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Osteoporosis International : a Journal... Jun 2021Bisphosphonates can inhibit osteoclast-mediated bone resorption, prevent bone loss, and reduce the risk of osteoporotic fractures. Our meta-analysis of studies shows... (Meta-Analysis)
Meta-Analysis
The efficacy and safety of bisphosphonate analogs for treatment of osteoporosis after spinal cord injury: a systematic review and meta-analysis of randomized controlled trials.
UNLABELLED
Bisphosphonates can inhibit osteoclast-mediated bone resorption, prevent bone loss, and reduce the risk of osteoporotic fractures. Our meta-analysis of studies shows that early bisphosphonate administration after SCI was safe and beneficial to the BMD of the total hip and lumbar spine at 12 months.
INTRODUCTION
Rapid bone loss in the early stages of spinal cord injury (SCI) leads to an increased risk of osteoporotic fracture. A meta-analysis was conducted to assess the efficacy and safety of bisphosphonates for the treatment of osteoporosis after SCI.
METHODS
A literature search of the PubMed, EMBASE, Cochrane Library, and Web of Science databases identified nine randomized controlled trials with 206 individuals. This meta-analysis was performed using a random-effects model. The primary outcome was the percent change in bone mineral density (BMD) of the total hip, distal femur, and lumbar spine from baseline to 12 months. Bone turnover markers were secondary outcomes. The incidences of adverse events were assessed in order to evaluate safety.
RESULTS
There were significant differences in BMD of the total hip and lumbar spine or serum C-terminal telopeptide between the bisphosphonate and control groups but no difference in adverse events. The percent change in BMD of the distal femur and serum type 1 procollagen N-terminal peptide from baseline to 12 months was not superior in the treatment groups. Osteoclast-mediated bone resorption was inhibited by bisphosphonate administration. Subgroup analyses of participants treated with zoledronate at different sites revealed a beneficial effect on BMD of the total hip and lumbar spine but not the distal femur.
CONCLUSION
Early bisphosphonate administration after SCI was safe and beneficial to the BMD of the total hip and lumbar spine at 12 months.
Topics: Bone Density; Bone Density Conservation Agents; Diphosphonates; Humans; Osteoporosis; Randomized Controlled Trials as Topic; Spinal Cord Injuries
PubMed: 33386876
DOI: 10.1007/s00198-020-05807-0 -
European Review For Medical and... Dec 2020The purpose of this study was to conduct a systematic review and meta-analysis analyzing the efficacy of zoledronic acid in improving outcomes with percutaneous... (Meta-Analysis)
Meta-Analysis
Efficacy of zoledronic acid with percutaneous kyphoplasty/vertebroplasty in the treatment of osteoporotic vertebral compression fractures: a systematic review and meta-analysis.
OBJECTIVE
The purpose of this study was to conduct a systematic review and meta-analysis analyzing the efficacy of zoledronic acid in improving outcomes with percutaneous vertebroplasty (PVP) and percutaneous kyphoplasty (PKP) surgeries for osteoporotic vertebral compression fracture (OVCF).
MATERIALS AND METHODS
We electronically searched the databases of PubMed, Embase, ScienceDirect, CENTRAL, and Google Scholar up to 15th September 2020. All types of studies assessing the use of zoledronic acid with PKP/PVP surgeries were included.
RESULTS
Seven studies were included. On meta-analysis of data from five studies reporting bone mineral density (BMD) as g/cm2, we found a statistically significant increase in BMD in the zoledronic group (MD: 0.14; 95% CI: 0.07, 0.21, I2=97%; p<0.001). On pooled analysis of two studies reporting T scores, a similar result in favour of the zoledronic acid group was noted (MD: 0.60; 95% CI: 0.23, 0.98, I2=76%; p=0.002). We also found a statistically significant reduction in pain scores (MD: -1.23; 95% CI: -1.59, -0.86, I2=97%; p<0.00001), ODI scores (MD: -9.54; 95% CI: -12.76, -6.31, I2=95%; p<0.00001) and serum type I procollagen peptide (CTX) levels (MD: -0.19; 95% CI: -0.25, -0.12, I2=98%; p<0.00001) with zoledronic acid as compared to control. Our analysis also found a significantly reduced risk of further vertebral fractures in patients receiving zoledronic acid as compared to control (RR: 0.17; 95% CI: 0.07, 0.39, I2=0%; p<0.00001).
CONCLUSIONS
Our review indicates that the use of once-yearly zoledronic acid in the peri-operative period of PVP/PKP procedures for patients with OVCF leads to significant improvement of BMD, reduced pain scores, better ODI scores, and reduced incidence of further vertebral fractures. Our results have clinical significance as it encourages the use of zoledronic acid for such patients for better clinical outcomes.
Topics: Combined Modality Therapy; Humans; Osteoporotic Fractures; Treatment Outcome; Vertebroplasty; Zoledronic Acid
PubMed: 33336756
DOI: 10.26355/eurrev_202012_24030 -
Bone Feb 2021Bone turnover is the cellular machinery responsible for bone integrity and strength and, in the clinical setting, it is assessed using bone turnover markers (BTMs).... (Review)
Review
BACKGROUND
Bone turnover is the cellular machinery responsible for bone integrity and strength and, in the clinical setting, it is assessed using bone turnover markers (BTMs). Acute exercise can induce mechanical stress on bone which is needed for bone remodelling, but to date, there are conflicting results in regards to the effects of varying mechanical stimuli on BTMs.
OBJECTIVES
This systematic review examines the effects of acute aerobic, resistance and impact exercises on BTMs in middle and older-aged adults and examines whether the responses are determined by the exercise mode, intensity, age and sex.
METHODS
We searched PubMed, SCOPUS, Web of Science and EMBASE up to 22nd April 2020. Eligibility criteria included randomised controlled trials (RCTs) and single-arm studies that included middle-aged (50 to 65 years) and older adults (>65 years) and, a single-bout, acute-exercise (aerobic, resistance, impact) intervention with measurement of BTMs. PROSPERO registration number CRD42020145359.
RESULTS
Thirteen studies were included; 8 in middle-aged (n = 275, 212 women/63 men, mean age = 57.9 ± 1.5 years) and 5 in older adults (n = 93, 50 women/43 men, mean age = 68.2 ± 2.2 years). Eleven studies included aerobic exercise (AE, 7 middle-aged/4 older adults), and two included resistance exercise (RE, both middle-aged). AE significantly increased C-terminal telopeptide (CTX), alkaline phosphatase (ALP) and bone-ALP in middle-aged and older adults. AE also significantly increased total osteocalcin (tOC) in middle-aged men and Procollagen I Carboxyterminal Propeptide and Cross-Linked Carboxyterminal Telopeptide of Type I Collagen in older women. RE alone decreased ALP in older adults. In middle-aged adults, RE with impact had no effect on tOC or BALP, but significantly decreased CTX. Impact (jumping) exercise alone increased Procollagen Type 1 N Propeptide and tOC in middle-aged women.
CONCLUSION
Acute exercise is an effective tool to modify BTMs, however, the response appears to be exercise modality-, intensity-, age- and sex-specific. There is further need for higher quality and larger RCTs in this area.
Topics: Aged; Alkaline Phosphatase; Biomarkers; Bone Density; Bone Remodeling; Collagen Type I; Exercise; Female; Humans; Male; Middle Aged; Peptide Fragments; Procollagen
PubMed: 33227507
DOI: 10.1016/j.bone.2020.115766 -
Current Pharmaceutical Design 2020Total hip replacement (THR) is the standard surgical treatment of hip diseases. Periprosthetic bone mass density (BMD) loss may be a cause for revision surgery.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Total hip replacement (THR) is the standard surgical treatment of hip diseases. Periprosthetic bone mass density (BMD) loss may be a cause for revision surgery. Bisphosphonates (BPs) are now the principal class medications for osteoporosis.
OBJECTIVE
To demonstrate the effect of BPs on treating periprosthetic osteoporosis after THR via a meta-analysis of randomized controlled trials (RCTs).
METHODS
A comprehensive search of PubMed, EMBASE, the Web of Science and the Cochrane Central Register of Controlled Trials was performed for RCTs on the effect of BPs on treating periprosthetic osteoporosis after THR and clinical outcomes relative to controls. The primary outcome measures were the change in BMD in each region of interest (ROI), the change in serum bone turnover marker levels, the change in functional parameters and the risk of adverse effects (AEs). The final search was performed in March, 2020.
RESULTS
Nine RCTs were included. A total of 359 patients met the inclusion criteria. BPs can clearly maintain periprosthetic BMD in ROIs at 1, 2, 3, 4, 6 and 7 at 6, 12 and 24 months. In addition, BPs can clearly decrease serum procollagen type 1 N-terminal propeptide (P1NP) levels at 12 months. There was no significant difference in the risk of AEs between the BP and control groups; however, BPs can cause more patients to decline participation.
CONCLUSION
BPs can effectively maintain overall periprosthetic BMD, but BMD in ROI 5 remains controversial. In addition, the safety of BPs is relatively high, but the compliance may be relatively low.
Topics: Arthroplasty, Replacement, Hip; Bone Density; Bone Density Conservation Agents; Diphosphonates; Humans; Osteoporosis
PubMed: 32321394
DOI: 10.2174/1381612826666200422093213 -
Journal of Hepatology Aug 2020The enhanced liver fibrosis (ELF) test has been proposed for the non-invasive assessment of advanced fibrosis in patients with non-alcoholic fatty liver disease (NAFLD).... (Meta-Analysis)
Meta-Analysis
BACKGROUND & AIMS
The enhanced liver fibrosis (ELF) test has been proposed for the non-invasive assessment of advanced fibrosis in patients with non-alcoholic fatty liver disease (NAFLD). We performed a systematic review to estimate the accuracy of this test against biopsy.
METHODS
In this systematic review, we searched MEDLINE, Embase, Web of Science and the Cochrane Library for studies that included patients with NAFLD and that used both liver biopsy (as the reference standard) and the ELF test. Two authors independently screened the references, extracted the data and assessed the quality of included studies. Due to the variation in reported thresholds, we used a multiple thresholds random effects model for meta-analysis (diagmeta R-package).
RESULTS
The meta-analysis of 11 studies reporting advanced fibrosis and 5 studies reporting significant fibrosis showed that the ELF test had a sensitivity of >0.90 for excluding fibrosis at a threshold of 7.7. However, as a diagnostic test at high thresholds, the test only achieved specificity and positive predictive value >0.80 in very high prevalence settings (>50%). To achieve a specificity of 0.90 for advanced and significant fibrosis, thresholds of 10.18 (sensitivity: 0.57) and 9.86 (sensitivity: 0.55) were required, respectively.
CONCLUSION
The ELF test showed high sensitivity but limited specificity to exclude advanced and significant fibrosis at low cut-offs. The diagnostic performance of the test at higher thresholds was found to be more limited in low-prevalence settings. We conclude that clinicians should carefully consider the likely disease prevalence in their practice setting and adopt suitable test thresholds to achieve the desired performance.
LAY SUMMARY
The enhanced liver fibrosis test has been suggested as a non-invasive blood test to aid the diagnosis of severe liver fibrosis in patients with non-alcoholic fatty liver disease (NAFLD). Our study results showed that the test has a high negative predictive value, especially in populations with low disease prevalence (likely encountered in primary care); so, it can exclude advanced fibrosis in patients with NAFLD. However, when prevalence is low, the positive predictive value of the enhanced liver fibrosis test is low, suggesting that additional strategies may be needed to make a positive diagnosis in such settings.
Topics: Algorithms; Biomarkers; Biopsy; Disease Progression; Humans; Hyaluronic Acid; Liver; Liver Cirrhosis; Non-alcoholic Fatty Liver Disease; Peptide Fragments; Predictive Value of Tests; Procollagen; Reference Standards; Tissue Inhibitor of Metalloproteinase-1
PubMed: 32275982
DOI: 10.1016/j.jhep.2020.03.036 -
Maturitas Nov 2019To systematically evaluate the effects of bone anabolic therapies (BATs) - specifically, drug therapy with teriparatide, abaloparatide or romosozumab - on fractures,... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To systematically evaluate the effects of bone anabolic therapies (BATs) - specifically, drug therapy with teriparatide, abaloparatide or romosozumab - on fractures, bone mineral density (BMD), and bone metabolites in postmenopausal osteoporosis.
METHODS
Six computerized engines were searched through to November 2018. We selected randomized controlled trials (RCTs) evaluating the effect of BATs on postmenopausal osteoporosis and with at least 6 months of follow-up. Controls were placebo, no treatment, or bisphosphonates. Primary outcomes were vertebral and non-vertebral fractures. Secondary outcomes were: BMD determined by dual energy X-ray absorptiometry at total hip, lumbar spine, and femoral neck; N-terminal propeptide of type I procollagen (PINP); C-terminal telopeptide of type I collagen (CTX); and severe adverse events (SAE). We followed the PRISMA guidelines for reporting, and used version 2 of the Cochrane risk-of-bias tool. Frequentist network meta-analyses were performed per outcome. Effects for dichotomous and continuous outcomes were expressed as relative risks and mean differences and their 95% confidence intervals. We used p-scores to rank best treatments per outcome.
RESULTS
Sixteen RCTs (n = 18,940) were evaluated. Mean ages ranged between 61 and 74 years, and follow-up times between 6 and 30 months. Four RCTs (n = 971) excluded patients with previous fractures. In contrast to placebo/no treatment, all BATs significantly reduced the risk of vertebral fractures, but no intervention significantly reduced the risk of non-vertebral fractures; abaloparatide ranked better than other interventions for both fracture types (p-scores: 0.95, and 0.89, respectively). All BATs significantly increased BMD at all locations in comparison with placebo/no treatment; romosozumab consistently ranked better than other interventions at all BMD locations (p-scores >0.86). Teriparatide ranked better than other interventions for increasing PINP. No differences in SAE were observed among treatments.
CONCLUSIONS
Abaloparatide, romosozumab, and teriparatide are the best treatments, respectively, to reduce vertebral/non-vertebral fractures, increase BMD, and increase bone formation.
Topics: Antibodies, Monoclonal; Bone Density; Bone Density Conservation Agents; Collagen Type I; Female; Humans; Network Meta-Analysis; Osteoporosis, Postmenopausal; Osteoporotic Fractures; Parathyroid Hormone-Related Protein; Peptide Fragments; Peptides; Procollagen; Randomized Controlled Trials as Topic; Teriparatide
PubMed: 31547908
DOI: 10.1016/j.maturitas.2019.08.003 -
Annals of the New York Academy of... Dec 2019The current study presents a comprehensive systematic review and meta-analysis of randomized controlled trials (RCTs) on resveratrol and bone health biomarkers. PubMed,... (Meta-Analysis)
Meta-Analysis
The current study presents a comprehensive systematic review and meta-analysis of randomized controlled trials (RCTs) on resveratrol and bone health biomarkers. PubMed, Scopus, and Web of Science (until September 2018) were searched to identify the potential RCTs with information on resveratrol supplementation and bone metabolism biomarkers. Mean differences (MD) were analyzed using a random-effects model. Pooling six RCTs (eight treatment arms with 264 subjects) together identified no significant reduction of serum Ca, osteocalcin, C-terminal telopeptide of type I collagen, and procollagen I N-terminal propeptide values after resveratrol supplementation over placebo treatment. However, a significant increase in serum alkaline phosphatase (ALP) (MD: 5.69 mg/mL, 95% CI: 3.58-7.80, I = 95.7%, P < 0.001) and bone alkaline phosphatase (BAP) (MD: 10.57 mmHg, 95% CI: 5.36-15.78, I = 99.2%, P < 0.001) values was observed after resveratrol treatment relative to placebo. The findings of this study indicate that resveratrol supplementation increased some key bone biomarkers, such as ALP and BAP. Further precise clinical trials of the effects of resveratrol supplementation on bone health should be conducted.
Topics: Alkaline Phosphatase; Antioxidants; Biomarkers; Bone Density; Bone and Bones; Calcium; Collagen Type I; Enzyme Inhibitors; Humans; Osteocalcin; Parathyroid Hormone; Peptide Fragments; Peptides; Procollagen; Randomized Controlled Trials as Topic; Resveratrol
PubMed: 31490554
DOI: 10.1111/nyas.14226 -
Osteoporosis International : a Journal... Dec 2019To assess the time from fracture until bone turnover markers (BTM), which are biochemical markers reflecting in vivo bone formation and resorptive activity, have...
To assess the time from fracture until bone turnover markers (BTM), which are biochemical markers reflecting in vivo bone formation and resorptive activity, have returned to a stable level since BTM have been shown to be at least as good as bone mineral density in monitoring the effect of anti-resorptive treatment in osteoporosis. This study searched for articles in PUBMED, CINAHL, Medline, EM-BASE, and Cochrane, and identified 3486 unique articles. These articles were screened based on predefined inclusion and exclusion criteria. Seven articles addressing time to normalization of either CTX, PINP, osteocalcin, or bone-specific alkaline phosphatase after a recent fracture were identified and these were analyzed qualitatively. CTX appeared to return to baseline within 6 months. PINP appeared to return to baseline within 6 months and interestingly dip below baseline after a year. Osteocalcin was elevated throughout the first year after a fracture, with most changes in the first 6 months. Bone-specific alkaline phosphatase (BAP) was increased for up to a year, however with a discrepancy between used assays. Seven studies were identified, showing CTX and PINP to return to baseline within 6 months. OC was elevated for 12 months. BAP was increased for up to a year. However, none of these studies had fasting patients and a long follow-up period with regular measurements. The studies could indicate that the BTM CTX and PINP have returned to baseline within 6 months; however, further studies are needed assessing pre-analytical factors while having a long follow-up. Bone turnover markers appear as good as or better than bone mineral density in monitoring the effect of anti-resorptive medication in osteoporosis. This study tries to identify the time from fracture until BTM are back at baseline. Most studies did not however take pre-analytical variation into consideration. Further research is therefore needed.
Topics: Alkaline Phosphatase; Biomarkers; Bone Remodeling; Collagen Type I; Fractures, Bone; Humans; Osteocalcin; Peptide Fragments; Peptides; Procollagen
PubMed: 31446441
DOI: 10.1007/s00198-019-05132-1 -
Pediatric Diabetes Aug 2019Type 1 diabetes (T1D) is associated with impaired bone health and both osteocalcin (OCN) and procollagen type 1 amino terminal propetide (P1NP) (markers of bone... (Meta-Analysis)
Meta-Analysis
Type 1 diabetes (T1D) is associated with impaired bone health and both osteocalcin (OCN) and procollagen type 1 amino terminal propetide (P1NP) (markers of bone formation) and C-terminal cross-linked telopeptide (CTX) (marker of bone resorption) are decreased in adult patients with T1D. We review the existing literature characterizing these bone turnover markers in children and adolescents with T1D and by meta-analysis examine whether alterations in OCN, P1NP, and CTX are evident and if potential changes correlate to the metabolic control (hemoglobin A1c, HbA1c). Systematic searches at MEDLINE and EMBASE were conducted in January 2018 identifying all studies describing OCN, P1NP, or CTX in children and adolescents with T1D. A total of 26 studies were included, representing data from more than 1000 patients with T1D. Pooled analyses of standard mean difference and summary effects analysis were performed when sufficient data were available. Pooled analysis revealed mean OCN to be significantly lower in children and adolescents with T1D compared to healthy controls (standard mean difference: -1.87, 95% confidence interval, CI: -2.83; -0.91) whereas both P1NP and CTX did not differ from the controls. Only data on OCN was sufficient to make pooled correlation analysis revealing a negative correlation between OCN and HbA1c (-0.31 95% CI: -0.45; -0.16). In conclusion, OCN is decreased in children and adolescents with T1D, whether CTX and P1NP are affected as well is unclear, due to very limited data available. New and large studies including OCN, P1NP, and CTX (preferably as z-scores adjusting for age variability) is needed to further elucidate the status of bone turnover in children and adolescents with T1D.
Topics: Adolescent; Biomarkers; Bone Remodeling; Child; Collagen Type I; Diabetes Mellitus, Type 1; Glycated Hemoglobin; Humans; Osteocalcin; Peptide Fragments; Peptides; Procollagen
PubMed: 30941847
DOI: 10.1111/pedi.12853