scholarly journals Effect of GH/IGF-1 on Bone Metabolism and Osteoporsosis

2014 ◽  
Vol 2014 ◽  
pp. 1-25 ◽  
Author(s):  
Vittorio Locatelli ◽  
Vittorio E. Bianchi
Keyword(s):  
Bone Metabolism ◽  
Bone Healing ◽  
Clinical Studies ◽  
Bone Growth ◽  
Bone Fractures ◽  
Human Subjects ◽  
Target Cells ◽  
Clinical Effects ◽  
Gh Treatment ◽  
Gh Secretion

Background. Growth hormone (GH) and insulin-like growth factor (IGF-1) are fundamental in skeletal growth during puberty and bone health throughout life. GH increases tissue formation by acting directly and indirectly on target cells; IGF-1 is a critical mediator of bone growth. Clinical studies reporting the use of GH and IGF-1 in osteoporosis and fracture healing are outlined.Methods. A Pubmed search revealed 39 clinical studies reporting the effects of GH and IGF-1 administration on bone metabolism in osteopenic and osteoporotic human subjects and on bone healing in operated patients with normal GH secretion. Eighteen clinical studies considered the effect with GH treatment, fourteen studies reported the clinical effects with IGF-1 administration, and seven related to the GH/IGF-1 effect on bone healing.Results. Both GH and IGF-1 administration significantly increased bone resorption and bone formation in the most studies. GH/IGF-1 administration in patients with hip or tibial fractures resulted in increased bone healing, rapid clinical improvements. Some conflicting results were evidenced.Conclusions. GH and IGF-1 therapy has a significant anabolic effect. GH administration for the treatment of osteoporosis and bone fractures may greatly improve clinical outcome. GH interacts with sex steroids in the anabolic process. GH resistance process is considered.

scholarly journals NSAID Use and Effects on Pediatric Bone Healing: A Review of Current Literature

Children ◽  
2021 ◽  
Vol 8 (9) ◽  
pp. 821
Author(s):  
Stephanie Choo ◽  
Julia A. V. Nuelle
Keyword(s):  
Systematic Review ◽  
Bone Healing ◽  
Clinical Studies ◽  
Pain Control ◽  
Bone Fractures ◽  
Long Bone ◽  
Evidence Based ◽  
Skeletally Immature ◽  
Inflammatory Drugs ◽  
The Impact

This systematic review evaluates and synthesizes the available peer-reviewed evidence regarding the impact of non-steroidal anti-inflammatory drugs (NSAIDs) on fracture healing in skeletally immature patients. Evidence supports the use of NSAIDs in this patient population for adequate pain control without increasing the risk of nonunion, particularly in long bone fractures and pseudoarthrosis after spine fusion. However, further clinical studies are needed to fill remaining gaps in knowledge, specifically with respect to the spectrum of available NSAIDs, dosage, and duration of use, in order to make broad evidence-based recommendations regarding the optimal use of NSAIDs during bone healing in skeletally immature patients.

scholarly journals Is Deqi an Indicator of Clinical Efficacy of Acupuncture? A Systematic Review

2013 ◽  
Vol 2013 ◽  
pp. 1-15 ◽  
Author(s):  
Shuo Zhang ◽  
Wei Mu ◽  
Lu Xiao ◽  
Wen-Ke Zheng ◽  
Chun-Xiang Liu ◽  
...  
Keyword(s):  
Clinical Efficacy ◽  
Clinical Studies ◽  
Human Subjects ◽  
Physiological Mechanism ◽  
Evidence Base ◽  
Preliminary Evidence ◽  
Current Evidence ◽  
Clinical Effects ◽  
Current Evidence Base

Objective. Despite the systematic literature review of the current evidence, we aim to answer the question “ is Deqi an indicator of clinical effects in acupuncture treatment?”Methods. We systematically searched CNKI, VIP, Wanfang Data, PubMed, Embase, and the CENTRAL for three types of study: (1) empirical research probing into the role of Deqi in acupuncture; (2) mechanism studies examining the effect of Deqi on physiological parameters in animal models and human subjects; (3) clinical studies that compared the outcome of acupuncture with Deqi with that of acupuncture without Deqi. Two reviewers independently extracted data, undertook qualitative or quantitative analysis, and summarized findings.Results. The ancient Chinese acupuncturists valued the role of Deqi as a diagnostic tool, a prognosis predictor, and a necessary part of the therapeutic procedure. Findings from modern experimental research provided preliminary evidence for the physiological mechanism that produced Deqi. Few clinical studies generated conflicting evidence of the comparative effectiveness of acupuncture with Deqi versus acupuncture without Deqi for a variety of conditions.Conclusion. The current evidence base is not solid enough to draw any conclusion regarding the predicative value of natural Deqi for clinical efficacy or the therapeutic value of manipulation-facilitated Deqi.

scholarly journals Ribavirin and Alpha Interferon Enhance Death Receptor-Mediated Apoptosis and Caspase Activation in Human Hepatoma Cells

2003 ◽  
Vol 47 (6) ◽  
pp. 1912-1921 ◽  
Author(s):  
Stephan F. Schlosser ◽  
Markus Schuler ◽  
Christoph P. Berg ◽  
Kirsten Lauber ◽  
Klaus Schulze-Osthoff ◽  
...  
Keyword(s):  
Hepg2 Cells ◽  
Molecular Mechanisms ◽  
Caspase 3 ◽  
Death Receptor ◽  
Alpha Interferon ◽  
Target Cells ◽  
Clinical Effects ◽  
Caspase Activation ◽  
Human Hepatoma Cells ◽  
Promoting Effect

ABSTRACT The molecular mechanisms underlying the clinical effects of alpha interferon (IFN) and ribavirin are not understood. Elimination of infected cells occurs in part by cytotoxic T lymphocytes (CTLs) expressing CD95 ligand and thereby attacking target cells which are positive for the death receptor CD95. Since many viruses have evolved mechanisms to inhibit apoptosis, the opposite, namely, promotion of apoptosis, could be a strategy to strengthen the host antiviral response. In the present study, we have asked whether the antiviral substances IFN and ribavirin could support CD95-mediated apoptosis by interfering with the activation of caspases, a family of proteases known for their essential role in apoptosis. HepG2 cells, stimulated with the agonistic anti-CD95 antibody, served as a minimal model to mimic the CD95 stimulation ocurring during a CTL attack of target cells in vivo. Apoptosis was quantitated by flow cytometric detection of hypodiploid nuclei. Caspase activity was measured by cytofluorometry, immunocytochemistry, and immunoblot analysis. IFN and ribavirin sensitized HepG2 cells for CD95-mediated apoptosis. This effect was correlated with an increase in CD95-mediated caspase activation and enhanced cleavage of the caspase substrate poly(ADP-ribose) polymerase. Furthermore, the positive effect on CD95-mediated caspase activation by IFN and ribavirin was confirmed by immunocytochemistry for activated caspase-3 and by immunoblot detection of activated caspase-3, caspase-7, and caspase-8. Our data demonstrate that the antiviral substances IFN and ribavirin are able to sensitize for CD95-mediated apoptosis. IFN and ribavirin also enhance CD95-mediated caspase activation, which might in part be responsible for the apoptosis-promoting effect of these antiviral compounds.

scholarly journals Phenotype and Genetic Analysis of a Syndrome Caused by an Inactivating Mutation in the Growth Hormone-Releasing Hormone Receptor: Dwarfism of Sindh1

1998 ◽  
Vol 83 (11) ◽  
pp. 4065-4074
Author(s):  
Hiralal G. Maheshwari ◽  
Bernard L. Silverman ◽  
Josée Dupuis ◽  
Gerhard Baumann
Keyword(s):  
Gh Deficiency ◽  
Postnatal Growth ◽  
N Gene ◽  
Molecular Characteristics ◽  
Clinical Genetic ◽  
Gh Treatment ◽  
Gh Secretion ◽  
Absolute Requirement ◽  
Igf I ◽  
Igf Binding

We report, in detail, a new form of familial dwarfism, including its phenotypic features, hormonal profile, and molecular basis. Following a newspaper report of severe dwarfism in two villages in the province of Sindh, Pakistan, we organized an expedition to study its clinical, genetic, and molecular characteristics. We identified 18 dwarfs (15 male, 3 female), all members of a consanguineous kindred, ranging in age from newborn to 28 yr. Mean height was 7.2 sd below the norm, with mean adult heights of 130 cm for males and 113.5 cm for females. Body proportions and habitus were normal; but head circumference was 4.1 sd, and blood pressure approximately 3 sd below the norm. There was no dysmorphism, no microphallus, and no history of hypoglycemia. Serum GH did not respond to provocative stimuli (GHRH, l-dopa, or clonidine). Insulin-like growth factor I (IGF-I) and IGF-binding protein 3 were low (5.2 ± 2.0 ng/mL and 0.42 ± 0.13 μg/mL, respectively; mean ± sd) but rose normally with GH treatment. One affected, dwarfed couple had a son, demonstrating fertility in both sexes. Clinical and endocrinological evidence suggested isolated GH deficiency with a recessive inheritance pattern. The GH-N gene was found to be intact. Linkage analysis of microsatellite chromosomal markers near other candidate genes yielded a high LOD score (6.26) for the GHRH receptor (GHRH-R) locus. DNA sequencing revealed a nonsense mutation (Glu50→Stop) in the extracellular domain of the GHRH-R. This mutation predicts a severely truncated GHRH-R; it is identical to that recently reported in four patients from two other families. Inheritance is autosomal recessive (chromosome 7p) with a high degree of penetrance. Relatives heterozygous for the mutation had moderately decreased IGF-I levels and slightly blunted GH responses to GHRH and l-dopa, but they showed only minimal or no height deficit. This syndrome represents the human homologue of the little (lit/lit) mouse and closely resembles its phenotype. It demonstrates the absolute requirement of GHRH signaling for pituitary GH secretion and postnatal growth in humans, and its relatively minor (but discernible) biological importance in extrapituitary sites. The syndrome is distinct from other forms of GH deficiency with respect to microcephaly, asymptomatic hypotension, and absence of features such as facial dysplasia, significant truncal obesity, microphallus, or hypoglycemia. Its discovery raises the possibility of milder mutations in the GHRH-R gene as potential causes for partial GH insufficiency and idiopathic short stature.

scholarly journals The effect of intravenous zoledronic acid on glucocorticoid-induced multiple vertebral fractures in juvenile systemic lupus erythematosus

2004 ◽  
Vol 59 (5) ◽  
pp. 302-305 ◽  
Author(s):  
Sonia Cristina de Magalhães Souza ◽  
Claudia Tereza Lobato Borges ◽  
Vanda Jorgetti ◽  
Rosa Maria Rodrigues Pereira
Keyword(s):  
Zoledronic Acid ◽  
Lupus Erythematosus ◽  
Bone Growth ◽  
Bone Fractures ◽  
Young Patients ◽  
Systemic Lupus ◽  
Treatment Of Osteoporosis ◽  
The Us ◽  
Us Fda ◽  
Intravenous Bisphosphonate

Glucocorticoids are widely used in the treatment of lupus patients, and adverse effects, which include osteoporosis and associated fractures, are frequent. Treatment of osteoporosis of young patients should be effective and not harmful to bone growth and remodeling. Bisphosphonates are drugs that decrease the incidence of bone fractures, but their use in juvenile patients is still controversial because of their possible side effects on the growing skeleton. However, recently published studies showed that linear growth continued normally after treatment with these drugs, and there was no excessive suppression of bone remodeling or mineralization defects. Zoledronic acid is a new intravenous bisphosphonate that has been approved by the US FDA for use with hypercalcemia of malignancies and might be an effective treatment for postmenopausal osteoporosis. The authors report a case of a young girl with systemic lupus who developed multiple vertebral collapses due to glucocorticoid therapy, and zoledronic acid was used producing significant clinical and densitometric improvement.

Osteocytes

2018 ◽  
Vol 157 (02) ◽  
pp. 154-163 ◽  
Author(s):  
Markus Rupp ◽  
Felix Merboth ◽  
Diaa Daghma ◽  
Christoph Biehl ◽  
Thaqif El Khassawna ◽  
...  
Keyword(s):  
Wnt Signaling ◽  
Fracture Healing ◽  
Bone Metabolism ◽  
Bone Remodeling ◽  
Bone Healing ◽  
Wnt Signaling Pathway ◽  
Monoklonaler Antikörper ◽  
Orthopädie Und Unfallchirurgie ◽  
Healing Bone ◽  
Fgf 23

ZusammenfassungLange Zeit galten Osteozyten als passive Zuschauer der Knochenhomöostase, dem Gleichgewicht zwischen Knochenaufbau durch Osteoblasten und Knochenabbau durch Osteoklasten. Das Dogma der ruhenden, im Knochen eingemauerten funktionslosen Zellen hat sich seit der Jahrtausendwende grundlegend gewandelt. Osteozyten stehen vielmehr im Mittelpunkt des Knochenstoffwechsels und können somit als dessen Dirigent angesehen werden. Auf Grundlage einer Literaturrecherche in PubMed und Google Scholar mit den einzeln oder in Kombination verwendeten Suchbegriffen „osteocyte“, „fracture healing“, „bone healing“, „bone remodeling“, „bone metabolism“, „sclerostin“, „RANKL/OPG“, „Wnt-signaling pathway“, „FGF-23“ wurde die Rolle der Osteozyten im Knochenstoffwechsel anhand von präklinischen und klinischen Studien sowie Übersichtsarbeiten erarbeitet. Einzelne Fallberichte wurden hierfür nicht verwandt. Im Rahmen der Literaturrecherche wurden nur Publikationen in englischer oder deutscher Sprache berücksichtigt. Die sich aus Osteoblasten entwickelnden Osteozyten sind funktionell die zentrale Schaltstelle im Knochenmetabolismus. Morphologisch bildet ein Netzwerk von Osteozyten, die 90 – 95% der Zellen im Knochen ausmachen und im Gegensatz zu Osteoblasten und Osteoklasten das Alter des Gesamtorganismus erreichen können, durch mit Nexus miteinander verbundenen Dendriten innerhalb des Knochens die optimale Grundlage für deren funktionelle Aufgaben. Neben der Aufgabe als Mechanosensor im Knochen wird die Osteoblastenfunktion über Sclerostin, die Osteoklastenfunktion über den RANK/RANKL/OPG-Signalweg gesteuert. Ferner wird die Mineralisierung des Knochens über die lokale Phosphatkonzentration, der systemische Phosphathaushalt in Interaktion mit der Niere über FGF23 hormonell gesteuert. Das Verständnis der Rolle der Osteozyten verspricht eine weitere Verbesserung möglicher Therapiealternativen. Hinsichtlich des Knochenstoffwechsels sind bereits Sclerostinantikörper und Denosumab, ein monoklonaler Antikörper, der als OPG-Agonist fungiert, eingeführt worden. Neben den in der Osteoporosetherapie bereits etablierten Therapieansätzen sind Antikörper gegen FGF23 oder dessen Rezeptoren in der präklinischen und klinischen Erprobung. Auch Bortezomib, ein Proteasomeninhibitor, der die Lebensfähigkeit von Osteozyten verbessert, ist zur Therapie des multiplen Myeloms im klinischen Einsatz. Das zunehmende Verständnis der osteozytären Funktion lässt darüber hinaus weitere Therapiemöglichkeiten erwarten – in Orthopädie und Unfallchirurgie sind dies insbesondere die ossäre Integration von Implantaten und die medikamentöse Beeinflussung der (gestörten) Frakturheilung.

scholarly journals Bone Biomarkers in Mucopolysaccharidoses

2021 ◽  
Vol 22 (23) ◽  
pp. 12651
Author(s):  
Akari Nakamura-Utsunomiya
Keyword(s):  
Bone Metabolism ◽  
Daily Living ◽  
Endochondral Ossification ◽  
Bone Growth ◽  
Bone Biomarkers ◽  
Enzyme Replacement ◽  
Replacement Treatment ◽  
Bone Disorder ◽  
New Biomarkers ◽  
And Cartilage

The accumulation of glycosaminoglycans (GAGs) in bone and cartilage leads to progressive damage in cartilage that, in turn, reduces bone growth by the destruction of the growth plate, incomplete ossification, and growth imbalance. The mechanisms of pathophysiology related to bone metabolism in mucopolysaccharidoses (MPS) include impaired chondrocyte function and the failure of endochondral ossification, which leads to the release of inflammatory cytokines via the activation of Toll-like receptors by GAGs. Although improvements in the daily living of patients with MPS have been achieved with enzyme replacement, treatment for the bone disorder is limited. There is an increasing need to identify biomarkers related to bone and cartilage to evaluate the progressive status and to monitor the treatment of MPS. Recently, new analysis methods, such as proteomic analysis, have identified new biomarkers in MPS. This review summarizes advances in clinical bone metabolism and bone biomarkers.

scholarly journals Time arrow in published clinical studies/trials indexed in MEDLINE: a systematic analysis of Retrospective vs Prospective study design, from 1960 to 2017.

2018 ◽  
Author(s):  
Michele M Ciulla ◽  
Patrizia Vivona
Keyword(s):  
Prospective Study ◽  
Study Design ◽  
Low Income ◽  
Clinical Studies ◽  
Human Subjects ◽  
Systematic Analysis ◽  
Time Line ◽  
Time Arrow ◽  
Prospective Study Design ◽  
Single Time Point

Clinical studies/trials are experiments or observations on human subjects considered by the scientific community the most appropriate instrument to answer specific research questions on interventions on health outcomes. The time-line of the observations might be focused on a single time point or to follow time, backward or forward, in the so called, respectively, retrospective and prospective study design. Since the retrospective approach has been criticized for the possible sources of errors due to bias and confounding, we aimed this study to assess if there is a prevalence of retrospective vs prospective design in the clinical studies/trials by querying MEDLINE. Our results on a sample of 1,438,872 studies/trials, (yrs 1960-2017), support a prevalence of retrospective, respectively 55% vs 45%. To explain this result, arandom sub-sample of studies where the country of origin was reported (n=1576) was categorized in high and low-income based onthe nominal Gross Domestic Product (GDP) and matched with the topic of the research. As expected, the absolute majority of studies/trials are carried on by high-income countries, respectively 86% vs 14%; even if a slight prevalence of retrospective was recorded in both income groups, nonetheless the most part of prospective studies are carried out by high-GDP countries, 85% vs 15%. Finally the differences in the design of the study are understandable when considering the topic of the research.

Aspects of neurotransmitter control of GH secretion: basic and clinical studies

1989 ◽  
pp. 263-281 ◽  
Author(s):  
F. Camanni ◽  
E. Ghigo ◽  
E. Mazza ◽  
E. Imperiale ◽  
S. Goffi ◽  
...  
Keyword(s):  
Clinical Studies ◽  
Gh Secretion
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