-
PeerJ 2022There have been promising results published regarding the potential of stem cells in regenerative medicine. However, the vast variety of choices of techniques and the...
BACKGROUND
There have been promising results published regarding the potential of stem cells in regenerative medicine. However, the vast variety of choices of techniques and the lack of a standard approach to analyse human osteoblast and osteoclast differentiation may reduce the utility of stem cells as a tool in medical applications. Therefore, this review aims to systematically evaluate the findings based on stem cell differentiation to define a standard gene expression profile approach.
METHODS
This review was performed following the PRISMA guidelines. A systematic search of the study was conducted by retrieving articles from the electronic databases PubMed and Web of Science to identify articles focussed on gene expression and approaches for osteoblast and osteoclast differentiation.
RESULTS
Six articles were included in this review; there were original articles of human stem cell differentiation into osteoblasts and osteoclasts that involved gene expression profiling. Quantitative polymerase chain reaction (qPCR) was the most used technique for gene expression to detect differentiated human osteoblasts and osteoclasts. A total of 16 genes were found to be related to differentiating osteoblast and osteoclast differentiation.
CONCLUSION
Qualitative information of gene expression provided by qPCR could become a standard technique to analyse the differentiation of human stem cells into osteoblasts and osteoclasts rather than evaluating relative gene expression. and could be applied to detect osteoblasts and osteoclasts, respectively, while could be applied to detect both osteoblasts and osteoclasts. This review provides future researchers with a central source of relevant information on the vast variety of gene expression approaches in analysing the differentiation of human osteoblast and osteoclast cells. In addition, these findings should enable researchers to conduct accurately and efficiently studies involving isolated human stem cell differentiation into osteoblasts and osteoclasts.
Topics: Humans; Osteoclasts; Transcriptome; Osteoblasts; Cell Differentiation; Stem Cells
PubMed: 36275474
DOI: 10.7717/peerj.14174 -
Rheumatology Advances in Practice 2021Denosumab is used for osteoporosis because it inhibits osteoclast maturation and suppresses bone resorption. Although denosumab is expected to inhibit the bone erosion...
OBJECTIVES
Denosumab is used for osteoporosis because it inhibits osteoclast maturation and suppresses bone resorption. Although denosumab is expected to inhibit the bone erosion in RA, its therapeutic efficacy is not well established. The aim of this study was to estimate the effects of denosumab on RA through a meta-analysis.
METHODS
A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. PubMed, Web of Science and Scopus were searched for original studies providing information on BMD, joint destruction and disease activity in denosumab-treated RA. A random-effects model was used in the meta-analysis.
RESULTS
Of the 367 studies identified, 18 met the selection criteria. The BMDs of the lumbar spine, total hip and femoral neck at 12 months after denosumab treatment increased by 5.27% (95% CI: 4.37, 6.18), 2.82% (2.46, 3.18) and 3.07% (2.66, 3.48), respectively. In the sensitivity analysis, age and sex tended to influence the effect of denosumab therapy on the rate of variation of BMD, but not glucocorticoid use. The changes in the modified total sharp, erosion and joint space narrowing scores at 12 months after denosumab treatment were significantly smaller with denosumab than with placebo, although the DAS did not change after denosumab treatment.
CONCLUSION
Although denosumab has an inhibitory effect on the bone resorption in RA, its effects might be influenced by the age and sex of RA patients, but not by glucocorticoid use.
PubMed: 34988358
DOI: 10.1093/rap/rkab099 -
Plants (Basel, Switzerland) May 2023Bone metabolism is a complex process which is influenced by the activity of bone cells (e.g., osteocytes, osteoblasts, osteoclasts); the effect of some specific... (Review)
Review
Bone metabolism is a complex process which is influenced by the activity of bone cells (e.g., osteocytes, osteoblasts, osteoclasts); the effect of some specific biomarkers (e.g., parathyroid hormone, vitamin D, alkaline phosphatase, osteocalcin, osteopontin, osteoprotegerin, osterix, RANKL, Runx2); and the characteristic signaling pathways (e.g., RANKL/RANK, Wnt/β, Notch, BMP, SMAD). Some phytochemical compounds-such as flavonoids, tannins, polyphenols, anthocyanins, terpenoids, polysaccharides, alkaloids and others-presented a beneficial and stimulating effect in the bone regeneration process due to the pro-estrogenic activity, the antioxidant and the anti-inflammatory effect and modulation of bone signaling pathways. Lately, nanomedicine has emerged as an innovative concept for new treatments in bone-related pathologies envisaged through the incorporation of medicinal substances in nanometric systems for oral or local administration, as well as in nanostructured scaffolds with huge potential in bone tissue engineering.
PubMed: 37653972
DOI: 10.3390/plants12102055 -
Dental Press Journal of Orthodontics Oct 2015Orthodontic anchorage is one of the most challenging aspects of Orthodontics. Preventing undesired movement of teeth could result in safer and less complicated... (Review)
Review
INTRODUCTION
Orthodontic anchorage is one of the most challenging aspects of Orthodontics. Preventing undesired movement of teeth could result in safer and less complicated orthodontic treatment. Recently, several reviews have been published about the effects of different molecules on bone physiology and the clinical side effects in Orthodontics. However, the effects of local application of these substances on the rate of orthodontic tooth movement have not been assessed.
OBJECTIVES
The aim of this research was to analyze the scientific evidence published in the literature about the effects of different molecules on orthodontic anchorage.
METHODS
The literature was systematically reviewed using PubMed/Medline, Scopus and Cochrane databases from 2000 up to July 31st, 2014. Articles were independently selected by two different researchers based on previously established inclusion and exclusion criteria, with a concordance Kappa index of 0.86. The methodological quality of the reviewed papers was performed.
RESULTS
Search strategy identified 270 articles. Twenty-five of them were selected after application of inclusion/exclusion criteria, and only 11 qualified for final analysis. Molecules involved in orthodontic anchorage were divided into three main groups: osteoprotegerin (OPG), bisphosphonates (BPs) and other molecules (OMs).
CONCLUSIONS
Different drugs are able to alter the bone remodeling cycle, influencing osteoclast function and, therefore, tooth movement. Thus, they could be used in order to provide maximal anchorage while preventing undesired movements. OPG was found the most effective molecule in blocking the action of osteoclasts, thereby reducing undesired movements.
Topics: Acetylcysteine; Animals; Anti-Inflammatory Agents; Antioxidants; Bone Remodeling; Celecoxib; Clodronic Acid; Diclofenac; Diphosphonates; Humans; Imidazoles; Interferon-gamma; Isoxazoles; Lactones; Mice; Orthodontic Anchorage Procedures; Osteoclasts; Osteoprotegerin; Pamidronate; Rats; Resveratrol; Stilbenes; Sulfones; Tooth Mobility; Tooth Movement Techniques; Zoledronic Acid
PubMed: 26560822
DOI: 10.1590/2177-6709.20.5.058-065.oar -
The Cochrane Database of Systematic... May 2022Osteoporosis is an abnormal reduction in bone mass and bone deterioration leading to increased fracture risk. Risedronate belongs to the bisphosphonate class of drugs... (Review)
Review
BACKGROUND
Osteoporosis is an abnormal reduction in bone mass and bone deterioration leading to increased fracture risk. Risedronate belongs to the bisphosphonate class of drugs which act to inhibit bone resorption by interfering with the activity of osteoclasts. This is an update of a Cochrane Review that was originally published in 2003.
OBJECTIVES
We assessed the benefits and harms of risedronate in the primary and secondary prevention of osteoporotic fractures for postmenopausal women at lower and higher risk for fractures, respectively.
SEARCH METHODS
With broader and updated strategies, we searched the Cochrane Central Register of Control Trials (CENTRAL), MEDLINE and Embase. A grey literature search, including the online databases ClinicalTrials.gov, International Clinical Trials Registry Platform (ICTRP), and drug approval agencies, as well as bibliography checks of relevant systematic reviews was also performed. Eligible trials published between 1966 to 24 March 2021 were identified.
SELECTION CRITERIA
We included randomised controlled trials that assessed the benefits and harms of risedronate in the prevention of fractures for postmenopausal women. Participants must have received at least one year of risedronate, placebo or other anti-osteoporotic drugs, with or without concurrent calcium/vitamin D. Major outcomes were clinical vertebral, non-vertebral, hip and wrist fractures, withdrawals due to adverse events, and serious adverse events. In the interest of clinical relevance and applicability, we classified a study as secondary prevention if its population fulfilled more than one of the following hierarchical criteria: a diagnosis of osteoporosis, a history of vertebral fractures, low bone mineral density (BMD)T score ≤ -2.5, and age ≥ 75 years old. If none of these criteria was met, the study was considered to be primary prevention.
DATA COLLECTION AND ANALYSIS
We used standard methodology expected by Cochrane. We pooled the relative risk (RR) of fractures using a fixed-effect model based on the expectation that the clinical and methodological characteristics of the respective primary and secondary prevention studies would be homogeneous, and the experience from the previous review suggesting that there would be a small number of studies. The base case included the data available for the longest treatment period in each placebo-controlled trial and a >15% relative change was considered clinically important. The main findings of the review were presented in summary of findings tables, using the GRADE approach. In addition, we looked at benefit and harm comparisons between different dosage regimens for risedronate and between risedronate and other anti-osteoporotic drugs.
MAIN RESULTS
Forty-three trials fulfilled the eligibility criteria, among which 33 studies (27,348 participants) reported data that could be extracted and quantitatively synthesized. We had concerns about particular domains of risk of bias in each trial. Selection bias was the most frequent concern, with only 24% of the studies describing appropriate methods for both sequence generation and allocation concealment. Fifty per cent and 39% of the studies reporting benefit and harm outcomes, respectively, were subject to high risk. None of the studies included in the quantitative syntheses were judged to be at low risk of bias in all seven domains. The results described below pertain to the comparisons for daily risedronate 5 mg versus placebo which reported major outcomes. Other comparisons are described in the full text. For primary prevention, low- to very low-certainty evidence was collected from four studies (one to two years in length) including 989 postmenopausal women at lower risk of fractures. Risedronate 5 mg/day may make little or no difference to wrist fractures [RR 0.48 ( 95% CI 0.03 to 7.50; two studies, 243 participants); absolute risk reduction (ARR) 0.6% fewer (95% CI 1% fewer to 7% more)] and withdrawals due to adverse events [RR 0.67 (95% CI 0.38 to 1.18; three studies, 748 participants); ARR 2% fewer (95% CI 5% fewer to 1% more)], based on low-certainty evidence. However, its preventive effects on non-vertebral fractures and serious adverse events are not known due to the very low-certainty evidence. There were zero clinical vertebral and hip fractures reported therefore the effects of risedronate for these outcomes are not estimable. For secondary prevention, nine studies (one to three years in length) including 14,354 postmenopausal women at higher risk of fractures provided evidence. Risedronate 5 mg/day probably prevents non-vertebral fractures [RR 0.80 (95% CI 0.72 to 0.90; six studies, 12,173 participants); RRR 20% (95% CI 10% to 28%) and ARR 2% fewer (95% CI 1% fewer to 3% fewer), moderate certainty], and may reduce hip fractures [RR 0.73 (95% CI 0.56 to 0.94); RRR 27% (95% CI 6% to 44%) and ARR 1% fewer (95% CI 0.2% fewer to 1% fewer), low certainty]. Both of these effects are probably clinically important. However, risedronate's effects are not known for wrist fractures [RR 0.64 (95% CI 0.33 to 1.24); three studies,1746 participants); ARR 1% fewer (95% CI 2% fewer to 1% more), very-low certainty] and not estimable for clinical vertebral fractures due to zero events reported (low certainty). Risedronate results in little to no difference in withdrawals due to adverse events [RR 0.98 (95% CI 0.90 to 1.07; eight studies, 9529 participants); ARR 0.3% fewer (95% CI 2% fewer to 1% more); 16.9% in risedronate versus 17.2% in control, high certainty] and probably results in little to no difference in serious adverse events [RR 1.00 (95% CI 0.94 to 1.07; six studies, 9435 participants); ARR 0% fewer (95% CI 2% fewer to 2% more; 29.2% in both groups, moderate certainty).
AUTHORS' CONCLUSIONS
This update recaps the key findings from our previous review that, for secondary prevention, risedronate 5 mg/day probably prevents non-vertebral fracture, and may reduce the risk of hip fractures. We are uncertain on whether risedronate 5mg/day reduces clinical vertebral and wrist fractures. Compared to placebo, risedronate probably does not increase the risk of serious adverse events. For primary prevention, the benefit and harms of risedronate were supported by limited evidence with high uncertainty.
Topics: Aged; Female; Hip Fractures; Humans; Osteoporosis; Osteoporosis, Postmenopausal; Osteoporotic Fractures; Postmenopause; Radius Fractures; Risedronic Acid; Secondary Prevention; Spinal Fractures; Wrist Injuries
PubMed: 35502787
DOI: 10.1002/14651858.CD004523.pub4 -
EFORT Open Reviews Jan 2022Patients with Gorham-Stout disease (GSD) present progressive destruction and resorption of bone. Typical bone-related symptoms include swelling, pain and functional... (Review)
Review
Patients with Gorham-Stout disease (GSD) present progressive destruction and resorption of bone. Typical bone-related symptoms include swelling, pain and functional impairment in the region involved. The three aspects of GSD etiopathology are osteoclasts, angiogenesis/lymphangiogenesis and osteoblast function. Multi-targeted pharmacological approach includes innovative options and represent milestones of treatment, sometimes associated with radiotherapy. Surgery is mainly used to treat complications: pathologic/impending fractures, spinal instability or deformities and chylothorax. In this narrative review, we highlight current standards in diagnosis, clinical management and therapeutic strategies.
PubMed: 35076412
DOI: 10.1530/EOR-21-0083 -
Journal of Oral and Maxillofacial... 2023Controversies exist in literature regarding nature, pathogenesis, and behaviour of giant cell lesions (GCLs) of jaws. Studies were attempted to solve these mysteries... (Review)
Review
Controversies exist in literature regarding nature, pathogenesis, and behaviour of giant cell lesions (GCLs) of jaws. Studies were attempted to solve these mysteries with immunohistochemical analysis, using various biological markers. Thus, the aim of this review is to appraise the role of immunohistochemistry (IHC) in evaluating the pathogenesis, cellular phenotype, nature, and behaviour of GCLs of jaws. PubMed, PubMed Central, and Clinical Key (Medline) databases were searched electronically irrespective of date of publication with assortment of several independent terms. Fifty-five articles that fulfilled the eligibility criteria were included in the review. Out of 55 included articles, 49 were associated with nature, pathogenesis, and behaviour and six articles were associated with treatment and outcome prediction. Although IHC solved some of the controversies associated with GCLs of jaws such as the osteoclastic phenotype of multinucleated giant cells, immunoexpression of proliferative markers does not distinct non-aggressive from aggressive central GCL but the nature, histogenesis, pathogenesis, and exact behaviour still remain debatable. With regard to formulation of treatment plan, immunohistochemical analysis revealed that expression of glucocorticoid and calcitonin receptors could act as a tool to decide the therapeutic strategy and aid in therapeutic adjustments according to evolution of the lesion.
PubMed: 37234327
DOI: 10.4103/jomfp.jomfp_18_22 -
Journal of Pharmacy & Bioallied Sciences Jul 2023Multiple myeloma is a malignant cancerous condition that is characterized by abnormal plasma cell production and can lead to bone destruction due to increased...
Multiple myeloma is a malignant cancerous condition that is characterized by abnormal plasma cell production and can lead to bone destruction due to increased osteoclastic activity and decreased osteoblastic activity. Many therapeutic therapies are used to treat diseases, such as chemotherapy and radiotherapy. In recent years, anti-sclerostin antibody treatment has been under investigation for its effect on the multiple myeloma. The present study was conducted to assess the effective therapeutic use of anti-sclerostin antibody in the treatment of multiple myeloma. The literature search was conducted using PubMed, Google Scholar, ScienceDirect, and PubMed Central using the following MeSH terms: "multiple myeloma", "anti-sclerostin antibody", "ubiquitin-proteasome pathway", "proteasome inhibitor", "Wnt pathway". A total of 348 articles were screened. Twenty-five out of 348 were full-text articles assessed for eligibility, and four articles were used in this systematic review. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used for the reporting of this systematic review. A total of four randomized control trials (RCT) were included and used in this systematic review. The anti-sclerostin antibodies were various other drugs, and it was found that the anti-sclerostin antibody was effective in preventing autoantibody formation, decreasing bone destruction, and increasing trabecular bone. Anti-sclerostin antibody was found to be effective in decreasing bone destruction by reducing osteoclastic activity and increasing osteoblastic activity associated with multiple myeloma.
PubMed: 37654355
DOI: 10.4103/jpbs.jpbs_560_22 -
Journal of Medicinal Food Jan 2016Osteoporosis is an age-related disorder that affects both women and men, although estrogen deficiency induced by menopause accelerates bone loss in older women. As the... (Review)
Review
Osteoporosis is an age-related disorder that affects both women and men, although estrogen deficiency induced by menopause accelerates bone loss in older women. As the demographic shifts to a more aged population, a growing number of men and women will be afflicted with osteoporosis. Since the current drug therapies available have multiple side effects, including increased risk of developing certain types of cancer or complications, a search for potential nonpharmacologic alternative therapies for osteoporosis is of prime interest. Soy isoflavones (SI) have demonstrated potential bone-specific effects in a number of studies. This article provides a systematic review of studies on osteoporotic bone loss in relation to SI intake from diet or supplements to comprehensively explain how SI affect the modulation of bone remodeling. Evidence from epidemiologic studies supports that dietary SI attenuate menopause-induced osteoporotic bone loss by decreasing bone resorption and stimulating bone formation. Other studies have also illustrated that bone site-specific trophic and synergistic effects combined with exercise intervention might contribute to improve the bioavailability of SI or strengthen the bone-specific effects. To date, however, the effects of dietary SI on osteoporotic bone loss remain inconclusive, and study results vary from study to study. The current review will discuss the potential factors that result in the conflicting outcomes of these studies, including dosages, intervention materials, study duration, race, and genetic differences. Further well-designed studies are needed to fully understand the underlying mechanism and evaluate the effects of SI on osteoporosis in humans.
Topics: Animals; Bone Remodeling; Humans; Isoflavones; Osteoporosis; Plant Extracts; Glycine max
PubMed: 26670451
DOI: 10.1089/jmf.2015.0045 -
Fitoterapia Apr 2021Members of the botanical families Apiaceae/Umbelliferae, Asteraceae, Fabaceae/Leguminosae, and Thymelaeaceae are rich in coumarins and have traditionally been used as...
BACKGROUND
Members of the botanical families Apiaceae/Umbelliferae, Asteraceae, Fabaceae/Leguminosae, and Thymelaeaceae are rich in coumarins and have traditionally been used as ethnomedicines in many regions including Europe, Asia, and South America. Coumarins are a class of secondary metabolites that are widely present in plants, fungi, and bacteria and exhibit several pharmacological, biochemical, and therapeutic effects. Recently, many plants rich in coumarins and their derivatives were found to affect bone metabolism.
OBJECTIVE
To review scientific literature describing the mechanisms of action of coumarins in osteoclastogenesis and bone resorption.
MATERIALS AND METHODS
For this systematic review, the PubMed, Scopus, and Periodical Capes databases and portals were searched. We included in vitro research articles published between 2010 and 2020 that evaluated coumarins using osteoclastogenic markers.
RESULTS
Coumarins have been reported to downregulate RANKL-RANK signaling and various downstream signaling pathways required for osteoclast development, such as NF-κB, MAPK, Akt, and Ca signaling, as well as pathways downstream of the nuclear factor of activated T-cells (NFATc1), including tartrate-resistant acid phosphatase (TRAP), cathepsin K (CTSK), and matrix metalloproteinase 9 (MMP-9).
CONCLUSIONS
Coumarins primarily inhibit osteoclast differentiation and activation by modulating different intracellular signaling pathways; therefore, they could serve as potential candidates for controlled randomized clinical trials aimed at improving human bone health.
Topics: Animals; Bone Resorption; Cells, Cultured; Coumarins; Humans; Osteogenesis; RANK Ligand; Receptor Activator of Nuclear Factor-kappa B; Signal Transduction
PubMed: 33556550
DOI: 10.1016/j.fitote.2021.104842