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The Archives of Bone and Joint Surgery May 2021Atypical femoral fractures are the femoral fractures located anywhere between the lesser trochanter and the supracondylar flare of the femur. Long-term bisphosphonates,... (Review)
Review
BACKGROUND
Atypical femoral fractures are the femoral fractures located anywhere between the lesser trochanter and the supracondylar flare of the femur. Long-term bisphosphonates, as the most common preventive and treatment medications for osteoporosis, are thought to have an important role in these fractures. Most of the fractures should be treated surgically, and the complications are considerable.
METHODS
We searched Medline, CENTRAL, Embase, and DART on February 26, 2020. One author reviewed and retrieved citations from these four databases for irrelevant and duplicate studies, and two other authors independently extracted data from the studies and rated their quality.Patients with surgical treatment of bisphosphonate-related atypical femoral fracture, according to the American Society for Bone and Mineral Research definition, were included. Animal studies, case reports, studies with high-energy trauma, pathological fracture, or malignancy-related fractures were excluded.
RESULTS
In total, 316 patients (348 fractures) were included in this study. Mean age of patients was 70.47 years, and 97.5% of them were female. Duration of using bisphosphonates was 4.04 to 8.8 years, and Alendronate was the most common type. Moreover, 65.27% and 34.72% of the reported fractures were in diaphyseal and subtrochanteric, respectively. Moreover, the most common fixation type was intramedullary. Rate of complication was 17.52%, and the most frequent one was non-union, followed by implant failure. The main limitation of this research was that most of the studies did not have a high level of evidence.
CONCLUSION
An increase in the rate of atypical femoral fracture with its challenging management makes it an important issue to be noted by orthopedic surgeons. Based on the results of this study, subtrochanteric fractures might have more complications post-operatively and are suggested to be operated on by more experienced surgeons. It was also found that extra-medullary fixation increases the risk of complications. Future studies on union time, outcomes of different surgical methods, and teriparatide therapy may help shed more light on the surgical management of these fractures.
PubMed: 34239955
DOI: 10.22038/abjs.2020.52698.2608 -
PharmacoEconomics Apr 2023Osteoporosis is often considered to be a disease of women. Over the last few years, owing to the increasing clinical and economic burden, the awareness and imperative...
BACKGROUND
Osteoporosis is often considered to be a disease of women. Over the last few years, owing to the increasing clinical and economic burden, the awareness and imperative for identifying and managing osteoporosis in men have increased substantially. With the approval of agents to treat men with osteoporosis, more economic evaluations have been conducted to assess the potential economic benefits of these interventions. Despite this concern, there is no specific overview of cost-effectiveness analyses for the treatment of osteoporosis in men.
OBJECTIVES
This study aims (1) to systematically review economic evaluations of interventions for osteoporosis in men; (2) to critically appraise the quality of included studies and the source of model input data; and (3) to investigate the comparability of results for studies including both men and women.
METHODS
A literature search mainly using MEDLINE (via Ovid) and Embase databases was undertaken to identify original articles published between 1 January, 2000 and 30 June, 2022. Studies that assessed the cost effectiveness of interventions for osteoporosis in men were included. The Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases and the International Osteoporosis Foundation osteoporosis-specific guideline was used to assess the quality of design, conduct, and reporting of included studies.
RESULTS
Of 2973 articles identified, 25 studies fulfilled the inclusion criteria, classified into economic evaluations of active drugs (n = 8) or nutritional supplements (n = 4), intervention thresholds (n = 5), screening strategies (n = 6), and post-fracture care programs (n = 2). Most studies were conducted in European countries (n = 15), followed by North America (n = 9). Bisphosphonates (namely alendronate) and nutritional supplements were shown to be generally cost effective compared with no treatment in men over 60 years of age with osteoporosis or prior fractures. Two other studies suggested that denosumab was cost effective in men aged 75 years and older with osteoporosis compared with bisphosphates and teriparatide. Intervention thresholds at which bisphosphonates were found to be cost effective varied among studies with a 10-year probability of a major osteoporotic fracture that ranged from 8.9 to 34.2% for different age categories. A few studies suggested cost effectiveness of screening strategies and post-fracture care programs in men. Similar findings regarding the cost effectiveness of drugs and intervention thresholds in women and men were captured, with slightly greater incremental cost-effectiveness ratios in men. The quality of the studies included had an average score of 18.8 out of 25 (range 13-23.5). Hip fracture incidence and mortality risk were mainly derived from studies in men, while fracture cost, treatment efficacy, and disutility were commonly derived from studies in women or studies combining both sexes.
CONCLUSIONS
Anti-osteoporosis drugs and nutritional supplements are generally cost effective in men with osteoporosis. Screening strategies and post-fracture care programs also showed economic benefits for men. Cost-effectiveness and intervention thresholds were generally similar in studies conducted in both men and women, with slightly greater incremental cost-effectiveness ratios in men.
Topics: Male; Female; Humans; Middle Aged; Aged; Osteoporosis, Postmenopausal; Cost-Effectiveness Analysis; Osteoporosis; Osteoporotic Fractures; Diphosphonates; Cost-Benefit Analysis; Bone Density Conservation Agents
PubMed: 36738425
DOI: 10.1007/s40273-022-01239-2 -
Journal of Clinical Rheumatology :... Mar 2023This study aims to evaluate ibandronate clinical effectiveness in the prevention of osteoporosis-related vertebral fractures (VFs) and nonvertebral fractures (NVFs) in...
BACKGROUND/OBJECTIVE
This study aims to evaluate ibandronate clinical effectiveness in the prevention of osteoporosis-related vertebral fractures (VFs) and nonvertebral fractures (NVFs) in the treatment of postmenopausal osteoporosis.
METHODS
This systematic review was conducted in accordance with the Centre for Reviews and Dissemination's guidance and reporting in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement 2020. A literature search was performed in PubMed and EMBASE since their inception until February 7, 2022. Randomized controlled trials (RCTs), meta-analysis, experimental, and observational studies evaluating adult patients treated with ibandronate and assessed to osteoporotic fractures prevention were included. The risk of bias was assessed according to study design. Data were analyzed using descriptive statistics.
RESULTS
Eight references from 4 RCTs, 7 meta-analyses, and 6 observational studies were included. In RCTs, oral ibandronate was superior to placebo in the prevention of VF. However, the doses were lower than those approved. The meta-analyses confirmed these results and showed that adequate doses of oral ibandronate reduce the risk of NVF compared with insufficient doses. In observational studies, oral ibandronate (in approved doses) reduced the risk of VF compared with no treatment or risedronate or alendronate and the risk of NVF versus risedronate or alendronate; the risk of hip fractures was similar between ibandronate and other oral bisphosphonates.
CONCLUSIONS
There is strong evidence that ibandronate reduces the risk of VF in postmenopausal osteoporosis. The available evidence further suggests that ibandronate may reduce the risk of NVF versus insufficient doses of ibandronate, as well as risedronate or alendronate.
Topics: Female; Humans; Alendronate; Bone Density Conservation Agents; Diphosphonates; Ibandronic Acid; Osteoporosis, Postmenopausal; Osteoporotic Fractures; Risedronic Acid; Observational Studies as Topic
PubMed: 36731043
DOI: 10.1097/RHU.0000000000001902 -
Iranian Journal of Public Health Jul 2022We aimed to review the systematic economic evaluation of denosumab versus than alternative drugs and oral bisphosphonates of postmenopausal osteoporosis in women and... (Review)
Review
BACKGROUND
We aimed to review the systematic economic evaluation of denosumab versus than alternative drugs and oral bisphosphonates of postmenopausal osteoporosis in women and help health system policy makers for prioritizing and optimally allocate limited health resources.
METHODS
We examined the databases of PubMed, Web of Science, Embase, Scopus, Cochrane Library, ProQuest. Strategy search was designed based on keywords. Inclusion criteria were: studies that conducted economic evaluation denosumab compared to oral bisphosphonates for the treatment of osteoporosis in postmenopausal women. Cost-effectiveness studies conducted using decision analysis models based on the economic evaluation approach; studies with available full-text papers; and studies written in English and published between 2010 and 2020. After selecting articles based on inclusion and exclusion criteria, data were extracted and the results were summarized. The quality of the articles was evaluated using the CHEERS checklist.
RESULTS
Among 214 initial studies, 8 studies met the inclusion criteria. Most studies focused on the cost-effectiveness of denosumab compared with oral bisphosphonates for the treatment of osteoporosis. The study agreed interval ranged from 3 months to 5 years. The costs investigated in the studies were direct medical costs. In most studies, the use of denosumab significantly prevented fractures.
CONCLUSION
Denosumab is generally more cost-effective than alternative drugs and oral bisphosphonates (alendronate, risedronate, strontium ranelate, ibandronate, and untreated).
PubMed: 36248303
DOI: 10.18502/ijph.v51i7.10084 -
Monoclonal Antibodies in... Apr 2020Sclerostin is a protein synthesized mainly by osteocytes whose function is to inhibit bone formation. A recent monoclonal antibody, Romosozumab, is able to block... (Meta-Analysis)
Meta-Analysis
Sclerostin is a protein synthesized mainly by osteocytes whose function is to inhibit bone formation. A recent monoclonal antibody, Romosozumab, is able to block sclerostin. The aim of this meta-analysis is to compare the safety of Romosozumab with placebo and alendronate. Five randomized controlled trials that described the safety of Romosozumab in healthy men and postmenopausal women were analyzed. The measures to be compared were the number of adverse events and the number of serious adverse events. Specific results included injection site reaction, arthralgia, nasopharyngitis, and back pain. A total of 11,741 patients were included in this meta-analysis, in three different groups: Romosozumab, alendronate, and placebo. Significant differences were seen between the groups with regard to injection site reaction: 5.88% in the Romosozumab group versus 3.62% in the placebo group (Mantel-Haenszel [M-H] 1.54, confidence interval [95% CI] 1.22-1.96; < 0.001) and 2.62% in the alendronate group (M-H 1.8, 95% CI 1.32-2.60; < 0.001). In addition, patients treated with Romosozumab had significantly fewer total adverse events than the alendronate group (M-H 0.85, 95% CI 0.74-0.98; < 0.05). In conclusion, Romosozumab may have lower adverse effects compared to alendronate and comparable to a placebo, except injection site reactions. Injection site reactions were more with romosozumab compared to alendronate and compared to the placebo as well. Romosozumab appears to have a similar safety profile to bisphosphonates.
Topics: Antibodies, Monoclonal; Female; Humans; Male; Osteoporosis; Osteoporosis, Postmenopausal; Postmenopause
PubMed: 32195618
DOI: 10.1089/mab.2019.0049 -
Clinical Rheumatology Nov 2020Osteoporosis is a chronic skeletal disease with an increasing prevalence. Romosozumab, as a monoclonal anti-sclerostin antibody with a dual function, has been produced.... (Meta-Analysis)
Meta-Analysis Review
Osteoporosis is a chronic skeletal disease with an increasing prevalence. Romosozumab, as a monoclonal anti-sclerostin antibody with a dual function, has been produced. In this meta-analysis, we aimed to examine the efficacy of Romosozumab in patients with low bone mineral density. A systematic search was conducted in the most important electronic search engines like Cochrane Library, PubMed, Web of Science, Scopus, Google Scholar, and ClinicalTrials.gov at the end of July 2019 to retrieve randomized controlled trials (RCTs), which evaluated the effect of Romosozumab in patients with osteoporosis and/or low bone mineral density. After evaluating the quality of articles with the Cochrane checklist, data related to the outcomes of bone mineral density (BMD) of lumbar spine, femoral neck, and total hip, risk of clinical, vertebral and non-vertebral fractures, and risk of adverse events were extracted. Quality of evidence was assessed according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Heterogeneity between studies was evaluated by I2 and Q statistics. The meta-analysis was performed using CMA v.2.0 software. Of all the 671 initially retrieved articles, seven articles were entered into the meta-analysis after removing duplicates and reviewing papers with inclusion and exclusion criteria. The results of the meta-analysis showed that Romosozumab 210, 140, and 70 mg compared with Alendronate, Teriparatide, and placebo can increase the bone mineral density in the lumbar spine, femoral neck, and total hip. The risk of adverse events like adjudicated cardiovascular serious adverse events and adjudicated cardiovascular death was more in Romosozumab 210 mg in comparison with placebo. However, this difference was not statistically significant. Treatment with anti-sclerostin antibodies can be a proper therapeutic option in patients with osteoporosis and low bone mineral density. Based on the results of this meta-analysis, it seems that Romosozumab, with its dual function, has a positive role in the treatment of osteoporosis and low bone mineral density.
Topics: Antibodies, Monoclonal; Bone Density; Bone Density Conservation Agents; Humans; Teriparatide
PubMed: 32385757
DOI: 10.1007/s10067-020-04948-1 -
BMC Oral Health Jan 2022This systematic review and meta-analysis aimed to investigate the role of alendronate combined with step 2 of periodontal therapy in reducing probing pocket depth,... (Meta-Analysis)
Meta-Analysis
Added effect of 1% topical alendronate in intra-bony and inter-radicular defects as part of step II periodontal therapy: a systematic review with meta-analysis and trial sequential analysis.
BACKGROUND
This systematic review and meta-analysis aimed to investigate the role of alendronate combined with step 2 of periodontal therapy in reducing probing pocket depth, improving clinical attachment level, and reducing bone defect depth in intra-bony and inter-radicular defects.
METHODS
RCTs with more than 6 months follow-up were included in this study. Risk of bias assessment was performed using the Cochrane collaboration tool. In addition, meta-analysis and trial sequential analysis were used to aggregate the available evidence.
RESULTS
Seven studies met the inclusion criteria and were included in the systematic review. Topical application of alendronate during second step of periodontal therapy significantly improved PD and CAL.
CONCLUSION
Local application of alendronate may confer a beneficial effect when applied during step II of periodontal therapy even if long term studies are needed to confirm these results.
CLINICAL RELEVANCE
Considering the emerging role of host-inflammatory response in treatment of periodontitis and the antiresorptive and osteostimulative properties of bisphosphonates, several studies are focusing on the role of alendronate as an addition to non-surgical periodontal therapy.
Topics: Alendronate; Alveolar Bone Loss; Diphosphonates; Humans; Periodontal Attachment Loss; Periodontitis
PubMed: 35062940
DOI: 10.1186/s12903-022-02044-1 -
Health Technology Assessment... Oct 2016Fragility fractures are fractures that result from mechanical forces that would not ordinarily result in fracture. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Fragility fractures are fractures that result from mechanical forces that would not ordinarily result in fracture.
OBJECTIVES
To evaluate the clinical effectiveness and safety of bisphosphonates [alendronic acid (Fosamax and Fosamax Once Weekly, Merck Sharp & Dohme Ltd), risedronic acid (Actonel and Actonel Once a Week, Warner Chilcott UK Ltd), ibandronic acid (Bonviva, Roche Products Ltd) and zoledronic acid (Aclasta, Novartis Pharmaceuticals UK Ltd)] for the prevention of fragility fracture and to assess their cost-effectiveness at varying levels of fracture risk.
DATA SOURCES
For the clinical effectiveness review, six electronic databases and two trial registries were searched: MEDLINE, EMBASE, The Cochrane Library, Cumulative Index to Nursing and Allied Health Literature, Web of Science and BIOSIS Previews, Clinicaltrials.gov and World Health Organization International Clinical Trials Registry Platform. Searches were limited by date from 2008 until September 2014.
REVIEW METHODS
A systematic review and network meta-analysis (NMA) of effectiveness studies were conducted. A review of published economic analyses was undertaken and a de novo health economic model was constructed. Discrete event simulation was used to estimate lifetime costs and quality-adjusted life-years (QALYs) for each bisphosphonate treatment strategy and a strategy of no treatment for a simulated cohort of patients with heterogeneous characteristics. The model was populated with effectiveness evidence from the systematic review and NMA. All other parameters were estimated from published sources. A NHS and Personal Social Services perspective was taken, and costs and benefits were discounted at 3.5% per annum. Fracture risk was estimated from patient characteristics using the QFracture (QFracture-2012 open source revision 38, Clinrisk Ltd, Leeds, UK) and FRAX (web version 3.9, University of Sheffield, Sheffield, UK) tools. The relationship between fracture risk and incremental net benefit (INB) was estimated using non-parametric regression. Probabilistic sensitivity analysis (PSA) and scenario analyses were used to assess uncertainty.
RESULTS
Forty-six randomised controlled trials (RCTs) were included in the clinical effectiveness systematic review, with 27 RCTs providing data for the fracture NMA and 35 RCTs providing data for the femoral neck bone mineral density (BMD) NMA. All treatments had beneficial effects on fractures versus placebo, with hazard ratios varying from 0.41 to 0.92 depending on treatment and fracture type. The effects on vertebral fractures and percentage change in BMD were statistically significant for all treatments. There was no evidence of a difference in effect on fractures between bisphosphonates. A statistically significant difference in the incidence of influenza-like symptoms was identified from the RCTs for zoledronic acid compared with placebo. Reviews of observational studies suggest that upper gastrointestinal symptoms are frequently reported in the first month of oral bisphosphonate treatment, but pooled analyses of placebo-controlled trials found no statistically significant difference. A strategy of no treatment was estimated to have the maximum INB for patients with a 10-year QFracture risk under 1.5%, whereas oral bisphosphonates provided maximum INB at higher levels of risk. However, the PSA suggested that there is considerable uncertainty regarding whether or not no treatment is the optimal strategy until the QFracture score is around 5.5%. In the model using FRAX, the mean INBs were positive for all oral bisphosphonate treatments across all risk categories. Intravenous bisphosphonates were estimated to have lower INBs than oral bisphosphonates across all levels of fracture risk when estimated using either QFracture or FRAX.
LIMITATIONS
We assumed that all treatment strategies are viable alternatives across the whole population.
CONCLUSIONS
Bisphosphonates are effective in preventing fragility fractures. However, the benefit-to-risk ratio in the lowest-risk patients may be debatable given the low absolute QALY gains and the potential for adverse events. We plan to extend the analysis to include non-bisphosphonate therapies.
STUDY REGISTRATION
This study is registered as PROSPERO CRD42013006883.
FUNDING
The National Institute for Health Research Health Technology Assessment programme.
Topics: Alendronate; Bone Density Conservation Agents; Cost of Illness; Cost-Benefit Analysis; Diphosphonates; Humans; Ibandronic Acid; Imidazoles; Models, Econometric; Osteoporotic Fractures; Quality-Adjusted Life Years; Randomized Controlled Trials as Topic; Risedronic Acid; Risk Factors; Social Work; State Medicine; United Kingdom; Zoledronic Acid
PubMed: 27801641
DOI: 10.3310/hta20780 -
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