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The Korean Journal of Internal Medicine Sep 2011The aim of this study was to assess the efficacy and safety of monthly oral 150 mg ibandronate in women with postmenopausal osteoporosis (PMO). (Meta-Analysis)
Meta-Analysis Review
BACKGROUND/AIMS
The aim of this study was to assess the efficacy and safety of monthly oral 150 mg ibandronate in women with postmenopausal osteoporosis (PMO).
METHODS
A systematic review and meta-analysis were performed to determine treatment efficacy and safety outcomes between monthly oral 150 mg ibandronate and weekly 70 mg alendronate, daily 2.5 mg ibandronate, and a placebo.
RESULTS
Eight randomized controlled trials were included in this systematic review and meta-analysis. Once-monthly 150 mg ibandronate therapy was clinically comparable to weekly 70 mg alendronate, showing increased bone mineral density (BMD) in both the lumbar spine and total hip. Pooled data from two cross-over trials showed that significantly more women with PMO preferred once-monthly ibandronate therapy to once-weekly alendronate therapy (relative risk [RR], 2.422; 95% confidence interval [CI], 2.111 to 2.825; p < 1 × 10(-8)) and found the monthly ibandronate regimen more convenient than the weekly alendronate regimen (RR, 3.096; 95% CI, 2.622 to 3.622; p < 1 × 10(-8)). Monthly 150 mg ibandronate therapy resulted in a significantly higher change in BMD of the lumbar spine than with the placebo. A once monthly 150 mg regimen produced greater increases in lumbar spine, total hip, femoral neck, and trochanter BMD than daily treatment, with a similar incidence of adverse events between the groups.
CONCLUSIONS
Once monthly 150 mg ibandronate therapy was clinically comparable to weekly 70 mg alendronate, and patients strongly preferred the convenience of monthly ibandronate over weekly alendronate. Monthly 150 mg ibandronate was superior to, and as well tolerated as, the daily treatment.
Topics: Administration, Oral; Alendronate; Bone Density; Bone Density Conservation Agents; Bone and Bones; Diphosphonates; Drug Administration Schedule; Evidence-Based Medicine; Female; Humans; Ibandronic Acid; Osteoporosis, Postmenopausal; Patient Preference; Radiography; Randomized Controlled Trials as Topic; Time Factors; Treatment Outcome
PubMed: 22016595
DOI: 10.3904/kjim.2011.26.3.340 -
BMC Musculoskeletal Disorders Sep 2011In the absence of head-to-head trials, indirect comparisons of randomized placebo-controlled trials may provide a viable option to assess relative efficacy. The purpose... (Review)
Review
BACKGROUND
In the absence of head-to-head trials, indirect comparisons of randomized placebo-controlled trials may provide a viable option to assess relative efficacy. The purpose was to estimate the relative efficacy of reduction of fractures in post-menopausal women, and to assess robustness of the results.
METHODS
A systematic literature review of multiple databases identified randomized placebo-controlled trials with nine drugs for post-menopausal women. Odds ratio and 95% credibility intervals for the rates of hip, non-vertebral, vertebral, and wrist fractures for each drug and between drugs were derived using a Bayesian approach. A drug was ranked as the most efficacious if it had the highest posterior odds ratio, or had the highest effect size.
RESULTS
30 studies including 59,209 patients reported fracture rates for nine drugs: alendronate (6 studies), denosumab (1 study), etidronate (8 studies), ibandronate (4 studies), raloxifene (1 study), risedronate (7 studies), strontium (2 study), teriparatide (1 study), and zoledronic acid (1 study). The drugs with the highest probability of reducing non-vertebral fractures was etidronate and teriparatide while the drugs with the highest probability of reducing vertebral, hip or wrist fractures were teriparatide, zoledronic acid and denosumab. The drugs with the largest effect size for vertebral fractures were zoledronic acid, teriparatide and denosumab, while the drugs with the highest effect size for non-vertebral, hip or wrist fractures were alendronate or risedronate. Estimates were consistent between Bayesian and classical approaches.
CONCLUSION
Teriparatide, zoledronic acid and denosumab have the highest probabilities of being most efficacious for non-vertebral and vertebral fractures, and having the greatest effect sizes. The estimates from indirect comparisons were robust to differences in methodology.
Topics: Bone Density Conservation Agents; Female; Humans; Osteoporosis, Postmenopausal; Osteoporotic Fractures; Postmenopause; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 21943363
DOI: 10.1186/1471-2474-12-209 -
BMJ Clinical Evidence May 2011The lifetime risk of fracture in white women is 20% for the spine, 15% for the wrist, and 18% for the hip, with an exponential increase in risk beyond the age of 50... (Review)
Review
INTRODUCTION
The lifetime risk of fracture in white women is 20% for the spine, 15% for the wrist, and 18% for the hip, with an exponential increase in risk beyond the age of 50 years.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of bisphosphonates to prevent fractures in postmenopausal women? What are the effects of pharmacological treatments other than bisphosphonates to prevent fractures in postmenopausal women? What are the effects of non-pharmacological treatments to prevent fractures in postmenopausal women? We searched: Medline, Embase, The Cochrane Library, and other important databases up to September 2010 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 71 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: alendronate, calcitonin, calcium, calcium plus vitamin D, clodronate, denosumab, etidronate, exercise, hip protectors, hormone replacement therapy, ibandronate, multifactorial non-pharmacological interventions, pamidronate, parathyroid hormone, raloxifene, risedronate, strontium ranelate, vitamin D, vitamin D analogues, and zoledronate.
Topics: Administration, Oral; Alendronate; Bone Density Conservation Agents; Calcium, Dietary; Etidronic Acid; Evidence-Based Medicine; Female; Fractures, Bone; Humans; Incidence; Postmenopause; Raloxifene Hydrochloride
PubMed: 21542947
DOI: No ID Found -
Health Technology Assessment... Sep 2009To determine the clinical and cost-effectiveness of vitamin K in preventing osteoporotic fractures in postmenopausal women. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To determine the clinical and cost-effectiveness of vitamin K in preventing osteoporotic fractures in postmenopausal women.
DATA SOURCES
Searches were conducted in May 2007 in MEDLINE, MEDLINE In-Process, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Controlled Trials Register, BIOSIS, CINAHL, DARE, NHS EED and HTA databases, AMED, NRR, Science Citation Index and Current Controlled Trials. The MEDLINE search was updated in March 2009.
REVIEW METHODS
Selected studies were assessed and subjected to data extraction and quality assessment using standard methods. Where appropriate, meta-analysis was carried out. A mathematical model was constructed to estimate the cost-effectiveness of vitamin K1.
RESULTS
The electronic literature searches identified 1078 potentially relevant articles. Of these, 14 articles relating to five trials that compared vitamin K with a relevant comparator in postmenopausal women with osteoporosis or osteopenia met the review inclusion criteria. The double-blind ECKO trial compared 5 mg of phylloquinone (vitamin K1) with placebo in Canadian women with osteopenia but without osteoporosis. Four open-label trials used 45 mg of menatetrenone (vitamin K2) in Japanese women with osteoporosis; the comparators were no treatment, etidronate or calcium. The methodological quality of the ECKO trial was good; however, all four menatetrenone trials were poorly reported and three were very small (n < 100 in each group). Phylloquinone was associated with a statistically significant reduction in the risk of clinical fractures relative to placebo [relative risk 0.46, 95% confidence interval (CI) 0.22 to 0.99]; morphometric vertebral fractures were not reported. The smaller menatetrenone trials found that menatetrenone was associated with a reduced risk of morphometric vertebral fractures relative to no treatment or calcium; however, the larger Osteoporosis Fracture (OF) study found no evidence of a reduction in vertebral fracture risk. The three smaller trials found no significant difference between treatment groups in non-vertebral fracture incidence. In the ECKO trial, phylloquinone was not associated with an increase in adverse events. In the menatetrenone trials, adverse event reporting was generally poor; however, in the OF study, menatetrenone was associated with a significantly higher incidence of skin and skin appendage lesions. No published economic evaluations of vitamin K were found and a mathematical model was thus constructed to estimate the cost-effectiveness of vitamin K1. Comparators were alendronate, risedronate and strontium ranelate. Vitamin K1 and alendronate were markedly more cost-effective than either risedronate or strontium ranelate. The base-case results favoured vitamin K1, but this relied on many assumptions, particularly on the efficacy of preventing hip and vertebral fractures. Calculation of the expected value of sampled information was conducted assuming a randomised controlled trial of 5 years' duration comparing alendronate with vitamin K1. The costs incurred in obtaining updated efficacy data from a trial with 2000 women per arm were estimated to be a cost-effective use of resources.
CONCLUSIONS
There is currently large uncertainty over whether vitamin K1 is more cost-effective than alendronate; further research is required. It is unlikely that the present prescribing policy (i.e. alendronate as first-line treatment) would be altered.
Topics: Aged; Aged, 80 and over; Bone Density Conservation Agents; Cost-Benefit Analysis; Female; Fractures, Bone; Humans; Models, Econometric; Osteoporosis, Postmenopausal; Quality-Adjusted Life Years; Vitamin K; Vitamin K 1; Vitamin K 2; Vitamins
PubMed: 19818211
DOI: 10.3310/hta13450 -
Alimentary Pharmacology & Therapeutics Jun 2009Due to suppression of gastric acidity during antisecretory therapy, an impaired absorption of co-administered drugs may occur. (Review)
Review
BACKGROUND
Due to suppression of gastric acidity during antisecretory therapy, an impaired absorption of co-administered drugs may occur.
AIM
To review evidence of impaired drug absorption related to the use of co-administered PPIs or H2RAs.
METHODS
Systematic search of MEDLINE/EMBASE/SCOPUS databases (1980-September 2008) for English articles with keywords: drug malabsorption and absorption, stomach, anti-secretory/acid inhibitory drugs, histamine H2 antagonists, PPIs, gastric acid, pH, hypochlorhydria, gastric hypoacidity. From 2126 retrieved articles, 16 randomized crossover studies were identified investigating impaired absorption of nine different drugs in association with co-administration of PPIs or H2RAs. Information on investigated drug, study type, features of investigated subjects, study design, type of intervention, and study results were extracted.
RESULTS
The identified studies investigated the absorption kinetics of nine drugs. Acid suppression reduced absorption of ketoconazole, itraconazole, atazanavir, cefpodoxime, enoxacin and dipyridamole (median C(max) reduction by 66.5%). An increased absorption of nifedipine and digoxin (median AUC increase by 10%) and a 2-fold-increase in alendronate bioavailability were observed.
CONCLUSIONS
Gastric pH appears relevant for absorption of some cardiovascular or infectious disease agents. Antisecretory treatment may significantly modify the absorption of co-administered drugs.
Topics: Anti-Ulcer Agents; Drug Administration Schedule; Gastric Acid; Gastric Mucosa; Gastrointestinal Diseases; Histamine H2 Antagonists; Humans; Intestinal Absorption; Proton Pump Inhibitors; Randomized Controlled Trials as Topic
PubMed: 19302263
DOI: 10.1111/j.1365-2036.2009.03993.x -
Sao Paulo Medical Journal = Revista... Sep 2008Osteoporosis is defined as a disease characterized by low bone mass and deterioration of the bone tissue microarchitecture. Teriparatide stimulates the formation and... (Review)
Review
CONTEXT AND OBJECTIVE
Osteoporosis is defined as a disease characterized by low bone mass and deterioration of the bone tissue microarchitecture. Teriparatide stimulates the formation and action of osteoblasts, which are responsible for bone formation, thus promoting bone tissue increase. The aim was to assess the effectiveness and safety of teriparatide for treating postmenopausal osteoporosis.
METHODS
A systematic review was conducted using the Cochrane Collaboration methodology.
RESULTS
1) Teriparatide 20 microg or 40 microg versus placebo: there was a benefit from teriparatide, considering the following outcomes: reduction in the number of new vertebral and non-vertebral fractures, and increased whole-body, lumbar and femoral bone mineral density. 2) Teriparatide 40 microg versus alendronate 10 mg/day for 14 months: there was no statistical difference regarding the incidence of new vertebral or non-vertebral fractures, although in the group that received teriparatide there was greater bone mineral density increase in the whole body, lumbar column and femur. 3) Estrogen plus teriparatide 25 microg versus estrogen: there was a benefit, considering the following outcomes: reduction in the number of new vertebral fractures, and increased whole-body, lumbar and femoral bone mineral density after three years.
CONCLUSIONS
When teriparatide is intermittently administered in low doses, it reduces the incidence of vertebral fractures (67%) and non-vertebral fractures (38%) and increases bone mineral density in the lumbar column and femur. There is a need for studies with longer observation in order to allow conclusions regarding the safety and duration of the therapeutic effects.
Topics: Aged; Aged, 80 and over; Alendronate; Bone Density Conservation Agents; Estrogens; Female; Fertility Agents, Female; Humans; Middle Aged; Nafarelin; Osteoporosis, Postmenopausal; Teriparatide
PubMed: 19099162
DOI: 10.1590/s1516-31802008000500007 -
Cadernos de Saude Publica 2008Osteoporosis, a typical disease of the elderly, has become a frequent and relevant public health problem. Several drugs are available for treatment of osteoporosis, some... (Review)
Review
Osteoporosis, a typical disease of the elderly, has become a frequent and relevant public health problem. Several drugs are available for treatment of osteoporosis, some of which are currently dispensed by the Brazilian Unified National Health System. The objective of this study was to present a systematic review of drugs for treatment of osteoporosis, focusing on the adequacy of clinical protocols based on existing evidence in the scientific literature. We conducted a search for randomized clinical trials in PubMed and LILACS that presented results for bone mineral density, incidence of vertebral fractures, and adverse effects. 32 articles met the review's inclusion criteria. Bisphosphonates were reported to have consistently reduced the risk of vertebral fractures. Hormone replacement therapy showed positive outcomes, but its use has been found to increase the risk of cardiovascular disease and breast cancer. Teriparatide and monofluorophosphate also showed efficacy against osteoporosis. Calcium and vitamin D were given to patients as food supplements.
Topics: Alendronate; Bone Density; Bone Density Conservation Agents; Diphosphonates; Female; Fractures, Bone; Hormone Replacement Therapy; Humans; Osteoporosis, Postmenopausal; Randomized Controlled Trials as Topic
PubMed: 18797733
DOI: 10.1590/s0102-311x2008001600011 -
Annals of Internal Medicine Feb 2008Although several agents are available to treat osteoporosis, the relative efficacy and toxicity of these agents when used to prevent fractures has not been well... (Comparative Study)
Comparative Study Meta-Analysis
BACKGROUND
Although several agents are available to treat osteoporosis, the relative efficacy and toxicity of these agents when used to prevent fractures has not been well described.
PURPOSE
To compare the benefits in fracture reduction and the harms from adverse events of various therapies for osteoporosis.
DATA SOURCES
MEDLINE (1966 to November 2007) and other selected databases were searched for English-language studies.
STUDY SELECTION
For the efficacy analysis, investigators selected studies that reported the rate of or risk for fractures. For the adverse event analysis, they selected studies that reported the relationship between an agent and cardiovascular, thromboembolic, or upper gastrointestinal events; malignant conditions; and osteonecrosis.
DATA EXTRACTION
Using a standardized protocol, investigators abstracted data on fractures and adverse events, agents and comparators, study design, and variables of methodological quality.
DATA SYNTHESIS
Good evidence suggests that alendronate, etidronate, ibandronate, risedronate, zoledronic acid, estrogen, parathyroid hormone (1-34), and raloxifene prevent vertebral fractures more than placebo; the evidence for calcitonin was fair. Good evidence suggests that alendronate, risedronate, and estrogen prevent hip fractures more than placebo; the evidence for zoledronic acid was fair. The effects of vitamin D varied with dose, analogue, and study population for both vertebral and hip fractures. Raloxifene, estrogen, and estrogen-progestin increased the risk for thromboembolic events, and etidronate increased the risk for esophageal ulcerations and gastrointestinal perforations, ulcerations, and bleeding.
LIMITATION
Few studies have directly compared different agents or classes of agents used to treat osteoporosis.
CONCLUSION
Although good evidence suggests that many agents are effective in preventing osteoporotic fractures, the data are insufficient to determine the relative efficacy or safety of these agents.
Topics: Androgens; Bone Density; Bone Density Conservation Agents; Calcium; Estrogen Replacement Therapy; Estrogens; Female; Fractures, Bone; Humans; Male; Osteoporosis; Risk Factors; Selective Estrogen Receptor Modulators; Testosterone; Vitamin D
PubMed: 18087050
DOI: 10.7326/0003-4819-148-3-200802050-00198 -
The Cochrane Database of Systematic... Oct 2007Children with chronic illnesses are at increased risk for reductions in bone strength and subsequent fractures (osteoporosis), either due to the impact of the underlying... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Children with chronic illnesses are at increased risk for reductions in bone strength and subsequent fractures (osteoporosis), either due to the impact of the underlying condition on skeletal development or due to the osteotoxic effect of medications (e.g., glucocorticoids) used to treat the chronic illness. Bisphosphonates are being administered with increasing frequency to children with secondary osteoporosis; however, the efficacy and harm of these agents remains unclear.
OBJECTIVES
To examine the efficacy and harm of bisphosphonate therapy in the treatment and prevention of secondary osteoporosis in children and adolescents.
SEARCH STRATEGY
We searched the Cochrane Central Register of Controlled Trials (Issue 4, 2006), MEDLINE, EMBASE, CINAHL and ISI Web of Science (inception-December 2006). Further literature was identified through expert contact, key author searches, scanning reference lists of included studies, and contacting bisphosphonate manufacturers.
SELECTION CRITERIA
Randomized, quasi-randomized, controlled clinical trials, cohort, and case controls of bisphosphonate(s) in children 0-18 years of age with at least one low-trauma fracture event or reductions in bone mineral density in the context of secondary osteoporosis.
DATA COLLECTION AND ANALYSIS
Two reviewers independently extracted data and assessed quality. Case series were used for supplemental harms-related data.
MAIN RESULTS
Six RCTs, two CCTs, and one prospective cohort (n=281 children) were included and classified into osteoporosis due to: 1) neuromuscular conditions (one RCT) and 2) chronic illness (five RCTs, two CCTs, one cohort). Bisphosphonates examined were oral alendronate, clodronate, and intravenous (IV) pamidronate. Study quality varied. Harms data from 23 case series (n=241 children) were used. Heterogeneity precluded statistically combining the results. Percent change or Z-score change in lumbar spine areal BMD from baseline were consistently reported. Two studies carried out between-group analyses; one showed no significant difference (using oral alendronate in anorexia nervosa) while the other demonstrated a treatment effect on lumbar spine with IV pamidronate in burn patients. Frequently reported harms included the acute phase reaction, followed by gastrointestinal complaints, and bone/muscle pain.
AUTHORS' CONCLUSIONS
The results justify further evaluation of bisphosphonates among children with secondary osteoporosis. However, the evidence does not support bisphosphonates as standard therapy. Short-term (3 years or less) bisphosphonate use appears to be well-tolerated. An accepted criterion for osteoporosis in children, a standardized approach to BMD reporting, and examining functional bone health outcomes (e.g., fracture rates) will allow for appropriate comparisons across studies.
Topics: Adolescent; Bone Density; Bone Density Conservation Agents; Child; Controlled Clinical Trials as Topic; Diphosphonates; Humans; Osteoporosis
PubMed: 17943849
DOI: 10.1002/14651858.CD005324.pub2