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Degboé Y, Nezzar C, Alary P, Maëva M, Bulai Livideanu C, Laroche M. Management of Bone Health in Adult Mastocytosis. Curr Osteoporos Rep 2025; 23:10. [PMID: 39946039 PMCID: PMC11825596 DOI: 10.1007/s11914-025-00901-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 01/21/2025] [Indexed: 02/16/2025]
Abstract
PURPOSE OF REVIEW The present review will examine bone disease in mastocytosis, analyze the existing literature on its management, and propose a strategy for osteoporosis treatment in systemic mastocytosis. This strategy is based on both the available scientific evidence and the experience gained at our expert center (CEREMAST). RECENT FINDINGS Systemic mastocytosis is a rare disorder, primarily affecting the bone and leading to osteoporosis, bone pain, and bone structural abnormalities. While traditionally described in indolent systemic mastocytosis, bone involvement is also observed in bone marrow mastocytosis. The true prevalence of systemic mastocytosis is likely underreported, highlighting the importance for clinicians to be familiar with the condition, particularly in cases of osteoporosis. Osteoporosis management typically involves bisphosphonates, with potential benefits from combining them with specific treatments like interferon in severe osteoporosis with vertebral fractures. The potential of new mast cell-targeting molecules to treat bone involvement needs to be demonstrated. This review provides a guide for osteoporosis and bone pain management in systemic mastocytosis.
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Affiliation(s)
- Yannick Degboé
- Rheumatology Department, CHU de Toulouse and Université de Toulouse, Toulouse, France.
- Mastocytosis Expert Centre - CEREMAST Toulouse, Toulouse, France.
- INSERM U1291 INFINITY, Toulouse, France.
| | - Coralie Nezzar
- Rheumatology Department, CHU de Toulouse and Université de Toulouse, Toulouse, France
| | - Pauline Alary
- Rheumatology Department, CHU de Toulouse and Université de Toulouse, Toulouse, France
| | - Masson Maëva
- Rheumatology Department, CHU de Toulouse and Université de Toulouse, Toulouse, France
- INSERM U1291 INFINITY, Toulouse, France
| | - Cristina Bulai Livideanu
- Mastocytosis Expert Centre - CEREMAST Toulouse, Toulouse, France
- INSERM U1291 INFINITY, Toulouse, France
- Dermatology Department, CHU de Toulouse, Toulouse, France
| | - Michel Laroche
- Rheumatology Department, CHU de Toulouse and Université de Toulouse, Toulouse, France
- Mastocytosis Expert Centre - CEREMAST Toulouse, Toulouse, France
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Degboé Y, Severino-Freire M, Couture G, Apoil PA, Gaudenzio N, Hermine O, Ruyssen-Witrand A, Paul C, Laroche M, Constantin A, Livideanu CB. The Prevalence Of Osteoporosis Is Low in Adult Cutaneous Mastocytosis Patients. THE JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY. IN PRACTICE 2024; 12:1306-1312. [PMID: 38423295 DOI: 10.1016/j.jaip.2024.02.021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/29/2022] [Revised: 02/07/2024] [Accepted: 02/16/2024] [Indexed: 03/02/2024]
Abstract
BACKGROUND Systemic mastocytosis (SM) is a clonal disorder of mast cells (MCs) frequently associated with vertebral osteoporosis (OP) and subsequent vertebral fractures (VFs). The natural history of this OP remains unclear. Importantly, we do not know whether OP represents an early event triggered alongside MC abnormalities, and whether MC clonality is sufficient to trigger osteoporosis. OBJECTIVE To describe OP in patients with medullar clonality in cutaneous mastocytosis (CM) and monoclonal mast cell activation syndrome (MMAS) and to compare their osteoporosis characteristics with those of nonadvanced SM patients (bone marrow mastocytosis and indolent systemic mastocytosis). METHODS We retrospectively analyzed clinical, biological, and densitometric data of 27 CM, 13 MMAS, and 135 SM patients from the Mastocytosis Expert Center (CEREMAST) in Toulouse, France. RESULTS The OP (respectively 3.7, 30.8, and 34.1%) and VFs (0.0%, 15.4%, and 20%) were less frequent in CM than in MMAS and SM, despite the presence of clonal MCs in the bone marrow. Most patients with OP and VFs in the non-SM groups had the usual risk factors for OP. Interestingly, the only non-SM patient with a typical SM-like OP had high bone marrow tryptase, developed bone marrow KIT mutation during follow-up, and had a family history of SM. Our data show that OP is not a common clinical finding in CM but is frequent in MMAS. When OP and VFs occur in CM and MMAS patients, they differ from the usual phenotype of SM bone fragility. CONCLUSIONS Our findings suggest that, in most CM patients, the meaning and management of OP differs from that of OP in MMAS and nonadvanced SM. Prospective longitudinal studies and the validation of predictors are needed to identify CM and MMAS patients developing SM-related OP.
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Affiliation(s)
- Yannick Degboé
- Rheumatology Centre, Toulouse University Hospital and University Toulouse III, Toulouse, France; INFINITY-Toulouse Institute for Infectious and Inflammatory Diseases, INSERM UMR1291- CNRS UMR5051- University Toulouse III, Toulouse, France; Department of Dermatology and Mastocytosis Expert Centre (CEREMAST), Toulouse University Hospital and University Toulouse III, Toulouse, France.
| | - Maella Severino-Freire
- Department of Dermatology and Mastocytosis Expert Centre (CEREMAST), Toulouse University Hospital and University Toulouse III, Toulouse, France
| | - Guillaume Couture
- Rheumatology Centre, Toulouse University Hospital and University Toulouse III, Toulouse, France
| | - Pol-André Apoil
- Department of Dermatology and Mastocytosis Expert Centre (CEREMAST), Toulouse University Hospital and University Toulouse III, Toulouse, France; Department of Immunology, Toulouse University Hospital and University Toulouse III, Toulouse, France
| | - Nicolas Gaudenzio
- INFINITY-Toulouse Institute for Infectious and Inflammatory Diseases, INSERM UMR1291- CNRS UMR5051- University Toulouse III, Toulouse, France
| | - Olivier Hermine
- Department of Hematology and Mastocytosis Expert Centre (CEREMAST), Necker Children's Hospital and Paris Descartes University, Assistance Publique Hôpitaux de Paris, Paris, France
| | - Adeline Ruyssen-Witrand
- Rheumatology Centre, Toulouse University Hospital and University Toulouse III, Toulouse, France; Centre d'Investigation Clinique de Toulouse CIC1436, Inserm, Team PEPSS, Toulouse, France
| | - Carle Paul
- INFINITY-Toulouse Institute for Infectious and Inflammatory Diseases, INSERM UMR1291- CNRS UMR5051- University Toulouse III, Toulouse, France; Department of Dermatology and Mastocytosis Expert Centre (CEREMAST), Toulouse University Hospital and University Toulouse III, Toulouse, France
| | - Michel Laroche
- Rheumatology Centre, Toulouse University Hospital and University Toulouse III, Toulouse, France
| | - Arnaud Constantin
- Rheumatology Centre, Toulouse University Hospital and University Toulouse III, Toulouse, France; INFINITY-Toulouse Institute for Infectious and Inflammatory Diseases, INSERM UMR1291- CNRS UMR5051- University Toulouse III, Toulouse, France
| | - Cristina Bulai Livideanu
- INFINITY-Toulouse Institute for Infectious and Inflammatory Diseases, INSERM UMR1291- CNRS UMR5051- University Toulouse III, Toulouse, France; Department of Dermatology and Mastocytosis Expert Centre (CEREMAST), Toulouse University Hospital and University Toulouse III, Toulouse, France
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Selvaraj J, Prabha T, Yadav N. Identification of Drug Candidates for Breast Cancer Therapy Through Scaffold Repurposing: A Brief Review. Curr Drug Res Rev 2020; 13:3-15. [PMID: 32838729 DOI: 10.2174/2589977512666200824103019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2020] [Revised: 06/10/2020] [Accepted: 07/02/2020] [Indexed: 11/22/2022]
Abstract
Conventional drug discovery is a time consuming and expensive expedition with less clinical preference achievement proportion intended for breast cancer therapy. Even if numerous novel approaches to the conformation of drugs have been introduced for breast cancer therapy, they are yet to be implemented in clinical practice. This tempting strategy facilitates a remarkable chance to take the entire benefit of existing drugs. Despite drug repurposing significantly decrease the investigational period and cost, it has got many objections and issues. Scaffold repurposing is an approach that procures a novel significance on the decrepit motto of "to commencement with a pristine drug" . Hence, we move into a probable and nearer approach, the exploitation of scaffolds, which was originally developed for other purposes, including anti-tumor activity. In this review, we summarize different drugs and scaffolds used in breast cancer therapy.
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Affiliation(s)
- Jubie Selvaraj
- Department of Pharmaceutical Chemistry, JSS College of Pharmacy, JSS Academy of Higher Education & Research Ooty, Nilgiris, Tamilnadu, India
| | - Thangavelu Prabha
- Department of Pharmaceutical Chemistry, Nandha College of Pharmacy, Koorapalayam Pirivu, Pitchandam Palayam Post, Erode-638052, Tamilnadu, India
| | - Neetu Yadav
- Department of Pharmaceutical Chemistry, JSS College of Pharmacy, JSS Academy of Higher Education & Research Ooty, Nilgiris, Tamilnadu, India
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Ragipoglu D, Dudeck A, Haffner-Luntzer M, Voss M, Kroner J, Ignatius A, Fischer V. The Role of Mast Cells in Bone Metabolism and Bone Disorders. Front Immunol 2020; 11:163. [PMID: 32117297 PMCID: PMC7025484 DOI: 10.3389/fimmu.2020.00163] [Citation(s) in RCA: 55] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2019] [Accepted: 01/21/2020] [Indexed: 12/15/2022] Open
Abstract
Mast cells (MCs) are important sensor and effector cells of the immune system that are involved in many physiological and pathological conditions. Increasing evidence suggests that they also play an important role in bone metabolism and bone disorders. MCs are located in the bone marrow and secrete a wide spectrum of mediators, which can be rapidly released upon activation of mature MCs following their differentiation in mucosal or connective tissues. Many of these mediators can exert osteocatabolic effects by promoting osteoclast formation [e.g., histamine, tumor necrosis factor (TNF), interleukin-6 (IL-6)] and/or by inhibiting osteoblast activity (e.g., IL-1, TNF). By contrast, MCs could potentially act in an osteoprotective manner by stimulating osteoblasts (e.g., transforming growth factor-β) or reducing osteoclastogenesis (e.g., IL-12, interferon-γ). Experimental studies investigating MC functions in physiological bone turnover using MC-deficient mouse lines give contradictory results, reporting delayed or increased bone turnover or no influence depending on the mouse model used. By contrast, the involvement of MCs in various pathological conditions affecting bone is evident. MCs may contribute to the pathogenesis of primary and secondary osteoporosis as well as inflammatory disorders, including rheumatoid arthritis and osteoarthritis, because increased numbers of MCs were found in patients suffering from these diseases. The clinical observations could be largely confirmed in experimental studies using MC-deficient mouse models, which also provide mechanistic insights. MCs also regulate bone healing after fracture by influencing the inflammatory response toward the fracture, vascularization, bone formation, and callus remodeling by osteoclasts. This review summarizes the current view and understanding of the role of MCs on bone in both physiological and pathological conditions.
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Affiliation(s)
- Deniz Ragipoglu
- Trauma Research Center Ulm, Institute of Orthopedic Research and Biomechanics, Ulm University Medical Center, Ulm, Germany
| | - Anne Dudeck
- Medical Faculty, Institute for Molecular and Clinical Immunology, Otto-von-Guericke University Magdeburg, Magdeburg, Germany
| | - Melanie Haffner-Luntzer
- Trauma Research Center Ulm, Institute of Orthopedic Research and Biomechanics, Ulm University Medical Center, Ulm, Germany
| | - Martin Voss
- Medical Faculty, Institute for Molecular and Clinical Immunology, Otto-von-Guericke University Magdeburg, Magdeburg, Germany
| | - Jochen Kroner
- Trauma Research Center Ulm, Institute of Orthopedic Research and Biomechanics, Ulm University Medical Center, Ulm, Germany
| | - Anita Ignatius
- Trauma Research Center Ulm, Institute of Orthopedic Research and Biomechanics, Ulm University Medical Center, Ulm, Germany
| | - Verena Fischer
- Trauma Research Center Ulm, Institute of Orthopedic Research and Biomechanics, Ulm University Medical Center, Ulm, Germany
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Folwarczna J, Konarek N, Freier K, Karbowniczek D, Londzin P, Janas A. Effects of loratadine, a histamine H 1 receptor antagonist, on the skeletal system of young male rats. DRUG DESIGN DEVELOPMENT AND THERAPY 2019; 13:3357-3367. [PMID: 31576110 PMCID: PMC6767469 DOI: 10.2147/dddt.s215337] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/11/2019] [Accepted: 07/26/2019] [Indexed: 01/03/2023]
Abstract
Background Histamine H1 receptor antagonists are widely used in the treatment of allergic diseases. H1 receptors are expressed on bone cells and histamine takes part in regulation of bone metabolism. Loratadine is often prescribed to children. Purpose The aim of the present study was to investigate the effects of loratadine on the skeletal system of young rats. Material and methods Loratadine (0.5, 5, and 50 mg/kg p.o. daily) was administered for 4 weeks to male Wistar rats, 6-week-old at the start of the experiment. Bone mass, mass of bone mineral, calcium, and phosphorus content in the bone mineral of the tibia, femur, and L-4 vertebra, histomorphometric parameters of the femur, mechanical properties of the proximal tibial metaphysis, femoral diaphysis and femoral neck, and serum levels of bone turnover markers were examined. Results Loratadine at 0.5 and 5 mg/kg did not significantly affect the skeletal system of young rats. At 50 mg/kg, loratadine decreased the femoral length, increased content of calcium and phosphorus in the bone mineral of the vertebra, and tended to improve mechanical properties of the tibial metaphysis. Conclusion High-dose loratadine slightly but significantly affected development of the skeletal system in rapidly growing rats.
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Affiliation(s)
- Joanna Folwarczna
- Department of Pharmacology, School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia, Katowice, Sosnowiec 41-200, Poland
| | - Natalia Konarek
- Department of Pharmacology, School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia, Katowice, Sosnowiec 41-200, Poland
| | - Karolina Freier
- Department of Pharmacology, School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia, Katowice, Sosnowiec 41-200, Poland
| | - Dawid Karbowniczek
- Department of Pharmacology, School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia, Katowice, Sosnowiec 41-200, Poland
| | - Piotr Londzin
- Department of Pharmacology, School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia, Katowice, Sosnowiec 41-200, Poland
| | - Aleksandra Janas
- Department of Pharmacology, School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia, Katowice, Sosnowiec 41-200, Poland
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Abstract
As any pharmaceutical substance may influence the events associated with orthodontic tooth movement, it is of importance for the clinician to be able to recognize any prospective patient's history and patterns of medicinal consumption. This review presents the effects of various commonly prescribed medications on the rate of orthodontic tooth movement. The article concludes that it remains, to a degree, unclear which types of medication may have a clinically significant effect in everyday clinical scenarios. However, since both prescription and over-the-counter medication use have recently increased significantly among all age groups, good practice suggests that it is important to identify patients consuming medications and consider the possible implications in orthodontic therapy.
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Affiliation(s)
| | - Eleftherios G Kaklamanos
- 2 Hamdan Bin Mohammed College of Dental Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, United Arab Emirates
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Makrygiannakis MA, Kaklamanos EG, Athanasiou AE. Does common prescription medication affect the rate of orthodontic tooth movement? A systematic review. Eur J Orthod 2019. [PMID: 29522172 DOI: 10.1093/ejo/cjy001] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Background As the taking of any medication may theoretically affect the complex pathways responsible for periodontal tissue homeostasis and the events leading to orthodontic tooth movement, it is considered important for the orthodontist to be able to identify prospective patients' history and patterns of pharmaceutical consumption. Objective To systematically investigate and appraise the quality of the available evidence regarding the effect of commonly prescribed medications on the rate of orthodontic tooth movement. Search methods Search without restrictions in eight databases and hand searching until June 2017. Selection criteria Controlled studies investigating the effect of commonly prescribed medications with emphasis on the rate of orthodontic tooth movement. Data collection and analysis Following study retrieval and selection, relevant data was extracted and the risk of bias was assessed using the SYRCLE's Risk of Bias Tool. Results Twenty-seven animal studies, involving various pharmacologic and orthodontic interventions, were finally identified. Most studies were assessed to be at unclear or high risk of bias. The rate of orthodontic tooth movement was shown to increase after the administration of diazepam, Vitamin C and pantoprazole, while simvastatin, atorvastatin, calcium compounds, strontium ranelate, propranolol, losartan, famotidine, cetirizine, and metformin decreased the rate of orthodontic tooth movement. No interference with the rate of orthodontic tooth movement was reported for phenytoin, phenobarbital and zinc compounds, whereas, inconsistent or conflicting effects were noted after the administration of L-thyroxine, lithium compounds, fluoxetine and insulin. The quality of the available evidence was considered at best as low. Conclusions Commonly prescribed medications may exhibit variable effects on the rate of orthodontic tooth movement. Although the quality of evidence was considered at best as low, raising reservations about the strength of the relevant recommendations, the clinician should be capable of identifying patients taking medications and should take into consideration the possible implications related to the proposed treatment. Registration PROSPERO (CRD42015029130).
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Affiliation(s)
- Miltiadis A Makrygiannakis
- Hamdan Bin Mohammed College of Dental Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, United Arab Emirates
| | - Eleftherios G Kaklamanos
- Hamdan Bin Mohammed College of Dental Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, United Arab Emirates
| | - Athanasios E Athanasiou
- Hamdan Bin Mohammed College of Dental Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, United Arab Emirates
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Matuszewska A, Nowak B, Jędrzejuk D, Landwójtowicz M, Sadanowicz E, Sozański T, Kwiatkowska J, Pieśniewska M, Bolanowski M, Szeląg A. Effect of long-term administration of ranitidine, a histamine H2 receptor antagonist, on bone metabolism in young growing rats. Pharmacol Rep 2018; 70:951-954. [DOI: 10.1016/j.pharep.2018.03.005] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2017] [Revised: 02/12/2018] [Accepted: 03/15/2018] [Indexed: 01/24/2023]
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Presence of mast cells and the expression of metalloproteinase 9 in the gingiva of ovariectomized rats with periodontal disease. J Oral Biol Craniofac Res 2017; 8:54-57. [PMID: 29556465 DOI: 10.1016/j.jobcr.2017.10.002] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2017] [Accepted: 10/12/2017] [Indexed: 11/22/2022] Open
Abstract
Background The host's answer has an important role in periodontal disease, and the mast cells have a prime role. Such cells seem to be influenced by estrogen deficiency. The objective was to evaluate the mast cells and the expression of metalloproteinase(MMP)-9 in periodontal disease induced in ovariectomized rats. Methods For that purpose, 36 rats were used; 18 ovariectomized (OVX) and another 18 Sham-operated (SHAM). After 60 days the periodontal disease was induced by a ligature around the first lower right molars (group P). The opposite side was the control group (group C). The euthanasia occurred 3, 7 and 14 days after the placement of the ligature. The gingiva was removed and analyzed histochemically and immunohistochemically to quantify the mast cells and to analyze MMP 9 expression. Results By comparing the groups SHAM-P and C and groups OVX-C and P, it was noted that mast cells from group C were higher than P in all experimental periods. When comparing groups SHAM-C and OVX-C, significant factors were not found. When comparing groups SHAM-P and OVX-P, there was an inclination for mast cells reduction with time. The MMP-9 expression was related to the presence of periodontitis. Conclusions It was concluded that periodontitis led to mast cells reduction and MMP-9 increase. The ovariectomy itself did not alter the MMP-9 expression and did not influence the presence of mast cells in rat papilla, however, when associated to inflammation led to a reduction of mast cells.
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Maximiano WMA, da Silva EZM, Santana AC, de Oliveira PT, Jamur MC, Oliver C. Mast Cell Mediators Inhibit Osteoblastic Differentiation and Extracellular Matrix Mineralization. J Histochem Cytochem 2017; 65:723-741. [PMID: 28980852 DOI: 10.1369/0022155417734174] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Mast cells are multifunctional immune cells that participate in many important processes such as defense against pathogens, allergic reactions, and tissue repair. These cells perform their functions through the release of a wide variety of mediators. This release occurs mainly through cross-linking IgE (immunoglobulin E) bound to high affinity IgE receptors by multivalent antigens. The abundance of mast cells in connective tissue, surrounding blood vessels, and their involvement in the early stages of bone repair support the possibility of physiological and pathological interactions between mast cells and osteoblasts. However, the participation of mast cell mediators in osteogenesis is not fully understood. Therefore, the objective of this work was to investigate the role of mast cell mediators in the acquisition of the osteogenic phenotype in vitro. The results show that pooled mast cell mediators can affect proliferation, morphology, and cytoskeleton of osteoblastic cells, and impair the activity and expression of alkaline phosphatase as well as the expression of bone sialoprotein. Also, mast cell mediators inhibit the expression of mRNA for those proteins and inhibit the formation and maturation of calcium nodules and consequently inhibit mineralization. Therefore, mast cell mediators can modulate osteogenesis and are potential therapeutic targets for treatments of bone disorders.
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Affiliation(s)
- William Marcatti Amarú Maximiano
- Department of Cell and Molecular Biology and Pathogenic Bioagents, Ribeirão Preto Medical School, University of São Paulo, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
| | - Elaine Zayas Marcelino da Silva
- Department of Cell and Molecular Biology and Pathogenic Bioagents, Ribeirão Preto Medical School, University of São Paulo, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
| | - Ana Carolina Santana
- Department of Cell and Molecular Biology and Pathogenic Bioagents, Ribeirão Preto Medical School, University of São Paulo, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
| | - Paulo Tambasco de Oliveira
- Department of Morphology, Stomatology, and Basic Pathology, School of Dentistry of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
| | - Maria Célia Jamur
- Department of Cell and Molecular Biology and Pathogenic Bioagents, Ribeirão Preto Medical School, University of São Paulo, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
| | - Constance Oliver
- Department of Cell and Molecular Biology and Pathogenic Bioagents, Ribeirão Preto Medical School, University of São Paulo, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
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Marcatti Amarú Maximiano W, Marino Mazucato V, Tambasco de Oliveira P, Célia Jamur M, Oliver C. Nanotextured titanium surfaces stimulate spreading, migration, and growth of rat mast cells. J Biomed Mater Res A 2017; 105:2150-2161. [DOI: 10.1002/jbm.a.36076] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2017] [Revised: 03/20/2017] [Accepted: 03/24/2017] [Indexed: 12/14/2022]
Affiliation(s)
- William Marcatti Amarú Maximiano
- Department of Cell and Molecular Biology and Pathogenic Bioagents, Ribeirao Preto Medical School; University of Sao Paulo; Brazil
| | - Vivian Marino Mazucato
- Department of Cell and Molecular Biology and Pathogenic Bioagents, Ribeirao Preto Medical School; University of Sao Paulo; Brazil
| | - Paulo Tambasco de Oliveira
- Department of Morphology, Stomatology and Basic Pathology, School of Dentistry; University of Sao Paulo; Brazil
| | - Maria Célia Jamur
- Department of Cell and Molecular Biology and Pathogenic Bioagents, Ribeirao Preto Medical School; University of Sao Paulo; Brazil
| | - Constance Oliver
- Department of Cell and Molecular Biology and Pathogenic Bioagents, Ribeirao Preto Medical School; University of Sao Paulo; Brazil
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Aasarød KM, Stunes AK, Mosti MP, Ramezanzadehkoldeh M, Viggaklev BI, Reseland JE, Skallerud BH, Fossmark R, Syversen U. Effects of the Histamine 1 Receptor Antagonist Cetirizine on the Osteoporotic Phenotype in H(+) /K(+) ATPase Beta Subunit KO Mice. J Cell Biochem 2016; 117:2089-96. [PMID: 26869358 DOI: 10.1002/jcb.25514] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2015] [Accepted: 02/09/2016] [Indexed: 12/14/2022]
Abstract
Epidemiological studies suggest increased fracture risk in patients using proton pump inhibitors (PPIs). We have previously shown that the H(+) /K(+) ATPase beta subunit knockout (KO) mouse, which is a model of PPI-use, have lower bone mineral density (BMD) and impaired bone quality compared to wild type (WT) mice. Like PPI users, these KO mice display elevated gastric pH and hypergastrinemia, which in turn stimulates gastric histamine release. Previous studies have suggested a negative effect of histamine on bone, thus, we wanted to study whether a histamine 1 receptor (H1R) antagonist could improve bone quality in KO mice. Female KO and WT mice aged 8 weeks received either an H1R antagonist (cetirizine) or polyethylene glycol (PEG) for 6 months. At the end of the study, KO mice displayed elevated plasma histamine levels compared to WT. As demonstrated previously, the KO mice also exhibited lower whole body BMD, reduced mechanical bone strength, and impaired bone quality assessed by μCT. No significant differences, however, were found between the KO groups receiving cetirizine or PEG for any of the measured bone parameters. In vitro gene expression analyses of histamine receptors revealed the presence of H1R and H2R both in osteoblasts and osteoclasts, and H3R in late stage osteoblasts. In conclusion, administration of the H1R antagonist cetirizine in a concentration of 3 mg/kg did not rescue the osteoporotic phenotype in H(+) /K(+) ATPase beta subunit KO mice. It can, however, not be ruled out that histamine may influence bone via other receptors. J. Cell. Biochem. 117: 2089-2096, 2016. © 2016 Wiley Periodicals, Inc.
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Affiliation(s)
- Kristin M Aasarød
- Department of Cancer Research and Molecular Medicine, NTNU, Trondheim, Norway
| | - Astrid K Stunes
- Department of Cancer Research and Molecular Medicine, NTNU, Trondheim, Norway
| | - Mats P Mosti
- Department of Cancer Research and Molecular Medicine, NTNU, Trondheim, Norway
| | | | - Bjørn I Viggaklev
- Department of Cancer Research and Molecular Medicine, NTNU, Trondheim, Norway
| | - Janne E Reseland
- Department of Biomaterials, Institute for Clinical Dentistry, University of Oslo, Oslo, Norway
| | | | - Reidar Fossmark
- Department of Cancer Research and Molecular Medicine, NTNU, Trondheim, Norway.,Department of Gastroenterology and Hepatology, St. Olav's Hospital, Trondheim, Norway
| | - Unni Syversen
- Department of Cancer Research and Molecular Medicine, NTNU, Trondheim, Norway.,Department of Endocrinology, St. Olav's Hospital, Trondheim, Norway
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Ueno K. [Expression and function of the histamine receptors in dermal and articular tissues]. YAKUGAKU ZASSHI 2015; 134:1093-108. [PMID: 25366908 DOI: 10.1248/yakushi.14-00183] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Histamine was first identified in 1910 as a physiologically active amine. It is now recognized for its multiple regulatory activities in the digestive, neuronal, and immune systems, and new roles are still being elucidated. Histamine exerts its effects through four distinct receptor subtypes. The histamine H4 receptor was identified in 2000 and is the most recently identified of the four histamine receptors. It is expressed primarily in immune cells and is involved in physiologic functions related to inflammation and allergy. Recently, the H4 receptor was highlighted as a promising therapeutic target in atopic dermatitis, asthma, and chronic arthritis. In fact, some H4 receptor antagonists have reached clinical trials for the treatment of asthma, atopic dermatitis, and allergic rhinitis. Based on an initial assessment of its distribution, the H4 receptor has been referred to as the histamine receptor of the hematopoietic system. However, the H4 receptor has also been implicated in the regulation of other non-hematopoietic systems. Here, I review the expression and function of the identified histamine receptors, including the H4 receptor with a focus on articular and dermal tissues. In articular tissue, H4 receptor expression has been detected in synovial cells. Chondrocytes, a major cell source for cartilage tissue engineering, also express the H4 receptor. In skin, the H4 receptor is expressed in both the epidermis and dermis, with stronger receptor expression in the epidermis. Further understanding of the functions of H4 receptors in non-hematopoietic cells might lead to novel treatments for diseases with unmet medical needs.
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Affiliation(s)
- Koichi Ueno
- Department of Geriatric Pharmacology and Therapeutics, Graduate School of Pharmaceutical Sciences, Chiba University
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Kann PH, Hadji P, Bergmann RS. [Pharmacogenic osteoporosis beyond cortisone. Proton pump inhibitors, glitazones and diuretics]. Z Rheumatol 2015; 73:323-8. [PMID: 24728601 DOI: 10.1007/s00393-013-1286-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
BACKGROUND [corrected] There are many drugs which can cause osteoporosis or at least favor its initiation. The effect of hormones and drugs with antihormonal activity, such as glucocorticoids and aromatase inhibitors, on initiation of osteoporosis is well known. In addition, proton pump inhibitors, glitazones and diuretics also influence the formation of osteoporosis. MATERIAL AND METHODS The results of currently available studies on the correlation between proton pump inhibitors, glitazones and diuretics on formation of osteoporosis were evaluated and summarized. RESULTS Proton pump inhibitors and glitazones increase the risk for osteoporotic fractures. Loop diuretics may slightly increase fracture risk, whereas thiazides were shown to be osteoprotective by reducing fracture probability on a relevant scale. CONCLUSION Proton pump inhibitors should not be prescribed without serious consideration and then only as long as necessary. Alternatively, the administration of the less effective H2 antagonists should be considered when possible due to the reduction of acid secretion. Because the long-term intake of thiazides is associated with a clinically relevant reduction in the risk of fractures and they are economic and well-tolerated, prescription can be thoroughly recommended within the framework of differential diagnostic considerations in an appropriate clinical context. The briefly increased risk of falling immediately after starting diuretic therapy is the only point which needs to be considered.
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Affiliation(s)
- P H Kann
- Zentrum für Innere Medizin - Bereich Endokrinologie & Diabetologie, Philipps-Universität Marburg/Universitätsklinikum Marburg UKGM, 35033, Marburg, Deutschland,
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da Silva EZM, Jamur MC, Oliver C. Mast cell function: a new vision of an old cell. J Histochem Cytochem 2014; 62:698-738. [PMID: 25062998 PMCID: PMC4230976 DOI: 10.1369/0022155414545334] [Citation(s) in RCA: 421] [Impact Index Per Article: 38.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2014] [Accepted: 07/07/2014] [Indexed: 02/06/2023] Open
Abstract
Since first described by Paul Ehrlich in 1878, mast cells have been mostly viewed as effectors of allergy. It has been only in the past two decades that mast cells have gained recognition for their involvement in other physiological and pathological processes. Mast cells have a widespread distribution and are found predominantly at the interface between the host and the external environment. Mast cell maturation, phenotype and function are a direct consequence of the local microenvironment and have a marked influence on their ability to specifically recognize and respond to various stimuli through the release of an array of biologically active mediators. These features enable mast cells to act as both first responders in harmful situations as well as to respond to changes in their environment by communicating with a variety of other cells implicated in physiological and immunological responses. Therefore, the critical role of mast cells in both innate and adaptive immunity, including immune tolerance, has gained increased prominence. Conversely, mast cell dysfunction has pointed to these cells as the main offenders in several chronic allergic/inflammatory disorders, cancer and autoimmune diseases. This review summarizes the current knowledge of mast cell function in both normal and pathological conditions with regards to their regulation, phenotype and role.
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Affiliation(s)
- Elaine Zayas Marcelino da Silva
- Department of Cell and Molecular Biology and Pathogenic Bioagents, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil (EZMDS, MCJ, CO)
| | - Maria Célia Jamur
- Department of Cell and Molecular Biology and Pathogenic Bioagents, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil (EZMDS, MCJ, CO)
| | - Constance Oliver
- Department of Cell and Molecular Biology and Pathogenic Bioagents, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil (EZMDS, MCJ, CO)
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Longhini R, Aparecida de Oliveira P, Sasso-Cerri E, Cerri PS. Cimetidine Reduces Alveolar Bone Loss in Induced Periodontitis in Rat Molars. J Periodontol 2014; 85:1115-25. [DOI: 10.1902/jop.2013.130453] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
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Folwarczna J, Janas A, Pytlik M, Śliwiński L, Wiercigroch M, Brzęczek A. Modifications of histamine receptor signaling affect bone mechanical properties in rats. Pharmacol Rep 2014; 66:93-9. [PMID: 24905313 DOI: 10.1016/j.pharep.2013.08.010] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2012] [Revised: 08/01/2013] [Accepted: 08/13/2013] [Indexed: 12/31/2022]
Abstract
Histamine receptors are expressed on bone cells and histamine may be involved in regulation of bone metabolism. The aim of the present study was to investigate the effects of loratadine (an H(1) receptor antagonist), ranitidine (an H(2) receptor antagonist) and betahistine (an H(3) receptor antagonist and H(1) receptor agonist) on bone mechanical properties in rats. Loratadine (5 mg/kg/day, po), ranitidine (50 mg/kg/day, po), or betahistine dihydrochloride (5 mg/kg/day, po), were administered for 4 weeks to non-ovariectomized and bilaterally ovariectomized (estrogen-deficient) 3-month-old rats, and their effects were compared with appropriate controls. Serum levels of bone turnover markers, bone mineralization and mechanical properties of the proximal tibial metaphysis, femoral diaphysis and femoral neck were studied. In rats with normal estrogen level, administration of loratadine slightly favorably affected mechanical properties of compact bone, significantly increasing the strength of the femoral neck (p < 0.05), and tending to increase the strength of the femoral diaphysis. Ranitidine did not significantly affect the investigated parameters, and betahistine decreased the strength of the tibial metaphysis (cancellous bone, p < 0.01). There were no significant effects of the drugs on serum bone turnover markers. In estrogen-deficient rats, the drugs did not significantly affect the investigated skeletal parameters. In conclusion, the effects of histamine H(1), H(2) and H(3) receptor antagonists on the skeletal system in rats were differential and dependent on estrogen status.
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Affiliation(s)
- Joanna Folwarczna
- Department of Pharmacology, Medical University of Silesia, Katowice, Sosnowiec, Poland.
| | - Aleksandra Janas
- Department of Pharmacology, Medical University of Silesia, Katowice, Sosnowiec, Poland
| | - Maria Pytlik
- Department of Pharmacology, Medical University of Silesia, Katowice, Sosnowiec, Poland
| | - Leszek Śliwiński
- Department of Pharmacology, Medical University of Silesia, Katowice, Sosnowiec, Poland
| | - Marek Wiercigroch
- Department of Pharmacology, Medical University of Silesia, Katowice, Sosnowiec, Poland
| | - Anna Brzęczek
- Department of Pharmacology, Medical University of Silesia, Katowice, Sosnowiec, Poland
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Ezzat BA, Abbass MMS. The ability of H1 or H2 receptor antagonists or their combination in counteracting the glucocorticoid-induced alveolar bone loss in rats. J Oral Pathol Med 2013; 43:148-56. [PMID: 23845021 DOI: 10.1111/jop.12104] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/04/2013] [Indexed: 11/29/2022]
Abstract
BACKGROUND The aim of the present study was to compare between three possible osteoporotic treatments in prevention of glucocorticoid-induced alveolar bone loss. METHODS Fifty adult female Wistar rats with an average weight 150-200 g were randomized into five groups: group I (control) was intraperitoneally injected with saline. The other experimental groups (II & III, IV & V) were intraperitoneally injected with 200 µg/100 g body weight dexamethasone. The experimental groups III, IV and V received intraperitoneal injection of 10 mg/kg/day pheniramine maleate (H1 receptor antagonist), ranitidine hydrochloride (H2 receptor antagonist) and concomitant doses of both H1 & H2 receptor antagonists respectively. After 30 days, the rats have been sacrificed. The mandibles were examined histologically, histochemically and histomorphometrically. The bone mineral density was measured using dual-energy X-ray absorptiometry (DEXA). RESULTS Histopathologically the glucocorticoid group showed wide medullary cavities with wide osteocytic lacunae. These marrow cavities were reduced in the prophylactic groups (III, IV) but increased in group V. Bone histomorphometric analysis revealed improvement in static bone parameters in groups III and IV and deterioration in group V in comparison to group II. The DEXA revealed significant reduction in the bone mineral density in all experimental groups compared to the control group. CONCLUSIONS In a rat model, the administration of H1 or H2 receptor antagonists separately could minimize the alveolar bone loss caused by the administration of glucocorticoids while concomitant administration of both H1 and H2 receptor antagonists deteriorated the bone condition.
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Affiliation(s)
- Bassant A Ezzat
- Department of Oral Biology, Faculty of Oral and Dental Medicine, Cairo University, Cairo, Egypt
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Fujita T, Ohue M, Fujii Y, Jotoku T, Miyauchi A, Takagi Y, Tsuchiya M, Endo Y. Prompt Analgesic Effect of Antihistaminic Diphenhydramine Ointment on Bone-Joint-Muscle Pain as Assessed by Skin Impedance. Pharmacology 2013; 92:158-66. [DOI: 10.1159/000354151] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2013] [Accepted: 07/04/2013] [Indexed: 11/19/2022]
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Longhini R, de Oliveira PA, de Souza Faloni AP, Sasso-Cerri E, Cerri PS. Increased apoptosis in osteoclasts and decreased RANKL immunoexpression in periodontium of cimetidine-treated rats. J Anat 2012. [PMID: 23198931 DOI: 10.1111/joa.12011] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022] Open
Abstract
It has been demonstrated that histamine interferes with the recruitment, formation and activity of osteoclasts via H(1)- and H(2)-receptors. Cimetidine is a H(2)-receptor antagonist used for treatment of gastric ulcers that seems to prevent bone resorption. In this study, a possible cimetidine interference was investigated in the number of alveolar bone osteoclasts. The incidence of osteoclast apoptosis and immunoexpression of RANKL (receptor activator of nuclear factor κB ligand) was also evaluated. Adult male rats were treated with 100 mg kg(-1) of cimetidine for 50 days (CimG); the sham group (SG) received saline. Maxillary fragments containing the first molars and alveolar bone were fixed, decalcified and embedded in paraffin. The sections were stained by H&E or submitted to tartrate-resistant acid phosphatase (TRAP) method. TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling) method and immunohistochemical reactions for detecting caspase-3 and RANKL were performed. The number of TRAP-positive osteoclasts, the frequency of apoptotic osteoclasts and the numerical density of RANKL-positive cells were obtained. Osteoclast death by apoptosis was confirmed by transmission electron microscopy (TEM). In CimG, TRAP-positive osteoclasts with TUNEL-positive nuclei and caspase-3-immunolabeled osteoclasts were found. A significant reduction in the number of TRAP-positive osteoclasts and a high frequency of apoptotic osteoclasts were observed in CimG. Under TEM, detached osteoclasts from the bone surface showed typical features of apoptosis. Moreover, a significant reduction in the numerical density of RANKL-positive cells was observed in CimG. The significant reduction in the number of osteoclasts may be due to cimetidine-induced osteoclast apoptosis. However, RANKL immunoexpression reduction also suggests a possible interference of cimetidine treatment in the osteoclastogenesis.
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Affiliation(s)
- Renata Longhini
- Federal University of São Paulo, Department of Morphology and Genetics, Brazil
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Ikeda N, Sugiyama T, Suzuki T, Mukai K, Kusuhara S. Effects of β-Cryptoxanthin on Bone Metabolism in a Rat Model of Osteoporosis. ACTA ACUST UNITED AC 2012. [DOI: 10.3923/javaa.2012.30.35] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
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Risk of fracture and pneumonia from acid suppressive drugs. World J Methodol 2011; 1:15-21. [PMID: 25237609 PMCID: PMC4145558 DOI: 10.5662/wjm.v1.i1.15] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2011] [Revised: 09/08/2011] [Accepted: 09/19/2011] [Indexed: 02/06/2023] Open
Abstract
A recently published systematic review and meta-analysis, incorporating all relevant studies on the association of acid suppressive medications and pneumonia identified up to August 2009, revealed that for every 200 patients, treated with acid suppressive medication, one will develop pneumonia. They showed the overall risk of pneumonia was higher among people using proton pump inhibitors (PPIs) [adjusted odds ratio (OR) = 1.27, 95% CI: 1.11-1.46, I2 = 90.5%] and Histamine-2 receptor antagonists (H2RAs) (adjusted OR = 1.22, 95% CI: 1.09-1.36, I2 = 0.0%). In the randomized controlled trials, use of H2RAs was associated with an elevated risk of hospital-acquired pneumonia (relative risk 1.22, 95% CI: 1.01-1.48, I2 = 30.6%). Another meta-analysis of 11 studies published between 1997 and 2011 found that PPIs, which reduce stomach acid production, were associated with increased risk of fracture. The pooled OR for fracture was 1.29 (95% CI: 1.18-1.41) with use of PPIs and 1.10 (95% CI: 0.99-1.23) with use of H2RAs, when compared with non-use of the respective medications. Long-term use of PPIs increased the risk of any fracture (adjusted OR = 1.30, 95% CI: 1.15-1.48) and of hip fracture risk (adjusted OR = 1.34, 95% CI: 1.09-1.66), whereas long-term H2RA use was not significantly associated with fracture risk. Clinicians should carefully consider when deciding to prescribe acid-suppressive drugs, especially for patients who are already at risk for pneumonia and fracture. Since it is unnecessary to achieve an achlorhydric state in order to resolve symptoms, we recommend using the only minimum effective dose of drug required to achieve the desired therapeutic goals.
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Eom CS, Park SM, Myung SK, Yun JM, Ahn JS. Use of acid-suppressive drugs and risk of fracture: a meta-analysis of observational studies. Ann Fam Med 2011; 9:257-67. [PMID: 21555754 PMCID: PMC3090435 DOI: 10.1370/afm.1243] [Citation(s) in RCA: 84] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
PURPOSE Previous studies have reported inconsistent findings regarding the association between the use of acid-suppressive drugs such as proton pump inhibitors (PPIs) and histamine 2 receptor antagonists (H(2)RAs) and fracture risk. We investigated this association using meta-analysis. METHODS We searched MEDLINE (PubMed), EMBASE, and the Cochrane Library from inception through December 2010 using common key words. We included case-control, nested case-control, and cohort studies. Two evaluators independently reviewed and selected articles. We determined pooled effect estimates by using random-effects meta-analysis, because of heterogeneity. RESULTS Of 1,809 articles meeting our initial inclusion criteria, 5 case-control studies, 3 nested case-control studies, and 3 cohort studies were included in the final analyses. The pooled odds ratio (OR) for fracture was 1.29 (95% confidence interval [CI], 1.18-1.41) with use of PPIs and 1.10 (95% CI, 0.99-1.23) with use of H(2)RAs when compared with nonuse of the respective medications. Long-term use of PPIs increased the risk of any fracture (adjusted OR = 1.30; 95% CI, 1.15-1.48) and hip fracture risk (adjusted OR = 1.34; 95% CI, 1.09-1.66), whereas long-term H(2)RA use was not significantly associated with fracture risk. CONCLUSIONS We found possible evidence linking PPI use to an increased risk of fracture, but no association between H(2)RA use and fracture risk. Widespread use of PPIs with the potential risk of fracture is of great importance to public health. Clinicians should carefully consider their decision to prescribe PPIs for patients already having an elevated risk of fracture because of age or other factors.
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Affiliation(s)
- Chun-Sick Eom
- Department of Family Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea
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Turner RT, Iwaniec UT, Marley K, Sibonga JD. The role of mast cells in parathyroid bone disease. J Bone Miner Res 2010; 25:1637-49. [PMID: 20200965 PMCID: PMC3154003 DOI: 10.1002/jbmr.49] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2009] [Revised: 11/22/2009] [Accepted: 01/19/2010] [Indexed: 12/21/2022]
Abstract
Chronic hyperparathyroidism (HPT) is a common cause of metabolic bone disease. These studies investigated the underlying cellular and molecular mechanisms responsible for the detrimental actions of elevated parathyroid hormone (PTH) on the skeleton. Bone biopsies from hyperparathyroid patients revealed an association between parathyroid bone disease and increased numbers of bone marrow mast cells. We therefore evaluated the role of mast cells in the etiology of parathyroid bone disease in a rat model for chronic HPT. In rats, mature mast cells were preferentially located at sites undergoing bone turnover, and the number of mast cells at the bone-bone marrow interface was greatly increased following treatment with PTH. Time-course studies and studies employing parathyroid hormone-related peptide (PTHrP), as well as inhibitors of platelet-derived growth factor-A (PDGF-A, trapidil), kit (gleevec), and PI3K (wortmannin) signaling revealed that mature mast cell redistribution from bone marrow to bone surfaces precedes and is associated with osteitis fibrosa, a hallmark of parathyroid bone disease. Importantly, mature mast cells were not observed in the bone marrow of mice. Mice, in turn, were resistant to the development of PTH-induced bone marrow fibrosis. These findings suggest that the mast cell may be a novel target for treatment of metabolic bone disease.
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Affiliation(s)
- Russell T Turner
- Department of Nutrition and Exercise Sciences, Oregon State University, Corvallis, OR 97331, USA.
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Cerri PS, Pereira-Júnior JA, Biselli NB, Sasso-Cerri E. Mast cells and MMP-9 in the lamina propria during eruption of rat molars: quantitative and immunohistochemical evaluation. J Anat 2010; 217:116-25. [PMID: 20557403 DOI: 10.1111/j.1469-7580.2010.01249.x] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022] Open
Abstract
During the active tooth eruption process, structural changes in the lamina propria are necessary to provide extracellular matrix remodelling and for the establishment of the eruptive pathway. A large number of resident cells, recruited cells and proteases have been demonstrated in the eruptive process, but the participation of MMP-9 and mast cells has not yet been demonstrated. In this study, we set out to evaluate the intensity of MMP-9 immunoexpression, the frequency of mast cells and the correlation between the incidence of mast cells and bone resorption in different phases of tooth eruption. Fragments of maxilla containing first molars, obtained from 9-, 11-, 13- and 16-day-old rats, were fixed in 4% formaldehyde, decalcified and embedded in paraffin. Sagittal sections were stained with Masson's trichrome or submitted to the tartrate-resistant acid phosphatase method for quantification of osteoclasts. Sections stained by 1% toluidine blue were used for quantification of metachromatic mast cells mm(-2) of lamina propria. The expression of MMP-9 in the lamina propria was evaluated by immunohistochemistry. In the 9-day-old rats, the lamina propria contained few mast cells and occasional osteoclasts were found in the bone surface overlying the occlusal portion of the tooth germs. Otherwise, a significant increase in the number of mast cells was observed in the intra-osseous phase of tooth eruption (11-day-old rats), period in which numerous TRAP-positive osteoclasts were found in the bone surface. MMP-9 immunolabelling was detected in fibroblasts, mast cells and macrophage-like cells of the lamina propria in all ages studied. However, an enhanced immunolabelling was evident in the advanced phase of tooth eruption (16-day-old rats). During the intra-osseous phase, the parallel between the high frequency of both mast cells and osteoclasts suggests that mast cells could exert a paracrine function on the osteoclasts and then stimulate bone resorption. The immunoexpression of MMP-9 in different cells of lamina propria, including mast cells, indicates that this enzyme participates in the degradation of ECM, mainly during late phase of mucosal penetration. Thus mast cells and MMP-9 are involved in the complex process of degradation of the eruptive pathway extracellular matrix.
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Affiliation(s)
- Paulo Sérgio Cerri
- Department of Morphology, Laboratory of Histology and Embryology, Dental School, UNESP - Univ. Estadual Paulista, Araraquara, São Paulo, Brazil.
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Gallina S, Barranco-Piedra S, Torres-Lagares D, Baroukh B, Llorens A, Gutiérrez-Pérez JL, Saffar JL, Cherruau M, Lesclous P. Estrogen Withdrawal Transiently Increased Bone Turnover Without Affecting the Bone Balance Along the Tooth Socket in Rats. J Periodontol 2009; 80:2035-44. [DOI: 10.1902/jop.2009.090297] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
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Abstract
STUDY DESIGN Case report and clinical discussion. OBJECTIVE To describe a rare case of vertebral involvement of systemic mastocytosis and its multimodal therapy. SUMMARY OF BACKGROUND DATA Vertebral fractures in young men are rare events. A thorough diagnostic work-up that unravels the underlying cause of osteoporosis and appropriate therapy are crucial to prevent further fractures. METHODS A 36-year-old man was evaluated for severe back pain and was found to suffer from progressive osteoporosis and multiple vertebral fractures. Bone biopsy analysis revealed tryptase-positive mast cells that were positive for c-KIT, thus confirming the diagnosis of systemic mastocytosis. RESULTS In addition to zoledronic acid (4 mg per month) and prednisolone (50 mg per day) treatment, the patient underwent kyphoplasty. The procedure was associated with arterial hypotension which was most likely because of pressure-induced mast cell degranulation. Follow-up visits demonstrated stable bone mineral density and tolerable back pain while on zoledronic acid. CONCLUSION Systemic mastocytosis is a rare cause of vertebral fractures in young men. Because of the potential risk of pressure-induced release of the allergy mediator histamine, kyphoplasty for vertebral involvement of systemic mastocytosis should be conducted with appropriate precautions.
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Biosse-Duplan M, Baroukh B, Dy M, de Vernejoul MC, Saffar JL. Histamine promotes osteoclastogenesis through the differential expression of histamine receptors on osteoclasts and osteoblasts. THE AMERICAN JOURNAL OF PATHOLOGY 2009; 174:1426-34. [PMID: 19264900 DOI: 10.2353/ajpath.2009.080871] [Citation(s) in RCA: 75] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
In addition to the numerous roles of histamine in both the immune and nervous systems, previous studies have suggested that this bioamine might also be involved in bone metabolism. Following our observations of impaired bone resorption in ovariectomized rats after histamine receptor antagonist treatment, we focused in this study on osteoclasts and osteoclast precursors. We looked for a direct action of histamine on these cells using both in vivo and in vitro approaches. In vivo, we triggered a remodeling sequence in rat mandibular bone and treated the animals with either histamine or histamine receptor antagonists. Histamine was shown to increase the number of osteoclasts and osteoclast precursors whereas antagonists of histamine receptor-1 and -2 decreased both osteoclast recruitment and resorption. In vitro, spleen cells from histamine-deficient mice were treated with receptor activator for nuclear factor kappa B ligand and macrophage colony stimulating factor, giving rise to both reduced numbers of osteoclasts and decreased resorption on dentin slices. Histamine enhanced resorption in these cultures in a dose-dependent manner. In addition, we identified osteoclast precursors as a source of histamine. In contrast, histamine increased the receptor activator for nuclear factor kappa B ligand/osteoprotegerin ratio in primary osteoblasts that did not secrete histamine. We observed a differential expression of histamine receptor-1 and -2 mRNAs in both primary osteoclasts and osteoblasts, confirming their functional roles with selective antagonists. Thus, histamine acts directly on osteoclasts, osteoclast precursors, and osteoblasts, promoting osteoclastogenesis through autocrine/paracrine mechanisms.
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Kinjo M, Setoguchi S, Solomon DH. Antihistamine therapy and bone mineral density: analysis in a population-based US sample. Am J Med 2008; 121:1085-91. [PMID: 19028205 PMCID: PMC2943241 DOI: 10.1016/j.amjmed.2008.06.036] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2008] [Revised: 06/15/2008] [Accepted: 06/17/2008] [Indexed: 11/26/2022]
Abstract
BACKGROUND Histamine may play an important role in bone turnover. The data regarding histamine 1 receptor antagonist (H1RA), histamine 2 receptor antagonist (H2RA), and bone mineral density in humans are sparse. We examined bone mineral density in subjects using histamine receptor antagonists in a representative US population-based sample from the Third National Health and Nutrition Examination Survey (1988-1994). METHODS Adult subjects aged 60 years and more using H1RA or H2RA who underwent dual energy x-ray absorptiometry scanning in the Third National Health and Nutrition Examination Survey were identified. We compared the femoral neck bone mineral density among users of these agents with nonusers in adjusted linear regression models that included known demographic, anthropometric, and medical risk factors for osteoporosis. RESULTS The mean age of the study subjects was 72.6 years; 52% were women and 59% were white. Among subjects with femoral neck bone mineral density measured, 199 used H1RAs, 297 used H2RAs, and 4162 were nonusers of histamine receptor antagonists. Femoral neck bone mineral density adjusting for age and gender and other covariates was slightly higher in H1RA users (0.74 g/cm(2)) versus nonusers (0.72 g/cm(2); P=.037). H2RA users showed slightly lower adjusted bone mineral density compared with nonusers (0.69 g/cm(2) vs 0.72 g/cm(2); P=.003), but bone densities were similar between H2RA users and nonusers when daily calcium intake exceeded 800 mg per day. CONCLUSION Femoral neck bone mineral density may be higher in H1RA users than nonusers among older adults. H2RA users with reduced calcium intake had lower bone mineral density than nonusers.
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Affiliation(s)
- Mitsuyo Kinjo
- Department of Medicine, Okinawa Chubu Hospital, Okinawa, Japan.
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Vestergaard P. Adverse Effects of Drugs on Bone and Calcium Metabolism/Physiology. Clin Rev Bone Miner Metab 2008. [DOI: 10.1007/s12018-007-9002-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
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Adamo V, Caristi N, Maugeri Saccà M, Ferraro G, Arcanà C, Maisano R, Santini D, Tonini G. Current knowledge and future directions on bisphosphonate-related osteonecrosis of the jaw in cancer patients. Expert Opin Pharmacother 2008; 9:1351-61. [DOI: 10.1517/14656566.9.8.1351] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
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McKeage K, Plosker GL. Zoledronic acid: a pharmacoeconomic review of its use in the management of bone metastases. PHARMACOECONOMICS 2008; 26:251-268. [PMID: 18282018 DOI: 10.2165/00019053-200826030-00007] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/25/2023]
Abstract
Zoledronic acid (Zometa is a third-generation nitrogen-containing parenteral bisphosphonate indicated for the treatment of bone metastases due to solid tumours or multiple myeloma and for hypercalcaemia of malignancy (HCM). In patients with advanced breast or prostate cancer, zoledronic acid 4 mg every 3-4 weeks for up to 15 months significantly reduced the proportion of patients with > or =1 skeletal-related event (SRE), excluding HCM, compared with placebo. In patients with advanced breast cancer or multiple myeloma, the incidence of SREs was similar in patients treated with zoledronic acid 4 mg or pamidronic acid 90 mg every 3-4 weeks for up to 25 months but, in breast cancer patients, zoledronic acid reduced the risk of SREs, including HCM, by an additional 20% compared with pamidronic acid. In modelled cost-utility studies comparing direct costs based on efficacy and resource-use data from these and/or other trials, results have varied. In the most recent study performed from the perspective of the UK NHS and modelled over a 10-year treatment period in women with advanced breast cancer, intravenous zoledronic acid and oral ibandronic acid were dominant over no treatment. Intravenous zoledronic acid was the most cost effective, in terms of incremental costs per QALY gained, followed by oral ibandronic acid, intravenous pamidronic acid and intravenous ibandronic acid. Two other modelled analyses in patients with advanced breast cancer, also conducted from the perspective of the NHS, evaluated the cost utility of three bisphosphonate therapies in patients receiving hormonal therapy or intravenous chemotherapy. Analyses were modelled over 14.3 months (i.e. expected survival) and assumptions varied markedly from results in clinical breast cancer trials. Also, efficacy assumptions for zoledronic acid were not based on clinical trials with the drug. The results of these analyses suggest that oral ibandronic acid is more cost effective than intravenous zoledronic acid and intravenous pamidronic acid in terms of incremental cost per QALY gained. In a global, 15-month modelled cost-effectiveness analysis of patients with advanced prostate cancer, conducted from a third-party perspective, the incremental cost per QALY gained for zoledronic acid versus no treatment was $US159 200 (year 2000 value), which is about 3-fold greater than commonly accepted thresholds for cost effectiveness. In conclusion, a recent modelled economic analysis suggests that intravenous zoledronic acid 4 mg is dominant relative to no treatment in the management of bone metastases in patients with advanced breast cancer. In contrast, in patients with advanced prostate cancer, the incremental cost per QALY gained for zoledronic acid 4 mg versus no treatment was predicted to be higher than commonly accepted thresholds. Compared with other bisphosphonates in the setting of advanced breast cancer, intravenous zoledronic acid was more cost effective than oral or intravenous ibandronic acid and intravenous pamidronic acid in one study, but less cost effective than oral ibandronic acid in another. Further efficacy and economic data comparing intravenous zoledronic acid with oral ibandronic acid are needed. Meanwhile, zoledronic acid appears to be the most cost effective intravenous bisphosphonate for the management of bone metastases in patients with advanced breast cancer and possibly in patients with different types of advanced solid tumours.
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Affiliation(s)
- Kate McKeage
- Wolters Kluwer Health | Adis, Auckland, New Zealand.
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Belot MP, Abdennebi-Najar L, Gaudin F, Lieberherr M, Godot V, Taïeb J, Emilie D, Machelon V. Progesterone reduces the migration of mast cells toward the chemokine stromal cell-derived factor-1/CXCL12 with an accompanying decrease in CXCR4 receptors. Am J Physiol Endocrinol Metab 2007; 292:E1410-7. [PMID: 17468394 DOI: 10.1152/ajpendo.00286.2006] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Mast cell recruitment is implicated in many physiological functions and several diseases. It depends on microenvironmental factors, including hormones. We have investigated the effect of progesterone on the migration of HMC-1(560) mast cells toward CXCL12, a chemokine that controls the migration of mast cells into tissues. HMC-1(560) mast cells were incubated with 1 nM to 1 microM progesterone for 24 h. Controls were run without progesterone. Cell migration toward CXCL12 was monitored with an in vitro assay, and statistical analysis of repeated experiments revealed that progesterone significantly reduced cell migration without increasing the number of apoptotic cells (P = 0.0084, n = 7). Differences between progesterone-treated and untreated cells were significant at 1 microM (P < 0.01, n = 7). Cells incubated with 1 microM progesterone showed no rearrangment of actin filaments in response to CXCL12. Progesterone also reduced the calcium response to CXCL12 and Akt phosphorylation. Cells incubated with progesterone had one-half the control concentrations of CXCR4 (mRNA, total protein, and membrane-bound protein). Progesterone also inhibited the migration of HMC-1(560) cells transfected with hPR-B-pSG5 plasmid, which contained 2.5 times as much PR-B as the control. These transfected cells responded differently (P < 0.05, n = 5) from untreated cells to 1 nM progesterone. We conclude that progesterone reduces mast cell migration toward CXCL12 and that CXCR4 may be a progesterone target in mast cells.
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MESH Headings
- Actins/metabolism
- Androstadienes/pharmacology
- Blotting, Western
- Calcium/metabolism
- Cell Movement/drug effects
- Cell Movement/physiology
- Chemokine CXCL12
- Chemokines, CXC/biosynthesis
- Chemokines, CXC/genetics
- Chemokines, CXC/metabolism
- Flow Cytometry
- Humans
- Mast Cells/cytology
- Mast Cells/drug effects
- Mast Cells/metabolism
- Oncogene Protein v-akt/metabolism
- Phosphorylation/drug effects
- Progesterone/pharmacology
- Protein Kinase Inhibitors/pharmacology
- RNA, Messenger/biosynthesis
- RNA, Messenger/genetics
- Receptors, CXCR4/biosynthesis
- Receptors, CXCR4/genetics
- Receptors, CXCR4/metabolism
- Receptors, Progesterone/metabolism
- Reverse Transcriptase Polymerase Chain Reaction
- Wortmannin
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Affiliation(s)
- Marie-Pierre Belot
- Institut National de la Santé et de la Recherche Médicale, Univ Paris-Sud 11, Institut Fédératif de Recherche 13, Assistance Publique-Hôpitaux de Paris, Hôpital Antoine Béclère, Service de Microbiologie-Immunologie Biologique, Clamart, France
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Abstract
OBJECTIVES The notion that mast cells and their secreted products play a potentially pathogenic role in osteoporosis bone loss is novel, but gaining substantial support. We reviewed the literature from 1950 to present to demonstrate an association between mast cells and bone turnover. The effect of primary increase in mast cells, deficiency in mast cells, and effect of mast cells during high remodeling states is discussed in this review. METHODS A retrospective review of the literature was performed using Medline and MD Consult databases from 1957 to 2004. The keywords mast cell and osteoporosis revealed 200 abstracts, limited to English and review articles. The references were further selected based on relevance to pathogenesis, research, and histamine's role in osteoporosis. RESULTS Using the model of systemic mastocytosis, increased numbers of mast cells led to an acceleration of bone turnover. Activation mutations in tyrosine growth factor receptor, KIT, may be responsible for this occurrence. Mast cell deficiency demonstrates delayed osteoclastic recruitment and a delayed osteoblastic formation phase. Histamine deficiencies lead to a decrease in osteoclast number as reflected by tartrate-resistant acid phosphatase staining. Osteoblasts stimulated by parathyroid hormone synthesize abundant stem cell factor, which contributes to enhanced osteoclastogenesis. CONCLUSIONS Mast cells appear to be relevant in the pathogenesis of bone turnover. Their deficiency has been associated with low remodeling states, while their excess is associated with accelerated bone loss. Even their byproducts are responsible for increased bone resorption. Inhibiting mast cells and/or their products many be a novel therapy for treating osteoporosis in the future.
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Affiliation(s)
- Nicole Chiappetta
- Department of Rheumatology, Stony Brook University Hospital, Stony Brook, NY 11733, USA.
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Vestergaard P, Rejnmark L, Mosekilde L. Proton pump inhibitors, histamine H2 receptor antagonists, and other antacid medications and the risk of fracture. Calcif Tissue Int 2006; 79:76-83. [PMID: 16927047 DOI: 10.1007/s00223-006-0021-7] [Citation(s) in RCA: 253] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2006] [Accepted: 04/26/2006] [Indexed: 12/22/2022]
Abstract
We studied the effect of proton pump inhibitors, histamine H(2) receptor antagonists, and other types of antacid drugs on fracture risk. All cases were subjects with any fracture sustained during the year 2000 (n = 124,655). For each case, three controls (n = 373,962) matched on age and gender were randomly drawn from the background population. The primary exposure variables were use of proton pump inhibitors, histamine H(2) antagonists, and other antacid drugs. Adjustments were made for several confounders, including diagnosis of an ulcer, nonsteroidal anti-inflammatory drug use, use of histamine H(1) antagonists, stomach resection, previous fracture, and use of corticosteroids. The effect of dose was examined by stratifying for cumulated dose (defined daily dose). Use of proton pump inhibitors was associated with an increase in fracture risk for use within the last year [odds ratio (OR) = 1.18, 95% confidence interval (CI) 1.12-1.43 for overall fracture risk; OR = 1.45, 95% CI 1.28-1.65 for hip fractures; and OR = 1.60, 95% CI 1.25-2.04 for spine fractures). Histamine H(2) antagonists were associated with a decreased fracture risk if they had been used within the last year (OR = 0.88, 95% CI 0.82-0.95 for any fracture, OR = 0.69, 95% CI 0.57-0.84 for hip fractures). Other antacids were not associated with overall fracture risk but were associated with hip and spine fractures. Proton pump inhibitors appeared to be associated with a limited increase in fracture risk, in contrast to histamine H( 2 ) antagonists, which seemed to be associated with a small decrease in fracture risk. In all cases, the changes in risk estimates were small and the clinical significance was limited.
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Affiliation(s)
- P Vestergaard
- The Osteoporosis Clinic, Aarhus Amtssygehus, Aarhus University Hospital, Tage Hansens Gade 2, DK-8000, Aarhus C, Denmark.
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Lesclous P, Schramm F, Gallina S, Baroukh B, Guez D, Saffar JL. Histamine mediates osteoclastic resorption only during the acute phase of bone loss in ovariectomized rats. Exp Physiol 2006; 91:561-70. [PMID: 16513821 DOI: 10.1113/expphysiol.2006.033217] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
Short-term studies have shown that histamine is involved, via its H2 receptors (H2R), in the mediator network regulating trabecular bone loss in long bones of ovariectomized (OVX) rats. It is not known whether this effect of histamine persists over time or involves other skeletal sites. In this study, rats were maintained for 6 months postOVX and treated daily with saline or famotidine (10 mg kg(-1)), an H2R antagonist. At the end of the experimental period, femur trabecular bone mass was markedly decreased in OVX rats, whether or not they were treated with famotidine. In contrast, in the fourth lumbar vertebra, where bone loss starts later than in the femur, famotidine treatment attenuated the decline in trabecular bone volume, protected the trabecular architecture, maintained the thickness of the cortices and reduced the numbers of osteoclasts and tartrate-resistant acid phosphatase-positive preosteoclasts, whereas it had no influence on bone formation parameters. In vertebral bone marrow of OVX rats, the numbers of mast cells (MCs) and non-MC histamine-producing cells increased, while famotidine treatment significantly diminished both cell populations. These data show that H2R antagonism does not protect trabecular bone mass in the long term, and that short-term protection involves all bones. Histamine is involved during the early phase of strong osteoclastic resorption but not during the late phase of slower resorption, suggesting that different mediator networks control the two phases of destruction. Histamine would be part of the network mediating the early phase.
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Affiliation(s)
- Ph Lesclous
- Laboratoire sur la réparation et les remodelages oro-faciaux, EA 2496, Faculté de Chirurgie Dentaire, Université Paris Descartes, 1 rue Maurice Arnoux, 92120 Montrouge, France
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Fouilloux I, Duplan MB, Baroukh B, Cherruau M, Saffar JL, Lesclous P. Mast cell activation and degranulation occur early during induction of periosteal bone resorption. Bone 2006; 38:59-66. [PMID: 16249129 DOI: 10.1016/j.bone.2005.07.026] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2005] [Revised: 06/22/2005] [Accepted: 07/19/2005] [Indexed: 02/02/2023]
Abstract
We have previously postulated that mast cells participate in the cellular network involved in osteoclastic resorption, probably through histamine release. In this study, we examined mast cell activation and histamine release during origination of resorption. Groups of 10 rats were killed 0, 0.5, 1, 1.5, 3, 6, 9, 12 and 18 h after induction of resorption in a synchronized model of cortical resorption along the mandible. The total number of mast cells was transiently decreased by about one-third at 1 and 9 h. Mast cell activation was monitored by Alcian blue-safranin staining. Early after induction, mast cells started to release their mediator stores; complete release led to the apparent disappearance of the cells with the staining technique used. Histamine immunostaining confirmed the release of histamine and its diffusion in the extracellular environment. Massive degranulation was observed at 1.5 and 9 h with toluidine blue staining. Cell recovery, assessed in terms of histidine decarboxylase expression, occurred gradually. The number of ED1+ osteoclast precursors strongly increased from 12 h up to 18 h. Most parameters had returned to baseline at 18 h, except the ED1+ cells. H2 receptor inhibition with famotidine strongly decreased ED1+ osteoclast precursors at 12 h and subsequently osteoclasts at the peak of resorption. These data support a role of mast cells in resorption origination. They show an early and transient intervention of mast cells in the events regulating the recruitment of circulating osteoclast precursors and ultimately of resorption. Mast cell activation and degranulation induce the release of mediators, particularly histamine acting through its H2 receptors, which are likely involved in these reactions.
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Affiliation(s)
- I Fouilloux
- Laboratoire sur la Réparation et les Remodelages Oro-Faciaux, EA 2496, Université Paris-Descartes, Faculté de Chirurgie Dentaire, 1 rue M. Arnoux, 92120 Montrouge, France
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Liu YZ, Dvornyk V, Lu Y, Shen H, Lappe JM, Recker RR, Deng HW. A Novel Pathophysiological Mechanism for Osteoporosis Suggested by an in Vivo Gene Expression Study of Circulating Monocytes. J Biol Chem 2005; 280:29011-6. [PMID: 15965235 DOI: 10.1074/jbc.m501164200] [Citation(s) in RCA: 106] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
Bone mineral density (BMD) is a major risk factor for osteoporosis. Circulating monocytes may serve as early progenitors of osteoclasts and produce a wide variety of factors important to bone metabolism. However, little is known about the roles of circulating monocytes in relation to the pathophysiology of osteoporosis. Using the Affymetrix HG-U133A GeneChip(R) array, we performed a comparative gene expression study of circulating monocytes in subjects with high and low BMD. We identified in total 66 differentially expressed genes including some novel as well as some already known to be relevant to bone metabolism. Three genes potentially contributing to bone metabolism, CCR3 (chemokine receptor 3), HDC (histidine decarboxylase, i.e. the histamine synthesis enzyme), and GCR (glucocorticoid receptor), were confirmed by quantitative real-time reverse transcriptase-PCR as up-regulated in subjects with lower BMD. In addition, significant negative correlation was observed between expression levels of the genes and BMD Z-scores. These three genes and/or their products mediate monocyte chemotaxis, histamine production, and/or sensitivity to glucocorticoids. Our results suggest a novel pathophysiological mechanism for osteoporosis that is characterized by increased recruitment of circulating monocyte into bone, enhanced monocyte differentiation into osteoclasts, as well as osteoclast stimulation via monocyte functional changes. This is the first in vivo microarray study of osteoporosis in humans. The results may contribute to identification of new genes and their functions for osteoporosis and suggest genetic markers to discern individuals at higher risk to osteoporosis with an aim for preventive intervention and treatment.
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Affiliation(s)
- Yao-Zhong Liu
- Osteoporosis Research Center, Creighton University Medical Center,Creighton University, Omaha, NE 68131, USA
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