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Bone Jan 2022Fractures secondary to osteoporosis, particularly those of the hip and spine, are a major public health concern with high social and economic costs. The Local...
BACKGROUND
Fractures secondary to osteoporosis, particularly those of the hip and spine, are a major public health concern with high social and economic costs. The Local Osteo-Enhancement Procedure (LOEP) is an approach intended to strengthen skeletal areas that are at the highest risk for fracture due to osteoporosis. LOEP involves the implantation of AGN1, a triphasic, calcium-based, osteoconductive material which is then resorbed and replaced by bone. Since alendronate is the most prescribed osteoporotic treatment, the purpose of this canine study is to determine if the newly formed bone has the same properties as normal bone and whether alendronate treatment impacts AGN1 resorption and replacement with bone.
METHODS
Sixty skeletally mature male hounds (24-38 kg) were evenly divided between alendronate (0.2 mg/kg/day) and non-alendronate treatment groups. A critical-size core bone defect created in one proximal humerus was implanted with AGN1 while the contralateral non-operated humerus served as a paired control in each animal. Animals were sacrificed 13, 26, and 52 weeks post-operatively (10 per treatment per timepoint). The control and treatment site bone specimens from each animal were examined using radiographic, histomorphometric, and biomechanical techniques. Results between alendronate-treated and non-alendronate-treated animals were compared as groups.
RESULTS
AGN1 implant material was consistently resorbed and replaced by bone in all animals. At 52 weeks, only minimal residual implant material could be detected (0.9 ± 2.3% non-alendronate group; 2.2 ± 3.1% alendronate group), and new bone filled the defects in both the non-alendronate and alendronate groups. At 13 and 26 weeks, microCT revealed the newly formed bone in the defects had significantly higher trabecular bone volume and number connectivity than control bone in both groups. Mechanical testing demonstrated that the new bone had ultimate compressive strength and modulus equivalent to control bone as early as 13 weeks post-surgery which was maintained to 52 weeks in both groups.
CONCLUSIONS
In this canine critical-sized humeral core defect model, AGN1 was progressively replaced by normal bone as evaluated by all outcome measures. Concurrent alendronate therapy did not significantly impact AGN1 resorption or new bone formation. These results demonstrate that AGN1 can be used in conjunction with alendronate in non-osteoporotic animals.
CLINICAL RELEVANCE
This study suggests that the AGN1 implant material demonstrates potential for local restoration of bone in critical-size core defects, and that the material is compatible with alendronate drug therapy. Further studies will be required to determine if these results apply to other osteoporosis medications.
Topics: Alendronate; Animals; Dogs; Humerus; Male; Osteogenesis; Osteoporosis; Prostheses and Implants
PubMed: 34744020
DOI: 10.1016/j.bone.2021.116246 -
Medicine Jul 2020Ankylosing spondylitis (AS) is a very tricky orthopedic disorder. If such condition cannot be managed fairly well, it may significantly affect quality of life and even...
BACKGROUND
Ankylosing spondylitis (AS) is a very tricky orthopedic disorder. If such condition cannot be managed fairly well, it may significantly affect quality of life and even leads to disability among such population. A variety of studies have reported that alendronate is utilized for the treatment of AS. However, their results are still contrary, and no systematic review has addressed on this topic. Thus, this study will systematically assess the efficacy and safety of alendronate for the treatment of patients with AS.
METHODS
A comprehensive literature search will be performed from the below electronic databases from their commencement to the January 31, 2020 without language and publication status limitations: PubMed, Embase, Cochrane Library, Web of Science, Allied and Complementary Medicine Database, WANGFANG, and China National Knowledge Infrastructure. Only randomized controlled trials focusing on the alendronate for the treatment of patients with AS will be considered for inclusion in this study. Two authors will independently select all identified records, extract essential data from all included studies, and appraise study quality for each eligible trial using Cochrane risk of bias. If any differences occur, another experienced author will be invited to solve them by discussion and a consensus decision will be made. We will implement RevMan 5.3 software to analyze the extracted data.
RESULTS
This study will summarize high-quality randomized controlled trials to assess the efficacy and safety of alendronate for the treatment of patients with AS through primary outcome of bone densitometry; and secondary outcomes of pain intensity, quality of life, disease activity, functional status, and adverse events.
CONCLUSION
This study will provide evidence to help determine whether alendronate is an effective and safe management for patient with AS or not.
STUDY REGISTRATION
INPLASY202040153.
Topics: Alendronate; Bone Density; Bone Density Conservation Agents; Humans; Meta-Analysis as Topic; Musculoskeletal Pain; Pain Measurement; Quality of Life; Randomized Controlled Trials as Topic; Research Design; Spondylitis, Ankylosing; Systematic Reviews as Topic
PubMed: 32791682
DOI: 10.1097/MD.0000000000021089 -
Talanta May 2023Bone is the primary metastasis site for lethal prostate cancer, often resulting in poor prognosis, crippling pain, and diminished functioning that drastically reduce...
Bone is the primary metastasis site for lethal prostate cancer, often resulting in poor prognosis, crippling pain, and diminished functioning that drastically reduce both quality of life and survivability Uniquely, prostate cancer bone metastasis induces aberrant bone overgrowth, due to an increase of osteoblasts induced by tumor-secreted bone morphogenetic protein 4 (BMP4). Conjugating drugs to substances that target the tumor-induced bone area within the metastatic tumor foci would be a promising strategy for drug delivery. To develop such a strategy, we conjugated a near infrared (NIR) fluorescent probe, the dye Cy5.5, to serve as a surrogate for drugs, with alendronate, which targets bone. Characterization, such as infrared spectroscopy, confirmed the synthesis of the Cy5.5-ALN conjugate. The maximum absorbance of free Cy5.5, which was at 675 nm, did not change upon conjugation. Alendronate targeted the bone component hydroxyapatite in a dose-dependent manner up to 2.5 μM, with a maximum of 85% of Cy5.5-ALN bound to hydroxyapatite, while free Cy5.5 alone had 6% binding. In in vitro cell binding studies, Cy5.5-ALN bound specifically with mineralized bone matrix of differentiated MC3T3-E1 cells or 2H11 endothelial cells that were induced to become osteoblasts through endothelial-to-osteoblast transition, the underlying mechanism of prostate-cancer-induced bone formation. Neither Cy5.5-ALN nor free Cy5.5 bound to undifferentiated MC3T3-E1 or 2H11 cells. Bone-targeting efficiency studies in non-tumor-bearing mice revealed accumulation over time in the spine, jaw, knees, and paws injected with Cy5.5-ALN, and quantification showed higher accumulation in femurs than in muscle at up to 28 days, while the free Cy5.5 dye was observed circulating without preferential accumulation and decreased over time. There was a linear relationship with fluorescence when the injected concentration of Cy5.5-ALN was between 0.313 and 1.25 nmol/27 g of mouse, as quantified in mouse femurs both in vivo and ex vivo. Ex vivo evaluation of bone-targeting efficiency in nude mice was 3 times higher for bone-forming C4-2b-BMP4 tumors compared to non-bone-forming C4-2b tumors (p-value <0.001). Fluorescence microscopy imaging of the tumors showed that Cy5.5-ALN co-localized with the bone matrix surrounding tumor-induced bone, but not with the viable tumor cells. Together, these results suggest that a drug-ALN conjugate is a promising approach for targeted delivery of drug to the tumor-induced bone area in the metastatic foci of prostate cancer.
Topics: Humans; Male; Mice; Animals; Alendronate; Cell Line, Tumor; Mice, Nude; Endothelial Cells; Quality of Life; Bone Neoplasms; Prostatic Neoplasms; Hydroxyapatites
PubMed: 36774896
DOI: 10.1016/j.talanta.2023.124308 -
American Family Physician Sep 2008Osteoporosis is an abnormal reduction in bone mass and bone deterioration leading to increased fracture risk. Alendronate (Fosamax) belongs to the bisphosphonate class... (Review)
Review
BACKGROUND
Osteoporosis is an abnormal reduction in bone mass and bone deterioration leading to increased fracture risk. Alendronate (Fosamax) belongs to the bisphosphonate class of drugs, which act to inhibit bone resorption by interfering with the activity of osteoclasts.
OBJECTIVES
To assess the effectiveness of alendronate in the primary and secondary prevention of osteoporotic fractures in postmenopausal women.
SEARCH STRATEGY
The authors searched Central, Medline, and EMBASE for relevant randomized controlled trials published from 1966 to 2007.
DATA COLLECTION AND ANALYSIS
The authors undertook study selection and data abstraction in duplicate. The authors performed meta-analysis of fracture outcomes using relative risks, and a relative change greater than 15 percent was considered clinically important. The authors assessed study quality through reporting of allocation concealment, blinding, and withdrawals.
MAIN RESULTS
Eleven trials representing 12,068 women were included in the review. Relative and absolute risk reductions for the 10-mg dose were as follows. For vertebral fractures, a 45 percent relative risk reduction was found (relative risk [RR] = 0.55; 95% confidence interval [CI], 0.45 to 0.67). This was significant for primary prevention, with a 45 percent relative risk reduction (RR = 0.55; 95% CI, 0.38 to 0.80) and 2 percent absolute risk reduction; and for secondary prevention, with 45 percent relative risk reduction (RR = 0.55; 95% CI, 0.43 to 0.69) and 6 percent absolute risk reduction. For nonvertebral fractures, a 16 percent relative risk reduction was found (RR = 0.84; 95% CI, 0.74 to 0.94). This was significant for secondary prevention, with a 23 percent relative risk reduction (RR = 0.77; 95% CI, 0.64 to 0.92) and a 2 percent absolute risk reduction, but not for primary prevention (RR = 0.89; 95% CI, 0.76 to 1.04). There was a 40 percent relative risk reduction in hip fractures (RR = 0.60; 95% CI, 0.40 to 0.92), but only secondary prevention was significant, with a 53 percent relative risk reduction (RR = 0.47; 95% CI, 0.26 to 0.85) and a 1 percent absolute risk reduction. The only significance found for wrist fractures was in secondary prevention, with a 50 percent relative risk reduction (RR = 0.50; 95% CI, 0.34 to 0.73) and a 2 percent absolute risk reduction. For adverse events, the authors found no statistically significant difference in any included study. However, observational data raise concerns about potential risk for upper gastrointestinal injury and, less commonly, osteonecrosis of the jaw.
AUTHORS' CONCLUSIONS
At 10 mg of alendronate per day, clinically important and statistically significant reductions in vertebral, nonvertebral, hip, and wrist fractures were observed for secondary prevention. The authors found no statistically significant results for primary prevention, with the exception of vertebral fractures, for which the reduction was clinically important.
Topics: Alendronate; Bone Density Conservation Agents; Female; Fractures, Spontaneous; Humans; Middle Aged; Osteoporosis, Postmenopausal
PubMed: 18788232
DOI: No ID Found -
Genetics and Molecular Research : GMR Mar 2017Alendronate regulates the activity of osteoclasts and healing of osteoporosis. This study investigated the effect of alendronate on bone healing and changes in the...
Alendronate regulates the activity of osteoclasts and healing of osteoporosis. This study investigated the effect of alendronate on bone healing and changes in the levels of cytokines. Bilateral ovaries of 10 adult female rabbits were removed surgically in aseptic condition to establish the animal model of osteoporosis. Five rabbits in group A were treated with alendronate (1.15 mg·kg·week) once a week by a stomach tube, whereas the remaining 5 in group B were treated with physiological saline. The success of the animal model establishment and the efficacy of alendronate treatment were evaluated by the sports ability score and the Basso, Beattie, and Bresnahan (BBB) score; the healing degree of osteoporosis was determined by X-ray analysis and measurement of biomechanical properties; the changes in the levels of related cytokines were measured by enzyme-linked immunosorbent assay (ELISA) and immunohistochemical staining. Treatment improved dyskinesia of the animals in group A than that in group B, with significant improvement occurring in the 4th week of treatment. The BBB score of the group A animals revealed movements similar to normal, but that of the group B animals exhibited significant motor disturbance (P < 0.01). X-ray examination showed that with time, the X-ray ratings increased. Measurement of the biomechanical properties further showed that alendronate had a positive effect on osteoporosis healing. The results of ELISA and immunohistochemistry showed that the levels of ALP, BMP-2, bFGF, and IGF-1 were upregulated in group A. In conclusion, alendronate accelerated osteoporosis healing probably via certain cytokine-related mechanism.
Topics: Alendronate; Animals; Bone Density Conservation Agents; Bone Morphogenetic Protein 2; Cytokines; Disease Models, Animal; Dyskinesias; Female; Fibroblast Growth Factor 2; Humans; Insulin-Like Growth Factor I; Osteoporosis; Ovariectomy; Rabbits; Treatment Outcome; Up-Regulation
PubMed: 28362987
DOI: 10.4238/gmr16019485 -
Archives of Osteoporosis Jan 2023Persistence with initial treatment was highest after 1 year, decreasing afterwards. Persistence was highest for denosumab followed by alendronate. We identified several...
UNLABELLED
Persistence with initial treatment was highest after 1 year, decreasing afterwards. Persistence was highest for denosumab followed by alendronate. We identified several factors associated with treatment persistence, some of which were the same irrespective of OTx agent, which could help target subgroups of patients in terms of social and healthcare support.
PURPOSE
To describe patient characteristics, persistence, and factors associated with the persistence of new users of the bisphosphonates (alendronate, risedronate, and ibandronate) and the RANKL inhibitor denosumab in Denmark.
METHODS
A population-based cohort study using health registries (2010-2018). We included alendronate (n = 128,590), risedronate (n = 892), ibandronate (n = 5,855), and denosumab (n = 16,469) users, aged ≥ 50 years.
RESULTS
The 1-year persistence was 68.2% in the alendronate cohort; 39.3% in the risedronate cohort; 56.3% in the ibandronate cohort; and 84.0% in the denosumab cohort. The 2-year persistence was 58.7% in the alendronate cohort; 28.0% in the risedronate cohort; 42.9% in the ibandronate cohort; and 71.9% in the denosumab cohort. The 4-year persistence was 46.3%, 15.4%, 29.6%, and 56.9%, respectively. Later years of treatment initiation were associated with lower persistence for alendronate (adjusted odds ratio (OR) with 95% CI was 0.86 (0.81-0.91) in 2016 compared to 2010), but not for risedronate (OR was 1.56 (0.60-4.06), ibandronate (OR was 0.92 (0.71-1.19) or denosumab (OR was 1.11 (0.87-1.43). Older age was associated with higher persistence for all medications and the same goes for the female sex except for ibandronate. Dementia was associated with higher persistence for alendronate but not denosumab, whereas prior osteoporosis treatment (OT) was the opposite. Several comorbidities were associated with lower persistence for alendronate, but not denosumab.
CONCLUSION
Persistence was highest for denosumab followed by alendronate. We identified several factors associated with treatment persistence, some of which were the same irrespective of OTx agent, which could help target subgroups of patients in terms of social and healthcare support.
Topics: Humans; Female; Alendronate; Bone Density Conservation Agents; Risedronic Acid; Ibandronic Acid; Cohort Studies; Diphosphonates; Denmark; Osteoporosis, Postmenopausal
PubMed: 36629929
DOI: 10.1007/s11657-023-01210-4 -
Endokrynologia Polska 2011Osteoporosis is a growing problem in an ageing society. It affects women of post-menopausal age, as well as elderly subjects of both sexes, often with dysfunction of the... (Review)
Review
Osteoporosis is a growing problem in an ageing society. It affects women of post-menopausal age, as well as elderly subjects of both sexes, often with dysfunction of the cardiovascular system or with an increased risk of circulation disorders. It has been found that the mortality rate of subjects with osteoporosis is comparable to that of patients suffering from such diseases as obturative pulmonary disease or myocardial ischaemia. Bisphosphonates are the most thoroughly studied group of drugs prescribed for the treatment of osteoporosis. Their administration is, however, associated with a risk of adverse symptoms, which can occur as gastro-intestinal tract disturbances, muscular-osseous pains, mandible necrosis, atypical fractures and other symptoms. Recently, there has been discussion about an increased risk of atrial fibrillation in bisphosphonate-using female patients. This paper focuses on this particular problem, while summing up the actual status of knowledge regarding possible associations of bisphosphonates with cardiac rhythm disturbances.
Topics: Aged; Alendronate; Atrial Fibrillation; Bone Density Conservation Agents; Diphosphonates; Female; Humans; Male; Middle Aged; Osteoporosis, Postmenopausal
PubMed: 21365587
DOI: No ID Found -
Yonsei Medical Journal Feb 2003The present study was designed to determine if levels of serum cytokines, such as interleukin (IL)-1beta, IL-2, IL-2r, IL-6, IL-6r, IL-8, IL-10, and TNF-alpha are... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
The present study was designed to determine if levels of serum cytokines, such as interleukin (IL)-1beta, IL-2, IL-2r, IL-6, IL-6r, IL-8, IL-10, and TNF-alpha are different in osteoporotic and non-osteoporotic postmenopausal women, and to evaluate the effects of calcitonin and alendronate therapies over a six month period on serum cytokine levels in postmenopausal osteoporotic women. Serum levels of IL-2, TNF-alpha and IL-8 were found to be significantly higher (p < 0.05), and serum IL-10, and IL-6r significantly lower in the calcitonin (N=60) and the alendronate (N=60) treatment groups than in the control group (N=50) (p < 0.05). But, no significant difference was apparent between the calcitonin and alendronate treated groups before treatment. Statistically significant changes occurred in patients, with respect to the levels of serum IL-6r, and IL-8 after one month (p < 0.05), in IL-2r, IL-6r, IL-8, IL-10 after three months, and in IL-1beta, IL-6r, IL-8, IL-10 and TNF-alpha after six months of calcitonin therapy (p < 0.05). No significant difference was observed in IL-6r after one month, in IL-8 and IL-10 after three months, and in TNF-alpha after six months in the calcitonin treated group and in the control group, whereas these parameters were significantly different at baseline. In the alendronate treated group, statistically significant changes occurred in the levels of serum IL-1alpha and IL-6 after three months, and in IL-1beta, IL-6, IL-6r and TNF-alpha after six months (p < 0.05). No significant difference was observed in IL-6r after one month, in IL-10 after three months or in TNF-alpha after six months between the alendronate treatment group and the control group, whereas these parameters were significantly different at baseline. In conclusion, we suggest that; 1) not only IL-1, IL-6, TNF-alpha and IL-11 but also IL-2, IL-8 and IL-10 may have roles in the etiopathogenesis of osteoporosis, 2) calcitonin therapy have a more distinct influence on serum levels of some cytokines and have an earlier effect than alendronate therapy (especially upon IL-2r, IL-8, and IL-10). Nevertheless, further longitudinal studies are needed to identify the cytokines involved in the pathogenesis of postmenopausal osteoporosis and to evaluate the influence of different treatments on these cytokines.
Topics: Aged; Alendronate; Calcitonin; Cytokines; Female; Humans; Middle Aged; Osteoporosis, Postmenopausal; Time Factors
PubMed: 12619182
DOI: 10.3349/ymj.2003.44.1.99 -
British Journal of Clinical Pharmacology Mar 2017The aim of this systematic review was to assess the efficacy of bisphosphonate therapy as an adjunct to scaling and root planing (SRP) in the management of periodontitis. (Meta-Analysis)
Meta-Analysis Review
AIMS
The aim of this systematic review was to assess the efficacy of bisphosphonate therapy as an adjunct to scaling and root planing (SRP) in the management of periodontitis.
METHODS
Databases (MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and Cochrane Oral Health Group Trials Register databases) were searched up to and including July 2016. The primary outcome was probing depth (PD), and the secondary outcomes were changes in clinical attachment level (CAL) and bone defect (BD) fill. The mean differences (MD) of outcomes and 95% confidence intervals (CI) for each variable were calculated using random effect model.
RESULTS
Eight clinical studies were included. Seven studies used alendronate as an adjunct to SRP; of these, four studies used topical application and three used oral alendronate. Considering the effects of adjunctive bisphosphonates as compared to SRP alone, a high degree of heterogeneity for PD (Q value = 39.6, P < 0.0001, I = 87.38%), CAL (Q value = 13.65, P = 0.008, I = 70.71%), and BD fill (Q value = 53.26, P < 0.0001, I = 92.49%) was noticed among both the groups. Meta-analysis showed a statistically significant PD reduction (MD = -1.18, 95% CI = -1.91 to -0.44, P = 0.002), CAL gain (MD = -0.69, 95% CI = -1.20 to -0.18, P = 0.008) and BD fill (MD = -2.36, 95% CI = -3.64 to -1.08, P < 0.001) for SRP + bisphosphonate treatment vs. SRP alone.
CONCLUSIONS
Adjunctive bisphosphonate therapy appears to be effective in managing periodontitis, however, due to the potential risk of osteonecrosis of the jaws and short-term follow-up of the studies, their clinical application is debatable.
Topics: Administration, Oral; Administration, Topical; Alendronate; Chronic Periodontitis; Combined Modality Therapy; Dental Scaling; Diphosphonates; Humans; Root Planing
PubMed: 27718252
DOI: 10.1111/bcp.13147 -
Journal of Bone and Mineral Research :... Feb 2013Many postmenopausal women have osteopenia, a condition characterized by loss of bone mineral density (BMD) that is not as severe as in osteoporosis. The objective of...
Many postmenopausal women have osteopenia, a condition characterized by loss of bone mineral density (BMD) that is not as severe as in osteoporosis. The objective of this study was to estimate the cost-effectiveness of alendronate to prevent fractures in osteopenic postmenopausal women without a history of fracture in Japan. An individual simulation model was developed to predict lifetime costs and quality-adjusted life years (QALYs) of 5 years of preventive alendronate therapy versus no preventive therapy. The risk of hip and vertebral fracture associated with age and BMD was derived from epidemiologic studies in Japan. We ran the model with different combinations of age (65, 70, and 75 years), BMD (70%, 75%, and 80% of young adult mean [YAM]), and additional clinical risk factors. For 70-year-old women with a BMD of 70% of the YAM having one of the following risk factors: a family history of hip fracture, high alcohol intake, or current smoking, the incremental cost-effectiveness ratio (ICER) of alendronate was $92,937, $126,251, and $129,067 per QALY, respectively. These results were sensitive to age, BMD, and number of clinical risk factors. Probabilistic sensitivity analysis for the base case showed that in the presence of one, two, and three risk factors, alendronate was cost-effective in 0.2% to 2.6%, 13.1% to 56.1%, and 99.1% of the simulations, respectively, if society is willing to pay $50,000 per QALY. Additional analysis indicated that alendronate can be a good value in osteopenic women if the 10-year probability for a osteoporotic hip or vertebral fracture is more than 26.2%. Our results indicate that whether to treat osteopenia with alendronate should be determined on the basis of age, BMD, and number of clinical risk factors in terms of cost-effectiveness.
Topics: Adult; Aged; Aged, 80 and over; Alendronate; Bone Density; Bone Diseases, Metabolic; Cost-Benefit Analysis; Female; Hip Fractures; Humans; Japan; Osteoporosis, Postmenopausal; Postmenopause; Risk Factors; Young Adult
PubMed: 22991163
DOI: 10.1002/jbmr.1755