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BioMed Research International 2019Periodontal bone regeneration relies on coupled and cooperative bone formation and resorption. Accordingly a novel strategy on concurrent use of platelet-rich fibrin... (Meta-Analysis)
Meta-Analysis Review
Periodontal bone regeneration relies on coupled and cooperative bone formation and resorption. Accordingly a novel strategy on concurrent use of platelet-rich fibrin (PRF) (anabolic agent) and 1% alendronate (ALN) (anticatabolic agent) was proposed recently in regenerative periodontal treatment. It was supposed to enhance bone formation and reduce bone resorption simultaneously. However, there is a lack of evidence-based studies to answer whether this concurrent application was superior to single application until now. Besides, concerns on ALN lead to some reservation on this synergistic way. ALN may impair new bone formation and necrotize jaws. Thus, in order to compare the clinical efficacy between PRF plus 1%ALN and PRF alone on periodontal bone regeneration, we performed present systematic review and meta-analysis. Because it is the prerequisite for measuring the combined efficacy of PRF plus 1%ALN, firstly we evaluated the effectiveness of 1%ALN. Our data indicated that adjunctive 1%ALN was effective in promoting periodontal bone repair. Further, PRF plus 1%ALN showed a greater capacity for periodontal regeneration than PRF alone with statistical significance. The findings of this study revealed the promising prospects on synergistic application of bone anabolic agents (PRF) and antiresorption medications (1%ALN) in regenerative periodontal treatment.
Topics: Alendronate; Bone Regeneration; Fibrin; Guided Tissue Regeneration, Periodontal; Humans; Osteogenesis; Platelet-Rich Fibrin
PubMed: 31531371
DOI: 10.1155/2019/9148183 -
Journal of Bone and Mineral Research :... Jun 2019Mineral and bone disorders including osteoporosis are common in dialysis patients and contribute to increased morbimortality. However, whether denosumab and alendronate... (Randomized Controlled Trial)
Randomized Controlled Trial
Mineral and bone disorders including osteoporosis are common in dialysis patients and contribute to increased morbimortality. However, whether denosumab and alendronate are effective and safe treatments in hemodialysis patients is not known. Thus, we conducted a prospective, three-center study of 48 hemodialysis patients who were diagnosed as having osteoporosis and had not received anti-osteoporotic agents previously. Participants were randomized to either denosumab or intravenous alendronate, and all subjects received elemental calcium and calcitriol during the initial 2 weeks. The primary endpoint was the percent change in lumbar spine bone mineral density (LSBMD) at 12 months of treatment. The secondary endpoints included the following: change in BMD at other sites; change of serum bone turnover markers (BTM), coronary artery calcium score (CACS), ankle-brachial pressure index (ABI), brachial-ankle pulse wave velocity (baPWV), flow mediated dilation (FMD), and intima-media thickness at the carotid artery (CA-IMT); change from day 0 to day 14 in serum levels of Ca and P; time course of serum calcium (Ca), phosphorus (P), and intact parathyroid hormone (i-PTH); new fractures; and adverse events. Initial supplementation with elemental calcium and calcitriol markedly ameliorated the decrease of serum corrected calcium (cCa) levels induced by denosumab during the first 2 weeks, whereas serum cCa levels in the alendronate group were increased. Denosumab and alendronate markedly decreased serum levels of BTM and increased LSBMD at 12 months compared with baseline. However, no significant differences were found in the changes in LSBMD between the two groups. The serum cCa, P, and i-PTH levels in the two groups were maintained within the appropriate range. In contrast to the anti-osteoporotic effects, no significant differences after 12 months of treatment were found in the CACS, CA-IMT, ABI, baPWV, and FMD compared with pretreatment in both groups. Denosumab and alendronate treatment improved LSBMD, reduced BTM, and appeared to be safe in hemodialysis patients with osteoporosis. © 2019 American Society for Bone and Mineral Research.
Topics: Aged; Alendronate; Arteriosclerosis; Biomarkers; Blood Vessels; Bone Density; Bone Remodeling; Bone and Bones; Calcinosis; Denosumab; Female; Humans; Male; Minerals; Renal Dialysis
PubMed: 30690785
DOI: 10.1002/jbmr.3676 -
Expert Opinion on Investigational Drugs 2023Pharmacological 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... (Review)
Review
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.
Topics: Humans; Female; Child; Adolescent; Young Adult; Adult; Middle Aged; Aged; Aged, 80 and over; Male; Fracture Healing; Bone Density Conservation Agents; Diphosphonates; Alendronate; Vitamin D
PubMed: 37740660
DOI: 10.1080/13543784.2023.2263352 -
Journal of Applied Toxicology : JAT Nov 2021Neurological disturbances including cholinergic dysfunction, oxidative stress, neuroinflammation, and cognitive impairments are the well-reported consequences of old...
Neurological disturbances including cholinergic dysfunction, oxidative stress, neuroinflammation, and cognitive impairments are the well-reported consequences of old age-related disorders like Alzheimer's disease (AD) or dementia. Bisphosphonates were shown to ameliorate dementia in osteoporotic patients, neuroinflammation, and cholinesterase activity in rodents. Thus, the present study has been designed to examine the role of alendronate against cognitive and neurological disturbances in mice induced by a combined oral dose of d-galactose and aluminum chloride (AlCl ) for 6 weeks. d-galactose acts as a senescence agent, whereas AlCl is a neurotoxin and in combination generates neuropathologies and cognitive depletion resembling aging and AD. It was found that memory was markedly impaired in d-galactose + AlCl -treated mice as assessed in different behavioral paradigms. Additionally, d-galactose + AlCl led to neurotoxicity assessed on the basis of neuroinflammation, oxidative stress, glial cell activation, neuronal damage, and augmented GSK-3β level in mice hippocampus. Consequently, alendronate administration orally for 15 days in d-galactose + AlCl -exposed mice prominently reversed all these behavioral and neuropathological changes. These findings show that alendronate can be a potential therapeutic molecule with multiple targets for the management of age-related neurological disorders such as AD.
Topics: Alendronate; Aluminum Chloride; Alzheimer Disease; Animals; Cognitive Dysfunction; Female; Galactose; Male; Mice; Neuroinflammatory Diseases; Neuroprotective Agents
PubMed: 33694194
DOI: 10.1002/jat.4160 -
BMC Women's Health Apr 2022Postmenopausal women compliance to alendronate therapy is suboptimal due to the complex dosing requirements. The poor compliance may increase their potential of...
BACKGROUND
Postmenopausal women compliance to alendronate therapy is suboptimal due to the complex dosing requirements. The poor compliance may increase their potential of fractures and the prevalence of side effects. In this study, the compliance of osteoporotic women on bisphosphonate therapy to the complex dosing instructions and their knowledge of alendronate-interactions were assessed.
METHODS
This is a cross-sectional study, using self-administered questionnaire involving 224 osteoporotic women on alendronate therapy, who visited the orthopedic clinics and community pharmacies in the West Bank. Data was collected using a validated questionnaire consisting of 4 sections and analyzed by descriptive statistics. Moreover, associations between patient's socio-demographic characteristics and the extent of compliance and knowledge of alendronate interactions are established in this study.
RESULTS
A total of 300 questionnaires were distributed and 224 were completed. The median compliance score to alendronate dosing instructions was 5 out of a possible maximum 7, and the median knowledge score about alendronate interactions was 7 out of a possible maximum 14. Factors found to affect either or both the knowledge and compliance to alendronate dosing instructions were, residency, and the source of instructions.
CONCLUSION
This study identified the importance of compliance and knowledge gaps among postmenopausal women treated with alendronate. Therefore, appropriate knowledge about the importance of proper compliance to dosing instructions and avoidance of interactions is of a great benefit for maximizing clinical effectiveness, lowering fracture risk and prevention of adverse effects of alendronate among patients treated with alendronate in Palestine.
Topics: Alendronate; Bone Density Conservation Agents; Cross-Sectional Studies; Female; Humans; Osteoporosis; Osteoporosis, Postmenopausal; Postmenopause
PubMed: 35392893
DOI: 10.1186/s12905-022-01690-5 -
Journal of Physiology and Biochemistry Nov 2021Alendronate, a bisphosphonate used to prevent osteoporosis, stimulates osteogenesis but impairs adipogenesis. Different clinical trials suggest that the incidence of...
Alendronate inhibits triglyceride accumulation and oxidative stress in adipocytes and the inflammatory response of macrophages which are associated with adipose tissue dysfunction.
Alendronate, a bisphosphonate used to prevent osteoporosis, stimulates osteogenesis but impairs adipogenesis. Different clinical trials suggest that the incidence of diabetes may be lower in patients treated with alendronate. Taking into account the importance of adipocytes and macrophages of adipose tissue in insulin resistance and type 2 diabetes, it is necessary to evaluate the effect of alendronate in both cell types. In this paper, we investigated the effect of alendronate on the differentiation to adipocytes of 3T3-L1 fibroblasts, the cell line most used to study adipogenesis, and also its effect on lipid content and oxidative stress in mature adipocytes as well as on the inflammatory response of macrophages. We found that alendronate inhibits differentiation of 3T3-L1 fibroblasts to adipocytes in keeping with reports in other cell lines. On the other hand, treatment of 3T3-L1 adipocytes with alendronate was able to decrease triglyceride content and to prevent HO-induced lipid peroxidation which was evaluated as an indicator of oxidative stress. In addition, it was found that activation of RAW 264.7 macrophages to a pro-inflammatory M1 type is inhibited by this bisphosphonate. These results suggest that alendronate may contribute to prevent adipocyte excessive enlargement and the induction of oxidative stress in 3T3-L1 adipocytes as well as the activation of macrophages to a pro-inflammatory M1 type, which are events associated with adipose tissue dysfunction and insulin resistance. In this study, we unraveled the underlying mechanisms of events that were previously observed in clinical trials.
Topics: 3T3-L1 Cells; Adipocytes; Adipogenesis; Adipose Tissue; Alendronate; Animals; Cell Differentiation; Diabetes Mellitus, Type 2; Humans; Hydrogen Peroxide; Macrophages; Mice; Oxidative Stress; Triglycerides
PubMed: 34302624
DOI: 10.1007/s13105-021-00826-9 -
International Journal of Nanomedicine 2022Osteoporosis is defined as a systemic skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue, with a consequent increase in... (Review)
Review
Osteoporosis is defined as a systemic skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture. Because of the systemic nature of osteoporosis, the associated escalation in fracture risk affects virtually all skeletal sites. The problem is serious since it is estimated that more than 23 million men and women are at high risk of osteoporotic-like breakages in the European Union. Alendronate (ALN) is the most commonly prescribed oral nitrogen-containing bisphosphonate (BP) for the prevention and the therapy of osteoporosis. This is also one of the most intensely studied drugs in this field. However, ALN is characterized by restricted oral absorption and bioavailability and simultaneously its administration has serious side-effects (jaw osteonecrosis, irritation of the gastrointestinal system, nausea, musculoskeletal pain, and cardiovascular risks). Therefore, delivery systems enabling controlled release and local action of this drug are of great interest, being widely researched and presented in the literature. In this review, we discuss the current trends in the design of various types of alendronate carriers. Our paper is focused on the most recent developments in the field of nano/biomaterials-based systems for ALN delivery, including nano/microformulations, synthetic/natural polymeric and inorganic materials, hydrogel-based materials, scaffolds, coated-like structures, as well as organic-inorganic hybrids. Topics related to the treatment of complex bone diseases including osteoporosis have been covered in several more general reviews; however, the systems for this particular drug have not yet been discussed in detail.
Topics: Male; Female; Humans; Alendronate; Biocompatible Materials; Osteoporosis; Diphosphonates; Bone and Bones; Bone Density Conservation Agents
PubMed: 36510618
DOI: 10.2147/IJN.S388430 -
Journal of Bone and Mineral Research :... Apr 2023Although bone mineral density (BMD) is a predictor of fracture, many fractures occur in women with T-scores > -2.5. Bone microarchitecture, assessed by trabecular bone... (Randomized Controlled Trial)
Randomized Controlled Trial
Although bone mineral density (BMD) is a predictor of fracture, many fractures occur in women with T-scores > -2.5. Bone microarchitecture, assessed by trabecular bone score (TBS), predicts fracture risk independent of BMD. We evaluated whether abaloparatide improves TBS and whether TBS trends were associated with vertebral fracture risk reduction. Women with osteoporosis randomized to abaloparatide or placebo for 18 months (ACTIVE), followed by alendronate for 24 months (ACTIVExtend), with evaluable TBS, were included in this post hoc analysis (N = 911). TBS was calculated from spine BMD scans using an algorithm adjusted for tissue thickness (TBS ) at baseline, 6, 18, and 43 months. Mean increments in TBS from baseline within and between treatment groups, proportion of women with TBS increments above least significant change (LSC) and proportion with degraded TBS (<1.027) were calculated. Risk estimates for vertebral fracture were compared using binary logistic regressions adjusted for baseline age and spine BMD. At baseline, 42% had degraded TBS . Mean TBS increased 4% after 18 months abaloparatide (p < 0.001) and was unchanged with placebo. After 2 subsequent years of alendronate, the total cumulative TBS increase was 4.4% with abaloparatide/alendronate and 1.7% with placebo/alendronate (group difference, p < 0.001). At 43 months, the proportion of women with degraded TBS had declined to 21% with abaloparatide/alendronate and 37% with placebo/alendronate (p < 0.05). An increase in TBS ≥ LSC was observed in 50% of abaloparatide-treated women at 18 months and was associated with decreased odds (odds ratio [OR]; 95% confidence interval [CI]) of vertebral fracture (0.19; 95% CI, 0.04-0.80, 6 months; 0.30; 95% CI, 0.11-0.79, 43 months). In conclusion, abaloparatide increased TBS rapidly and progressively over 18 months and increments were maintained over 2 years with alendronate. TBS increase was associated with vertebral fracture risk reduction. Microarchitectural improvement may be one mechanism by which abaloparatide strengthens vertebral bone. © 2023 Radius Health, Inc and The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
Topics: Female; Humans; Alendronate; Cancellous Bone; Osteoporotic Fractures; Spinal Fractures; Osteoporosis; Bone Density; Bone Density Conservation Agents; Lumbar Vertebrae; Osteoporosis, Postmenopausal
PubMed: 36588166
DOI: 10.1002/jbmr.4764 -
Osteoporosis International : a Journal... Nov 2016Bisphosphonates are the mainstay treatment for postmenopausal osteoporosis. Although bisphosphonates are safety drugs, they have numerous side-effects such as...
Bisphosphonates are the mainstay treatment for postmenopausal osteoporosis. Although bisphosphonates are safety drugs, they have numerous side-effects such as arthralgia, elevated erythrocyte sedimentation rate and C-reactive protein, gastrointestinal disturbances, and flu-like illness with symptoms of fatigue, fever, chills, malaise, and myalgia. We present a case of acute polyarthritis after administration of alendronate and risedronate in a 52-year-old woman. To the best of the author's knowledge, this is the first case of acute polyarthritis induced by per os administration of both alendronate and risedronate during weekly usage. This is a report of a 52-year-old woman admitted to our hospital every week in a month, within 48 h, after receiving three times alendronate and one time risedronate with diffuse arthralgias, miyalgias, and swelling with effusions in both wrists, both ankles, interphalangeal joints in both hands and feet, and in both knees. When we discontinued alendronate and risedronate, oral raloxifene (60 mg/day) with oral calcium (1 g/day), and vitamin D3 (800 IU/day) was initiated. The symptoms regressed in 1 week. During the 1 year follow-up period, no myalgia, arthritis, or synovitis was detected. The side-effects of bisphosphonates are rarely reported in the literature. We believe that the prevalance of these side-effects would increase by closer follow-up of patients receiving these medications. To our knowledge, this patient is the first reported case of acute polyarthritis induced by per os administration of both alendronate and risedronate during weekly usage.
Topics: Alendronate; Arthritis; Bone Density Conservation Agents; Female; Humans; Middle Aged; Osteoporosis, Postmenopausal; Risedronic Acid
PubMed: 27376840
DOI: 10.1007/s00198-016-3695-3 -
Journal of Orthopaedic Research :... Oct 2022This study evaluated the effects of AGN1, a triphasic calcium-based material, and alendronate (A) on distal femoral defect bone repair in ovariectomized (OVX) rats. Of...
This study evaluated the effects of AGN1, a triphasic calcium-based material, and alendronate (A) on distal femoral defect bone repair in ovariectomized (OVX) rats. Of 106 rats, 92 were OVX'ed at 12 weeks old and underwent a 12-week induction period. Animals were randomized into five groups: OVX Control, OVX Alendronate Control, Normal Control, OVX Implantation, OVX Alendronate + Implantation. OVX Alendronate Control and OVX Alendronate + Implantation groups received alendronate injection twice weekly (0.015 mg/kg) from 6 weeks until sacrifice. Twelve weeks after OVX, 2.5 mm diameter by 4.0 mm long cylindrical, bilateral distal femoral defects were created in experimental animals. One defect was left empty, and one filled with AGN1. Dual-energy X-ray absorptiometry, microcomputed tomography, and histomorphometry were performed 0-, 6-, 12-, and 18-week postdefect/implantation surgery (N = 6-8/group). Results showed OVX induced significant and progressive bone loss which alendronate prevented. Histomorphometry demonstrated rapid AGN1 resorption: AGN1 resorbed from 95.1 ± 0.7% filling of the implant site (week 0) to 1.3 ± 1.0% (18 weeks) with no significant alendronate effect (1.6 ± 1.1%, 18 weeks). Bone formation in empty defects consisted primarily of cortical wall healing, whereas AGN1 implants demonstrated cortical wall healing with new trabecular bone filling the subcortical space. Alendronate dramatically increased bone formation in empty and AGN1 defects. We conclude AGN1 is resorbed and replaced by new cortical and trabecular bone in this OVX model, and alendronate did not compromise these effects.
Topics: Alendronate; Animals; Bone Density; Bone Density Conservation Agents; Calcium; Diphosphonates; Female; Ovariectomy; Rats; X-Ray Microtomography
PubMed: 34935182
DOI: 10.1002/jor.25255