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International Journal of Surgery... Dec 2015The etiology of osteonecrosis of the femoral head (ONFH) is multifactorial. Treatment of ONFH is disease stage dependent. For early stages, femoral head preservation... (Review)
Review
The etiology of osteonecrosis of the femoral head (ONFH) is multifactorial. Treatment of ONFH is disease stage dependent. For early stages, femoral head preservation procedures are preferred including core decompression, muscle pedicle grafting and de-rotational osteotomy. Core decompression with bone grafting is considered the gold standard. However, the results are inconsistence and unpredictable. An effective non-invasive method of treatment is imperative. Recently, extracorporeal shockwave therapy (ESWT) has shown beneficial effects in ONFH. ESWT improves pain and function of the hip and regression of the ONFH lesion. ESWT is more effective than core decompression with or without bone grafting, cocktail therapy that combined HBO, ESWT and oral alendronate is shown effective for patients with early osteonecrosis. The purpose of the article is to review, update and summarize the clinical treatment of ONFH using shockwave therapy.
Topics: Alendronate; Bone Density Conservation Agents; Combined Modality Therapy; Femur Head Necrosis; High-Energy Shock Waves; Humans; Hyperbaric Oxygenation; Lupus Erythematosus, Systemic
PubMed: 26188081
DOI: 10.1016/j.ijsu.2015.06.080 -
European Review For Medical and... 2014Alendronate is a second generation bisphosphonate which has been widely used in medical practice for two decades to treat osteoporosis and prevent fragility fractures... (Review)
Review
OBJECTIVE
Alendronate is a second generation bisphosphonate which has been widely used in medical practice for two decades to treat osteoporosis and prevent fragility fractures both in elderly people and in younger patients.
METHODS
Since many papers have been recently published and new formulations or dosages have been developed, our aim was to review the most significant medical literature addressing the issues of efficacy, safety, posology and formulations of the treatment with alendronate in osteoporotic patients.
RESULTS
The efficacy of alendronate in reducing the risk of vertebral and non-vertebral fractures has been demonstrated in several studies. Despite favourable data coming from clinical trials, tolerability of alendronate represented a critical issue since its introduction into real clinical practice, possibly leading to early discontinuation of the therapy, especially when combined with lack of motivation of the patient. For this reason, new dosages and formulations of alendronate have been developed, alone or in combination with vitamin D, which have shown to reduce the impact of gastro-oesophageal adverse events, and minimize discomfort due to the need of adopting unfavourable postural positions every day, fasting for at least one hour.
CONCLUSIONS
Alendronate is the most frequently used antifracture therapy among those currently available. The increasing use of the 70 mg weekly dosages and newest formulations of this drug are expected to reduce adverse events and increase adherence to the antifracture therapy, thus resulting in better clinical outcomes when treating osteoporotic patients.
Topics: Alendronate; Animals; Bone Density Conservation Agents; Chemistry, Pharmaceutical; Female; Fractures, Bone; Gastrointestinal Diseases; Humans; Male; Medication Adherence; Osteoporosis; Osteoporosis, Postmenopausal; Treatment Outcome
PubMed: 25555868
DOI: No ID Found -
Medical Science Monitor : International... Nov 2014Osteonecrosis or avascular osteonecrosis (AVN) of the femoral head is a devastating multifactorial disease that affects 20 000 persons each year in the United States.... (Meta-Analysis)
Meta-Analysis Review
Osteonecrosis or avascular osteonecrosis (AVN) of the femoral head is a devastating multifactorial disease that affects 20 000 persons each year in the United States. The purpose of this systematic review was to determine the efficacy and safety of alendronate for adult AVN during short- and long-term follow-up. Electronic databases were searched for randomized or nonrandomized clinical trials, cohort, case-control studies, and series of cases in which alendronate was used for treatment of adult AVN of the femoral head. Relevant articles with adequate data on reduction of pain, improvement of articular function, slowing of bone collapse progression, or need for total hip arthroplasty (THA) were included after applying inclusion and exclusion criteria. Eight articles involving 788 hips with evidence level 1b to 3b were included in this systematic review. Most studies suggested a positive short-term efficacy of alendronate treatment in reducing pain, improving articular function, slowing of bone collapse progression, and delaying the need for THA for adult AVN patients. The favorable long-term results were also presented in those treated patients after 10-year follow-up. In addition, there were no severe adverse effects associated with alendronate treatment observed during short- and long-term follow-up, and most of the included studies suggested use of alendronate in early AVN with small necrotic lesion to achieve better outcomes. The findings support consideration of alendronate use for adult AVN, particularly with early stage and small necrotic size. The lack of large-scale, randomized, and double-blind studies justifies new studies to demonstrate the detailed indication and the optimized strategy of alendronate treatment. Level of evidence: Level 3a.
Topics: Adolescent; Adult; Aged; Alendronate; Demography; Female; Femur Head Necrosis; Humans; Male; Middle Aged; Time Factors; Treatment Outcome; Young Adult
PubMed: 25424061
DOI: 10.12659/MSM.891123 -
Alimentary Pharmacology & Therapeutics Apr 1999It appears likely that drugs other than NSAIDs may cause ulcers and ulcer complications (e.g. potassium chloride). Alendronate (Fosamax) is used in the treatment and... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
BACKGROUND
It appears likely that drugs other than NSAIDs may cause ulcers and ulcer complications (e.g. potassium chloride). Alendronate (Fosamax) is used in the treatment and prevention of metabolic bone disease and has also been associated with severe oesophageal damage and stricture. We have previously shown that the dose of alendronate used for Paget's disease (40 mg) causes gastric damage similar to NSAIDs. The usual dose for the treatment of postmenopausal osteoporosis is 10 mg per day.
AIM
To investigate whether the 10 mg dose of alendronate causes gastric ulcers.
METHODS
We performed an endoscopist-blind, crossover, randomized, single-centre comparison of 10 mg of alendronate/day and placebo in volunteers aged 40 years or more. Video-endoscopy was used to evaluate the presence and degree of mucosal damage to the oesophagus, stomach, or duodenal bulb after 7 and 14 days of treatment.
RESULTS
Twenty-four healthy volunteers participated, including 15 women and nine men, ranging in age from 41 to 52 years. Visible gastric mucosal damage was present in nine (38%) who received alendronate compared to three (13%) in the placebo group. There was a marked difference in the severity of mucosal damage; there were no ulcers or large erosions in those receiving placebo. In contrast, potentially clinically significant gastric mucosal injury was seen in six subjects receiving alendronate (two developed antral ulcers and four had large (4-8 mm) superficial antral erosions) compared to none in the placebo group (P = 0.0219). One subject developed oesophageal damage in the form of multiple linear superficial erosions in the mid and distal oesophagus. Duodenal injury was not seen.
CONCLUSION
Alendronate causes gastric ulceration, suggesting that alendronate use may be associated with ulcer complications such as acute upper gastrointestinal bleeding. The results of this study suggest the need for post-marketing surveillance to clarify the nature, frequency and magnitude of any potential gastrointestinal side-effects associated with the use of this drug.
Topics: Adult; Alendronate; Cross-Over Studies; Double-Blind Method; Esophagus; Female; Gastric Mucosa; Humans; Male; Middle Aged; Stomach Ulcer
PubMed: 10215737
DOI: 10.1046/j.1365-2036.1999.00488.x -
Advanced Science (Weinheim,... May 2023Ovarian cancer is the most lethal gynecological malignancy. Most patients are diagnosed at an advanced stage with widespread peritoneal dissemination and ascites....
Ovarian cancer is the most lethal gynecological malignancy. Most patients are diagnosed at an advanced stage with widespread peritoneal dissemination and ascites. Bispecific T-cell engagers (BiTEs) have demonstrated impressive antitumor efficacy in hematological malignancies, but the clinical potency is limited by their short half-life, inconvenient continuous intravenous infusion, and severe toxicity at relevant therapeutic levels in solid tumors. To address these critical issues, the design and engineering of alendronate calcium (CaALN) based gene-delivery system is reported to express therapeutic level of BiTE (HER2×CD3) for efficient ovarian cancer immunotherapy. Controllable construction of CaALN nanosphere and nanoneedle is achieved by the simple and green coordination reactions that the distinct nanoneedle-like alendronate calcium (CaALN-N) with a high aspect ratio enabled efficient gene delivery to the peritoneum without system in vivo toxicity. Especially, CaALN-N induced apoptosis of SKOV3-luc cell via down-regulation of HER2 signaling pathway and synergized with HER2×CD3 to generate high antitumor response. In vivo administration of CaALN-N/minicircle DNA encoding HER2×CD3 (MC-HER2×CD3) produces sustained therapeutic levels of BiTE and suppresses tumor growth in a human ovarian cancer xenograft model. Collectively, the engineered alendronate calcium nanoneedle represents a bifunctional gene delivery platform for the efficient and synergistic treatment of ovarian cancer.
Topics: Female; Humans; Alendronate; Calcium; Cell Line, Tumor; Ovarian Neoplasms; T-Lymphocytes; Animals
PubMed: 36932888
DOI: 10.1002/advs.202204654 -
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 -
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 -
Bone Jul 2022Despite their ability to reduce fracture-risk and increase Bone Mineral Density (BMD) in osteoporotic women, bisphosphonates are reported to reduce formation of new...
Despite their ability to reduce fracture-risk and increase Bone Mineral Density (BMD) in osteoporotic women, bisphosphonates are reported to reduce formation of new bone. Reduced bone formation has been suggested to lead to accumulation of microfractures and contribute to rare side effects in cortical bone such as atypical femur fractures. However, most studies are limited to trabecular bone. In this study, the cortical bone remodeling in human iliac bone specimens of 65 non-treated and 24 alendronate-treated osteoporotic women was investigated using a new histomorphometric classification of intracortical pores. The study showed that only 12.4 ± 11% of the cortical pore area reflected quiescent pores/osteons in alendronate-treated patients versus 8.5 ± 5% in placebo, highlighting that new cortical remodeling events remain to be activated. The percent and size of eroded pores (events in resorption-reversal phase) remained unchanged, but their contribution to total pore area was 1.4-fold higher in alendronate versus placebo treated patients (66 ± 22% vs 48 ± 22%, p < 0.001). On the other hand, the mixed eroded-formative pores (events with mixed resorption-reversal-formation phases) was 2-fold lower in alendronate versus placebo treated patients (19 ± 14% vs 39 ± 23% of total pore area, p < 0.001), and formative pores (event in formation phase) was 2.2-fold lower in alendronate versus placebo treated patients (2.1 ± 2.4% vs 4.6 ± 3.6%, p < 0.01), and their contribution to total pore area was 2.4-fold lower (1.3 ± 2.1% vs 3.1 ± 4.4%, p < 0.05). Importantly, these differences between alendronate and placebo treated patients were significant in patients after 3 years of treatment, not after 2 years of treatment. Collectively, the results support that cortical remodeling events activated during alendronate treatment has a prolonged reversal-resorption phase with a delayed transition to formation, becoming increasingly evident after 3-years of treatment. A potential contributor to atypical femur fractures associated with long-term bisphosphonate treatment.
Topics: Alendronate; Bone Density; Bone Remodeling; Bone and Bones; Cortical Bone; Diphosphonates; Female; Humans
PubMed: 35413490
DOI: 10.1016/j.bone.2022.116419 -
The New England Journal of Medicine Jan 2017
Review
Topics: Alendronate; Bone Density Conservation Agents; Clinical Trials as Topic; Clinical Trials, Phase III as Topic; Drug Discovery; Drug Industry; Humans; Rotavirus Vaccines
PubMed: 28052221
DOI: 10.1056/NEJMra1510069 -
Archives of Osteoporosis Apr 2022This study evaluated the cost-effectiveness of 1 year of romosozumab followed by alendronate versus oral bisphosphonates alone in women with postmenopausal osteoporosis...
UNLABELLED
This study evaluated the cost-effectiveness of 1 year of romosozumab followed by alendronate versus oral bisphosphonates alone in women with postmenopausal osteoporosis at very high risk for fracture in Canada. Results showed that romosozumab sequenced to alendronate is a cost-effective treatment option, dominating both alendronate and risedronate alone.
PURPOSE
To demonstrate the value of romosozumab sequenced to alendronate compared to alendronate or risedronate alone, for the treatment of osteoporosis in postmenopausal women with a history of osteoporotic fracture and who are at very high risk for future fracture in Canada.
METHODS
A Markov model followed a hypothetical cohort of postmenopausal osteoporotic women at very high risk for future fractures, to estimate the cost-effectiveness of romosozumab and alendronate compared to oral bisphosphonates alone. A total treatment period of 5 years was assumed. Quality-adjusted life years and costs were estimated for each comparator across health states defined by different types of fragility fractures.
RESULTS
Romosozumab/alendronate was associated with a lifetime gain of 0.103 and 0.127 QALYs and a cost reduction of $343 and $3805, relative to alendronate and risedronate, respectively. These results were driven by a reduction of the number of fractures (2561 per 1000 patients, versus 2700 for alendronate and 2724 for risedronate over lifetime). Romosozumab/alendronate had the highest probability of being cost-effective, relative to alendronate and risedronate, at any willingness to pay threshold value.
CONCLUSION
Romosozumab/alendronate was associated with reduced costs and greater benefit relative to other comparators. Probabilistic, deterministic, and scenario analyses indicate that romosozumab/alendronate represents the best value for money; the uncertainty analyses are robust, and therefore romosozumab should be considered for reimbursement by public drug plans in Canada .
Topics: Alendronate; Antibodies, Monoclonal; Bone Density Conservation Agents; Cost-Benefit Analysis; Female; Humans; Osteoporosis, Postmenopausal; Osteoporotic Fractures; Postmenopause; Quality-Adjusted Life Years; Risedronic Acid
PubMed: 35471711
DOI: 10.1007/s11657-022-01106-9