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The Cochrane Database of Systematic... May 2012Bisphosphonates are specific inhibitors of osteoclastic activity and used in the treatment of patients with multiple myeloma (MM). While bisphosphonates are shown to be... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Bisphosphonates are specific inhibitors of osteoclastic activity and used in the treatment of patients with multiple myeloma (MM). While bisphosphonates are shown to be effective in reducing vertebral fractures and pain, their role in improving overall survival (OS) remains unclear. This is an update of a Cochrane review first published in 2002 and previously updated in 2010.
OBJECTIVES
To assess the evidence related to benefits and harms associated with use of various types of bisphosphonates (aminobisphosphonates versus nonamino bisphosphonates) in the management of patients with MM. Our primary objective was to determine whether adding bisphosphonates to standard therapy in MM improves OS and progression-free survival (PFS), and decreases skeletal-related morbidity. Our secondary objectives were to determine the effects of bisphosphonates on pain, quality of life, incidence of hypercalcemia, incidence of bisphosphonate-related gastrointestinal toxicities, osteonecrosis of jaw and hypocalcemia.
SEARCH METHODS
We searched MEDLINE, LILACS, EMBASE (December 2009 to October 2011) and the Cochrane Controlled Trials Register (all years, latest Issue September 2011) to identify all randomized trials in MM up to October 2011 using a combination of text and MeSH terms. We also handsearched relevant meeting proceedings (December 2009 to October 2011).
SELECTION CRITERIA
Any randomized controlled trial (RCT) assessing the role of bisphosphonates and observational studies or case reports examining bisphosphonate-related osteonecrosis of the jaw in patients with MM were eligible for inclusion.
DATA COLLECTION AND ANALYSIS
Two review authors extracted the data. Data were pooled and reported as hazard ratio (HR) or risk ratio (RR) under a random-effects model. Statistical heterogeneity was explored using metaregression.
MAIN RESULTS
In this update, we included 2 studies (2464 patients) that were not part of our last Cochrane review published in 2010. In this review we included 16 RCTs comparing bisphosphonates with either placebo or no treatment and 4 RCTs with a different bisphosphonate as a comparator. The 20 included RCTs enrolled 6692 patients. Overall methodological quality of reporting was moderate. Thirty per cent (6/20) of trials reported the method of generating the randomization sequence. Forty per cent (8/20) of trials had adequate allocation concealment. Withdrawals and dropouts were described in 60% (12/20) of trials. Pooled results showed no direct effect of bisphosphonates on OS compared with placebo or no treatment (HR 0.96, 95% CI 0.82 to 1.13; P = 0.64). However, there was a statistically significant heterogeneity among the included RCTs (I(2) = 55%, P = 0.01) for OS. To explain this heterogeneity we performed a metaregression assessing the relationship between bisphosphonate potency and improvement in OS, which found indicating an OS benefit with zoledronate (P = 0.058). This provided a further rationale for performing network meta-analyses of the various types of bisphosphonates that were not compared head to head in RCTs. Results from network meta-analyses showed superior OS with zoledronate compared with etidronate (HR 0.43, 95% CI 0.16 to 0.86) and placebo (HR 0.61, 95% CI 0.28 to 0.98). However, there was no difference between zoledronate and other bisphosphonates. Pooled analysis did not demonstrate a beneficial effect of bisphosphonates compared with placebo or no treatment in improving PFS (HR 0.70, 95% CI 0.41 to 1.19; P = 0.18) There was no heterogeneity among trials reporting PFS estimates (I(2) = 35%, P = 0.20).Pooled analysis demonstrated a beneficial effect of bisphosphonates compared with placebo or no treatment on prevention of pathological vertebral fractures (RR 0.74, 95% CI 0.62 to 0.89; I(2) = 7%), skeletal-related events (SRE) (RR 0.80, 95% CI 0.72 to 0.89; I(2) = 2%) and amelioration of pain (RR 0.75, 95% CI 0.60 to 0.95; I(2) = 63%). The network meta-analysis did not show any difference in the incidence of osteonecrosis of the jaw (5 RCTs, 3198 patients) between bisphosphonates. Rates of osteonecrosis of the jaw in observational studies (9 studies, 1400 patients) ranged from 0% to 51%. The pooled results (6 RCTs, 1689 patients) showed no statistically significant increase in frequency of gastrointestinal symptoms with the use of bisphosphonates compared with placebo or no treatment (RR 1.23, 95% CI 0.95 to 1.60; P = 0.11).The pooled results (3 RCTs, 1002 patients) showed no statistically significant increase in frequency of hypocalcemia with the use of bisphosphonates compared with placebo or no treatment (RR 2.19, 95% CI 0.49 to 9.74). The network meta-analysis did not show any differences in the incidence of hypocalcemia, renal dysfunction and gastrointestinal toxicity between the bisphosphonates used.
AUTHORS' CONCLUSIONS
Use of bisphosphonates in patients with MM reduces pathological vertebral fractures, SREs and pain. Assuming a baseline risk of 20% to 50% for vertebral fracture without treatment, between 8 and 20 MM patients should be treated to prevent vertebral fracture(s) in one patient. Assuming a baseline risk of 31% to 76% for pain amelioration without treatment, between 5 and 13 MM patients should be treated to reduce pain in one patient. With a baseline risk of 35% to 86% for SREs without treatment, between 6 and 15 MM patients should be treated to prevent SRE(s) in one patient. Overall, there were no significant adverse effects associated with the administration of bisphosphonates identified in the included RCTs. We found no evidence of superiority of any specific aminobisphosphonate (zoledronate, pamidronate or ibandronate) or nonaminobisphosphonate (etidronate or clodronate) for any outcome. However, zoledronate appears to be superior to placebo and etidronate in improving OS.
Topics: Antineoplastic Agents; Bone Density Conservation Agents; Bone Diseases; Clodronic Acid; Diphosphonates; Etidronic Acid; Fractures, Bone; Humans; Imidazoles; Multiple Myeloma; Pamidronate; Randomized Controlled Trials as Topic; Zoledronic Acid
PubMed: 22592688
DOI: 10.1002/14651858.CD003188.pub3 -
Dental Press Journal of Orthodontics Oct 2015Orthodontic anchorage is one of the most challenging aspects of Orthodontics. Preventing undesired movement of teeth could result in safer and less complicated... (Review)
Review
INTRODUCTION
Orthodontic anchorage is one of the most challenging aspects of Orthodontics. Preventing undesired movement of teeth could result in safer and less complicated orthodontic treatment. Recently, several reviews have been published about the effects of different molecules on bone physiology and the clinical side effects in Orthodontics. However, the effects of local application of these substances on the rate of orthodontic tooth movement have not been assessed.
OBJECTIVES
The aim of this research was to analyze the scientific evidence published in the literature about the effects of different molecules on orthodontic anchorage.
METHODS
The literature was systematically reviewed using PubMed/Medline, Scopus and Cochrane databases from 2000 up to July 31st, 2014. Articles were independently selected by two different researchers based on previously established inclusion and exclusion criteria, with a concordance Kappa index of 0.86. The methodological quality of the reviewed papers was performed.
RESULTS
Search strategy identified 270 articles. Twenty-five of them were selected after application of inclusion/exclusion criteria, and only 11 qualified for final analysis. Molecules involved in orthodontic anchorage were divided into three main groups: osteoprotegerin (OPG), bisphosphonates (BPs) and other molecules (OMs).
CONCLUSIONS
Different drugs are able to alter the bone remodeling cycle, influencing osteoclast function and, therefore, tooth movement. Thus, they could be used in order to provide maximal anchorage while preventing undesired movements. OPG was found the most effective molecule in blocking the action of osteoclasts, thereby reducing undesired movements.
Topics: Acetylcysteine; Animals; Anti-Inflammatory Agents; Antioxidants; Bone Remodeling; Celecoxib; Clodronic Acid; Diclofenac; Diphosphonates; Humans; Imidazoles; Interferon-gamma; Isoxazoles; Lactones; Mice; Orthodontic Anchorage Procedures; Osteoclasts; Osteoprotegerin; Pamidronate; Rats; Resveratrol; Stilbenes; Sulfones; Tooth Mobility; Tooth Movement Techniques; Zoledronic Acid
PubMed: 26560822
DOI: 10.1590/2177-6709.20.5.058-065.oar -
Seminars in Arthritis and Rheumatism Apr 2011To examine the efficacy of available drugs in undifferentiated spondyloarthritis (u-SpA). (Review)
Review
OBJECTIVE
To examine the efficacy of available drugs in undifferentiated spondyloarthritis (u-SpA).
METHODS
Systematic review of studies retrieved from Medline (1961-July 2009), Embase (1961-July 2009), and Cochrane Library (up to July 2009). A complementary hand search was also performed. The selection criteria were as follows: (population) u-SpA patients; (intervention) nonsteroidal anti-inflammatory agents, disease-modifying antirheumatic drugs, anti-tumor necrosis factor α, anakinra, abatacept, biphosphonates, or thalidomide; (outcome) pain, function, structural damage and quality of life; (study design) randomized controlled trials (RCT), cohort studies, and case reports; (level of evidence) according to The Oxford Centre for Evidence-based Medicine (update 2009). An additional narrative review was performed to analyze the effects of drug therapies in patients with spondyloarthritis according new Assessment of Spondyloarthritis International Society criteria.
RESULTS
The following 7 studies were included: 2 RCT, 1 cohort study, and 4 case reports, which included 117 patients with u-SpA (mostly young men). No evidence related to the effect of nonsteroidal anti-inflammatory agents or disease-modifying antirheumatic drugs on u-SpA patients was found. Infliximab and etanercept showed some benefit regarding clinical outcomes, function, and quality of life. Two RCT reported important benefit of infliximab and adalimumab also in patients with predominantly axial spondyloarthritis. Rifampicin plus doxycycline improved some clinical outcomes but ciprofloxacin had no benefit. Anecdotal positive evidence was reported with pamidronate. No serious adverse events were reported in the retrieved studies.
CONCLUSION
Low-quality evidence suggests a benefit of tumor necrosis factor α blockers in u-SpA and good-quality evidence in predominantly axial spondyloarthritis. The use of antibiotics remains controversial. High-quality trials are needed to definitively assess the effect of available drugs in these patients.
Topics: Anti-Bacterial Agents; Antibodies, Monoclonal; Antirheumatic Agents; Etanercept; Humans; Immunoglobulin G; Infliximab; Receptors, Tumor Necrosis Factor; Spondylarthropathies; Treatment Outcome; Tumor Necrosis Factor-alpha
PubMed: 20832101
DOI: 10.1016/j.semarthrit.2010.06.003 -
BMJ Clinical Evidence Sep 2007The 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 question: What are the effects of treatments to prevent fractures in postmenopausal women? We searched: Medline, Embase, The Cochrane Library and other important databases up to January 2007. (BMJ 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 61 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, etidronate, exercise, hip protectors, hormone replacement therapy, ibandronate, multifactorial non-pharmacological interventions, pamidronate, parathyroid hormone, raloxifene, risedronate, strontium ranelate, vitamin D, and vitamin D analogues.
Topics: Bone Density; Calcium, Dietary; Etidronic Acid; Female; Fractures, Bone; Humans; Managed Care Programs; Osteoporotic Fractures; Postmenopause; Vitamin D
PubMed: 19450301
DOI: No ID Found -
The Cochrane Database of Systematic... Mar 2015Pain is one of the most common symptoms in children and young people (CYP) with life-limiting conditions (LLCs) which include a wide range of diagnoses including cancer.... (Review)
Review
BACKGROUND
Pain is one of the most common symptoms in children and young people (CYP) with life-limiting conditions (LLCs) which include a wide range of diagnoses including cancer. The current literature indicates that pain is not well managed, however the evidence base to guide clinicians is limited. There is a clear need for evidence from a systematic review to inform prescribing.
OBJECTIVES
To evaluate the evidence on the effectiveness of different pharmacological interventions used for pain in CYP with LLCs.
SEARCH METHODS
The following electronic databases were searched up to December 2014: CENTRAL (in the Cochrane Library), MEDLINE, EMBASE, PsycINFO and CINAHL. In addition, we searched conference proceedings and reference lists of included studies. For completeness, we also contacted experts in the field. No language restrictions were applied.
SELECTION CRITERIA
Randomised controlled trials (RCTs), quasi-randomised studies and other studies that included a clearly defined comparator group were included. The studies investigated pharmacological treatments for pain associated with LLCs in CYP. The treatment included those specifically developed to treat pain and those that acted as an adjuvant, where the treatment was not primarily developed to treat pain but has pain relieving properties. The LLC was identified by its inclusion in the Richard Hain Directory of LLCs.
DATA COLLECTION AND ANALYSIS
Citations were screened by five review authors. Data were extracted by one review author and checked by a second. Two review authors assessed the risk of bias of included studies. A sufficient number of studies using homogeneous outcomes was not identified so a meta-analysis was not possible.
MAIN RESULTS
We identified 24,704 citations from our database search. Nine trials with 379 participants fulfilled our inclusion criteria. Participants had cerebral palsy (CP) in five of the studies and osteogenesis imperfecta (OI) in the other four. Participants across the trials ranged in age from 2 to 19 years. All studies, apart from one cross-over trial, were parallel designed RCTs. Three of the trials on CP evaluated intrathecal baclofen (ITB) and two botulinum toxin A (BoNT-A). All of the OI trials evaluated the use of bisphosphonates (two alendronate and one pamidronate). No trials were identified that evaluated a commonly used analgesic in this patient group. Pain was a secondary outcome in five of the eight identified studies. Overall the quality of the trials was mixed. Only one study involved over 100 participants.For the two ITB studies for pain in CP, in the same study population but assessed at different time points in their disease, both found an effect on pain favouring the intervention compared to the control group (standard care or placebo) (mean difference (MD) 4.20, 95% confidence interval (CI) 2.15 to 6.25; MD 26.60, 95% CI 2.61 to 50.59, respectively). In these studies most of the adverse events related to the procedure or device for administration rather than the drug, such as swelling at the pump site. In one trial there were also eight serious adverse effects; these included difficulty swallowing and an epileptic seizure. The trial did not state if these occurred in the intervention group. At follow-up in both BoNT-A trials there was no evidence of a difference in pain between the trial arms among CP participants. The adverse events in the BoNT-A trials mostly involved those who received the intervention drug and involved seizures. Gastrointestinal problems were the most frequent adverse event in those who received alendronate. The trial investigating pamidronate found no evidence of a difference in pain compared to the control group. No adverse events were reported in this trial.
AUTHORS' CONCLUSIONS
Published, controlled evidence on the pharmacological interventions for pain in CYP with LLCs is limited. The evidence that is currently available evaluated pain largely as a secondary outcome and the drugs used were all adjuvants and not always commonly used in general paediatric palliative care for pain. Based on current data this systematic review is unable to determine the effects of pharmacological interventions for pain for CYP with LLCs. Future trials with larger populations should examine the effects of the drugs commonly used as analgesics; with the rising prevalence of many LLCs this becomes more necessary.
Topics: Adolescent; Alendronate; Baclofen; Botulinum Toxins, Type A; Cerebral Palsy; Child; Child, Preschool; Diphosphonates; Gastrointestinal Diseases; Humans; Injections, Spinal; Neuromuscular Agents; Osteogenesis Imperfecta; Pain; Pamidronate; Seizures; Young Adult
PubMed: 25768935
DOI: 10.1002/14651858.CD010750.pub2 -
The Cochrane Database of Systematic... 2001Osteoporosis is a disorder of bone mineralization that can lead to reduced bone mineral density and an increased risk for fractures. It is found in about one third of... (Review)
Review
BACKGROUND
Osteoporosis is a disorder of bone mineralization that can lead to reduced bone mineral density and an increased risk for fractures. It is found in about one third of adults with cystic fibrosis. Bisphosphonates have been shown to increase bone mineral density and decrease the risk of new fractures in post-menopausal women and in patients receiving long-term oral corticosteroids.
OBJECTIVES
To assess the effects of bisphosphonates on the frequency of fractures, bone mineral density, quality of life, adverse events, study withdrawals, and survival in people with cystic fibrosis.
SEARCH STRATEGY
Relevant trials were identified in the Cochrane Cystic Fibrosis and Genetic Disorders Review Group specialised register of controlled trials by the centre co-ordinator. This register comprises references identified from comprehensive electronic database searches, handsearching of relevant journals and of conference proceedings. Additional sources such as abstract books for osteoporosis conferences were hand-searched by the authors. The most recent search(es) were conducted in February 2001.
SELECTION CRITERIA
Randomised controlled trials of at least six months duration that studied the use of bisphosphonates in adults with cystic fibrosis were considered for inclusion. Outcomes included one of the following: fractures, bone mineral density, quality of life, adverse events, study withdrawals, or survival.
DATA COLLECTION AND ANALYSIS
Information on study design, participants, interventions, and outcomes was abstracted from included studies. Two independent reviewers abstracted the information. Authors were contacted to obtain missing data.
MAIN RESULTS
Two trials were identified in the trials search. Both trials with a total of 65 participants were included in this review. One study examined patients without lung transplants while the other study included only patients who had received a lung transplant. The intervention in both trials was pamidronate administered intravenously every three months. In patients who had not received a lung transplant, bone mineral density at axial sites was increased after six months of treatment in the treatment group compared to the control group (lumbar spine WMD [for % change BMD] = 5.8 [95% CI 4.63 to 6.97], hip WMD = 3.00 [95% CI 1.99 to 4.01]). There was a small decrease in forearm bone mineral density in patients treated with pamidronate versus controls (distal forearm WMD = -1.70 [95% CI -2.46 to -0.94]). Bone pain was the most common adverse event occurring in 11/15 participants not using corticosteroids (RR = 24.40, 95% CI 1.57 to 381.48). There was no difference in survival (RR = 1.00, 95% CI 0.83 to 1.20), although this may be due to short follow-up and small sample size. In patients who had received a lung transplant, the number of new fractures did not change with the use of pamidronate (non-vertebral RR = 3.38 [95% CI 0.39 to 29.29], vertebral RR = 0.56 [95% CI 0.17 to 1.89]). Bone mineral density at axial sites was increased after two years of treatment in the treatment group compared to the control group (lumbar spine WMD [for % change in BMD] = 6.20 [95% CI 4.28 to 8.12], femur WMD = 7.90 [95% CI 5.78 to 10.03]).
REVIEWER'S CONCLUSIONS
Intravenous pamidronate increases bone mineral density at axial sites in people with cystic fibrosis, although it can cause severe bone pain in patients not receiving corticosteroids. Additional studies in larger populations are needed to determine the effect on fracture rate and survival.
Topics: Bone Density; Cystic Fibrosis; Diphosphonates; Fractures, Bone; Humans; Lung Transplantation; Osteoporosis; Randomized Controlled Trials as Topic
PubMed: 11687132
DOI: 10.1002/14651858.CD002010 -
Cancer Management and Research 2018Compared with application of bone-modifying agents (BMAs) every 4 weeks, it is unclear whether 12-weekly de-escalated therapy can be used as a substitute strategy.
BACKGROUND
Compared with application of bone-modifying agents (BMAs) every 4 weeks, it is unclear whether 12-weekly de-escalated therapy can be used as a substitute strategy.
METHODS
A systematic search of PubMed, EMBASE, and the Cochrane Register of Controlled Trials until November 22, 2017, was performed. Randomized controlled trials (RCTs) were included to assess skeletal-related event (SRE) rates, adverse events, and bone turnover biomarkers, comparing 12-weekly de-escalated treatments with standard 4-weekly dosage regimens. Risk ratios (RRs) with 95% CIs were pooled in fixed-effect meta-analyses.
RESULTS
A total of eight citations were eligible comprising 2,878 patients: zoledronate (three studies, 2,650 patients), pamidronate (two studies, 68 patients), and denosumab (three studies, 160 patients). Summary RR (0.98; 95% CI 0.87-1.12; =0.82) for SRE rates between de-escalated and standard arms was produced when seven low risk of bias trials (695 patients) were pooled, and results without statistical significance also appeared in the analysis of adverse events and bone turnover biomarkers. Due to the limited sample size and methodological differences, the data for skeletal morbidity rates (SMRs), time to first SRE, serum C-telopeptide (sCTx) levels, and hypocalcemia were not combined, but systematic review still obtained similar indistinguishableness.
CONCLUSION
In this meta-analysis of randomized clinical trials, the results "appeared" to show non-inferiority of the 12-weekly treatment. Due to the difference in available data, the results for bisphosphonates are more solid than for the receptor activator of nuclear factor-κB ligand (RANKL) antibodies.
PubMed: 30288112
DOI: 10.2147/CMAR.S176811 -
The Canadian Journal of Urology Aug 2006A systematic review of randomized controlled trials (RCTs) was performed to assess the benefits of bisphosphonate therapy in men with hormone-refractory prostate cancer... (Review)
Review
PURPOSE
A systematic review of randomized controlled trials (RCTs) was performed to assess the benefits of bisphosphonate therapy in men with hormone-refractory prostate cancer (HRPC).
METHODS
The literature was searched to identify RCTs or meta-analyses comparing treatment with bisphosphonates to placebo or no treatment.
RESULTS
Ten trials that studied clodronate (five trials, 404 patients), pamidronate (two trials, 350 patients), alendronate (one trial, 49 patients), etidronate (one trial, 51 patients), and zoledronic acid (one trial, 643 patients) in men with HRPC and bone metastases met the eligibility criteria. Pain response was the most frequently reported primary outcome (eight trials). Only the smallest trial demonstrated a statistically significant improvement in pain, but other non-statistically significant trends and subgroup analyses showing improvement in pain were observed in six clodronate and pamidronate trials. Three trials reported skeletal-related events (SREs). A trial studying zoledronic acid reported a statistically and clinically significant reduction in the number of patients having at least one SRE; however, there were higher rates of some adverse effects, and quality of life was not improved.
CONCLUSION
Zoledronic acid appears to reduce the number of patients having at least one SRE in men with bone metastases from HRPC that are causing minimal or no pain. This benefit should be weighed against the associated toxicities, and the neutral effect on quality of life. Bisphosphonates may reduce bone pain in men with HRPC, but the evidence is less robust. Further investigations to identify the role of bisphosphonates alone and in combination with other therapies proven effective for men with HRPC are warranted.
Topics: Diphosphonates; Humans; Male; Prostatic Neoplasms; Randomized Controlled Trials as Topic
PubMed: 16952326
DOI: No ID Found -
The Cochrane Database of Systematic... Apr 2012Osteoporosis is a bone mineralisation disorder occurring in about one third of adults with cystic fibrosis. Bisphosphonates can increase bone mineral density and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Osteoporosis is a bone mineralisation disorder occurring in about one third of adults with cystic fibrosis. Bisphosphonates can increase bone mineral density and decrease the risk of new fractures in post-menopausal women and people receiving long-term oral corticosteroids.
OBJECTIVES
To assess the effects of bisphosphonates on the frequency of fractures, bone mineral density, quality of life, adverse events, trial withdrawals, and survival in people with cystic fibrosis.
SEARCH METHODS
We searched the Cystic Fibrosis and Genetic Disorders Group Trials Register of references (identified from electronic database searches and handsearches of journals and abstract books) on 15 February 2012.Additional searches of PubMed were performed on 14 May 2011.
SELECTION CRITERIA
Randomised controlled trials of at least six months duration studying bisphosphonates in people with cystic fibrosis.
DATA COLLECTION AND ANALYSIS
Two authors independently selected trials and extracted data. Trial investigators were contacted to obtain missing data.
MAIN RESULTS
Nine trials were identified and seven (with a total of 237 adult participants) were included.Data were combined (when available) from six included studies in participants without a lung transplant. Data showed that there was no significant reduction in fractures between treatment and control groups at 12 months, odds ratio 0.72 (95% confidence interval 0.13 to 3.80). No fractures were reported in studies with follow-up at 24 months. However, in patients taking bisphosphonates after six months the percentage change in bone mineral density increased at the lumbar spine, mean difference 4.61 (95% confidence interval 3.90 to 5.32) and at the hip or femur, mean difference 3.35 (95% confidence interval 1.63 to 5.07); but did not significantly change at the distal forearm, mean difference -0.49 (95% confidence interval -2.42 to 1.45). In patients taking bisphosphonates, at 12 months the percentage change in bone mineral density increased at the lumbar spine, mean difference 6.10 (95% confidence interval 5.10 to 7.10) and at the hip or femur, mean difference 4.35 (95% confidence interval 2.99 to 5.70). At 24 months, in patients treated with bisphosphonates the percentage change in bone mineral density also increased at the lumbar spine, mean difference 5.49 (95% confidence interval 4.38 to 6.60) and at the hip or femur, mean difference 6.05 (95% confidence interval 3.74 to 8.36). There was clinical heterogeneity between studies and not all studies reported all outcomes. Bone pain was the most common adverse event with intravenous agents. Flu-like symptoms were also increased in those taking bisphosphonates.In participants with a lung transplant (one study), intravenous pamidronate did not change the number of new fractures. At axial sites, bone mineral density increased with treatment compared to controls: percentage change in bone mineral density at lumbar spine, mean difference 6.20 (95% confidence interval 4.28 to 8.12); and femur mean difference 7.90 (95% confidence interval 5.78 to 10.02).
AUTHORS' CONCLUSIONS
Oral and intravenous bisphosphonates increase bone mineral density in people with cystic fibrosis. Severe bone pain and flu-like symptoms may occur with intravenous agents. Additional trials are needed to determine if bone pain is more common or severe (or both) with the more potent zoledronate and if corticosteroids ameliorate or prevent these adverse events. Additional trials are also required to further assess gastrointestinal adverse effects associated with oral bisphosphonates. Trials in larger populations are needed to determine effects on fracture rate and survival.
Topics: Adult; Bone Density; Bone Density Conservation Agents; Cystic Fibrosis; Diphosphonates; Female; Fractures, Bone; Humans; Lung Transplantation; Male; Osteoporosis; Randomized Controlled Trials as Topic
PubMed: 22513903
DOI: 10.1002/14651858.CD002010.pub3 -
Clinical Rheumatology Jun 2008Up to now, there is no uniformly accepted treatment for avascular necrosis (AN) that alleviates pain and retards its progression. The aim of clinical and surgical... (Review)
Review
Up to now, there is no uniformly accepted treatment for avascular necrosis (AN) that alleviates pain and retards its progression. The aim of clinical and surgical treatments is usually only to improve blood support in the avascular area. The objective of the present study was to make a systematic review of the use of bisphosphonates in the treatment of AN. Studies in which bisphosphonate was used for the treatment of AN were researched through the MEDLINE databases (from 1966 to 2007) and the Cochrane Central Register of Controlled Trials and using the following terms: "avascular necrosis," "aseptic necrosis," "bisphosphonates," "alendronate," "pamidronate," "zoledronate," and "risedronate". Only seven articles that met the previously established criteria were obtained from MEDLINE, and none were obtained from the Cochrane Central Register of Controlled Trials. Of these seven articles, two were randomized clinical trials and five were prospective comparative studies; one of them corresponded to an extension of a previous study. The present review demonstrates that there are no controlled and double-blind studies about the efficacy of bisphosphonates in the treatment of AN. Therefore, the data are still insufficient for justifying its use for this indication. On the other hand, noncontrolled studies appear to demonstrate favorable results, particularly in diminishing pain, improving mobility, and lowering the incidence of articular collapse, which justifies new studies being developed in this area.
Topics: Bone Density Conservation Agents; Diphosphonates; Humans; Osteonecrosis
PubMed: 18270760
DOI: 10.1007/s10067-008-0861-9