Treatment To Prevent Fractures in Men and Women With Low Bone Density or Osteoporosis: Update of a 2007 Report [Entered Retrospectively]

Project Summary Title and Description

Title
Treatment To Prevent Fractures in Men and Women With Low Bone Density or Osteoporosis: Update of a 2007 Report [Entered Retrospectively]
Description
Objectives: To update a 2007 systematic review on the effectiveness and safety of treatments to prevent fractures in persons with low bone density or osteoporosis and factors affecting adherence to these treatments, and to assess whether monitoring helps identify those most likely to benefit from treatment and the benefits of long-term treatment. Data Sources: MEDLINE®, Embase, the Cochrane Database of Systematic Reviews, and Clinical Trials.gov were searched from January 2005 through March 2011. Review Methods: After review by two investigators against predetermined inclusion/exclusion criteria, we included existing systematic reviews, randomized controlled clinical trials, and large observational studies, where appropriate, for assessment of treatment efficacy, safety, and adherence. Results: Alendronate, risedronate, zoledronic acid, denosumab, and teriparatide reduce the risk of vertebral and nonvertebral fractures among postmenopausal women with osteoporosis. Ibandronate and raloxifene reduce the risk of vertebral but not nonvertebral fractures. Alendronate, risedronate, zoledronic acid, and denosumab prevent hip fractures among postmenopausal women with osteoporosis. Risedronate decreases the risk of vertebral and nonvertebral fracture among men with osteoporosis. Among those treated with glucocorticoids, fracture risk reduction was demonstrated for risedronate and alendronate compared to placebo; and for teriparatide compared to alendronate. Few studies have compared osteoporosis therapies head-to-head. Adherence to pharmacotherapy is poor in patients with osteoporosis, as with other chronic conditions. Many factors affect adherence to medications, including dosing frequency, side effects of medications, knowledge about osteoporosis, and cost. Age, prior history of fracture, and concomitant medication use do not appear to have an independent association with adherence. Dosing frequency appears to affect adherence: Adherence is improved with weekly compared to daily regimens, but evidence is lacking to show that monthly regimens improve adherence over that of weekly regimens. Decreased adherence to bisphosphonates is associated with less than optimal reduction in the risk of fracture. Insufficient evidence is available to make conclusions about how adherence to and persistence with newer osteoporosis therapies compare to that with bisphosphonates. Assessment of adverse effects finds that raloxifene is associated with an increased risk for pulmonary embolism and vasomotor flushing; and limited data support a possible association between bisphosphonate use and atypical subtrochanteric fractures of the femur. Evidence is limited on the utility of monitoring and long-term treatment. Conclusions: There is a high level of evidence that shows that fracture risk reduction is greatest in women with a diagnosis of osteoporosis and/or prevalent fractures. The level of evidence is low to moderate for fracture risk reduction in postmenopausal women with osteopenia and without prevalent fractures. The evidence is low for benefits of treatment for other populations, including men; for the benefits and risks of long-term treatment; and for the need (if any) for monitoring bone density; and mixed with regard to factors that influence adherence.
Attribution
N/A
Authors of Report
N/A
Methodology description
Search Strategy: Our basic search strategy used the National Library of Medicine’s Medical Subject Headings (MeSH) keyword nomenclature. Using the same basic search rules used for the original report (with the addition of several new terms for additional drugs), we searched MEDLINE® for the period from January 2005 through March 2011. We also searched Embase, the American College of Physicians (ACP) Journal Club database, the Cochrane controlled trials register, and relevant pharmacological databases. In searching for efficacy and effectiveness studies, we used terms for osteoporosis, osteopenia, low bone density, and the drugs listed in Key Question 1. In our search for the key adverse events (AE), we used terms for the AE and each of the drugs of interest. In our search for studies of adherence and persistence, we used terms for adherence and persistence and the drugs of interest. In all cases, both generic and trade names were used. In our search for studies on the effects of monitoring, we searched on terms related to monitoring and DXA in combination with the drugs of interest. For new drugs, we reviewed the list of excluded studies from the original report to retrieve articles that had been rejected on the basis of drugs that were now included within the scope of the update, to find studies prior to 2005. The search was not limited to English-language publications and not limited by study design (e.g., reports of randomized controlled trials (RCT), observational studies, systematic reviews). The texts of the major search strategies are given in Appendix A. To identify additional systematic reviews not captured in our primary search strategy, we also searched MEDLINE®, the Cochrane Database of Systematic Reviews, the websites of the National Institute for Clinical Excellence, and the NHA Health Technology Assessment Programme. We also manually searched the reference lists of review articles obtained as part of our search ("reference mining"). To augment those searches, the EPC’s Scientific Resource Center (SRC) conducted several "grey literature" searches, including a search of relevant trials in the NIH Clinical Trials database, the Web of Science, FDA Medwatch files, and Health Canada files. Study Selection: Each title list was screened separately by two reviewers with clinical training and experience in systematic review to eliminate obviously irrelevant titles. Abstracts were obtained for all selected titles. Full text articles were then obtained for all selected abstracts. The reviewers then conducted a second round of screening to ascertain which articles met the inclusion criteria and would go on to data abstraction. Selections at this stage were reconciled, and disagreements were settled by consensus (with the project leaders resolving remaining disagreements). During the second round of screening, we imposed inclusion criteria based on the particular Key Question(s) addressed by the study. For effectiveness/efficacy questions (Key Questions 1, 2, and 5), we accepted any abstracts that indicated the manuscript might include information on the treatment/prevention of osteoporotic fracture (but not bone density alone). Controlled clinical trials and large observational studies (N>1,000) that reported fracture outcomes for one or more of the drugs of interest were accepted for the efficacy analysis and went on to data extraction. Data Extraction: Study level details, such as population characteristics, comorbidities, inclusion and exclusion criteria, interventions, and outcomes assessed, were extracted and recorded onto specially designed forms.
PROSPERO
N/A
DOI
10.7301/Z0J1012P
Notes
This systematic review of the literature will address the following key questions: Key Question 1. What are the comparative benefits in fracture risk reduction among the following therapeutic modalities for low bone density: bisphosphonate medications (specifically: Alendronate (Fosamax®, oral); Risedronate (Actonel®; oral once-a-week); Ibandronate (Boniva®); Zoledronic acid (Reclast®, Zometa®, oral and IV).), Denosumab (Prolia®), Menopausal Estrogen therapy for women (numerous brands and routes of administration), Parathyroid hormone (PTH) (specifically: 1-34 (teriparatide) (Forteo®)), Selective estrogen receptor modulators (SERMs), (specifically: Raloxifene (Evista®)), Calcium, Vitamin D, Combinations or sequential use of above, and Exercise in comparison to above agents. Key Question 2. How does fracture risk reduction resulting from treatments vary between individuals with different risks for fracture as determined by the following factors: Bone mineral density, FRAX or other risk assessment score, Prior fractures (prevention vs. treatment), Age, Sex, Race/ethnicity, Glucocorticoid use, Other factors (e.g., community dwelling vs. institutionalized, vitamin D deficient vs. not). Key Question 3. Regarding treatment adherence and persistence: a) What are the levels of adherence and persistence with medications for the treatment and prevention of osteoporosis? b) What factors affect adherence and persistence? c) What are the effects of adherence and persistence on the risk of fractures? Key Question 4. What are the short- and long-term harms (adverse effects) of the above therapies (when used specifically to treat or prevent low bone density/osteoporotic fracture), and do these vary by any specific subpopulations (e.g., the subpopulations identified in Key Question 2)? Key Question 5. With regard to treatment for preventing osteoporotic fracture: a) How often should patients be monitored (via measurement of bone mineral density) during therapy, how does bone density monitoring predict antifracture benefits during pharmacotherapy, and does the ability of monitoring to predict antifracture effects of a particular pharmacologic agent vary among the pharmacotherapies? b) How does the antifracture benefit vary with long-term continued use of pharmacotherapy, and what are the comparative antifracture effects of continued long-term therapy with the various pharmacotherapies? *** The systematic review data of this published project was retrospectively imported into SRDR by the Brown EPC on behalf of the Southern California Evidence-based Practice Center-RAND Corporation and the Agency for Healthcare Research and Quality (AHRQ). For access to the full report available on the AHRQ website, follow this link: http://effectivehealthcare.ahrq.gov/search-for-guides-reviews-and-reports/?pageaction=displayproduct&productID=1007 ***
Funding Source
The Agency for Healthcare Research and Quality (AHRQ)

Key Questions

1. Key Question 1 - What are the comparative benefits in fracture risk reduction among the following therapeutic modalities for low bone density: bisphosphonate medications (specifically: Alendronate (Fosamax®, oral); Risedronate (Actonel®; oral once-a-week); Ibandronate (Boniva®); Zoledronic acid (Reclast®, Zometa®, oral and IV).), Denosumab (Prolia®), Menopausal Estrogen therapy for women (numerous brands and routes of administration), Parathyroid hormone (PTH) (specifically: 1-34 (teriparatide) (Forteo®)), Selective estrogen receptor modulators (SERMs), (specifically: Raloxifene (Evista®)), Calcium, Vitamin D, Combinations or sequential use of above, and Exercise in comparison to above agents.
2. Key Question 2 - How does fracture risk reduction resulting from treatments vary between individuals with different risks for fracture as determined by the following factors: Bone mineral density, FRAX or other risk assessment score, Prior fractures (prevention vs. treatment), Age, Sex, Race/ethnicity, Glucocorticoid use, Other factors (e.g., community dwelling vs. institutionalized, vitamin D deficient vs. not).
3. Key Question 3 - Regarding treatment adherence and persistence: a) What are the levels of adherence and persistence with medications for the treatment and prevention of osteoporosis? b) What factors affect adherence and persistence? c) What are the effects of adherence and persistence on the risk of fractures?
4. Key Question 4 - What are the short- and long-term harms (adverse effects) of the above therapies (when used specifically to treat or prevent low bone density/osteoporotic fracture), and do these vary by any specific subpopulations (e.g., the subpopulations identified in Key Question 2)?
5. Key Question 5 - Applicability Assessments

Associated Extraction Forms

Associated Studies (each link opens a new tab)

TitleAuthorsYear
Superiority of a combined treatment of Alendronate and Alfacalcidol compared to the combination of Alendronate and plain vitamin D or Alfacalcidol alone in established postmenopausal or male osteoporosis (AAC-Trial).2007
Alendronate or alfacalcidol in glucocorticoid-induced osteoporosis.2006
Risedronate and ergocalciferol prevent hip fracture in elderly men with Parkinson disease.2007
Effects of raloxifene on fracture risk in postmenopausal women: the Raloxifene Use for the Heart Trial.
The effect of raloxifene treatment in postmenopausal women with CKD.2008
Efficacy of bazedoxifene in reducing new vertebral fracture risk in postmenopausal women with osteoporosis: results from a 3-year, randomized, placebo-, and active-controlled clinical trial.2008
Denosumab for prevention of fractures in postmenopausal women with osteoporosis.2009
Osteoporosis in primary biliary cirrhosis: a randomized trial of the efficacy and feasibility of estrogen/progestin.2006
Effects of calcium supplementation on bone loss and fractures in congestive heart failure.2007
Reappraisal of Katsuragi calcium study, a prospective, double-blind, placebo-controlled study of the effect of active absorbable algal calcium (AAACa) on vertebral deformity and fracture.2004
Vitamin D supplementation and the prevention of fractures and falls: results of a randomised trial in elderly people in residential accommodation.2006
Preventing fractures among older people living in institutional care: a pragmatic randomised double blind placebo controlled trial of vitamin D supplementation.2007
Annual high-dose oral vitamin D and falls and fractures in older women: a randomized controlled trial.2010
Effects of 2 years' treatment of osteoporosis with 1 alpha-hydroxy vitamin D3 on bone mineral density and incidence of fracture: a placebo-controlled, double-blind prospective study.1996
Effect of annual intramuscular vitamin D on fracture risk in elderly men and women--a population-based, randomized, double-blind, placebo-controlled trial.2007
Vitamin D and calcium supplementation prevents osteoporotic fractures in elderly community dwelling residents: a pragmatic population-based 3-year intervention study.2004
Effect of vitamin D(3) and calcium on fracture risk in 65- to 71-year-old women: a population-based 3-year randomized, controlled trial--the OSTPRE-FPS.2010
The efficacy and safety of calcitriol and/or Caltrate D in elderly Chinese women with low bone mass.2009
Long-term outcomes of exercise: follow-up of a randomized trial in older women with osteopenia.2010
Effect of alendronate on risk of fracture in women with low bone density but without vertebral fractures: results from the Fracture Intervention Trial.-- Not Found --
Risedronate reverses bone loss in postmenopausal women with low bone mass: results from a multinational, double-blind, placebo-controlled trial. BMD-MN Study Group.2000
Effects of risedronate treatment on vertebral and nonvertebral fractures in women with postmenopausal osteoporosis: a randomized controlled trial. Vertebral Efficacy With Risedronate Therapy (VERT) Study Group.1999
Randomized trial of the effects of risedronate on vertebral fractures in women with established postmenopausal osteoporosis. Vertebral Efficacy with Risedronate Therapy (VERT) Study Group.2000
Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis.2007
Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene: results from a 3-year randomized clinical trial. Multiple Outcomes of Raloxifene Evaluation (MORE) Investigators.1999
Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis.
Alendronate once weekly for the prevention and treatment of bone loss in Canadian adult cystic fibrosis patients (CFOS trial).
Ibandronate prevents bone loss and reduces vertebral fracture risk in male cardiac transplant patients: a randomized double-blind, placebo-controlled trial.
Once-weekly risedronate in men with osteoporosis: results of a 2-year, placebo-controlled, double-blind, multicenter study.2009
Monthly dosing of 75 mg risedronate on 2 consecutive days a month: efficacy and safety results.2008
Efficacy and safety of risedronate 150 mg once a month in the treatment of postmenopausal osteoporosis.2008
Effectiveness of risedronate in osteoporotic postmenopausal women with inflammatory bowel disease: a prospective, parallel, open-label, two-year extension study.-- Not Found --
Sustained efficacy of risedronate in men with primary and secondary osteoporosis: results of a 2-year study.2009
Intravenous zoledronate improves bone density in adults with cystic fibrosis (CF).2009
Zoledronic acid and clinical fractures and mortality after hip fracture.2007
Effects of teriparatide versus alendronate for treating glucocorticoid-induced osteoporosis: thirty-six-month results of a randomized, double-blind, controlled trial.2009
Alendronate protects premenopausal women from bone loss and fracture associated with high-dose glucocorticoid therapy.2008
Hormone replacement therapy (HRT) or etidronate for osteoporosis in postmenopausal asthmatics on glucocorticoids: a randomised factorial trial.2009
Efficacy of continued alendronate for fractures in women with and without prevalent vertebral fracture: the FLEX trial.
Effects of continuing or stopping alendronate after 5 years of treatment: the Fracture Intervention Trial Long-term Extension (FLEX): a randomized trial.2006
Alendronate treatment in women with normal to severely impaired renal function: an analysis of the fracture intervention trial.
Increases in hip and spine bone mineral density are predictive for vertebral antifracture efficacy with ibandronate.2010
Relationship between changes in BMD and nonvertebral fracture incidence associated with risedronate: reduction in risk of nonvertebral fracture is not related to change in BMD.2005
Effects of risedronate on fracture risk in postmenopausal women with osteopenia.2008
Assessment of the relationship between age and the effect of risedronate treatment in women with postmenopausal osteoporosis: a pooled analysis of four studies.
Risedronate on 2 consecutive days a month reduced vertebral fracture risk at 1year compared with historical placebo.-- Not Found --
The incidence of osteonecrosis of the jaw in patients receiving 5 milligrams of zoledronic acid: data from the health outcomes and reduced incidence with zoledronic acid once yearly clinical trials program.2010
The effects of intravenous zoledronic acid in Chinese women with postmenopausal osteoporosis.2011
Effect of once-yearly zoledronic acid five milligrams on fracture risk and change in femoral neck bone mineral density.2009
Antifracture efficacy and reduction of mortality in relation to timing of the first dose of zoledronic acid after hip fracture.2009
Efficacy and safety of a once-yearly intravenous zoledronic acid 5 mg for fracture prevention in elderly postmenopausal women with osteoporosis aged 75 and older.2010
Skeletal effects of raloxifene after 8 years: results from the continuing outcomes relevant to Evista (CORE) study.
Effect of raloxifene on clinical fractures in Asian women with postmenopausal osteoporosis.2006
Benefits and risks of raloxifene by vertebral fracture status.
A meta-analysis of the efficacy of raloxifene on all clinical and vertebral fractures and its dependency on FRAX.2010
Teriparatide in postmenopausal women with osteoporosis and mild or moderate renal impairment.2007
Change in lumbar spine BMD and vertebral fracture risk reduction in teriparatide-treated postmenopausal women with osteoporosis.2006
Safety and efficacy of teriparatide in elderly women with established osteoporosis: bone anabolic therapy from a geriatric perspective.2006
Teriparatide vertebral fracture risk reduction determined by quantitative and qualitative radiographic assessment.2009
Vertebral fracture risk is reduced in women who lose femoral neck BMD with teriparatide treatment.
Subtrochanteric and diaphyseal femur fractures in patients treated with alendronate: a register-based national cohort study.
Adherence to bisphosphonate treatment by elderly women.-- Not Found --
Low acceptance of treatment in the elderly for the secondary prevention of osteoporotic fracture in the acute rehabilitation setting.2010
Discontinuation of antiresorptive therapies: a comparison between 1998-2001 and 2002-2004 among osteoporotic women.
Impact of noncompliance with alendronate and risedronate on the incidence of nonvertebral osteoporotic fractures in elderly women.2008
Consequences of poor compliance with bisphosphonates.2007
Adoption of once-monthly oral bisphosphonates and the impact on adherence.2010
Adherence and occurrence of fractures after switching to once-monthly oral bisphophonates.2010
Adherence to osteoporosis drugs and fracture prevention: no evidence of healthy adherer bias in a frail cohort of seniors.
Treatment persistence and compliance with a combination of calcium and vitamin D.2010
Physician perception of patient adherence compared to patient adherence of osteoporosis medications from pharmacy claims.2010
Adherence to monthly and weekly oral bisphosphonates in women with osteoporosis.2010
The effect of dosing frequency on compliance and persistence with bisphosphonate therapy in postmenopausal women: a comparison of studies in the United States, the United Kingdom, and France.2006
Benefit of adherence with bisphosphonates depends on age and fracture type: results from an analysis of 101,038 new bisphosphonate users.2008
Uptake of treatment for osteoporosis and compliance after bone density measurement in the community.2010
Medication persistence with weekly versus daily doses of orally administered bisphosphonates.-- Not Found --
Effectiveness of bisphosphonate therapy in a community setting.2009
Longitudinal change in hip fracture incidence after starting risedronate or raloxifene: an observational study.2011
Adherence and persistence with teriparatide among patients with commercial, Medicare, and Medicaid insurance.2011
Fracture outcomes related to persistence and compliance with oral bisphosphonates.
Patient preference and adherence: comparative US studies between two bisphosphonates, weekly risedronate and monthly ibandronate.2006
A claims database analysis of persistence with alendronate therapy and fracture risk in post-menopausal women with osteoporosis.2007
Weekly versus monthly drug regimens: 1-year compliance and persistence with bisphosphonate therapy.
Persistence of weekly alendronate: a real-world study in Croatia.2008
GRAND: the German retrospective cohort analysis on compliance and persistence and the associated risk of fractures in osteoporotic women treated with oral bisphosphonates.2012
The association of adherence to osteoporosis therapies with fracture, all-cause medical costs, and all-cause hospitalizations: a retrospective claims analysis of female health plan enrollees with osteoporosis.-- Not Found --
Adherence to alendronate in male veterans.2008
Risk of fracture in women treated with monthly oral ibandronate or weekly bisphosphonates: the eValuation of IBandronate Efficacy (VIBE) database fracture study.2009
Influence on persistence and adherence with oral bisphosphonates on fracture rates in osteoporosis.2009
Compliance and treatment satisfaction of post menopausal women treated for osteoporosis. Compliance with osteoporosis treatment.2010
Persistence with bisphosphonate therapy including treatment courses with multiple sequential bisphosphonates in the real world.2007
Outcomes after switching from one bisphosphonate to another in 146 patients at a single university hospital.2008
Factors affecting discontinuation of alendronate treatment in postmenopausal Japanese women with osteoporosis.2009
Determinants of persistence with weekly bisphosphonates in patients with osteoporosis.2008
Factors affecting long-term compliance of osteoporotic patients with bisphosphonate treatment and QOL assessment in actual practice: alendronate and risedronate.2007
Factors contributing to compliance with osteoporosis medication.2008
Adherence to treatment of primary osteoporosis and its association to fractures--the Swedish Adherence Register Analysis (SARA).2012
The impact of osteoporosis medication beliefs and side-effect experiences on non-adherence to oral bisphosphonates.2007
Adherence and profile of non-persistence in patients treated for osteoporosis--a large-scale, long-term retrospective study in The Netherlands.2011
Knowledge and compliance from patients with postmenopausal osteoporosis treatment.2009
Loss of treatment benefit due to low compliance with bisphosphonate therapy.2008
Determinants of non-compliance with bisphosphonates in women with postmenopausal osteoporosis.2008
Adherence to bisphosphonates therapy and hip fracture risk in osteoporotic women.2008
Low incidence of anti-osteoporosis treatment after hip fracture.2008
Patient compliance with alendronate, risedronate and raloxifene for the treatment of osteoporosis in postmenopausal women.2007
Differences in persistence, safety and efficacy of generic and original branded once weekly bisphosphonates in patients with postmenopausal osteoporosis: 1-year results of a retrospective patient chart review analysis.2009
Medication adherence, first episode duration, overall duration and time without therapy: the example of bisphosphonates.2009
Association of medication attitudes with non-persistence and non-compliance with medication to prevent fractures.2010
Compliance with alendronate 10 treatment in elderly women with postmenopausal osteoporosis.-- Not Found --
Differences in persistence among different weekly oral bisphosphonate medications.2009
Estimating bisphosphonate use and fracture reduction among US women aged 45 years and older, 2001-2008.
Predictors of very low adherence with medications for osteoporosis: towards development of a clinical prediction rule.2011
Persistence and switching patterns among women with varied osteoporosis medication histories: 12-month results from POSSIBLE US.2010
Persistent bisphosphonate use and the risk of osteoporotic fractures in clinical practice: a database analysis study.2006
Self-reported compliance with osteoporosis medication-qualitative aspects and correlates.-- Not Found --
Persistence across weekly and monthly bisphosphonates: analysis of US retail pharmacy prescription refills.2007
Compliance with pharmacologic therapy for osteoporosis.2003
Adherence and persistence in patients with postmenopausal osteoporosis treated with raloxifene.2011
Cumulative alendronate dose and the long-term absolute risk of subtrochanteric and diaphyseal femur fractures: a register-based national cohort analysis.
Upper gastrointestinal tolerability of alendronate sodium monohydrate 10 mg once daily in postmenopausal women: a 12-week, randomized, double-blind, placebo-controlled, exploratory study.2009
A double-blinded head-to-head trial of minodronate and alendronate in women with postmenopausal osteoporosis.2009
Use of alendronate and risk of incident atrial fibrillation in women.2008
Positive effect of alendronate on bone mineral density and markers of bone turnover in patients with rheumatoid arthritis on chronic treatment with low-dose prednisone: a randomized, double-blind, placebo-controlled trial.2006
The efficacy and tolerability of once-weekly alendronate 70 mg on bone mineral density and bone turnover markers in postmenopausal Chinese women with osteoporosis.2009
Relation of bisphosphonate therapies and risk of developing atrial fibrillation.2009
Exposure to oral bisphosphonates and risk of esophageal cancer.2010
Bisphosphonate use and the risk of adverse jaw outcomes: a medical claims study of 714,217 people.2008
Oral bisphosphonates and risk of cancer of oesophagus, stomach, and colorectum: case-control analysis within a UK primary care cohort.
Preferences of patients with post-menopausal osteoporosis treated with bisphosphonates--the VIVA II study.-- Not Found --
Efficacy and tolerability of intravenous ibandronate injections in postmenopausal osteoporosis: 2-year results from the DIVA study.
Ibandronate does not increase risk of atrial fibrillation in analysis of pivotal clinical trials.2010
Efficacy and safety of monthly oral ibandronate in the prevention of postmenopausal bone loss.2009
Efficacy and safety of monthly ibandronate in men with low bone density.2010
Monthly oral ibandronate is effective and well tolerated after 3 years: the MOBILE long-term extension.2008
Upper gastrointestinal tract safety of daily oral risedronate in patients taking NSAIDs: a randomized, double-blind, placebo-controlled trial.2005
Prescription-event monitoring study on 13,164 patients prescribed risedronate in primary care in England.2005
Effect of monitoring bone turnover markers on persistence with risedronate treatment of postmenopausal osteoporosis.2007
Efficacy and safety of risedronate sodium in treatment of postmenopausal osteoporosis.2005
Comparison of the effects of once-monthly versus once-daily risedronate in postmenopausal osteoporosis: a phase II, 6-month, multicenter, randomized, double-blind, active-controlled, dose-ranging study.2009
Renal safety of annual zoledronic acid infusions in osteoporotic postmenopausal women.2008
Prolonged antiresorptive activity of zoledronate: a randomized, controlled trial.2010
Intravenous zoledronic acid 5 mg in the treatment of postmenopausal women with low bone density previously treated with alendronate.2007
Zoledronic acid for the prevention of bone loss in postmenopausal women with low bone mass: a randomized controlled trial.2009
Use of oral bisphosphonates and the risk of aseptic osteonecrosis: a nested case-control study.2008
Efficacy and tolerability of once-monthly oral ibandronate (150 mg) and once-weekly oral alendronate (70 mg): additional results from the Monthly Oral Therapy With Ibandronate For Osteoporosis Intervention (MOTION) study.2009
Treatment preference for monthly oral ibandronate and weekly oral alendronate in women with postmenopausal osteoporosis: A randomized, crossover study (BALTO II).2008
Infusion of ibandronate once every 3 months effectively decreases bone resorption markers and increases bone mineral density in Chinese postmenopausal osteoporotic women: a 1-year study.2010
Comparative gastrointestinal safety of weekly oral bisphosphonates.2009
Alendronic acid produces greater effects than risedronic acid on bone density and turnover in postmenopausal women with osteoporosis : results of FACTS -international.2006
Osteoporosis and venous thromboembolism: a retrospective cohort study in the UK General Practice Research Database.2010
A single zoledronic acid infusion reduces bone resorption markers more rapidly than weekly oral alendronate in postmenopausal women with low bone mineral density.2007
Zoledronic acid and risedronate in the prevention and treatment of glucocorticoid-induced osteoporosis (HORIZON): a multicentre, double-blind, double-dummy, randomised controlled trial.2009
Oral bisphosphonates and risk of atrial fibrillation and flutter in women: a self-controlled case-series safety analysis.2009
Oral bisphosphonate-related osteonecrosis of the jaw: the first report in Asia.2010
Risk of severe gastrointestinal events in women treated with monthly ibandronate or weekly alendronate and risedronate.2009
Treatment with alendronate plus calcium, alendronate alone, or calcium alone for postmenopausal low bone mineral density.2007
Comparison of the effect of denosumab and alendronate on BMD and biochemical markers of bone turnover in postmenopausal women with low bone mass: a randomized, blinded, phase 3 trial.2009
Effects of denosumab on bone mineral density and bone turnover in postmenopausal women transitioning from alendronate therapy.2010
Effect of denosumab on bone density and turnover in postmenopausal women with low bone mass after long-term continued, discontinued, and restarting of therapy: a randomized blinded phase 2 clinical trial.
Effects of alendronate combined with hormone replacement therapy on osteoporotic postmenopausal Chinese women.2006
Elevations in serum and urinary calcium with parathyroid hormone (1-84) with and without alendronate for osteoporosis.2007
Osteoporosis treatment and atrial fibrillation: alendronate versus raloxifene.-- Not Found --
Comparison of alendronate and raloxifene in postmenopausal women with osteoporosis.2011
Alendronate/vitamin D3 70 mg/2800 IU with and without additional 2800 IU vitamin D3 for osteoporosis: results from the 24-week extension of a 15-week randomized, controlled trial.2009
Effects of two years of daily teriparatide treatment on BMD in postmenopausal women with severe osteoporosis with and without prior antiresorptive treatment.2008
Oral bisphosphonates and risk of subtrochanteric or diaphyseal femur fractures in a population-based cohort.
Alendronate with calcium and vitamin D supplementation is safe and effective for the treatment of decreased bone mineral density in HIV.2007
Risk of atrial fibrillation associated with use of bisphosphonates and other drugs against osteoporosis: a cohort study.
Use of bisphosphonates and raloxifene and risk of deep venous thromboembolism and pulmonary embolism.2010
Assessment of adherence to treatment of postmenopausal osteoporosis with raloxifene and/or alfacalcidol in postmenopausal Japanese women.2010
Effects of bazedoxifene on BMD and bone turnover in postmenopausal women: 2-yr results of a randomized, double-blind, placebo-, and active-controlled study.2008
Raloxifene for prevention of glucocorticoid-induced bone loss: a 12-month randomised double-blinded placebo-controlled trial.2011
Effect of raloxifene on stroke and venous thromboembolism according to subgroups in postmenopausal women at increased risk of coronary heart disease.2009
Raloxifene plus ossein-hydroxyapatite compound versus raloxifene plus calcium carbonate to control bone loss in postmenopausal women: a randomized trial.-- Not Found --
Head-to-head comparison of risedronate vs. teriparatide on bone turnover markers in women with postmenopausal osteoporosis: a randomised trial.2008
Occurrence of hypercalciuria in patients with osteoporosis treated with teriparatide.2007
Comparative effects of teriparatide and strontium ranelate on bone biopsies and biochemical markers of bone turnover in postmenopausal women with osteoporosis.2009
Effects of denosumab on bone mineral density and bone turnover in postmenopausal women.2008
Denosumab treatment effects on structural damage, bone mineral density, and bone turnover in rheumatoid arthritis: a twelve-month, multicenter, randomized, double-blind, placebo-controlled, phase II clinical trial.2008
Vascular events in healthy older women receiving calcium supplementation: randomised controlled trial.2008
Calcium supplementation and the risks of atherosclerotic vascular disease in older women: results of a 5-year RCT and a 4.5-year follow-up.2011
A new active vitamin D, ED-71, increases bone mass in osteoporotic patients under vitamin D supplementation: a randomized, double-blind, placebo-controlled clinical trial.2005

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