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Breast (Edinburgh, Scotland) Dec 2022Mammographic density is a well-defined risk factor for breast cancer and having extremely dense breast tissue is associated with a one-to six-fold increased risk of... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
Mammographic density is a well-defined risk factor for breast cancer and having extremely dense breast tissue is associated with a one-to six-fold increased risk of breast cancer. However, it is questioned whether this increased risk estimate is applicable to current breast density classification methods. Therefore, the aim of this study was to further investigate and clarify the association between mammographic density and breast cancer risk based on current literature.
METHODS
Medline, Embase and Web of Science were systematically searched for articles published since 2013, that used BI-RADS lexicon 5th edition and incorporated data on digital mammography. Crude and maximally confounder-adjusted data were pooled in odds ratios (ORs) using random-effects models. Heterogeneity regarding breast cancer risks were investigated using I statistic, stratified and sensitivity analyses.
RESULTS
Nine observational studies were included. Having extremely dense breast tissue (BI-RADS density D) resulted in a 2.11-fold (95% CI 1.84-2.42) increased breast cancer risk compared to having scattered dense breast tissue (BI-RADS density B). Sensitivity analysis showed that when only using data that had adjusted for age and BMI, the breast cancer risk was 1.83-fold (95% CI 1.52-2.21) increased. Both results were statistically significant and homogenous.
CONCLUSIONS
Mammographic breast density BI-RADS D is associated with an approximately two-fold increased risk of breast cancer compared to having BI-RADS density B in general population women. This is a novel and lower risk estimate compared to previously reported and might be explained due to the use of digital mammography and BI-RADS lexicon 5th edition.
Topics: Female; Humans; Breast Density; Breast Neoplasms; Mammography; Breast; Risk Factors
PubMed: 36183671
DOI: 10.1016/j.breast.2022.09.007 -
Osteoporosis International : a Journal... Jan 2022The study was conducted to illustrate the effect of Romosozumab in postmenopausal osteoporosis patients. Romosozumab decreased the incidence of vertebral, nonvertebral,... (Meta-Analysis)
Meta-Analysis Review
The study was conducted to illustrate the effect of Romosozumab in postmenopausal osteoporosis patients. Romosozumab decreased the incidence of vertebral, nonvertebral, and clinical fractures significantly. In addition, decreased incidence of falls and increased bone mineral density at lumbar spine, total hip, and femoral neck was observed. Romosozumab is a monoclonal antibody that acts against the sclerostin pathway leading to enhanced bone formation and reduced bone resorption in patients with osteoporosis. Electronic search was performed on Medline (via PubMed), The Cochrane Central Register of Controlled Trials, and clinicaltrials.gov, till May 2020, for RCTs evaluating the effectiveness of Romosozumab in postmenopausal osteoporosis. RCTs evaluating the effect of Romosozumab on fractures and bone mineral density in postmenopausal osteoporosis patients. Meta-analysis was performed by Cochrane review manager 5 (RevMan) version 5.3. Cochrane risk of bias 2.0 tool and GRADE pro-GDT were applied for methodological quality and overall evidence quality, respectively. One hundred seventy-nine studies were screened, and 10 eligible studies were included in the analysis, with a total of 6137 patients in romosozumab group and 5732 patients in control group. Romosozumab significantly reduced the incidence of vertebral fractures [OR = 0.43 (95%CI = 0.35-0.52), High-quality evidence], nonvertebral fractures [OR = 0.78 (95%CI = 0.66-0.92), High quality], and clinical fractures [OR = 0.70 (95%CI = 0.60-0.82), High quality] at 24 months. Significant reduction in incidence risk of falls [OR = 0.87 (95%CI = 0.78-0.96), High quality] was observed with romosozumab. Bone mineral density was significantly increased in the romosozumab treated groups at lumbar spine [MD = 12.66 (95%CI = 12.66-12.67), High quality], total hip [MD = 5.69 (95%CI = 5.68 - 5.69), Moderate quality], and femoral neck [MD = 5.18 (95%CI = 5.18-5.19), Moderate quality] at 12 months. The total adverse events [RR = 0.98(95%CI = 0.96-1.01), Moderate quality] and serious adverse events [RR = 0.98(95%CI = 0.88-1.08), Moderate quality] with romosozumab were comparable to the control group. The current analysis with evidence on efficacy and safety of Romosozumab, authors opine to recommend the use of Romosozumab treatment for post-menopausal osteoporosis.Systematic review registration: PROSPERO registration number: CRD42019112196.
Topics: Antibodies, Monoclonal; Bone Density; Bone Density Conservation Agents; Female; Humans; Osteoporosis, Postmenopausal
PubMed: 34432115
DOI: 10.1007/s00198-021-06095-y -
Journal of Clinical Nursing Aug 2022To systematically review and compare the efficacy of different exercise interventions on bone mineral density (BMD, g/cm ) in patients with osteoporosis and osteopenia. (Meta-Analysis)
Meta-Analysis Review
AIMS AND OBJECTIVES
To systematically review and compare the efficacy of different exercise interventions on bone mineral density (BMD, g/cm ) in patients with osteoporosis and osteopenia.
BACKGROUND
It is vitally important to prevent and treat bone loss in patients with osteoporosis and osteopenia. Exercise can effectively increase bone density and slow down bone loss in middle-aged and older people. However, it is still unclear which type of exercise intervention is the most effective on bone mineral density.
DESIGN
Systematic review and network meta-analysis (NMA) according to PRISMA.
METHODS
Randomised controlled trials of different exercise treatments for osteopenia and primary osteoporosis were included. A Frequentist network meta-analysis was conducted to appraise the efficacy of different types of exercise. The outcome was bone mineral density of different parts of the body.
RESULTS
Ninety-seven studies were included. The network meta-analysis showed that combined exercise, resistance exercise, aerobic exercise and mind-body exercise had a significant effect in improving the bone density of lumbar spine. The surface under the cumulative ranking area (SUCRA) values for mind-body exercise was 0.99 and ranked first. For BMD of the femoral neck, all kinds of exercise interventions increased the bone density significantly compared with no exercise and the optimal type was mind-body exercise (SUCRA = 0.99). In terms of the total hip bone mineral density, aerobic exercise and resistance exercise could improve hip bone density, with the resistance exercise (SUCRA = 0.95) ranking as first.
CONCLUSIONS
This NMA demonstrated the mind-body exercise might be the optimal exercise type to increase the BMD of the lumbar spine and femoral neck and resistance exercise is the most promising type for total hip BMD.
Topics: Aged; Bone Density; Bone Diseases, Metabolic; Exercise; Humans; Middle Aged; Network Meta-Analysis; Osteoporosis
PubMed: 34725872
DOI: 10.1111/jocn.16101 -
The American Journal of Clinical... Jun 2017: Considerable attention has recently focused on dietary protein's role in the mature skeleton, prompted partly by an interest in nonpharmacologic approaches to maintain... (Meta-Analysis)
Meta-Analysis Review
: Considerable attention has recently focused on dietary protein's role in the mature skeleton, prompted partly by an interest in nonpharmacologic approaches to maintain skeletal health in adult life. The aim was to conduct a systematic review and meta-analysis evaluating the effects of dietary protein intake alone and with calcium with or without vitamin D (Ca±D) on bone health measures in adults. Searches across 5 databases were conducted through October 2016 including randomized controlled trials (RCTs) and prospective cohort studies examining ) the effects of "high versus low" protein intake or ) dietary protein's synergistic effect with Ca±D intake on bone health outcomes. Two investigators independently conducted abstract and full-text screenings, data extractions, and risk of bias (ROB) assessments. Strength of evidence was rated by group consensus. Random-effects meta-analyses for outcomes with ≥4 RCTs were performed. Sixteen RCTs and 20 prospective cohort studies were included in the systematic review. Overall ROB was medium. Moderate evidence suggested that higher protein intake may have a protective effect on lumbar spine (LS) bone mineral density (BMD) compared with lower protein intake (net percentage change: 0.52%; 95% CI: 0.06%, 0.97%, : 0%; = 5) but no effect on total hip (TH), femoral neck (FN), or total body BMD or bone biomarkers. Limited evidence did not support an effect of protein with Ca±D on LS BMD, TH BMD, or forearm fractures; there was insufficient evidence for FN BMD and overall fractures. Current evidence shows no adverse effects of higher protein intakes. Although there were positive trends on BMD at most bone sites, only the LS showed moderate evidence to support benefits of higher protein intake. Studies were heterogeneous, and confounding could not be excluded. High-quality, long-term studies are needed to clarify dietary protein's role in bone health. This trial was registered at www.crd.york.ac.uk as CRD42015017751.
Topics: Bone Density; Bone Density Conservation Agents; Calcium; Calcium, Dietary; Dietary Proteins; Female; Fractures, Bone; Humans; Lumbar Vertebrae; Male; Osteoporosis; Vitamin D
PubMed: 28404575
DOI: 10.3945/ajcn.116.145110 -
BioMed Research International 2020Osteoporosis is a chronic disease that seriously affects human health and quality of life. This study is aimed at determining whether swimming had an effect on the bone... (Meta-Analysis)
Meta-Analysis
Osteoporosis is a chronic disease that seriously affects human health and quality of life. This study is aimed at determining whether swimming had an effect on the bone mineral density (BMD) of the spine and femoral neck in postmenopausal and premenopausal osteoporosis patients. We retrieved relevant literature and analyzed data from randomized controlled trials to assess the effect of swimming on BMD in postmenopausal and premenopausal women. Relevant studies, with no language restrictions, from inception to September 2019, were retrieved from the PubMed, Cochrane, EMBASE, and EBSCO databases independently by two investigators. The keywords used for the literature search were "osteoporosis" and "swimming." The main results included BMD and -score. We searched 256 relevant articles and finally screened five articles, including 263 participants. Lumbar spine density was mentioned in three articles. Although the heterogeneity of lumbar vertebral density is moderate, the analysis of swimmers to nonswimmers shows that the lumbar vertebral density in swimmers is improved [heterogeneity: chi = 5.16, df = 2 ( = 0.08); = 61%]. We analyzed the following heterogeneous subgroups: subgroup 1 (3-6 hours) and subgroup 2 (<3 hours). The BMD in subgroup 1 was significantly higher than that in the placebo, while no effect on BMD was found in subgroup 2 [heterogeneity: chi = 0.15, df = 3 ( = 0.70); = 0%]. According to the current evidence, swimming may improve the BMD of postmenopausal women participants, if the swimming time is between 3 and 6 hours, especially in long-term swimmers. However, the effectiveness of swimming does require further investigation.
Topics: Adult; Bone Density; Exercise Therapy; Female; Femur Neck; Humans; Lumbar Vertebrae; Middle Aged; Osteoporosis; Osteoporosis, Postmenopausal; Postmenopause; Premenopause; Swimming
PubMed: 32509864
DOI: 10.1155/2020/6210201 -
The Cochrane Database of Systematic... Oct 2016Osteogenesis imperfecta is caused by a genetic defect resulting in an abnormal type I collagen bone matrix which typically results in multiple fractures with little or... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Osteogenesis imperfecta is caused by a genetic defect resulting in an abnormal type I collagen bone matrix which typically results in multiple fractures with little or no trauma. Bisphosphonates are used in an attempt to increase bone mineral density and reduce these fractures in people with osteogenesis imperfecta. This is an update of a previously published Cochrane Review.
OBJECTIVES
To assess the effectiveness and safety of bisphosphonates in increasing bone mineral density, reducing fractures and improving clinical function in people with osteogenesis imperfecta.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Inborn Errors of Metabolism Trials Register which comprises references identified from comprehensive electronic database searches, handsearches of journals and conference proceedings. We additionally searched PubMed and major conference proceedings.Date of the most recent search of the Cochrane Cystic Fibrosis and Genetic Disorders Group's Inborn Errors of Metabolism Register: 28 April 2016.
SELECTION CRITERIA
Randomised and quasi-randomised controlled trials comparing bisphosphonates to placebo, no treatment, or comparator interventions in all types of osteogenesis imperfecta.
DATA COLLECTION AND ANALYSIS
Two authors independently extracted data and assessed the risk of bias of the included trials.
MAIN RESULTS
Fourteen trials (819 participants) were included. Overall, the trials were mainly at a low risk of bias, although selective reporting was an issue in several of the trials. Data for oral bisphosphonates versus placebo could not be aggregated; a statistically significant difference favouring oral bisphosphonates in fracture risk reduction and number of fractures was noted in two trials. No differences were reported in the remaining three trials which commented on fracture incidence. Five trials reported data for spine bone mineral density; all found statistically significant increased lumbar spine density z scores for at least one time point studied. For intravenous bisphosphonates versus placebo, aggregated data from two trials showed no statistically significant difference for the number of participants with at least one fracture, risk ratio 0.56 (95% confidence interval 0.30 to 1.06). In the remaining trial no statistically significant difference was noted in fracture incidence. For spine bone mineral density, no statistically significant difference was noted in the aggregated data from two trials, mean difference 9.96 (95% confidence interval -2.51 to 22.43). In the remaining trial a statistically significant difference in mean per cent change in spine bone mineral density z score favoured intravenous bisphosphonates at six and 12 months. Data describing growth, bone pain, and functional outcomes after oral or intravenous bisphosphonate therapy, or both, as compared to placebo were incomplete among all studies, but do not show consistent improvements in these outcomes. Two studies compared different doses of bisphosphonates. No differences were found between doses when bone mineral density, fractures, and height or length z score were assessed. One trial compared oral versus intravenous bisphosphonates and found no differences in primary outcomes. Two studies compared the intravenous bisphosphonates zoledronic acid and pamidronate. There were no significant differences in primary outcome. However, the studies were at odds as to the relative benefit of zoledronic acid over pamidronate for lumbosacral bone mineral density at 12 months.
AUTHORS' CONCLUSIONS
Bisphophonates are commonly prescribed to individuals with osteogenesis imperfecta. Current evidence, albeit limited, demonstrates oral or intravenous bisphosphonates increase bone mineral density in children and adults with this condition. These were not shown to be different in their ability to increase bone mineral density. It is unclear whether oral or intravenous bisphosphonate treatment consistently decreases fractures, though multiple studies report this independently and no studies report an increased fracture rate with treatment. The studies included here do not show bisphosphonates conclusively improve clinical status (reduce pain; improve growth and functional mobility) in people with osteogenesis imperfecta. Given their current widespread and expected continued use, the optimal method, duration of therapy and long-term safety of bisphosphonate therapy require further investigation. In addition, attention should be given to long-term fracture reduction and improvement in quality of life indicators.
Topics: Administration, Oral; Bone Density; Bone Density Conservation Agents; Diphosphonates; Fractures, Bone; Humans; Injections, Intravenous; Osteogenesis Imperfecta; Randomized Controlled Trials as Topic
PubMed: 27760454
DOI: 10.1002/14651858.CD005088.pub4 -
Osteoporosis International : a Journal... Aug 2020This systematic review and meta-analysis set out to determine the effect of dynamic resistance exercise (DRT) on areal bone mineral density (aBMD) in postmenopausal... (Meta-Analysis)
Meta-Analysis
Effects of dynamic resistance exercise on bone mineral density in postmenopausal women: a systematic review and meta-analysis with special emphasis on exercise parameters.
This systematic review and meta-analysis set out to determine the effect of dynamic resistance exercise (DRT) on areal bone mineral density (aBMD) in postmenopausal women and derive evidence-based recommendations for optimized training protocols. A systematic review of the literature according to the PRISMA statement included (a) controlled trials, (b) of isolated DRT with at least one exercise and one control group, (c) with intervention durations ≥ 6 months, (d) aBMD assessments at lumbar spine or proximal femur, (e) in cohorts of postmenopausal women. We searched eight electronic databases up to March 2019 without language restrictions. The meta-analysis was performed using a random-effects model. Standardized mean differences (SMD) for BMD changes at lumbar spine (LS), femoral neck (FN), and total hip (TH) were defined as outcome measures. Moderators of the exercise effects, i.e., "intervention length," "type of DRT," "training frequency," "exercise intensity," and "exercise volume," were addressed by sub-group analyses. The study was registered in the international prospective register of systematic reviews (PROSPERO) under ID: CRD42018095097. Seventeen articles with 20 exercise and 18 control groups were eligible. SMD average is 0.54 (95% CI 0.22-0.87) for LS-BMD, 0.22 (0.07-0.38) for FN-BMD, and 0.48 (0.22-0.75) for TH-BMD changes (all p ≤ 0.015). While sub-group analysis for FN-BMD revealed no differences within categories of moderators, lower training frequency (< 2 sessions/week) resulted in significantly higher BMD changes at LS and TH compared to higher training frequency (≥ 2 sessions/week). Additionally, free weight training was significantly superior to DRT devices for improving TH-BMD. This work provided further evidence for significant, albeit only low-moderate, effects of DRT on LS-, FN-, and TH-BMD. Unfortunately, sub-analysis results did not allow meaningful exercise recommendations to be derived. This systematic review and meta-analysis observed a significant low-moderate effect of dynamic resistance exercise on bone mineral density changes in postmenopausal women. However, sub-group analyses focusing on exercise characteristics found no results that enable the derivation of meaningful exercise recommendations in the area of exercise and osteoporosis prevention or therapy.
Topics: Aged; Bone Density; Exercise; Female; Femur Neck; Humans; Lumbar Vertebrae; Middle Aged; Osteoporosis, Postmenopausal; Postmenopause; Resistance Training
PubMed: 32399891
DOI: 10.1007/s00198-020-05441-w -
Food & Function Dec 2020The aim of the present study was to explore whether combined calcium and vitamin D supplementation is beneficial for osteoporosis in postmenopausal women. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The aim of the present study was to explore whether combined calcium and vitamin D supplementation is beneficial for osteoporosis in postmenopausal women.
METHODS
We searched the PubMed, Cochrane library, Web of science and Embase databases and reference lists of eligible articles up to Feb, 2020. Randomized controlled trials (RCTs) evaluating the effect of combined calcium and vitamin D on osteoporosis in postmenopausal women were included in the present study.
RESULTS
Combined calcium and vitamin D significantly increased total bone mineral density (BMD) (standard mean differences (SMD) = 0.537; 95% confidence interval (CI): 0.227 to 0.847), lumbar spine BMD (SMD = 0.233; 95% CI: 0.073 to 0.392; P < 0.001), arms BMD (SMD = 0.464; 95% CI: 0.186 to 0.741) and femoral neck BMD (SMD = 0.187; 95% CI: 0.010 to 0.364). It also significantly reduced the incidence of hip fracture (RR = 0.864; 95% CI: 0.763 to 0.979). Subgroup analysis showed that combined calcium and vitamin D significantly increased femoral neck BMD only when the dose of the vitamin D intake was no more than 400 IU d (SMD = 0.335; 95% CI: 0.113 to 0.558), but not for a dose more than 400 IU d (SMD = -0.098; 95% CI: -0.109 to 0.305), and calcium had no effect on the femoral neck BMD. Subgroup analysis also showed only dairy products fortified with calcium and vitamin D had a significant influence on total BMD (SMD = 0.784; 95% CI: 0.322 to 1.247) and lumbar spine BMD (SMD = 0.320; 95% CI: 0.146 to 0.494), but not for combined calcium and vitamin D supplement.
CONCLUSION
Dairy products fortified with calcium and vitamin D have a favorable effect on bone mineral density. Combined calcium and vitamin D supplementation could prevent osteoporosis hip fracture in postmenopausal women.
Topics: Bone Density; Bone Density Conservation Agents; Calcium; Calcium, Dietary; Dairy Products; Databases, Factual; Dietary Supplements; Female; Fractures, Bone; Humans; Lumbar Vertebrae; Osteoporosis, Postmenopausal; Postmenopause; Randomized Controlled Trials as Topic; Vitamin D
PubMed: 33237064
DOI: 10.1039/d0fo00787k -
Journal of Neurosurgery. Spine Apr 2023Osteoporosis has significant implications in spine fusion surgery, for which reduced spinal bone mineral density (BMD) can result in complications and poorer outcomes.... (Review)
Review
OBJECTIVE
Osteoporosis has significant implications in spine fusion surgery, for which reduced spinal bone mineral density (BMD) can result in complications and poorer outcomes. Currently, dual-energy x-ray absorptiometry (DEXA) is the gold standard for radiographic diagnosis of osteoporosis, although DEXA accuracy may be limited by the presence of degenerative spinal pathology. In recent years, there has been an evolving interest in using alternative imaging, including CT and MRI, to assess BMD. In this systematic review of the literature, the authors assessed the use and effectiveness of MRI, opportunistic CT (oCT), and quantitative CT (qCT) to measure BMD.
METHODS
In accordance with the PRISMA guidelines, the authors conducted a systematic search for articles posted on PubMed between the years 2000 and 2022 by using the keywords "opportunistic CT, quantitative CT, MRI" AND "bone density" AND "spine." Inclusion criteria consisted of articles written in English that reported studies pertaining to human or cadaveric subjects, and studies including a measure of spinal BMD. Articles not related to spinal BMD, osteoporosis, or spinal surgery or reports of studies that did not include the use of spinal MRI or CT were excluded. Key study outcomes were extracted from included articles, and qualitative analysis was subsequently performed.
RESULTS
The literature search yielded 302 articles. Forty-two articles reported studies that met the final inclusion criteria. Eighteen studies utilized MRI protocols to correlate spinal BMD with vertebral bone quality scores, M-scores, and quantitative perfusion markers. Eight studies correlated oCT with spinal BMD, and 16 studies correlated qCT with spinal BMD. With oCT and qCT imaging, there was consensus that Hounsfield unit (HU) values > 160 demonstrated significant reduction in risk of osteoporosis, whereas HU values < 110 were significantly correlated with osteoporosis.
CONCLUSIONS
Osteoporosis is increasingly recognized as a significant risk factor for complications after spinal fusion surgery. Consequently, preoperative assessment of BMD is a critical factor to consider in planning surgical treatment. Although DEXA has been the gold standard for BMD measurement, other imaging modalities, including MRI, oCT, and qCT, appear to be viable alternatives and may offer cost and time savings.
Topics: Humans; Bone Density; Absorptiometry, Photon; Tomography, X-Ray Computed; Osteoporosis; Spine; Lumbar Vertebrae; Retrospective Studies
PubMed: 36609369
DOI: 10.3171/2022.11.SPINE22875 -
Current Medical Research and Opinion May 2022Network meta-analysis was used to derive estimates of the relative efficacy of inclisiran, evolocumab, alirocumab, bempedoic acid, and ezetimibe in patients with... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Network meta-analysis was used to derive estimates of the relative efficacy of inclisiran, evolocumab, alirocumab, bempedoic acid, and ezetimibe in patients with hypercholesterolemia and/or at increased cardiovascular risk due to elevated low-density lipoprotein cholesterol taking maximum tolerated dose statins.
METHODS
Clinical trials published through February 2021 comparing percent change from baseline in low-density lipoprotein cholesterol were identified a systematic review. Bayesian network meta-analyses were performed for patients with atherosclerotic cardiovascular disease and/or high cardiovascular risk on maximally tolerated statins in the base case, which included 23 trials.
RESULTS
Results from the base-case analyses demonstrated that inclisiran, evolocumab, and alirocumab provide superior efficacy over placebo, bempedoic acid, and ezetimibe in terms of reduction in low-density lipoprotein cholesterol. Inclisiran was also comparable to alirocumab (mean difference: 0.78% [95% CrI: -8.35, 9.88]) and evolocumab (8.16%, [95% CrI: -1.82, 18.49]). Findings of a scenario which also included trials conducted in patients with heterozygous familial hypercholesterolemia were consistent with the base case. There was evidence of statistical heterogeneity across the included trials, roughly equivalent to variation of 5-10% change in low-density lipoprotein cholesterol, suggesting that any differences between treatments that were greater than 5-10% are generalizable.
CONCLUSIONS
This study provides insight regarding the comparative efficacy of drugs for which no head-to-head trials exist and suggests that inclisiran, alirocumab, and evolocumab are expected to provide similar clinically meaningful improvements in low-density lipoprotein cholesterol in patients with hypercholesterolemia on maximally tolerated statins who are at increased cardiovascular risk.
Topics: Anticholesteremic Agents; Bayes Theorem; Cardiovascular Diseases; Cholesterol; Cholesterol, LDL; Ezetimibe; Heart Disease Risk Factors; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Hyperlipidemias; Network Meta-Analysis; Risk Factors; Treatment Outcome
PubMed: 35262430
DOI: 10.1080/03007995.2022.2049164