisphosphonate (alendronate) at concentrations of 1, 5, and 10 µM. Alendronate was then withdrawn at different time points. The negative control consisted of untreated cells (0 µM), while the positive control consisted of cells incubated with alendronate throughout the experiment. Cell viability, cell adhesion, cell cytoskeleton, mineralization, and gene expressions were investigated. Pre-osteoblasts and osteoblasts showed a decrease in cell viability after treatment with 5-10 μM alendronate for 4 days or longer. Two days of alendronate discontinuation significantly increased cell viability compared with the positive control. However, these levels did not reach those of the negative control. Bone nodule formation was reduced by alendronate. Discontinuation of alendronate regained bone nodule formation. Longer periods of discontinuation were more effective in restoring nodule formation than shorter periods. Addition of alendronate resulted in an increase in the percentage of dead cells, which, in turn, decreased when alendronate was discontinued. Alendronate affected the cell cytoskeleton by disassembling actin stress fibers. Cell adhesion and cell morphological parameters were also affected by alendronate. Discontinuation of alendronate restored cell adhesion and these parameters. Overall, the highest improvement after alendronate discontinuation was seen at 10 µM. However, alendronate treatment and discontinuation did not affect osteoblast gene expression. Discontinuation of alendronate helps to reverse the negative effects of the drug on cell viability, cell adhesion, and mineralization by restoring the cell cytoskeleton. Our data suggest the benefits of drug holiday and/or intermittent strategies for alendronate administration at the cellular level.

Análisis histológico e histomorfométrico de la reparación ósea de mandíbulas de ratas usando geles de alendronato y aloe vera

The maintenance of bone mass in the jaws is a concern for dental professionals. Objective: To study the effect of local administration of Alendronate (AL) and Aloe vera (AV) on the tissue regeneration of the post-exodontia alveolus in rats. Materials and methods: Absorbable gelatin hemostatic sponges were used; they were embedded with a solution of LA (0.5 mg/Kg) and 70% AV gel; control group (C) used saline. The effect was evaluated in male Wistar rats (n=64), divided into 4 groups: C, AL, AV and AL+AV. The first lower molars were extracted, the embedded hemostatic sponges were placed in the alveoli. The handling of the animals was carried out following the norms established by SECyT according to CICUAL. Determinations were made at 0, 7, 15, 30 days. The lower jaw was extracted, placed in a sterile jar and fixed in 10% formalin; the samples were decalcified and then embedded in paraffin. Histological sections were made and stained with Hematoxylin/Eosin. Histological and histomorphometric parameters were analyzed. An analysis of Variance (ANOVA) was performed for two classification criteria. Results: In the histomorphological analysis, at 15 days the AV group presented greater new formation of bone tissue. At 30 days, the presence of mature bone with the presence of Haversian systems was observed in the AV and AL+AV group. The histomorphometric study at 15 and 30 days showed significant differences in the number of osteoblasts per linear mm, between the AV and AL+AV group with respect to group C (p&lt;0.01). Whenmeasuring trabecular thickness, significant differences were observed at 30 days between the AV group and the C group (p&lt;0.01). Conclusions: The parameters studied demonstrated that Aloe vera administered locally favored bone repair in the post-exodontia alveoli

Osteolytic Bone Loss and Skeletal Deformities in a Mouse Model for Early-Onset Paget's Disease of Bone with PFN1 Mutation Are Treatable by Alendronate.

A novel osteolytic disorder due to PFN1 mutation was discovered recently as early-onset Paget's disease of bone (PDB). Bone loss and pain in adult PDB patients have been treated using bisphosphonates. However, therapeutic strategies for this specific disorder have not been established. Here, we evaluated the efficiency of alendronate (ALN) on a mutant mouse line, recapitulating this disorder. Five-week-old conditional osteoclast-specific Pfn1-deficient mice (Pfn1-cKOOCL) and control littermates (33 females and 22 males) were injected with ALN (0.1 mg/kg) or vehicle twice weekly until 8 weeks of age. After euthanizing, bone histomorphometric parameters and skeletal deformities were analyzed using 3D μCT images and histological sections. Three weeks of ALN administration significantly improved bone mass at the distal femur, L3 vertebra, and nose in Pfn1-cKOOCL mice. Histologically increased osteoclasts with expanded distribution in the distal femur were normalized in these mice. Geometric bone shape analysis revealed a partial recovery from the distal femur deformity. A therapeutic dose of ALN from 5 to 8 weeks of age significantly improved systemic bone loss in Pfn1-cKOOCL mice and femoral bone deformity. Our study suggests that preventive treatment of bony deformity in early-onset PDB is feasible.

Administration of alendronate exacerbates ammonium chloride-induced acidosis in mice.

Bone disease is highly prevalent in patients with chronic kidney disease (CKD), leading to an increased risk of bone fractures. This is due in part to metabolic acid-induced bone dissolution. Bisphosphonates (BPPs) are a potential treatment for inhibiting bone dissolution; however, there are limited studies observing the use of BPPs on acidotic patients. We aimed to determine efficacy of BPPs on maintaining bone health and pH regulation in acid-exposed mice. Using a diet-induced murine model of metabolic acidosis, we examined bone structure, composition, and mechanics as well as blood gases for three groups: control, acidosis, and acidosis + bisphosphonates (acidosis+BPP). Acidosis was induced for 14 days and alendronate was administered every 3 days for the acidosis+BPP group. The administration of BPP had little to no effect on bone structure, mechanics, and composition of the acidosis bones. However, administration of BPP did cause the mice to develop more severe acidosis than the acidosis only group. Overall, we discovered that BPPs may exacerbate acidosis symptoms by inhibiting the release of buffering ions from bone. Therefore, we propose that BPP administration should be carefully considered for those with CKD and that alkali supplementation could help minimize acidifying effects.

Association ofbisphosphonate with bone loss andpain-related behaviour inan adjuvant-induced osteoporosis model.

Osteoporosis animal models are used extensively to determine the mechanisms of disease pathology and identify potential biological targets. The study aimed to establish a bone loss model, identify pain-related behaviour in neighbouring joints using an adjuvant-induced osteoporosis model, and examine the therapeutic effect of bisphosphonates. Complete Freund's adjuvant was injected subcutaneously into the back of the right foot of 8-week-old female ddY mice. Subsequently, pain, arthritis, and bone density in the right knee were monitored over time. Pain evaluation using von Frey filaments showed a significantly exacerbated knee pain threshold compared to the control group (saline administration) at 7- and 14-day intervals after complete Freund's adjuvant administration, and bone density during the same period also significantly declined. The adjuvant-induced osteoporosis model was created similarly; alendronate 40 μg/kg was subcutaneously injected twice and vehicle once from 7 to 14 days after onset. In the alendronate administration group on the 14th day, significant improvements in bone density, arthritis, and pain threshold around the knee were observed compared to the untreated group. Alendronate may contribute to pain improvement through the simultaneous effects of bone mass improvement and suppression of osteoporotic pain.

Changes in the Subchondral Bone, Visfatin, and Cartilage Biomarkers after Pharmacological Treatment of Experimental Osteoarthritis with Metformin and Alendronate.

Subchondral bone that has intense communication with the articular cartilage might be a potential target for pharmacological treatment in the early stages of osteoarthritis (OA). Considering the emerging data about the role of adipokines in the pathogenesis of OA, the administration of drugs that influence their level is also intriguing. Metformin and alendronate were administered in mice with collagenase-induced OA (CIOA) as a monotherapy and in combination. Safranin O staining was used for the assessment of changes in subchondral bone and articular cartilage. Before and after treatment, serum levels of visfatin and biomarkers of cartilage turnover (CTX-II, MMP-13, and COMP) were assessed. In the current study, the combined administration of alendronate and metformin in mice with CIOA led to the protection against cartilage and subchondral bone damage. In mice with CIOA, metformin led to a decrease in visfatin level. In addition, treatment with metformin, alendronate, or their combination lowered the level of cartilage biomarkers (CTX-II and COMP), while the level of MMP-13 was not influenced. In conclusion, personalized combination treatment in OA according to clinical phenotype, especially in the early stages of the disease, might lead to the identification of a successful disease-modifying therapeutic protocol in OA.

Influence of bisphosphonate treatment on bone substitute performance in osteoporotic conditions.

Considering the elevated number of osteoporotic patients in need of bone graft procedures, we here evaluated the effect of alendronate (ALN) treatment on the regeneration of bone defects in osteoporotic rats. Bone formation was histologically and histomorphometrically assessed in rat femoral condyle bone defects filled with bone graft (Bio-Oss®) or left empty. Male Wistar rats were induced osteoporotic through orchidectomy (ORX) and SHAM-operated. The animals were divided into three groups: osteoporotic (ORX), osteoporotic treated with ALN (ORX + ALN) and healthy (SHAM). Six weeks after ORX or SHAM surgeries, bone defects were created bilaterally in femoral condyles; one defect was filled with Bio-Oss® and the other one left empty. Bone regeneration within the defects was analyzed by histology and histomorphometry after 4 and 12 weeks. Histological samples showed new bone surrounding Bio-Oss® particles from week 4 onward in all three groups. At week 12, the data further showed that ALN treatment of osteoporotic animals enhanced bone formation to a 10-fold increase compared to non-treated osteoporotic control. Bio-Oss® filling of the defects promoted bone formation at both implantation periods compared to empty controls. Our histological and histomorphometric results demonstrate that the enteral administration of alendronate under osteoporotic bone conditions leverages bone defect regeneration to a level comparable to that in healthy bone. Additionally, Bio-Oss® is an effective bone substitute, increasing bone formation, and acting as an osteoconductive scaffold guiding bone growth in both healthy and osteoporotic bone conditions. Based on the results of this study, enteral use of ALN mitigates adverse effects of an osteoporotic condition on bone defect regeneration.

Placebo-controlled Trial of Oral Vitamin D and Alendronate Efficacy for Pain and Modic Changes in Lumbar Fusion Surgery

Background and Aim: Modic changes are alterations in the spine endplates and subchondral bone shock absorption, seen by magnetic resonance imaging (MRI). No studies have investigated the effect of vitamin D and alendronate as oral drugs on reducing and modifying Modic changes after degenerative spine fusion surgery. This study aimed to evaluate the efficacy of oral vitamin D and alendronate administration in patients with low back pain, and Modic changes undergoing lumbar fusion surgery. Methods and Materials/Patients: A total of 81 middle age women with a normal range of serum vitamin d were enrolled in three groups who underwent lumbar fusion surgery according to neurosurgical criteria. Group 1 (n=27) received additional oral alendronate, group 2 (n=27) received oral vitamin D for six months postoperatively, and group 3 (n=27) received no drug (except simple analgesics and antibiotics). The patients were followed up with a visual analog scale (VAS) and Oswestry disability index (ODI). MRI was done before and six months after surgery. Results: There was no significant difference between the three groups in VAS and ODI scores (P=0.416, P=0.601, respectively), but the mean VAS and ODI in all three groups decreased over six months, which was statistically significant (P&lt;0.001). Modic changes in all three groups changed significantly over 6 months (P&lt;0.01). In the vitamin D and alendronate groups, Modic type 3 increased significantly, but Modic type 2 and Modic type 1 decreased significantly in the vitamin d and no medication groups, respectively. Conclusion: Oral vitamin D administration has a desirable effect not only on clinical outcomes after lumbar spinal fusion surgery because of degenerative surgery but also on vertebral endplate Modic changes compared to oral bisphosphonate.

The Gradual Release of Alendronate for the Treatment of Critical Bone Defects in Osteoporotic and Control Rats.

Osteoporosis is a severe health problem with social and economic impacts on society. The standard treatment consists of the systemic administration of drugs such as bisphosphonates, with alendronate (ALN) being one of the most common. Nevertheless, complications of systemic administration occur with this drug. Therefore, it is necessary to develop new strategies, such as local administration. In this study, emulsion/dispersion scaffolds based on W/O emulsion of PCL and PF68 with ALN, containing hydroxyapatite (HA) nanoparticles as the dispersion phase were prepared using electrospinning. Scaffolds with different release kinetics were tested in vitro on the co-cultures of osteoblasts and osteoclast-like cells, isolated from adult osteoporotic and control rats. Cell viability, proliferation, ALP, TRAP and CA II activity were examined. A scaffold with a gradual release of ALN was tested in vivo in the bone defects of osteoporotic and control rats. The release kinetics were dependent on the scaffold composition and the used system of the poloxamers. The ALN was released from the scaffolds for more than 22 days. The behavior of cells cultured in vitro on scaffolds with different release kinetics was comparable. The difference was evident between cell co-cultures isolated from osteoporotic and control animals. The PCL/HA scaffold show slow degradation in vivo and residual scaffold limited new bone formation inside the defects. Nevertheless, the released ALN supported bone formation in the areas surrounding the residual scaffold. Interestingly, a positive effect of systemic administration of ALN was not proved. The prepared scaffolds enabled tunable control release of ALN. The effect of ALN was proved in vitro and in in vivo study supported peri-implant bone formation.

Effects of red and infrared laser on post extraction socket repair in rats subjected to alendronate therapy

This study evaluated the effect of photobiomodulation therapy (PBMT) with a red or infrared laser on the repair of post extraction sockets in rats administered alendronate (ALN). Forty male rats were randomly allocated into four groups: Control Group (CTR): subcutaneous administration of saline solution throughout the experimental period; Alendronate Group (ALN): subcutaneous administration of alendronate during the entire experimental period; Alendronate/Red Laser Group (ALN/RL): administration of ALN and irradiation with a GaAlAs laser (λ 660 nm); and Alendronate/Infrared Laser Group (ALN/IRL): administration of ALN and irradiation with a GaAlAs laser (λ 830 nm). The first lower molars were extracted 60 days after the beginning of the administration of the drugs. The PBMT was applied after tooth extraction (7 sessions with intervals of 48 hours between sessions). Thirty days after tooth extraction, the animals were euthanized. Micro-CT and histometric analysis were performed to assess the bone healing and soft tissue repair of the tooth socket. The ALN group presented with more bone than the CTR; however, most of this bone was necrotic. ALN does not affect the bone microarchitecture. On the other hand, PBMT with IRL enhances the bone density due to the increase in the number and reduction in the spacing of the trabeculae. The amount of vital bone and connective tissue matrix was higher in the ALN/RL and ALN/IRL groups than in the ALN and CTR groups. PBMT enhanced the healing of the post extraction sockets in rats subjected to ALN administration. Furthermore, IRL improved the new bone microarchitecture.

Significance of medication discontinuation on bisphosphonate-related jaw osteonecrosis in a rat model

Bisphosphonate (BP) discontinuation has been advised as a measure to prevent the incidence of bisphosphonate-related osteonecrosis of the jaw (BRONJ), however, its efficacy remains controversial. This study aimed to analyze the efficacy of BP discontinuation in reducing BRONJ severity following tooth extraction in a rat model. Thirty-four male Sprague–Dawley rats were divided into two BRONJ model categories: oral administration (PO) of alendronate (1 mg/kg) for 3 and 8 weeks and intraperitoneal (IP) injection of pamidronate (3 mg/kg) and dexamethasone (1 mg/kg) for 20 days. The PO model was divided into five groups (a control group without BPs and four experimental groups with 1-week discontinuation). The IP model was divided into two groups consisting of group I (without discontinuation) and group II (1-week discontinuation). One molar from both sides of the mandible was extracted. After extraction, the PO models were sacrificed at 3 and 5 weeks, and the IP models were sacrificed either immediately or at 2, 4, 6, and 8 weeks. Micro-CT showed non-significant differences among PO groups but significant differences were observed between IP groups. Most bone remodeling parameters within group I of the IP model differed significantly (p-value < 0.05). Histologically, group I showed a significantly higher percentage of necrotic bone than group II (51.93 ± 12.75%, p < 0.05) and a higher number of detached osteoclasts in TRAP staining. With discontinuation of medication for at least 1 week in rats, the effects of BPs on alveolar bone are suppressed and bone turnover and osteoclast functions are restored.

Alendronate Prevents Early Periprosthetic Bone Loss in Cementless Total Hip Arthroplasty Better Than Simvastatin

Background and Objectives: Cementless total hip arthroplasty leads to an early periprosthetic bone loss, which can impair the osseointegration process and lead to a femoral implant migration during early weight-bearing. An altered osseointegration process can lead to aseptic loosening, which is the most frequent late complication in these surgical procedures. The objective of this study was to compare the effect of alendronate and simvastatin in the prevention of early periprosthetic bone loss found in osteoporotic patients. This can lead to earlier weight-bearing in patients, as well as reduce the rate of aseptic loosening. Materials and Methods: Forty-five patients undergoing cementless total hip arthroplasty were equally distributed into three groups: group I (alendronate), group II (simvastatin), and group III (control). The alendronate group received 5 mg of alendronate postoperatively, daily for 8 weeks, and the simvastatin group received 20 mg daily for 4 weeks postoperatively, followed by 40 mg daily for 4 weeks. We determined bone mineral density (BMD), as well as bone serum markers beta cross-laps (β-CTx) and alkaline phosphatase (ALPL) preoperatively, 4 weeks postoperatively, and 8 weeks postoperatively. All patients were not allowed to fully bear weight for 6 weeks postoperatively. Results: Alendronate statistically significantly increases the BMD at one month postoperatively compared to the control group in Gruen zones 5 and 6 (p = 0.042 and p = 0.039). Overall, the BMD was higher in the alendronate group compared to the control group at one month postoperatively (p = 0.043). Alendronate decreased β-CTx bone serum marker compared to control at one month and two months (p = 0.024 and p = 0.012). Moreover, alendronate showed a higher decrease in β-CTx compared to simvastatin at both timelines (p = 0.028 and p = 0.03, respectively). Conclusions: The study shows that alendronate administration following cementless total hip arthroplasty offers better protection against periprosthetic bone loss compared to simvastatin.

Double-blind, placebo-controlled evaluation of biorest liposomal alendronate in diabetic patients undergoing PCI: The BLADE-PCI trial

Diabetes mellitus (DM) is an important predictor of neointimal hyperplasia (NIH) and adverse clinical outcomes after percutaneous coronary intervention (PCI). LABR-312, a novel intravenous formulation of liposomal alendronate, has been shown in animal models to decrease NIH at vascular injury sites and around stent struts. The aim of the Biorest Liposomal Alendronate Administration for Diabetic Patients Undergoing Drug-Eluting Stent Percutaneous Coronary Intervention trial was to assess the safety, effectiveness, and dose response of LABR-312 administered intravenously at the time of PCI withDES in reducing NIH as measured by optical coherence tomography postprocedure in patients with DM. Patients with DM were randomized to a bolus infusion of LABR-312 vs placebo at the time of PCI. Dose escalation of LABR-312 in the study arm was given: 0.01 mg, 0.03 mg, and 0.08 mg. The primary endpoint was the in-stent %NIH volume at 9 months as measured by optical coherence tomography. From September 2016 to December 2017, 271 patients with DM undergoing PCI were enrolled; 136 patients were randomized to LABR-312 infusion and 135 patients were randomized to placebo. At 9-month follow-up, no difference was seen in the primary endpoint of %NIH between LABR-312 and placebo (13.3% ± 9.2 vs 14.6% ± 8.5, P=.35). No differences were present with the varying LABR-312 doses. Clinical outcomes at 9 months were similar between groups. Among patients with DM undergoing PCI with drug-eluting stents, a bolus of LABR-312 injected systematically at the time of intervention did not result in a lower rate in-stent %NIH volume at 9-month follow-up.

Histomorphometry of Bone Microarchitecture in Rats Treated with Vitamin D and Bisphosphonate in the Management of Osteoporosis.

Objective To verify how the combined administration of alendronate (ALN) and vitamin D3 (VD) acts on the bone microarchitecture in rats with glucocorticoid-induced osteoporosis. Methods The experiment used 32 90-day-old female Wistar rats weighing between 300 and 400g. The induction of osteoporosis consisted of intramuscular administration of dexamethasone at a dose of 7.5 mg/kg of body weight once a week for 5 weeks, except for the animals in the control group. The animals were separated into the following groups: G1 (control group without osteoporosis), G2 (control group with osteoporosis without treatment), G3 (group with osteoporosis treated with ALN 0.2 mg/kg), G4 (group with osteoporosis treated with VD 10,000UI/500μL), and G5 (group with osteoporosis treated with ALN + VD). The right femurs of the rats were fixed in 10% buffered formaldehyde, decalcified, and processed for inclusion in paraffin. Histological sections were stained with hematoxylin-eosin for histomorphometric analysis. Cortical thickness and medullary cavity were measured in cross-sections. Results There was a statistical difference ( p < 0.05) between groups G3 and G5 compared with the positive control group (G2), both related to the measurement of cortical thickness and to the total diameter of the bone. In the evaluation of the spinal area, only the G3 group has shown to be statistically different from the G2 group. Conclusion Concomitant treatment with daily ALN and weekly VD is effective in preventing glucocorticoid-induced bone loss. However, there was no difference between the therapy tested and treatment with ALN alone.

The Effect of Alendronate on Bone Mineral Disorder in Renal Transplant Patients

In this study, we aimed to investigate the effect of long-term administration of alendronate to treat bone loss in renal transplant patients. Eighty-two renal transplant recipients were divided into 3 groups. Group 1 included patients who were treated with calcium, vitamin D3, and alendronate; group 2 included patients who were treated with calcium and vitamin D3; and group 3 included patients who did not receive these medications. All patients' sociodemographic data, biochemical parameters, and bone mineral density (BMD) measurements were recorded. There were no significant differences between sociodemographic and laboratory findings at the beginning of study in all groups. The BMD of lumbar spine and femoral neck was significantly less in group 1 at the beginning, 12 and 24 months of the study when compared with other group. At 12 and 24 months of the study, the BMD levels were decreased both group 2 and group 3, whereas in group 1, it was stable at 12 months and increased thereafter. In group 1, the initial femoral neck BMD was negatively correlated with parathormone, sex, and body mass index, and positively correlated with creatinine level. While there was a positive correlation between basal body mass index and femur neck BMD in group 2, there was no correlation between baseline parameters, demographic data, and bone mineral density in group 3 patients. In conclusion, bone loss is inevitable despite calcium and vitamin D replacement. However, bone loss can be stopped and even reversed with alendronate therapy.

Strontium ranelate improves post-extraction socket healing in rats submitted to the administration of bisphosphonates.

The aim of this study was to evaluate the effect of strontium ranelate (Sr) on post-extraction socket healing in rats submitted to the administration of bisphosphonates. Sixty rats were submitted to the tooth extraction of the first lower molar after 60days of the daily administration of saline solution (SS) or alendronate (ALN). Then, the animals were allocated into six groups namely CTR: administration of SS during the whole experiment, ALN: administration of ALN during the whole experiment, ALN/SS: application of SS for 30days after extraction in animals previously treated with ALN, ALN/Sr: application of Sr for 30days after extraction in animals previously treated with ALN, ALN/S60: ALN therapy interruption 30days before the extraction followed by the application of SS for 60days, and ALN/Sr60: ALN therapy interruption 30days before the tooth extraction followed by the application of Sr for 60days. The healing of the post-extraction sockets was evaluated by microCT and histomorphometry. The use of ALN induced partial bone necrosis, inflammatory infiltration, and a delay in soft tissue healing; the use of Sr improved the connective tissue organization. Sr has subtle positive effects on the post-extraction healing in animals submitted to the administration of bisphosphonate.

Bone matrix quality in paired iliac bone biopsies from postmenopausal women treated for 12months with strontium ranelate or alendronate.

Bone quality is altered mainly by osteoporosis, which is treated with modulators of bone quality. Knowledge of their mechanisms of action is crucial to understand their effects on bone quality. The goal of our study was to compare the action of alendronate (ALN) and strontium ranelate (SrRan) on the determinants of bone quality. The investigation was performed on over 60 paired human iliac biopsies. Paired samples correspond to biopsies obtained from the same patient, one before treatment (baseline) and one after 12months of treatment, in postmenopausal women with osteoporosis. Vibrational spectroscopy (Raman and FTIRM) and nanoindentation were used to evaluate the effect of both drugs on bone quality at the ultrastructural level. Outcomes measured by vibrational spectroscopy and nanoindentation are sensitive to bone age. New bone packets are distinguished from old bone packets. Thus, the effect of bone age is distinguished from the treatment effect. Both drugs modify the mineral and organic composition in new and old bone in different fashions after 12months of administration. The new bone formed during ALN administration is characterized by an increased mineral content, carbonation and apatite crystal size/perfection compared to baseline. Post-translational modifications of collagen are observed through an increase in the hydroxyproline/proline ratio in new bone. The proteoglycan content is also increased in new bone. SrRan directly modulates bone quality through its physicochemical actions, independent of an effect on bone remodeling. Strontium cations are captured by the hydrated layer of the mineral matrix. The mineral matrix formed during SrRan administration has a lower carbonate content and crystallinity after 12months than at baseline. Strontium might create bonds (crosslinks) with collagen and noncollagenous proteins in new and old bone. The nanomechanical properties of bone were not modified with either ALN or SrRan, probably due to the short duration of administration. Our results show that ALN and SrRan have differential effects on bone quality in relation to their mechanism of action.