Searchable abstracts of presentations at key conferences on calcified tissues
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43rd Annual European Calcified Tissue Society Congress

Rome, Italy
14 May 2016 - 17 May 2016

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Poster Presentations

Cell biology: osteoclasts and bone resorption

ba0005p171 | Cell biology: osteoclasts and bone resorption | ECTS2016

Notch 2 signaling promotes osteoclast resorption via activation of PYK2

Jong Jin Won , Kim Bongjun , Kim Jung-Wook , Kim Hong-Hee , Hee Lee Zang

Notch signaling plays a central role in various cell fate decisions, including skeletal development. Recently, Notch signaling was implicated in osteoclast differentiation and maturation, including the resorption activity of osteoclasts. However, the specific involvement of notch signaling in resorption activity was not fully investigated. Here, we investigated the roles of Notch signaling in the resorption activity of osteoclasts by use of the γ-secretase inhibitor diben...

ba0005p172 | Cell biology: osteoclasts and bone resorption | ECTS2016

Rooibos (Aspalathus Linearis) tea extract inhibits osteoclast formation and bone resorption in RAW264.7 murine macrophages, in vitro

Moosa Shaakirah , Kasonga Abe , Deepak Vishwa , Marais Sumari , Kruger Marlena , Coetzee Magdalena

Rooibos (Aspalathus linearis) tea is a refreshing and caffeine-free tea indigenous to the Western Cape regions of South Africa. This tea, which is rich in polyphenols and antioxidants, has shown many beneficial effects in health, however, its anti-osteoclastogenic potential remains unexplored. In this study, the in vitro effects of an aqueous extract of fermented rooibos tea were examined on osteoclast formation and bone resorption in RAW264.7 murine macropha...

ba0005p173 | Cell biology: osteoclasts and bone resorption | ECTS2016

Bone resorption by Tannerella forsythia GroEL

Choi Yu-Jung , Jung Young-Jung , An Sun-Jin , Choi Bong-Kyu

Tannerella forsythia is a gram-negative, anaerobic, asaccharolytic, fusiform bacterium. The presence of the bacterium is associated with various forms of periodontal disease, including gingivitis, chronic and aggressive periodontitis. The expression of GroEL, a bacterial heat shock protein, increases in stressful conditions such as infection. GroEL is a moonlighting protein that has multiple functions. The aim of this study was to evaluate the effect of T. forsyth...

ba0005p175 | Cell biology: osteoclasts and bone resorption | ECTS2016

A jumonji histone demethylase inhibits osteoclast differentiation through NFATc1 regulation

Chun Yang-Sook , Kim Seoun-Soung , Kim Hye-Jin , Park Jong-Wan

Osteoclasts are bone-resorbing multinucleated cells that differentiate from monocyte/macrophage-lineage precursors. Bone destruction and osteoporosis are attributed to excessively activated osteoclasts. Osteoclast differentiation is governed by diverse regulatory processes including nuclear factor-activated T cells c1 (NFATc1) activation in response to RANKL. The mechanism of epigenetic regulation of NFATc1 in osteoclastogenesis not investigated yet. Here we test a hypothesis ...

ba0005p176 | Cell biology: osteoclasts and bone resorption | ECTS2016

Impaired c-kit signaling couples bone resorption to bone formation through wnt10b in kitw-Sh/W-Sh mice

Lotinun Sutada , Krishnamra Nateetip , Horne William

Kit ligand/c-Kit receptor tyrosine kinase complex has been implicated as a target for bone remodeling process. Loss of function mutation in c-Kit causes low bone mass in KitW/W-v (W/Wv) mice. However, these mice are sterile and it is unclear whether the observed skeletal phenotype is secondary to sex hormone deficiency. To address this question, the skeletal phenotype of KitW...

ba0005p177 | Cell biology: osteoclasts and bone resorption | ECTS2016

A novel regulatory factor in osteoclastogenesis DCL-1/CD302: significance of its binding to CCN2/CTGF

Aoyama Eriko , Hoshijima Mitsuhiro , Kubota Satoshi , Takigawa Masaharu

CCN2/CTGF is known as a multi-functional growth factor for various mesenchymal cells including chondrocytes, osteoblasts, vascular endothelial cells and its function is suggested to be produced by its binding to other growth factors or membrane proteins. Therefore, finding out these binding partners are critically important in understanding the molecular function of the CCN2. As a result of screening, DCL-1/CD302 was found as a new candidate of CCN2-binding molecule. DCL-1/CD3...

ba0005p178 | Cell biology: osteoclasts and bone resorption | ECTS2016

Retrieval of resorptive human osteoclasts from temperature-responsive plastic

Gebraad Arjen , Hentunen Teuvo , Laitala-Leinonen Tiina

Osteoclasts are the major bone resorbing cells, essential for bone turnover and development. Human osteoclasts can be generated in vitro by stimulation of peripheral blood mononuclear cells (PBMCs) with M-CSF and RANK-L. Seeding fully differentiated osteoclasts onto mineralized surfaces facilitates the analysis of molecular interactions between the osteoclast and the mineralized matrix.Currently, a widely used protocol for harvesting osteoclasts...

ba0005p179 | Cell biology: osteoclasts and bone resorption | ECTS2016

Tensin 3 is a novel partner of dock5 that controls osteoclast podosome organization and activity

Touaitahuata Heiani , Morel Anne , Urbach Serge , Mateos-Langerak Julio , de Rossi Sylvain , Blangy Anne

Osteoclasts resorb bone matrix through a specific adhesion structure called the sealing zone or actin ring, which is based on a belt of podosome. Much remains to be uncovered regarding the molecular mechanisms driving podosome organization into superstructures in particular the osteoclast podosome belt. Proteomic analyses in osteoclasts revealed the adaptor protein tensin 3 as a partner of Dock5, a Rac exchange factor necessary for podosome belt formation and bone resorption. ...

ba0005p180 | Cell biology: osteoclasts and bone resorption | ECTS2016

High trabecular bone mass induced by reduced function of osteoclasts in GULP1-deficient mice

Park Gun-Il , Park Seung-Yoon , Lee Eun-Hye , Lee Yeon-Ju , Kim Soon-Young , Kim Seong-Hwan , Kim Yeo-Hyang , Kim In-San , Kim Jung-Eun

Engulfment adaptor phosphotyrosine-binding (PTB) domain containing 1 (GULP1) is an adaptor protein involved in the engulfment of apoptotic cells via phagocytosis. Although GULP1 is widely expressed in various tissues, including the brain, muscle, testis, and bone, the function of GULP1 has not been well studied. Here, we investigated whether GULP1 plays a role in the regulation of bone remodeling and examined its expression in bone cells. Conditional Gulp1 floxed mice...

ba0005p181 | Cell biology: osteoclasts and bone resorption | ECTS2016

Dual-specificity tyrosine-phosphorylation regulated kinase 2 negatively regulates osteoclast fusion

Guterman Ram Gali , Czeiger Tal , Marchinsky Anastasia , Levaot Noam

During the differentiation of the osteoclast, it transform from a mono-nucleated cell to multinucleated cell by fusion of its precursors. Although, cell fusion is a complicated process which likely involves many regulating proteins, only a few osteoclast fusion regulating proteins were identified. We have identified dual-specificity tyrosine-phosphorylation regulated kinase 2 (Dyrk2) as a novel regulator of the osteoclast fusion process. Dyrk2 belongs to a family of protein ki...

ba0005p182 | Cell biology: osteoclasts and bone resorption | ECTS2016

Human dendritic cell-derived osteoclasts have the ability for both bone absorption and T cell stimulation

Narisawa Manabu , Kubo Satoshi , Nakayamada Shingo , Zhao Jidong , Sakata Kei , Okada Yosuke , Yamaoka Kunihiro , Tanaka Yoshiya

Objective: It is well known that monocytes differentiate into osteoclasts. However, we found that human dendritic cells (DCs) also differentiate to osteoclast-like cells and assessed the role of dendritic cell-derived osteoclast (DC-OC) in pathological processes of inflammatory diseases such as rheumatoid arthritis (RA).Methods: DC-OCs were differentiated from human monocyte-derived DCs in vitro. The function of DC-OCs was compared to human mono...

ba0005p183 | Cell biology: osteoclasts and bone resorption | ECTS2016

Life span differs between osteoclasts derived from different bone marrow precursors: a time-lapse microscopy study

Cao Yixuan , Jansen Ineke , Sprangers Sara , Stap Jan , Everts Vincent , de Vries Teun

Osteoclasts are multinucleated bone-resorbing cells and can be cultured from different monocytic precursors. It is unknown whether osteoclasts derived from different precursors are phenotypically different. One of the aspects not known is the life span of the different osteoclasts and the effect of IL-1β hereupon. Here, we studied this using time-lapse microscopy. Bone marrow cells were isolated from 6-week-old male mice. Early blasts (CD31hiLy-6C-),...

ba0005p184 | Cell biology: osteoclasts and bone resorption | ECTS2016

Involvement of integrin beta 2/CD18 in attachment of monocytes to bone

Sprangers Sara , Schoenmaker Ton , Cao Yixuan , Everts Vincent , de Vries Teun J.

Background: Osteoclasts (OCs) are bone-degrading cells that differentiate from the monocyte/macrophage lineage. In human, three monocyte subsets have been identified: classical, intermediate and non-classical monocytes. We have previously demonstrated that comparable numbers of OCs can be generated from these subsets on plastic, but that the number of OCs significantly differs when the monocytes are cultured on bone. It is plausible that the observed differences are associated...

ba0005p185 | Cell biology: osteoclasts and bone resorption | ECTS2016

Characterising the role of the lysosomal membrane proteins MFSD1 and TMEM106b in osteoclasts

Lopez David Massa , Damme Markus , Saftig Paul

Osteoclasts are highly specialized cell types, responsible for the resorption of bone matrix. Coordinated with osteoblasts they contribute to a proper bone turnover. An impaired or reduced function of the osteoclast leads to a pathogenic increase of the bone mass and finally osteopetrosis. Lysosomal hydrolases, as exemplied by CTSK and Acp5 (TRAP), are known to play an important role in the function of osteoclasts, and knockout mouse models of these proteins develop a bone res...

ba0005p186 | Cell biology: osteoclasts and bone resorption | ECTS2016

Inflammatory conditions induces a new subset of osteoclasts that prime TNFα-producing CD4+T cells

Ibanez Lidia , Abou-Ezzi Grazia , Ciucci Thomas , Amiot Vanessa , Mansour Anna , Roleau Matthieu , Wakkach Abdelilah , Blin-Wakkach Claudine

Chronic inflammatory diseases are characterized by a bone destruction mediated by an increased osteoclast (OCL) activity. OCLs are phagocytic cells arising from the myeloid lineage. Indeed, OCLs derive from monocytes (MN-OCLs) and, in an inflammatory context, they also derive from dendritic cells (DC-OCLs). Despite this origin, their role in the immune responses is still unclear. OCLs in steady state have been reported to act as antigen-presenting cells that activate CD8+ regu...

ba0005p187 | Cell biology: osteoclasts and bone resorption | ECTS2016

Identification of CX3CR1 as the first known marker of inflammatory osteoclasts

Ibanez Lidia , Belaid Nourhene , Rouleau Matthieu , Wakkach Abdelilah , Blin-Wakkach Claudine

Existence of inflammatory osteoclasts (iOCLs) contributing to pathological bone resorption associated with inflammatory diseases has been suspected for many years. However, specific markers of iOCLs are lacking, making impossible to establish the contribution of iOCLs to such pathologies. Whereas in steady state OCLs derive from monocytes (MN-OCLs), in inflammatory conditions, they also differentiate from dendritic cells (DC-OCLs). We recently showed that these 2 OCL populatio...

ba0005p188 | Cell biology: osteoclasts and bone resorption | ECTS2016

The Arf and Rho GTPase-activating protein (GAP) ARAP1 regulates osteoclast function

Segeletz Sandra , Hoflack Bernard

The ArfGAP with RhoGAP domain, ankyrin repeat and PH domain containing protein 1 (ARAP1) is a multi-domain protein that binds to phosphatidylinositol lipids within different biological membranes and integrates Rho and Arf signalling pathways. It is ubiquitously expressed in many cells including osteoclasts and its overexpression is known to affect Golgi and induce filopodia by activation of Cdc42. We therefore hypothesized that ARAP1 might also play an important role in osteoc...

ba0005p189 | Cell biology: osteoclasts and bone resorption | ECTS2016

Pathophysiological implication of Autotaxin on osteoclast function

Flammier Sacha , Gicquel Tristan , Duboeuf Francois , Peyruchaud Olivier , Coury Fabienne , Machuca-Gayet Irma

Autotaxin (ATX) is a secreted protein produced by various tissues in the body including the liver, adipose tissue and bone. Autotaxin (ATX) is an enzyme with a phospholipase D activity responsible for cleavage of lysophosphatidyl-choline (LPC) in lysophosphatidic acid (LPA). LPA is a bio phospholipid, which acts as a growth factor, affecting proliferation, differentiation, and migration. It has been shown that the biological effect of LPA could be the direct consequence of loc...

ba0005p190 | Cell biology: osteoclasts and bone resorption | ECTS2016

Identification and characterisation of vesicles in resorbing osteoclasts using electron tomography

McDermott Emma , Sunderhauf David , Mackenzie Kevin , Wilkinson Debbie , Helfrich Miep

Osteoclasts are the only cell type capable of resorption of mineralised matrix such as bone or dentine. Resorbing osteoclasts form distinct membrane domains: the functional secretory, the basolateral and the ruffled border (RB) domains. The RB allows acidification of the resorption lacuna, exocytosis of osteolytic enzymes and uptake of degraded bone material, processes that require directed vesicular transport. Few studies have tried to classify the vesicles near the RB into s...

ba0005p191 | Cell biology: osteoclasts and bone resorption | ECTS2016

Homer proteins modulate RANKL-induced NFATc1 signaling in osteoclast differentiation and bone metabolism

Yang Yu-Mi , Son Aran , Kang Jung Yun , Shin Dong Min

Ca2+ signaling and NFATc1 activation are essential for RANKL-induced osteoclast differentiation through the induction of Ca2+ oscillation, calcineurin activation, and translocation of NFATc1 into the nucleus. Homer proteins are scaffold proteins that have been proposed to modulate multiple Ca2+ signaling proteins, including inositol 1,4,5-triphosphate receptors, ryanodine receptors, transient receptor potential channels. In this study, we inves...

ba0005p192 | Cell biology: osteoclasts and bone resorption | ECTS2016

Regulation and function of lentiviral-mediated TCIRG1 expression in osteoclasts from infantile malignant osteopetrosis patients

Lofvall Henrik , Thudium Christian Schneider , Moscatelli Ilana , Montano Carmen , Schulz Ansgar , Richter Johan , Henriksen Kim

Infantile malignant osteopetrosis (IMO) is a rare, lethal, recessive disorder characterized by dysfunctional osteoclasts. TCIRG1, encoding the osteoclast V-ATPase, is mutated in 50% of IMO patients. We have previously shown that the resorptive function in osteoclasts derived from IMO patients can be restored in vitro by expressing TCIRG1 using a lentiviral vector. In this study, we aim to investigate the cellular response to vector-derived TCIRG1 expression and to det...

ba0005p193 | Cell biology: osteoclasts and bone resorption | ECTS2016

C-C chemokine receptor 5, a co-receptor of HIV, -mediated signal is required for geometric architecture and function of osteoclasts, thus for RANKL-induced bone destruction

Lee Ji-Won , Hoshino Akiyoshi , Saitou Takashi , Inoue Kazuki , Uehara Shunsuke , Kobayashi Yasuhiro , Matsushima Kouji , Imai Yuuki , Iimura Tadahiro

C-C chemokine receptor 5 (CCR5) is a co-receptor of macrophage-tropic viruses including HIV. Epidemiological and pathological findings have reported that functional changes in CCR5 correlate with HIV transmission bone destruction disease. However, the roles of CCR5 in bone pathophysiology have not been well documented.Ccr5-deficient osteoclasts showed decreased bone resorption activity accompanied with disorganized cellular architecture and impa...

ba0005p194 | Cell biology: osteoclasts and bone resorption | ECTS2016

Neuropetide Y Y1 receptor deletion impairs matrix demineralization and resorption

Sousa Daniela M , Conceicao Francisco , Leitao Luis , Neto Estrela , Alves Cecilia J , Alencastre Ines S , Herzog Herbert , Aguiar Paulo , Lamghari Meriem

Neuropeptide Y Y1 receptor (Y1R) signalling has been shown to play a key role in bone homeostasis, emerging as a novel therapeutic target in bone diseases. Y1R knockout mice (Y1−/−) display a high-bone mass phenotype that has been mainly attributed to increased osteoblast activity. Nevertheless, the Y1R regulatory role on osteoclastogenesis and matrix resorption remains largely unknown. To clarify th...

ba0005p195 | Cell biology: osteoclasts and bone resorption | ECTS2016

The role of LC3 and autophagy in bone resorption by osteoclasts

Tran Anh , Coxon Fraser , McDermott Emma , Ganley Ian , Odgren Paul , Martinez Jennifer , Green Douglas , Helfrich Miep

The autophagy protein LC3 is necessary for bone resorption by osteoclasts, although it has been suggested that this may be through a novel, autophagy-independent process, by promoting lysosomal fusion at the ruffled border (RB). This process would be analogous to LC3-associated phagocytosis (LAP), in which LC3 is acquired by phagosomes through an autophagy-independent process, and controls phagosome maturation by promoting fusion with lysosomes. We have investigated this possi...

ba0005p196 | Cell biology: osteoclasts and bone resorption | ECTS2016

The RECQL4 protein mutated in Rothmund-Thomson syndrome is involved in osteoclast differentiation and function

Tcheremisinova Iulia , Gritsaenko Tatiana , Pierrefite-Carle Valerie , Breuil Veronique , Cros Chantal , Carle Georges , Santucci-Darmanin Sabine

Homozygous or compound heterozygous mutations in the RECQL4 helicase gene are responsible for 65% cases of Rothmund-Thomson syndrome (RTS-type II), a rare premature ageing syndrome. RTS-II patients exhibit poikiloderma and various kinds of bone abnormalities: short stature, congenital radial ray anomalies, bone microarchitecture defects, diffuse or localized osteoporosis and increased risk of osteosarcoma. Mutations in the RECQL4 gene are also responsible for...

ba0005p197 | Cell biology: osteoclasts and bone resorption | ECTS2016

Effects of TGF-β inhibition on osteogenesis and osteoclastogenesis by periodontal ligament fibroblasts from patients with fibrodysplasia ossificans progressiva

de Vries Teun J. , Schoenmaker Ton , Micha Dimitra , Netelenbos Coen , Pals Gerard , Eekhoff Marelise W. , Bravenboer Nathalie

Background: Fibrodysplasia Ossificans Progressiva (FOP) is a progressive disease characterized by periods of heterotopic ossification, often in ligaments. The underlying mechanism is far from clear, partially due to limited access to patient-derived cell models. Periodontal ligament fibroblasts (PLF) from extracted teeth can potentially be used to study deviant bone remodelling processes in vitro since these cells are derived from actual ligaments. They further provid...

ba0005p198 | Cell biology: osteoclasts and bone resorption | ECTS2016

Development of a novel sandwich ELISA to quantify human Tartrate Resistant Acid Phosphatase (TRAP) isoforms 5a and 5b protein in one and the same sample

Patlaka Christina , Mira-Pascual Laia , Paulie Staffan , Lang Pernilla , Andersson Goran

Tartrate resistant acid phosphatase (TRAP) consists of two isoforms TRAP 5a and TRAP 5b suggested to exert different functions and clinical relevance. TRAP 5a is a 35 kDa monomer and a potential marker of inflammatory conditions e.g. atherosclerosis and rheumatoid arthritis. TRAP 5b, a heterodimer of 16 and 23 kDa generated by proteolytic cleavage of a repressive loop in TRAP 5a, is used as marker for osteoclast numbers/bone resorption and osteoclast-related pathological condi...

ba0005p199 | Cell biology: osteoclasts and bone resorption | ECTS2016

Identification of G protein-coupled receptor 137B (GPR137b) function in mouse and zebrafish osteoclasts

Urso Katia , Caetano-Lopes Joana , Lee Pui , Henke Katrin , Sury Meera , Duryea Jeff , Nigrovic Peter , Aliprantis Antonios , Harris Matt , Charles Julia

Analysis of genome wide data such as transcriptomics can identify genes of potential interest to bone biology. These techniques are primarily hypothesis-generating. Determining the role of candidate factors in bone ultimately requires in vivo experiments. Gene expression analysis of mouse osteoclast differentiation identified G protein-coupled receptor 137B (GPR137b) as highly upregulated. GPR137b is an orphan seven-pass transmembrane receptor of unknown func...

ba0005p200 | Cell biology: osteoclasts and bone resorption | ECTS2016

RAW264.7 subclones - an in vitro model for osteoclast heterogeneity?

Mira-Pascual Laia , Lang Pernilla , Andersson Goran

Site-specific osteoclasts (OC) and OC-like cells from different pathologies exhibit heterogeneity e.g. in the resorption machinery, influence of anti-resorptive drugs and response to local or systemic hormones e.g. PTH. The explanation for this is not known but different precursors, local regulation through osteoblasts (OB), osteocytes and extracellular matrix (ECM) could be involved. To study these differences a simple and reproducible cell model is an advantage in pre-clinic...

ba0005p201 | Cell biology: osteoclasts and bone resorption | ECTS2016

Galectin-1 is involved in osteoclast biology

Muller Josephine , Binsfeld Marilene , Dubois Sophie , Carmeliet Geert , Beguin Yves , Heusschen Roy , Caers Jo

Osteolytic bone disease (OBD) is a frequent complication of multiple cancers, such as multiple myeloma. OBD is due to the disruption of balanced bone remodelling, with higher bone resorption due to increased osteoclast activation and osteoblast inhibition. Lectin–glycoprotein interactions have been implicated in osteoclast formation. In the current study, we set out to identify lectins that are involved in osteoclastogenesis and to study their role in this process. We ant...

ba0005p202 | Cell biology: osteoclasts and bone resorption | ECTS2016

The effect of potassium citrate on human primary osteoclasts in vitro

Torreggiani Elena , Massa Annamaria , Di Pompo Gemma , Granchi Donatella , Baldini Nicola

An increasing amount of scientific evidence suggests that western diet is a risk factor for osteopenia and osteoporosis. Indeed, metabolic acidosis, occurring after high levels of protein intake, may adversely impact on the skeleton by disrupting calcium metabolism, and leads to a decrease of bone mineral density (BMD). Currently, the prevention and treatment of osteopenia and osteoporosis are mainly based on lifestyle modifications (i.e. exercise, quitting smoking and ensurin...

ba0005p203 | Cell biology: osteoclasts and bone resorption | ECTS2016

The role of light (TNFSF14) on bone remodeling

Brunetti Giacomina , Gigante Isabella , Oranger Angela , Colaianni Graziana , Di Benedetto Adriana , Tamma Roberto , Lippo Luciana , Pignataro Paolo , Di Comite Mariasevera , Mori Giorgio , Tamada Koji , Ware Carl , Colucci Silvia , Grano Maria

LIGHT (TNFSF14), expressed by different cells of the immune system, binds two trans-membrane receptors: HVEM and LTβR. It is over-expressed in erosive rheumatoid arthritis and lytic myeloma-bone disease and controversial data have been published on its role osteoclast (OC) formation in vitro. Here, we investigated the role of LIGHT on in vitro murine osteoclastogenesis model and bone phenotype in LIGHT−/− mice. Firstly, we showed that murin...

ba0005p204 | Cell biology: osteoclasts and bone resorption | ECTS2016

Fluoride modulates formation and function of bone marrow macrophage-derived osteoclasts in a strain-specific manner

de Oliveira Flavia Amadeu , Amaral Pereira Amanda , da Silva Ventura Talita , Rabelo Buzalaf Marilia Afonso , de Oliveira Rodrigo Cardoso , Peres-Buzalaf Camila

Osteoclast presents a central role in several inflammatory diseases that are associated to bone destruction. This condition results from increased osteoclastic bone resorption and/or decreased bone formation. Fluoride (F) is widely consumed in the drinking water due to its anticariogenic effect and has been shown to modulate in vivo bone metabolism in a strain-specific dependent manner. It enhances bone formation in 129P3/J mice but not in A/J mice. However, its effec...

ba0005p205 | Cell biology: osteoclasts and bone resorption | ECTS2016

Better understanding the potency and cytotoxicity of different bisphosphonates on murine osteoclast formation and activity: implications for its better clinical use in treatment cancers

Razai Mohammad , Orriss Isabel , Arnett Timothy

Bisphosphonates are widely used drugs in the fight against osteoclast-mediated bone loss, including osteoporosis and Paget’s disease of bone. The first generation of these potent drugs such as clodronate, a non nitrogen-containing bisphosphonate, has been shown to inhibit osteoclast formation and osteoclastic bone resorption both in vitro and in vivo as well as inducing apoptotic cell death. Recent interest has centred on the effects of more potent nitro...