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International Journal of Molecular... Sep 2023Osteoporosis is a major public health concern affecting millions of people worldwide and resulting in significant economic costs. The condition is characterized by... (Review)
Review
Osteoporosis is a major public health concern affecting millions of people worldwide and resulting in significant economic costs. The condition is characterized by changes in bone homeostasis, which lead to reduced bone mass, impaired bone quality, and an increased risk of fractures. The pathophysiology of osteoporosis is complex and multifactorial, involving imbalances in hormones, cytokines, and growth factors. Understanding the cellular and molecular mechanisms underlying osteoporosis is essential for appropriate diagnosis and management of the condition. This paper provides a comprehensive review of the normal cellular and molecular mechanisms of bone homeostasis, followed by an in-depth discussion of the proposed pathophysiology of osteoporosis through the osteoimmunological, gut microbiome, and cellular senescence models. Furthermore, the diagnostic tools used to assess osteoporosis, including bone mineral density measurements, biochemical markers of bone turnover, and diagnostic imaging modalities, are also discussed. Finally, both the current pharmacological and non-pharmacological treatment algorithms and management options for osteoporosis, including an exploration of the management of osteoporotic fragility fractures, are highlighted. This review reveals the need for further research to fully elucidate the molecular mechanisms underlying the condition and to develop more effective therapeutic strategies.
Topics: Humans; Pathology, Molecular; Osteoporosis; Osteoporotic Fractures; Bone Density; Bone and Bones
PubMed: 37834025
DOI: 10.3390/ijms241914583 -
Osteoporosis International : a Journal... Jul 2023The aim of this systematic review and meta-analysis was (1) to determine exercise effects on bone mineral density (BMD) in postmenopausal women and (2) to address the... (Meta-Analysis)
Meta-Analysis Review
Exercise training and bone mineral density in postmenopausal women: an updated systematic review and meta-analysis of intervention studies with emphasis on potential moderators.
The aim of this systematic review and meta-analysis was (1) to determine exercise effects on bone mineral density (BMD) in postmenopausal women and (2) to address the corresponding implication of bone and menopausal status or supervision in postmenopausal women. A comprehensive search of eight electronic databases according to the PRISMA statement up to August 9, 2022, included controlled exercise trials ≥ 6 months. BMD changes (standardized mean differences: SMD) at the lumbar spine (LS), femoral neck (FN), and total hip (TH) were considered as outcomes. Study group comparisons were conducted for osteopenia/osteoporosis versus normal BMD, early versus late postmenopausal women, and predominantly supervised versus predominantly non-supervised study arms. We applied an inverse heterogeneity (IVhet) model. In summary, 80 studies involving 94 training and 80 control groups with a pooled number of 5581 participants were eligible. The IVhet model determined SMDs of 0.29 (95% CI: 0.16-0.42), 0.27 (95% CI: 0.16-0.39), and 0.41 (95% CI: 0.30-0.52) for LS, FN, and THBMD, respectively. Heterogeneity between the trial results varied from low (I = 20%, TH BMD) to substantial (I = 68%, LS-BMD). Evidence for publication bias/small study effects was negligibly low (FN-, TH-BMD) to high (LSBMD). We observed no significant differences (p > .09) for exercise effects on LS-, FN-, or TH-BMD-LS between studies/study arms with or without osteopenia/osteoporosis, early versus late postmenopausal women, or predominantly supervised versus non-supervised exercise programs. Using robust statistical methods, the present work provides further evidence for a positive effect of exercise on BMD in postmenopausal women. Differences in bone status (osteopenia/osteoporosis versus normal bone), menopausal status (early versus late postmenopausal), and supervision (yes versus no) did not significantly affect the exercise effects on BMD at LS or proximal femur.
Topics: Female; Humans; Bone Density; Postmenopause; Osteoporosis, Postmenopausal; Exercise; Osteoporosis; Femur Neck; Lumbar Vertebrae
PubMed: 36749350
DOI: 10.1007/s00198-023-06682-1 -
Bone Research Jul 2023In this study, we aimed to investigate the causal associations of brain structure with bone mineral density (BMD). Based on the genome-wide association study (GWAS)...
In this study, we aimed to investigate the causal associations of brain structure with bone mineral density (BMD). Based on the genome-wide association study (GWAS) summary statistics of 1 325 brain imaging-derived phenotypes (BIDPs) of brain structure from the UK Biobank and GWAS summary datasets of 5 BMD locations, including the total body, femoral neck, lumbar spine, forearm, and heel from the GEFOS Consortium, linkage disequilibrium score regression (LDSC) was conducted to determine the genetic correlations, and Mendelian randomization (MR) was then performed to explore the causal relationship between the BIDPs and BMD. Several sensitivity analyses were performed to verify the strength and stability of the present MR outcomes. To increase confidence in our findings, we also performed confirmatory MR between BIDPs and osteoporosis. LDSC revealed that 1.93% of BIDPs, with a false discovery rate (FDR) < 0.01, were genetically correlated with BMD. Additionally, we observed that 1.31% of BIDPs exhibited a significant causal relationship with BMD (FDR < 0.01) through MR. Both the LDSC and MR results demonstrated that the BIDPs "Volume of normalized brain," "Volume of gray matter in Left Inferior Frontal Gyrus, pars opercularis," "Volume of Estimated Total Intra Cranial" and "Volume-ratio of brain segmentation/estimated total intracranial" had strong associations with BMD. Interestingly, our results showed that more left BIDPs were causally associated with BMD, especially within and around the left frontal region. In conclusion, a part of the brain structure causally influences BMD, which may provide important perspectives for the prevention of osteoporosis and offer valuable insights for further research on the brain-bone axis.
Topics: Humans; Bone Density; Genome-Wide Association Study; Correlation of Data; Mendelian Randomization Analysis; Polymorphism, Single Nucleotide; Osteoporosis; Femur Neck; Prefrontal Cortex
PubMed: 37474577
DOI: 10.1038/s41413-023-00270-z -
BMC Endocrine Disorders Aug 2023The weight-adjusted waist circumference index (WWI) is a novel obesity indicator that offers improved accuracy in assessing both muscle and fat mass compared to...
BACKGROUND
The weight-adjusted waist circumference index (WWI) is a novel obesity indicator that offers improved accuracy in assessing both muscle and fat mass compared to traditional measures. This study aimed to investigate the association between WWI and bone mineral density (BMD) in adults.
METHODS
Weighted multivariate logistic regression, subgroup analysis, interaction tests and restricted cubic spline (RCS) curves were used to explore the relationship between WWI and BMD based on data from the National Health and Nutrition Examination Survey (NHANES).
RESULTS
This study had 40,568 individuals in total. At all four measurement sites, we detected a negative linear correlation between WWI and BMD. Even when quartile factors for WWI were created, this unfavorable connection maintained. In comparison to those in the lowest quartile, those in the highest percentile of WWI showed declines in lumbar BMD of 0.08 g/cm and femoral neck BMD of 0.03 g/cm, respectively. This adverse correlation, nevertheless, differed among several categories.
CONCLUSIONS
Our findings suggest an adverse correlation between WWI and BMD among US adults. Employing WWI as a tool for osteoporosis prevention in the general population may enhance interventions.
Topics: Adult; Humans; Bone Density; Nutrition Surveys; Obesity; Waist Circumference; Absorptiometry, Photon
PubMed: 37537589
DOI: 10.1186/s12902-023-01418-y -
Aging Clinical and Experimental Research Sep 2023The objective of this systematic review and meta-analysis is to systematically identify and review the efficacy of pharmacological treatments in men with osteoporosis. (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
The objective of this systematic review and meta-analysis is to systematically identify and review the efficacy of pharmacological treatments in men with osteoporosis.
METHODS
Medline (via Ovid) and Cochrane CENTRAL were searched up to May 2023 for any randomized controlled trial (RCT) evaluating the efficacy of osteoporotic treatment on the evolution of Bone Mineral Density (BMD) and incidence of fractures of men suffering from primary osteoporosis. If at least two studies used the same pharmacological treatment and evaluated the same outcome, a random effect model meta-analysis was applied to reported pooled mean difference (MD) and 95% confidence interval (CI).
RESULTS
From the 1,061 studies identified through bibliographic search, 21 RCTs fitted the inclusion criteria. Bisphosphonates (k = 10, n = 2992 men with osteoporosis) improved all three BMD sites compared to placebo; lumbar spine: MD + 4.75% (95% CI 3.45, 6.05); total hip: MD + 2.72% (95% CI 2.06; 3.37); femoral neck: MD + 2.26% (95% CI 1.67; 2.85). Denososumab (k = 2, n = 242), Teriparatide (k = 2, n = 309) and Abaloparatide (k = 2, n = 248) also produced significant improvement of all sites BMD compared to placebo. Romosozumab was only identified in one study and was therefore not meta-analysed. In this study, Romosozumab increased significantly BMD compared to placebo. Incident fractures were reported in 16 RCTs but only four reported fractures as the primary outcome. Treatments were associated with a lower incidence of fractures.
CONCLUSIONS
Medications used in the management of osteoporosis in women appear to provide similar benefits in men with osteoporosis. Therefore, the algorithm for the management of osteoporosis in men could be similar to the one previously recommended for the management of osteoporosis in women.
Topics: Male; Female; Humans; Bone Density Conservation Agents; Osteoporosis; Bone Density; Diphosphonates; Fractures, Bone
PubMed: 37400668
DOI: 10.1007/s40520-023-02478-9 -
Nature Communications Jun 2023Osteoporosis is a condition characterized by decreased bone mineral density (BMD) and reduced bone strength, leading to an increased risk of fractures. Here, to identify...
Osteoporosis is a condition characterized by decreased bone mineral density (BMD) and reduced bone strength, leading to an increased risk of fractures. Here, to identify novel risk variants for susceptibility to osteoporosis-related traits, an exome-wide association study is performed with 6,485 exonic single nucleotide polymorphisms (SNPs) in 2,666 women of two Korean study cohorts. The rs2781 SNP in UBAP2 gene is suggestively associated with osteoporosis and BMD with p-values of 6.1 × 10 (odds ratio = 1.72) and 1.1 × 10 in the case-control and quantitative analyzes, respectively. Knockdown of Ubap2 in mouse cells decreases osteoblastogenesis and increases osteoclastogenesis, and knockdown of ubap2 in zebrafish reveals abnormal bone formation. Ubap2 expression is associated with E-cadherin (Cdh1) and Fra1 (Fosl1) expression in the osteclastogenesis-induced monocytes. UBAP2 mRNA levels are significantly reduced in bone marrow, but increased in peripheral blood, from women with osteoporosis compared to controls. UBAP2 protein level is correlated with the blood plasma level of the representative osteoporosis biomarker osteocalcin. These results suggest that UBAP2 has a critical role in bone homeostasis through the regulation of bone remodeling.
Topics: Animals; Female; Mice; Bone Density; Fractures, Bone; Osteogenesis; Osteoporosis; Zebrafish
PubMed: 37339951
DOI: 10.1038/s41467-023-39448-8 -
Current Osteoporosis Reports Aug 2023This review summarizes recently published data and other developments around osteoanabolic osteoporosis therapies in patients with very high fracture risk, including... (Review)
Review
PURPOSE OF REVIEW
This review summarizes recently published data and other developments around osteoanabolic osteoporosis therapies in patients with very high fracture risk, including those undergoing bone-related surgery.
RECENT FINDINGS
Two osteoanabolic agents, abaloparatide and romosozumab, were recently approved for treatment of patients with osteoporosis at high fracture risk. These agents, along with teriparatide, are valuable for primary and secondary fracture prevention. Orthopedic surgeons are well positioned to facilitate secondary fracture prevention via referrals to fracture liaison services or other bone health specialist colleagues. This review aims to help surgeons understand how to identify patients with sufficiently high fracture risk to warrant consideration of osteoanabolic therapy. Recent evidence around the perioperative use and potential benefits of osteoanabolic agents in fracture healing and other orthopedic settings (e.g., spinal fusion and arthroplasty) in individuals with osteoporosis is also discussed. Osteoanabolic agents should be considered for patients with osteoporosis at very high fracture risk, including those with prior osteoporotic fractures and those with poor bone health who are undergoing bone-related surgery.
Topics: Humans; Bone Density; Bone Density Conservation Agents; Osteoporosis; Osteoporotic Fractures; Teriparatide
PubMed: 37289382
DOI: 10.1007/s11914-023-00793-8 -
Endocrinology and Metabolism (Seoul,... Dec 2023Since our discovery in 2006 that acromegaly is associated with an increased risk of vertebral fractures, many authors have confirmed this finding in both cross-sectional... (Review)
Review
Since our discovery in 2006 that acromegaly is associated with an increased risk of vertebral fractures, many authors have confirmed this finding in both cross-sectional and prospective studies. Due to the high epidemiological and clinical impact of this newly discovered comorbidity of acromegaly, this topic has progressively become more important and prominent over the years, and the pertinent literature has been enriched by new findings on the pathophysiology and treatment. The aim of this narrative review was to discuss these novel findings, integrating them with the seminal observations, in order to give the reader an updated view of how the field of acromegaly and bone is developing, from strong clinical observations to a mechanistic understanding and possible prevention and treatment.
Topics: Humans; Acromegaly; Bone Density; Cross-Sectional Studies; Prospective Studies; Spinal Fractures
PubMed: 38164073
DOI: 10.3803/EnM.2023.601 -
Arthritis Research & Therapy Dec 2023To investigate the causal relationship between low bone mineral density (BMD) and osteoarthritis (OA) using Mendelian randomization (MR) design.
OBJECTIVE
To investigate the causal relationship between low bone mineral density (BMD) and osteoarthritis (OA) using Mendelian randomization (MR) design.
METHODS
Two-sample bi-directional MR analyses were performed using summary-level information on OA traits from UK Biobank and arcOGEN. Sensitivity analyses including MR-Egger, simple median, weighted median, MR pleiotropy residual sum, and outlier approaches were utilized in conjunction with inverse variance weighting (IVW). Gene ontology (GO) enrichment analyses and expression quantitative trait locus (eQTL) colocalization analyses were used to investigate the potential mechanism and shared genes between osteoporosis (OP) and OA.
RESULTS
The IVW method revealed that genetically predicted low femoral neck BMD was significantly linked with hip (β = 0.105, 95% CI: 0.023-0.188) and knee OA (β = 0.117, 95% CI: 0.049-0.184), but not with other site-specific OA. Genetically predicted low lumber spine BMD was significantly associated with OA at any sites (β = 0.048, 95% CI: 0.011-0.085), knee OA (β = 0.101, 95% CI: 0.045-0.156), and hip OA (β = 0.150, 95% CI: 0.077-0.224). Only hip OA was significantly linked with genetically predicted reduced total bone BMD (β = 0.092, 95% CI: 0.010-0.174). In the reverse MR analyses, no evidence for a causal effect of OA on BMD was found. GO enrichment analysis and eQTL analysis illustrated that DDN and SMAD-3 were the most prominent co-located genes.
CONCLUSIONS
These findings suggested that OP may be causally linked to an increased risk of OA, indicating that measures to raise BMD may be effective in preventing OA. More research is required to determine the underlying processes via which OP causes OA.
Topics: Humans; Osteoarthritis, Hip; Mendelian Randomization Analysis; Osteoporosis; Bone Diseases, Metabolic; Osteoarthritis, Knee; Genome-Wide Association Study; Polymorphism, Single Nucleotide; Bone Density
PubMed: 38093316
DOI: 10.1186/s13075-023-03213-5 -
Osteoporosis International : a Journal... Oct 2023It remains unclear whether the relationship between type 2 diabetes mellitus (T2DM) and bone mineral density (BMD) reflects causality in East Asian populations. Herein,...
UNLABELLED
It remains unclear whether the relationship between type 2 diabetes mellitus (T2DM) and bone mineral density (BMD) reflects causality in East Asian populations. Herein, a Mendelian randomization study conducted in East Asian population enhances the current clinical cognition that T2DM is not associated with reduction in BMD.
PURPOSE
A Mendelian randomization (MR) approach was utilized to investigate the relationship between type 2 diabetes mellitus (T2DM) and bone mineral density (BMD) in East Asian populations.
METHODS
Genome-wide association study summary data from BioBank Japan were used to identify genetic variants strongly related to T2DM risk (36,614 cases and 155,150 controls) and osteoporosis (7788 cases and 204,665 controls). Heel BMD GWAS data of 1260 East Asian people from ieu open gwas project was considered as a second outcome. Inverse variance-weighted (IVW) analysis was mainly applied; MR-Egger and the weighted median were also used to obtain robust estimates. A series of sensitivity analyses including Cochran's Q test, MR-Egger regression, and leave-one-out analysis were used to detect pleiotropy or heterogeneity.
RESULTS
In the main analysis, IVW estimates indicated that T2DM significantly associated with the risk of osteoporosis (odds ratio = 0.92, 95% CI: 0.86-0.99, p = 0.016) and with higher BMD (OR: 1.25, 95% CI: 1.06-1.46, p = 6.49 × 10). Results of comprehensive sensitivity analysis were consistent with the main causality estimate. Horizontal pleiotropy and heterogeneity were absent in our MR study.
CONCLUSIONS
T2DM is not associated with reduction in BMD in terms of genetic polymorphism in East Asian populations.
Topics: Humans; Bone Density; Diabetes Mellitus, Type 2; East Asian People; Genome-Wide Association Study; Mendelian Randomization Analysis; Osteoporosis; Polymorphism, Single Nucleotide
PubMed: 37306802
DOI: 10.1007/s00198-023-06807-6