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Rheumatology (Oxford, England) Feb 2023Chronic nonbacterial osteomyelitis (CNO) is a rare inflammatory bone disease. The distinct CNO subtype that affects the anterior chest wall is descriptively named... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Chronic nonbacterial osteomyelitis (CNO) is a rare inflammatory bone disease. The distinct CNO subtype that affects the anterior chest wall is descriptively named sternocostoclavicular hyperostosis (SCCH) and mainly occurs in adults. Literature on CNO/SCCH is scattered and lacks diagnostic and therapeutic consensus.
METHODS
Systematic review and meta-analysis aiming to characterize clinical presentation and therapeutic modalities applied in adult CNO/SCCH patients. Untransformed numerical data and double-arcsine transformed proportional data were pooled in a random effects model in R-4.0.5; proportions were reported with 95% CI.
RESULTS
Forty studies were included, containing data on 2030 and 642 patients for aim 1 and 2, respectively. A female predisposition (67%, 95% CI 60, 73) and major diagnostic delay (5 years 95% CI 3, 7) were noted. Clinical presentation included chest pain (89%, 95% CI 79, 96) and swelling (79%, 95% CI 62, 91). Patients suffered from pustulosis palmoplantaris (53%, 95% CI 37, 68), arthritis (24%, 95% CI 11, 39) and acne (8%, 95% CI 4, 13). Inflammatory markers were inconsistently elevated. Autoantibody and HLA-B27 prevalence was normal, and histopathology unspecific. Increased isotope uptake (99%, 95% CI 96, 100) was a consistent imaging finding. Among manifold treatments, pamidronate and biologicals yielded good response in 83%, 95% CI 60, 98 and 56%, 95% CI 26, 85, respectively.
CONCLUSION
CNO/SCCH literature proves heterogeneous regarding diagnostics and treatment. Timely diagnosis is challenging and mainly follows from increased isotope uptake on nuclear examination. Biopsies, autoantibodies and HLA status are non-contributory, and biochemical inflammation only variably detected. Based on reported data, bisphosphonates and biologicals seem reasonably effective, but due to limitations in design and heterogeneity between studies the precise magnitude of their effect is uncertain. Fundamentally, international consensus seems imperative to advance clinical care for CNO/SCCH.
Topics: Adult; Humans; Female; Acquired Hyperostosis Syndrome; Delayed Diagnosis; Osteomyelitis; Psoriasis
PubMed: 35961032
DOI: 10.1093/rheumatology/keac443 -
Archives of Osteoporosis Feb 2022Pseudomyogenic hemangioendothelioma (PMH) can be a challenge for diagnosis and might be confused with other tumors, such as epithelioid sarcoma. Here we present a case... (Review)
Review
Pseudomyogenic hemangioendothelioma (PMH) can be a challenge for diagnosis and might be confused with other tumors, such as epithelioid sarcoma. Here we present a case and a systematic review of the literature to identify and discuss PMH treatment in primary bone involvement. A 25-year-old woman was referred for bone pain (10/10) in the left lower limb. Magnetic resonance imaging (MRI) showed multiple bone lesions (left femur, tibia, patella, ankle, and foot) with well-defined borders without signs of local aggressiveness. Positron Emission Tomography-Computed Tomography (PET-CT) showed multiple metabolic musculoskeletal lesions in the left lower limb. A CT scan-guided biopsy was performed. Histological and immunohistochemical findings confirmed the diagnosis of PMH. After treatment with intravenous pamidronate (90 mg/monthly), the patient had clinical improvement, mild pain 2/10 without the use of non-steroidal anti-inflammatory drugs or opiates. Follow-up was assessed by MRI and PET-CT. PET-CT showed metabolic resolution of most of the bone and muscular lesions and a significant improvement of the femoral lesion. MRI showed that the lesions in the left femur, tibia, and foot had a marked decrease in size without intravenous post-contrast enhancement and smaller lesions had disappeared. After a 3-year follow-up, PET-CT showed no metabolically active images. Literature review identified 31 records including 58 clinical cases of PMH with primary bone involvement and treatment description for qualitative analysis. Most lesions (69%) were treated by local excision or curettage. In addition, amputations were performed in a significant percentage of cases (20.7%). In the last years, mTOR inhibitors (n = 7) and anti-resorptive treatments (n = 4) were considered as alternative treatment options, especially in multifocal lesions.
Topics: Adult; Bone and Bones; Female; Hemangioendothelioma; Humans; Magnetic Resonance Imaging; Pamidronate; Positron Emission Tomography Computed Tomography
PubMed: 35106633
DOI: 10.1007/s11657-022-01062-4 -
Journal of Orthopaedic Science :... Feb 2024Periprosthetic bone loss following total hip arthroplasty (THA) threatens prosthesis stability. This systematic review and network meta-analysis aimed to compare the...
BACKGROUND
Periprosthetic bone loss following total hip arthroplasty (THA) threatens prosthesis stability. This systematic review and network meta-analysis aimed to compare the efficacy of anti-osteoporotic drugs for measures of hip function according to functional outcomes, periprosthetic femoral bone mineral density loss in each Gruen zone, and revision surgery after THA.
METHODS
The systematic search of six literature databases was conducted in December 2021 in accordance with PRISMA guidelines. Adult participants who underwent primary THA were included. A random-effects network meta-analysis was performed within a frequentist framework, and the confidence in the evidence for each outcome was evaluated using the CINeMA tool, which assessed the credibility of results from the network meta-analysis. We included 22 randomized controlled trials (1243 participants) comparing the efficacy and safety of bisphosphonates (including etidronate, clodronate, alendronate, risedronate, pamidronate, and zoledronate), denosumab, selective estrogen receptor modulator, teriparatide, calcium + vitamin D, calcium, and vitamin D. We defined the period for revision surgery as the final follow-up period.
RESULTS
Raloxifene, bisphosphonate, calcium + vitamin D, and denosumab for prosthetic hip function might have minimal differences when compared with placebos. The magnitude of the anti-osteoporotic drug effect on periprosthetic femoral bone loss varied across different Gruen zones. Bisphosphonate, denosumab, teriparatide might be more effective than placebo in Gruen zone 1 at 12 months after THA. Additionally, bisphosphonate might be more effective than placebo in Gruen zones 2, 5, 6, and 7 at 12 months after THA. Denosumab was efficacious in preventing bone loss in Gruen zones 6 and 7 at 12 months after THA. Teriparatide was likely to be efficacious in preventing bone loss in Gruen zone 7 at 12 months after THA. Raloxifene was slightly efficacious in preventing bone loss in Gruen zones 2 and 3 at 12 months after THA. Calcium was slightly efficacious in preventing bone loss in Gruen zone 5 at 12 months after THA. None of the studies reported revision surgery.
CONCLUSIONS
Bisphosphonate and denosumab may be effective anti-osteoporotic drugs for preventing periprosthetic proximal femoral bone loss due to stress shielding after THA, particularly in cementless proximal fixation stems, which are the most commonly used prostheses worldwide.
PubMed: 38342711
DOI: 10.1016/j.jos.2024.01.011 -
PloS One 2021Bisphosphonate drugs can be used to improve the outcomes of women with breast cancer. Whilst many meta-analyses have quantified their potential benefits for patients,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Bisphosphonate drugs can be used to improve the outcomes of women with breast cancer. Whilst many meta-analyses have quantified their potential benefits for patients, attempts at comprehensive quantification of potential adverse effects have been limited. We undertook a meta-analysis with novel methodology to identify and quantify these adverse effects.
METHODS
We systematically reviewed randomised controlled trials in breast cancer where at least one of the treatments was a bisphosphonate (zoledronic acid, ibandronate, pamidronate, alendronate or clodronate). Neoadjuvant, adjuvant and metastatic settings were examined. Primary outcomes were adverse events of any type or severity (excluding death). We carried out pairwise and network meta-analyses to estimate the size of any adverse effects potentially related to bisphosphonates. In order to ascertain whether adverse effects differed by individual factors such as age, or interacted with other common adjuvant breast cancer treatments, we examined individual-level patient data for one large trial, AZURE.
FINDINGS
We identified 56 trials that reported adverse data, which included a total of 29,248 patients (18,301 receiving bisphosphonate drugs versus 10,947 not). 24 out of the 103 different adverse outcomes analysed showed a statistically and practically significant increase in patients receiving a bisphosphonate drug compared with those not (2 additional outcomes that appeared statistically significant came only from small studies with low event counts and no clinical suspicion so are likely artifacts). Most of these 24 are already clinically recognised: 'flu-like symptoms, fever, headache and chills; increased bone pain, arthralgia, myalgia, back pain; cardiac events, thromboembolic events; hypocalcaemia and osteonecrosis of the jaw; as well as possibly stiffness and nausea. Oral clodronate appeared to increase the risk of vomiting and diarrhoea (which may also be increased by other bisphosphonates), and there may be some hepatotoxicity. Four additional potential adverse effects emerged for bisphosphonate drugs in this analysis which have not classically be recognised: fatigue, neurosensory problems, hypertonia/muscle spasms and possibly dysgeusia. Several symptoms previously reported as potential side effects in the literature were not significantly increased in this analysis: constipation, insomnia, respiratory problems, oedema or thirst/dry mouth. Individual patient-level data and subgroup analysis revealed little variation in side effects between women of different ages or menopausal status, those with metastatic versus non-metastatic cancer, or between women receiving different concurrent breast cancer therapies.
CONCLUSIONS
This meta-analysis has produced estimates for the absolute frequencies of a range of side effects significantly associated with bisphosphonate drugs when used by breast cancer patients. These results show good agreement with previous literature on the subject but are the first systematic quantification of side effects and their severities. However, the analysis is limited by the availability and quality of data on adverse events, and the potential for bias introduced by a lack of standards for reporting of such events. We therefore present a table of adverse effects for bisphosphonates, identified and quantified to the best of our ability from a large number of trials, which we hope can be used to improve the communication of the potential harms of these drugs to patients and their healthcare providers.
Topics: Adult; Aged; Aged, 80 and over; Bone Density Conservation Agents; Breast Neoplasms; Diphosphonates; Female; Humans; Middle Aged; Network Meta-Analysis; Randomized Controlled Trials as Topic; Young Adult
PubMed: 33544765
DOI: 10.1371/journal.pone.0246441 -
Current Osteoporosis Reports Oct 2020The goal of this systematic review is to analyze the effectiveness of bisphosphonates (BPs) to treat bone pain in children and adolescents who have diseases with...
PURPOSE OF REVIEW
The goal of this systematic review is to analyze the effectiveness of bisphosphonates (BPs) to treat bone pain in children and adolescents who have diseases with skeletal involvement.
RECENT FINDINGS
We included 24 studies (2 randomized controlled trials, 3 non-randomized controlled trials, 10 non-randomized open-label uncontrolled studies, 8 retrospective studies, and 1 study with design not specified). The majority of included studies assessed pain from a unidimensional approach, with pain intensity the most frequently evaluated dimension. Only 38% of studies used validated tools; visual analogue scale was the most frequently employed. BPs were used to alleviate bone pain in a wide variety of pediatrics conditions such as osteogenesis imperfecta, secondary osteoporosis, osteonecrosis related to chemotherapy, chronic non-bacterial osteitis, idiopathic juvenile osteoporosis, unresectable benign bone tumor, and cancer-related pain. Twenty of the 24 studies reported a positive effect of BPs for alleviating pain in different pathologies, but 58% of the studies were categorized as having high risk of bias. Intravenous BPs are helpful in alleviating bone pain in children and adolescents. It is advised that our results be interpreted with caution due to the heterogeneity of the doses used, duration of treatments, and types of pathologies included. In addition, this review shows the paucity of high-quality evidence in the available literature and further research is needed.
TRIAL REGISTRATION
Before the completion of this review, the protocol was registered to PROSPERO (International prospective register of systematic reviews), PROSPERO 2020 ID # CRD42020158316. Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020158316.
Topics: Antineoplastic Agents; Bone Density Conservation Agents; Bone Neoplasms; Cancer Pain; Child; Diphosphonates; Humans; Osteitis; Osteogenesis Imperfecta; Osteonecrosis; Osteoporosis; Pain; Pain Management; Pain Measurement; Treatment Outcome
PubMed: 32960409
DOI: 10.1007/s11914-020-00621-3 -
The Angle Orthodontist Jul 2020To investigate and synthesize systematically the evidence from animal studies pertaining to the effect of pharmacological agents on tooth movement relapse following...
OBJECTIVES
To investigate and synthesize systematically the evidence from animal studies pertaining to the effect of pharmacological agents on tooth movement relapse following cessation of orthodontic force application.
MATERIALS AND METHODS
An electronic search was conducted in seven online databases (including gray sources) without restrictions until the third week of April 2019, followed by a hand search in the reference lists of eligible articles. Controlled animal studies investigating the effect of pharmacological agents on tooth movement relapse following orthodontic treatment were selected. Relevant data were extracted from eligible studies and the risk of bias assessment was done using SYRCLE's risk of bias tool. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation tool.
RESULTS
The search identified 2354 records, of which 7 studies were deemed eligible for inclusion in the qualitative synthesis, with the majority presenting an unclear risk of bias. Orthodontic relapse was shown to decrease with the administration of pamidronate disodium, atorvastatin, aspirin, and chemically modified tetracycline-3. Inconsistent effects on relapse were observed after the use of simvastatin. The overall quality of retrieved evidence was assessed as low at best.
CONCLUSIONS
The available evidence shows that the investigated pharmacological agents may demonstrate variable effects on tooth movement relapse following cessation of orthodontic force. Additional evidence of higher quality is required to draw definitive conclusions on their effects and to make potential recommendations for clinical application.
Topics: Animals; Dental Care; Health Behavior; Humans; Recurrence; Tooth Movement Techniques
PubMed: 33378496
DOI: 10.2319/092619-613.1 -
Long-term impact of bone-modifying agents for the treatment of bone metastases: a systematic review.Supportive Care in Cancer : Official... Feb 2021Bone-modifying agents (BMAs) for bone metastases are commonly prescribed for many years even though randomized clinical trials are only 1-2 years in duration. A...
PURPOSE
Bone-modifying agents (BMAs) for bone metastases are commonly prescribed for many years even though randomized clinical trials are only 1-2 years in duration. A systematic review on the risk-benefit of BMA use for > 2 years in breast cancer or castrate-resistant prostate cancer was conducted.
METHODS
MEDLINE, Embase, and Cochrane databases were searched (1970-February 2019) for randomized and observational studies, and case series reporting on BMA efficacy (skeletal-related events and quality of life) and toxicity (osteonecrosis of the jaw, renal impairment, hypocalcemia, and atypical femoral fractures) beyond 2 years.
RESULTS
Of 2107 citations, 64 studies were identified. Three prospective and 9 retrospective studies were eligible. Data beyond 2 years was limited to subgroup analyses in all studies. Only one study (n = 181) reported skeletal-related event rates based on bisphosphonate exposure, with decreased rates from 27.6% (0-24 months) to 15.5% (> 24 months). None reported on quality of life. All 12 studies (denosumab (n = 948), zoledronate (n = 1036), pamidronate (n = 163), pamidronate-zoledronate (n = 522), ibandronate (n = 118)) reported ≥ 1 toxicity outcome. Seven bisphosphonate studies (n = 1077) and one denosumab study (n = 948) reported on osteonecrosis of the jaw. Across three studies (n = 1236), osteonecrosis of the jaw incidence ranged from 1 to 4% in the first 2 years to 3.8-18% after 2 years. Clinically significant hypocalcemia ranged from 1 to 2%. Severe renal function decline was ≤ 3%. Atypical femoral fractures were rare.
CONCLUSIONS
Evidence informing the use of BMA beyond 2 years is heterogeneous and based on retrospective analysis. Prospective randomized studies with greater emphasis on quality of life are needed.
PROSPERO REGISTRATION NUMBER
CRD42019126813.
Topics: Bone Density Conservation Agents; Bone Neoplasms; Breast Neoplasms; Diphosphonates; Female; Humans; Male; Observational Studies as Topic; Prospective Studies; Prostatic Neoplasms; Quality of Life; Randomized Controlled Trials as Topic; Retrospective Studies
PubMed: 32535678
DOI: 10.1007/s00520-020-05556-0 -
Head & Neck Dec 2019We investigated the efficacy of hyperbaric oxygen (HBO), low-intensity laser (LIL), and platelet-rich plasma (PRP) in the management of medication-related osteonecrosis...
BACKGROUND
We investigated the efficacy of hyperbaric oxygen (HBO), low-intensity laser (LIL), and platelet-rich plasma (PRP) in the management of medication-related osteonecrosis of the jaws (MRONJ).
METHODS
A literature search was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Two examiners independently assessed eligibility and risk of bias and extracted data.
RESULTS
There was improvement in 75.6% of the 41 patients submitted to HBO, with positive effects on pain relief and decreased size and number of lesions at a faster rate, with better effects when the drug was discontinued. For LIL, 158 (64.2%) of the 246 patients/sites improved the symptoms and 98 (39.8%) healed completely. Fourteen (17.3%) of the 81 patients treated with PRP significantly improved the symptoms and 65 (80.2%) completely healed.
CONCLUSIONS
These therapies served as safe and effective adjuvant modalities for MRONJ treatment. The lack of randomized clinical trials evidences the need for more high-quality investigations on the subject.
Topics: Aged; Aged, 80 and over; Bisphosphonate-Associated Osteonecrosis of the Jaw; Bone Density Conservation Agents; Combined Modality Therapy; Denosumab; Diphosphonates; Female; Humans; Hyperbaric Oxygenation; Jaw Diseases; Laser Therapy; Male; Middle Aged; Osteonecrosis; Pain Management; Pamidronate; Platelet-Rich Plasma; Randomized Controlled Trials as Topic
PubMed: 31502752
DOI: 10.1002/hed.25944 -
JBMR Plus Oct 2019Osteogenesis imperfecta (OI) is a rare genetic connective tissue disorder that results in bone fragility and deformity. Management is multi-disciplinary. Although...
Osteogenesis imperfecta (OI) is a rare genetic connective tissue disorder that results in bone fragility and deformity. Management is multi-disciplinary. Although pharmacologic intervention with bisphosphonates (BP) is a standard of care for individuals with severe OI, no consensus or reviews were found that focus on the effects of bisphosphonates on function and mobility. PubMed, CINAHL, Cochrane Library, Web of Science, and PEDro databases were searched for eligible articles for this review. Methodological quality was assessed using the Cochrane Collaboration's tool for risk of bias. Twenty-six studies (801 children) were reviewed and five showed a low risk of bias. Included studies showed significant variability among clinical protocols for administering BP. Randomized controlled trials did not demonstrate a significant improvement in function and mobility with oral BP administration, while non-randomized open-label uncontrolled studies demonstrated that oral and intravenous BP administration objectively improved function and mobility. The most common outcome measure used by the studies included in this review was the Bleck score. Effect sizes (d = 0.28 - 4.5) varied among studies. This systematic review also summarized the apparent confounding variables affecting results of previous studies and provided suggestions to improve the quality of future studies.
PubMed: 31687649
DOI: 10.1002/jbm4.10216 -
Annals of Palliative Medicine Nov 2021Bone metastasis is a common complication in patients with advanced malignant tumors and seriously impairs the quality of life of patients. Bisphosphonates are effective... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Bone metastasis is a common complication in patients with advanced malignant tumors and seriously impairs the quality of life of patients. Bisphosphonates are effective drugs for the treatment of bone metastasis pain. Incardronate disodium belongs to the 3rd generation of bisphosphonates. The efficacy and safety of bisphosphonates were explored using a systematic review and meta-analysis.
METHODS
The databases PubMed (2000 to August 2021), EMBASE (2000 to August 2021), Cochrane library (August 2021), and CNKI (China National Knowledge Infrastructure, 2000 to August 2021) were searched. Randomized controlled studies involving patients being treated with incardronate for bone metastasis pain were included in the literature search. After screening and risk of bias assessment based on the Cochrane Handbook for Systematic Reviews of Interventions, Stata 16.0 software was used for analysis.
RESULTS
The seven articles included in this study involved a total of 510 patients. Meta-analysis showed that there was no significant difference between incardronate and pamidronate disodium in the effectiveness of treating bone metastasis pain [odds ratio (OR) =1.03, 95% confidence interval (CI): 0.78-1.34, Z=0.188, P=0.851). The incidence of febrile adverse reactions from incardronate was significantly lower than pamidronate disodium (OR =0.58, 95% CI: 0.39-0.86, Z=-2.727, P=0.006). The total incidence of adverse reactions from incardronate was significantly lower than pamidronate disodium (OR =0.58, 95% CI: 0.40-0.85, Z=-2.851, P=0.004).
DISCUSSION
The use of incardronate in the treatment of bone metastasis pain due to malignant tumors had comparable efficacy to the second-generation bisphosphonate pamidronate disodium. However, incardronate had fewer adverse reactions than pamidronate disodium.
Topics: Bone Neoplasms; Cancer Pain; Diphosphonates; Humans; Pamidronate; Quality of Life
PubMed: 34872319
DOI: 10.21037/apm-21-3056