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Women's Health (London, England) 2022Heart failure (HF) is a prevalent clinical syndrome that causes significant physical limitations. Osteoporosis is also an important cause of loss of functionality, and... (Review)
Review
Heart failure (HF) is a prevalent clinical syndrome that causes significant physical limitations. Osteoporosis is also an important cause of loss of functionality, and it mainly affects women. There are several reports linking HF and osteoporosis, and both share risk factors. Most of the data available so far point to bone fragility as a consequence of HF, and several mechanisms have been identified to explain this relationship. Among the proposed pathophysiological mechanisms are the hyperactivation of the renin-angiotensin-aldosterone system and the increase in parathyroid hormone, functional limitation, production of inflammatory mediators and the use of drugs for HF. The role of osteoprotegerin has gained attention owing to its cardiovascular and skeletal effects, its observed deficiency during the postmenopausal period along with its compensatory increases in HF and severe osteoporosis. The objective of this review was to perform a literature search for the main evidence on skeletal impairment in HF, with emphasis on women. As for epidemiological studies, we selected data from 3 meta-analyses and 20 individual observational studies, which together showed the interrelationship between the two clinical conditions in terms of both decreased bone density and increased fracture risk. In conclusion, HF and osteoporosis are interrelated conditions mediated by complex pathophysiological mechanisms which may be more relevant for postmenopausal women, considered to be a vulnerable population for both cardiovascular diseases and bone fragility.
Topics: Female; Humans; Bone Density; Osteoporosis; Fractures, Bone; Heart Failure; Risk Factors; Osteoporosis, Postmenopausal
PubMed: 36321835
DOI: 10.1177/17455057221135501 -
Journal of Bone and Mineral Research :... Jan 2022The bone-forming agent romosozumab is a monoclonal antibody that inhibits sclerostin, leading to increased bone formation and decreased resorption. The highest levels of... (Randomized Controlled Trial)
Randomized Controlled Trial
The bone-forming agent romosozumab is a monoclonal antibody that inhibits sclerostin, leading to increased bone formation and decreased resorption. The highest levels of bone formation markers in human patients are observed in the first 2 months of treatment. Histomorphometric analysis of bone biopsies from the phase 3 FRAME trial (NCT01575834) showed an early significant increase in bone formation with concomitant decreased resorption. Preclinical studies demonstrated that most new bone formation after romosozumab treatment was modeling-based bone formation (MBBF). Here we analyzed bone biopsies from FRAME to assess the effect of 2 months of romosozumab versus placebo on the surface extent of MBBF and remodeling-based bone formation (RBBF). In FRAME, postmenopausal women aged ≥55 years with osteoporosis were randomized 1:1 to 210 mg romosozumab or placebo sc every month for 12 months, followed by 60 mg denosumab sc every 6 months for 12 months. Participants in the bone biopsy substudy received quadruple tetracycline labeling and underwent transiliac biopsies at month 2. A total of 29 biopsies were suitable for histomorphometry. Using fluorescence microscopy, bone formation at cancellous, endocortical, and periosteal envelopes was classified based on the appearance of underlying cement lines as modeling (smooth) or remodeling (scalloped). Data were compared using the Wilcoxon rank-sum test, without multiplicity adjustment. After 2 months, the median percentage of MBBF referent to the total bone surface was significantly increased with romosozumab versus placebo on cancellous (18.0% versus 3.8%; p = 0.005) and endocortical (36.7% versus 3.0%; p = 0.001), but not on periosteal (5.0% versus 2.0%; p = 0.37) surfaces, with no significant difference in the surface extent of RBBF on all three bone surfaces. These data show that stimulation of bone formation in the first 2 months of romosozumab treatment in postmenopausal women with osteoporosis is predominately due to increased MBBF on endocortical and cancellous surfaces. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
Topics: Antibodies, Monoclonal; Bone Density; Bone Density Conservation Agents; Female; Humans; Middle Aged; Osteogenesis; Osteoporosis; Osteoporosis, Postmenopausal
PubMed: 34633116
DOI: 10.1002/jbmr.4457 -
Archives of Endocrinology and Metabolism Nov 2023Bisphosphonates (BPs) are medications widely used in clinical practice to treat osteoporosis and reduce fragility fractures. Its beneficial effects on bone tissue have... (Review)
Review
Bisphosphonates (BPs) are medications widely used in clinical practice to treat osteoporosis and reduce fragility fractures. Its beneficial effects on bone tissue have been consolidated in the literature for the last decades. They have a high affinity for bone hydroxyapatite crystals, and most bisphosphonates remain on the bone surface for a long period of time. Benefits of long-term use of BPs: Large and important trials (Fracture Intervention Trial Long-term Extension and Health Outcomes and Reduced Incidence with Zoledronic acid Once Yearly-Pivotal Fracture Trial) with extended use of alendronate (up to 10 years) and zoledronate (up to 6 years) evidenced significant gain of bone mineral density (BMD) and vertebral fracture risk reduction. Risks of long-term use of BPs: The extended use of antiresorptive therapy has drawn attention to two extremely rare, although severe, adverse events. That is, atypical femoral fracture and medication-related osteonecrosis of the jaw are more common in patients with high cumulative doses and longer duration of therapy. BPs have demonstrated safety and effectiveness throughout the years and evidenced increased BMD and reduced fracture risks, resulting in reduced morbimortality, and improved quality of life. These benefits overweight the risks of rare adverse events.
Topics: Humans; Female; Diphosphonates; Bone Density Conservation Agents; Quality of Life; Osteoporosis; Alendronate; Zoledronic Acid; Fractures, Bone; Osteoporosis, Postmenopausal
PubMed: 37948565
DOI: 10.20945/2359-4292-2022-0334 -
Journal of Orthopaedic Surgery and... Jul 2023Physical activity (PA) is generally encouraged for the treatment of osteoporosis. However, epidemiological statistics on the level of physical activity required for bone...
BACKGROUND
Physical activity (PA) is generally encouraged for the treatment of osteoporosis. However, epidemiological statistics on the level of physical activity required for bone health are scarce. The purpose of this research was to analyze the association between PA and total spine bone mineral density (BMD) in postmenopausal women.
METHODS
The research study included postmenopausal women aged ≥ 50 from the National Health and Nutrition Examination Survey. The metabolic equivalent (MET), weekly frequency, and duration of each activity were used to calculate PA. Furthermore, the correlations between BMD and PA were investigated by multivariable weighted logistic regression.
RESULTS
Eventually, 1681 postmenopausal women were included, with a weighted mean age of 62.27 ± 8.18 years. This study found that performing ≥ 38MET-h/wk was linked to a lower risk of osteoporosis after controlling for several covariates. Furthermore, the subgroup analysis revealed that the connection between total spine BMD and moderate-to-vigorous PA was more obvious among postmenopausal women aged < 65 years or individuals with normal BMI (< 25 kg/m).
CONCLUSION
Physical activity ranging from moderate to vigorous was linked to higher total spine BMD in postmenopausal women.
Topics: Humans; Female; Middle Aged; Aged; Bone Density; Nutrition Surveys; Cross-Sectional Studies; Postmenopause; Absorptiometry, Photon; Osteoporosis; Exercise; Osteoporosis, Postmenopausal
PubMed: 37454096
DOI: 10.1186/s13018-023-03976-2 -
Frontiers in Endocrinology 2022Osteoporosis is one of the most common systemic metabolic bone diseases, especially in postmenopausal women. Circular RNA (circRNA) has been implicated in various human...
Identification of Serum Exosome-Derived circRNA-miRNA-TF-mRNA Regulatory Network in Postmenopausal Osteoporosis Using Bioinformatics Analysis and Validation in Peripheral Blood-Derived Mononuclear Cells.
BACKGROUND
Osteoporosis is one of the most common systemic metabolic bone diseases, especially in postmenopausal women. Circular RNA (circRNA) has been implicated in various human diseases. However, the potential role of circRNAs in postmenopausal osteoporosis (PMOP) remains largely unknown. The study aims to identify potential biomarkers and further understand the mechanism of PMOP by constructing a circRNA-associated ceRNA network.
METHODS
The PMOP-related datasets GSE161361, GSE64433, and GSE56116 were downloaded from the Gene Expression Omnibus (GEO) database and were used to obtain differentially expressed genes (DEGs). Gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were applied to determine possible relevant functions of differentially expressed messenger RNAs (mRNAs). The TRRUST database was used to predict differential transcription factor (TF)-mRNA regulatory pairs. Afterwards, combined CircBank and miRTarBase, circRNA-miRNA as well as miRNA-TF pairs were constructed. Then, a circRNA-miRNA-TF-mRNA network was established. Next, the correlation of mRNAs, TFs, and PMOP was verified by the Comparative Toxicogenomics Database. And expression levels of key genes, including circRNAs, miRNAs, TFs, and mRNAs in the ceRNA network were further validated by quantitative real-time PCR (qRT-PCR). Furthermore, to screen out signaling pathways related to key mRNAs of the ceRNA network, Gene Set Enrichment Analysis (GSEA) was performed.
RESULTS
A total of 1201 DE mRNAs, 44 DE miRNAs, and 1613 DE circRNAs associated with PMOP were obtained. GO function annotation showed DE mRNAs were mainly related to inflammatory responses. KEGG analysis revealed DE mRNAs were mainly enriched in osteoclast differentiation, rheumatoid arthritis, hematopoietic cell lineage, and cytokine-cytokine receptor interaction pathways. We first identified 26 TFs and their target mRNAs. Combining DE miRNAs, miRNA-TF/mRNA pairs were obtained. Combining DE circRNAs, we constructed the ceRNA network contained 6 circRNAs, 4 miRNAs, 4 TFs, and 12 mRNAs. The expression levels of most genes detected by qRT-PCR were generally consistent with the microarray results. Combined with the qRT-PCR validation results, we eventually identified the ceRNA network that contained 4 circRNAs, 3 miRNAs, 3 TFs, and 9 mRNAs. The GSEA revealed that 9 mRNAs participate in many important signaling pathways, such as "olfactory transduction", "T cell receptor signaling pathway", and "neuroactive ligand-receptor interaction". These pathways have been reported to the occurrence and development of PMOP. To sum up, key mRNAs in the ceRNA network may participate in the development of osteoporosis by regulating related signal pathways.
CONCLUSIONS
A circRNA-associated ceRNA network containing TFs was established for PMOP. The study may help further explore the molecular mechanisms and may serve as potential biomarkers or therapeutic targets for PMOP.
Topics: Biomarkers; Computational Biology; Exosomes; Female; Gene Expression Profiling; Gene Regulatory Networks; Humans; MicroRNAs; Osteoporosis, Postmenopausal; RNA, Circular; RNA, Messenger; Transcription Factors
PubMed: 35757392
DOI: 10.3389/fendo.2022.899503 -
The American Journal of Clinical... Oct 2022Dietary consumption of prunes has favorable impacts on bone health, but more research is necessary to improve upon study designs and refine our understandings. (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Dietary consumption of prunes has favorable impacts on bone health, but more research is necessary to improve upon study designs and refine our understandings.
OBJECTIVES
We evaluated the effects of prunes (50 g or 100 g/d) on bone mineral density (BMD) in postmenopausal women during a 12-mo dietary intervention. Secondary outcomes include effects on bone biomarkers.
METHODS
The single-center, parallel-arm 12-mo randomized controlled trial tested the effects of 50 g and 100 g prunes compared with a control group on BMD (every 6 mo) and bone biomarkers in postmenopausal women.
RESULTS
In total, 235 women (age 62.1 ± 5.0 y) were randomly allocated into control (n = 78), 50-g prune (n = 79), or 100-g prune (n = 78) groups. Compliance was 90.2 ± 1.8% and 87.1 ± 2.1% in the 50-g and 100-g prune groups. Dropout was 22%; however, the dropout rate was 41% for the 100-g prune group (compared with other groups: 10%, control; 15%, 50 g prune; P < 0.001). A group × time interaction for total hip BMD was observed in control compared with 50-g prune groups (P < 0.05) but not in control compared with 100-g prune groups (P > 0.05). Total hip BMD decreased -1.1 ± 0.2% in the control group at 12 mo, whereas the 50-g prune group preserved BMD (-0.3 ± 0.2%) at 12 mo (P < 0.05). Although hip fracture risk (FRAX) worsened in the control group at 6 mo compared with baseline (10.3 ± 0.5% compared with 9.8 ± 0.5%, P < 0.05), FRAX score was maintained in the pooled (50 g + 100 g) prune groups.
CONCLUSIONS
A 50-g daily dose of prunes can prevent loss of total hip BMD in postmenopausal women after 6 mo, which persisted for 12 mo. Given that there was high compliance and retention at the 50-g dosage over 12 mo, we propose that the 50-g dose represents a valuable nonpharmacologic treatment strategy that can be used to preserve hip BMD in postmenopausal women and possibly reduce hip fracture risk. This trial was registered at clinicaltrials.gov as NCT02822378.
Topics: Aged; Biomarkers; Bone Density; Female; Hip Fractures; Humans; Middle Aged; Osteoporosis, Postmenopausal; Pelvic Bones; Postmenopause
PubMed: 35798020
DOI: 10.1093/ajcn/nqac189 -
Osteoporosis International : a Journal... Mar 2023A retrospective study of 121 patients who stopped denosumab (Dmab) then received no treatment (NT), risedronate (RIS), alendronate (ALN), or zoledronic acid (ZOL). Bone...
UNLABELLED
A retrospective study of 121 patients who stopped denosumab (Dmab) then received no treatment (NT), risedronate (RIS), alendronate (ALN), or zoledronic acid (ZOL). Bone density (spine and hip) during and after Dmab discontinuation was measured. Treatment with ALN or ZOL, not NT and RIS, mitigated BMD loss after Dmab discontinuation.
INTRODUCTION
Denosumab (Dmab) discontinuation is associated with bone loss and multiple vertebral fractures. The purpose was to compare bone mineral density (BMD) change in patients following Dmab discontinuation with no subsequent treatment (NT) and three bisphosphonate (BP) treatments: risedronate (RIS), alendronate (ALN), and zoledronic acid (ZOL).
METHODS
In a review of 121 patients aged 71.2 ± 8.1 years, discontinuing Dmab (mean 5.4 doses), 33 received NT and 88 received BP (22 RIS; 34 ALN; 32 ZOL). BMD change after 1 year was compared between groups at the lumbar spine (LS), femoral neck (FN), and total hip (TH). Risk factors for bone loss after Dmab discontinuation were compared between groups and incidence of vertebral fractures was determined.
RESULTS
Following Dmab discontinuation, LS mean change (g/cm; 95% CI) was for NT: - 0.041 (- 0.062 to - 0.021); RIS: - 0.035 (- 0.052 to - 0.017); ALN: - 0.005 (- 0.020 to 0.009); and ZOL: - 0.009 (- 0.025 to 0.008). Differences in LS were found between NT and ALN (p = 0.015), and NT and ZOL (p=0.037), but not between NT and RIS. The only significant difference in TH was found between NT and ZOL (p 0.034) with no group differences in FN. BMD gains during Dmab treatment were associated with BMD loss after Dmab discontinuation. In a subset, discontinuation after Dmab treatment (> 5 doses) followed by ALN (n = 22) and ZOL (n = 11) showed no difference in BMD. Five of 7 vertebral fractures occurred after Dmab discontinuation in NT.
CONCLUSION
Subsequent treatment with ALN or ZOL but not NT and RIS mitigates BMD loss after Dmab discontinuation.
Topics: Female; Humans; Alendronate; Bone Density; Bone Density Conservation Agents; Bone Diseases, Metabolic; Denosumab; Diphosphonates; Lumbar Vertebrae; Osteoporosis, Postmenopausal; Retrospective Studies; Risedronic Acid; Spinal Fractures; Zoledronic Acid
PubMed: 36602607
DOI: 10.1007/s00198-022-06648-9 -
Journal of Bone and Mineral Research :... Nov 2021The Active-Controlled Fracture Study in Postmenopausal Women With Osteoporosis at High Risk (ARCH) trial (NCT01631214; https://clinicaltrials.gov/ct2/show/NCT01631214)... (Clinical Trial)
Clinical Trial
Romosozumab improves lumbar spine bone mass and bone strength parameters relative to alendronate in postmenopausal women: results from the Active-Controlled Fracture Study in Postmenopausal Women With Osteoporosis at High Risk (ARCH) trial.
The Active-Controlled Fracture Study in Postmenopausal Women With Osteoporosis at High Risk (ARCH) trial (NCT01631214; https://clinicaltrials.gov/ct2/show/NCT01631214) showed that romosozumab for 1 year followed by alendronate led to larger areal bone mineral density (aBMD) gains and superior fracture risk reduction versus alendronate alone. aBMD correlates with bone strength but does not capture all determinants of bone strength that might be differentially affected by various osteoporosis therapeutic agents. We therefore used quantitative computed tomography (QCT) and finite element analysis (FEA) to assess changes in lumbar spine volumetric bone mineral density (vBMD), bone volume, bone mineral content (BMC), and bone strength with romosozumab versus alendronate in a subset of ARCH patients. In ARCH, 4093 postmenopausal women with severe osteoporosis received monthly romosozumab 210 mg sc or weekly oral alendronate 70 mg for 12 months, followed by open-label weekly oral alendronate 70 mg for ≥12 months. Of these, 90 (49 romosozumab, 41 alendronate) enrolled in the QCT/FEA imaging substudy. QCT scans at baseline and at months 6, 12, and 24 were assessed to determine changes in integral (total), cortical, and trabecular lumbar spine vBMD and corresponding bone strength by FEA. Additional outcomes assessed include changes in aBMD, bone volume, and BMC. Romosozumab caused greater gains in lumbar spine integral, cortical, and trabecular vBMD and BMC than alendronate at months 6 and 12, with the greater gains maintained upon transition to alendronate through month 24. These improvements were accompanied by significantly greater increases in FEA bone strength (p < 0.001 at all time points). Most newly formed bone was accrued in the cortical compartment, with romosozumab showing larger absolute BMC gains than alendronate (p < 0.001 at all time points). In conclusion, romosozumab significantly improved bone mass and bone strength parameters at the lumbar spine compared with alendronate. These results are consistent with greater vertebral fracture risk reduction observed with romosozumab versus alendronate in ARCH and provide insights into structural determinants of this differential treatment effect. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
Topics: Alendronate; Antibodies, Monoclonal; Bone Density; Bone Density Conservation Agents; Female; Humans; Lumbar Vertebrae; Osteoporosis; Osteoporosis, Postmenopausal; Postmenopause
PubMed: 34190361
DOI: 10.1002/jbmr.4409 -
The Journal of Clinical Endocrinology... Mar 2020The ACTIVE study demonstrated the antifracture efficacy of abaloparatide in postmenopausal women with osteoporosis. ACTIVExtend demonstrated sustained fracture risk... (Comparative Study)
Comparative Study Randomized Controlled Trial
CONTEXT
The ACTIVE study demonstrated the antifracture efficacy of abaloparatide in postmenopausal women with osteoporosis. ACTIVExtend demonstrated sustained fracture risk reduction with alendronate in abaloparatide-treated participants from ACTIVE. A direct comparison of the efficacy of abaloparatide and antiresorptive therapies has not been performed.
OBJECTIVE
The objective of this analysis is to compare the antifracture efficacy of abaloparatide in ACTIVE with that of alendronate in ACTIVExtend.
DESIGN
In this post hoc analysis, the rate of new vertebral fractures for women in ACTIVExtend (N = 1139) was calculated based on baseline and endpoint radiographs for placebo or abaloparatide in ACTIVE and alendronate in ACTIVExtend. Vertebral fracture rates between abaloparatide and alendronate were compared in a Poisson regression model. Fracture rates for nonvertebral and clinical fractures were compared based on a Poisson model during 18 months of abaloparatide or placebo treatment in ACTIVE and 18 months of alendronate treatment in ACTIVExtend.
RESULTS
The vertebral fracture rate was lower during abaloparatide treatment in ACTIVE (0.47 fractures/100 patient-years) than alendronate treatment in ACTIVExtend (1.66 fractures/100 patient-years) (relative risk reduction 71%; P = .027). Although the comparisons did not meet statistical significance, after switching from placebo (ACTIVE) to alendronate (ACTIVExtend), the rate of new vertebral fractures decreased from 2.49 to 1.66 fractures per 100 patient-years, and after switching from abaloparatide to alendronate from 0.47 to 0.19 fractures per 100 patient-years. The rates of nonvertebral fractures and clinical fractures were not significantly different.
CONCLUSION
Initial treatment with abaloparatide may result in greater vertebral fracture reduction compared with alendronate in postmenopausal women with osteoporosis.
Topics: Aged; Alendronate; Bone Density; Bone Density Conservation Agents; Drug Therapy, Combination; Female; Femur Neck; Humans; Lumbar Vertebrae; Middle Aged; Osteoporosis, Postmenopausal; Osteoporotic Fractures; Parathyroid Hormone-Related Protein; Placebos; Radiography; Risk Factors; Spinal Fractures; Treatment Outcome
PubMed: 31674644
DOI: 10.1210/clinem/dgz162 -
Bone Jul 2022The effects of daily teriparatide (20 μg) (D-PTH), weekly high-dose teriparatide (56.5 μg) (W-PTH), or bisphosphonates (BPs) on areal bone mineral density (aBMD),... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
The effects of daily teriparatide (20 μg) (D-PTH), weekly high-dose teriparatide (56.5 μg) (W-PTH), or bisphosphonates (BPs) on areal bone mineral density (aBMD), bone turnover markers (BTMs), volumetric BMD (vBMD), microarchitecture, and estimated strength were investigated in postmenopausal osteoporosis patients.
METHODS
The study participants were 131 women with a history of fragility fractures. They were randomized to receive D-PTH, W-PTH, or BPs (alendronate or risedronate) for 18 months. Dual-energy X-ray absorptiometry (DXA), BTMs, and high-resolution peripheral quantitative CT (HR-pQCT) parameters were evaluated at baseline and after 6 and 18 months of treatment. The primary endpoint was the change (%) in cortical thickness (Ct.Th) after 18 months' treatment compared with baseline.
RESULTS
DXA showed that D-PTH, W-PTH, and BPs increased lumbar spine aBMD (+12.0%, +8.5%, and +6.8%) and total hip aBMD (+3.0%, +2.1%, and +3.0%), but D-PTH and W-PTH decreased 1/3 radius aBMD (-4.1%, -3.0%, -1.4%) after 18 months. On HR-pQCT, D-PTH increased trabecular vBMD (Tb.vBMD) at the distal radius and tibia after 18 months (+6.4%, +3.7%) compared with the BPs group, decreased cortical volumetric tissue mineral density (Ct.vTMD) (-1.8%, -0.9%) compared with the other groups, increased Ct.Th (+1.3%, +3.9%), and increased failure load (FL) (+4.7%, +4.4%). W-PTH increased Tb.vBMD (+5.3%, +1.9%), maintained Ct.vTMD (-0.7%, +0.2%) compared with D-PTH, increased Ct.Th (+0.6%, +3.6%), and increased FL (+4.9%, +4.5%). The BPs increased Tb.vBMD only in the radius (+2.0%, +0.2%), maintained Ct.vTMD (-0.6%, +0.3%), increased Ct.Th (+0.5%, +3.4%), and increased FL (+3.9%, +2.8%).
CONCLUSIONS
D-PTH and W-PTH comparably increased Ct.Th, the primary endpoint. D-PTH had a strong effect on trabecular bone. Although D-PTH decreased Ct.vTMD, it increased Ct.Th and total bone strength. W-PTH had a moderate effect on trabecular bone, maintained Ct.vTMD, and increased Ct.Th and total bone strength to the same extent as D-PTH.
Topics: Absorptiometry, Photon; Bone Density; Diphosphonates; Female; Humans; Osteoporosis, Postmenopausal; Radius; Teriparatide; Tibia
PubMed: 35398293
DOI: 10.1016/j.bone.2022.116416