Influencia de la artroplastia total de cadera y el consejo médico en la actividad deportiva realizada después de la intervención / Influence of total hip arthroplasty and physicians advices in the sports activity performed after the surgery

ANTECEDENTES Y OBJETIVOS: No hay estudios prospectivos aleatorizados que evalúen la actividad deportiva tras una artroplastia total de cadera (ATC). El objetivo de este estudio es evaluar el nivel y el tipo de actividad deportiva en pacientes intervenidos de ATC y valorar las recomendaciones dadas por los médicos. MATERIALES Y MÉTODOS: Estudio descriptivo que analiza a 46 pacientes (edad media 41 años, rango 37-48) menores de 50 años que fueron intervenidos de ATC (58 caderas) en nuestro centro. El seguimiento medio fue 7,5 (1-11) años. Se evaluó la edad, el sexo, la actividad deportiva según la escala UCLA, las actividades deportivas practicadas antes y después de la intervención, las complicaciones y las recomendaciones dadas por los médicos. RESULTADOS: La media del tiempo para retomar la actividad deportiva tras la intervención fue de 5 (3-10) meses. No hubo diferencias en la escala UCLA antes y después de la intervención (p > 0,05). El deporte más practicado antes de la intervención fue la natación (17%). El 31% de los pacientes no recibió consejos de su médico y el 65,2% fue disuadido de realizar deporte tras la ATC. Los deportes aconsejados fueron la natación (44%) y la bicicleta estática (17,5%), correlacionándose con los deportes más practicados tras la intervención. CONCLUSIÓN: Los pacientes modificaron su actividad deportiva tras ser intervenidos de ATC, siendo la propia intervención y el consejo del médico los que influyeron en la elección de la actividad deportiva realizada tras ser intervenido

BACKGROUND AND OBJECTIVES: There are no randomized prospective studies that evaluate sports activity after total hip arthroplasty (THA). The objective of this study is to assess the level and type of sports activity in patients undergoing THA and to assess the recommendations given by physicians. MATERIALS AND METHODS: We performed a descriptive study that analyzes 46 patients (the average age was 41 years, range 37 - 48) under 50 years of age who underwent THA (58 hips) in our center. The average follow-up was 7.5 (1 - 11) years. Age, sex, sports activity according to the UCLA scale, sports activities practiced before and after the intervention, complications and recommendations given by doctors were evaluated. RESULTS: The average time to resume sport activity after the surgery was 5 (3-10) months. There were no differences in the UCLA scale before and after the operation (P> 0.05). The most practiced sport before the surgery was swimming (17%). The 31% of patients did not receive advice from their physician and the 65.2% were dissuaded from playing sports after ATC. The recommended sports were swimming (44%) and the static bicycle (17.5%), correlating with the most practiced sports after the operation. CONCLUSION: The patients modified their sport activity after having undergone a total hip arthroplasty. The surgery and the physician's advice were the ones that influenced the choice of the sports activity performed after being operated on

Influence of total hip arthroplasty and physicians advices in the sports activity performed after the surgery. / Influencia de la artroplastia total de cadera y el consejo médico en la actividad deportiva realizada después de la intervención.

BACKGROUND AND OBJECTIVES: There are no randomized prospective studies that evaluate sports activity after total hip arthroplasty (THA). The objective of this study is to assess the level and type of sports activity in patients undergoing THA and to assess the recommendations given by physicians. MATERIALS AND METHODS: We performed a descriptive study that analyzes 46 patients (the average age was 41 years, range 37 - 48) under 50 years of age who underwent THA (58 hips) in our center. The average follow-up was 7.5 (1 - 11) years. Age, sex, sports activity according to the UCLA scale, sports activities practiced before and after the intervention, complications and recommendations given by doctors were evaluated. RESULTS: The average time to resume sport activity after the surgery was 5 (3-10) months. There were no differences in the UCLA scale before and after the operation (P> 0.05). The most practiced sport before the surgery was swimming (17%). The 31% of patients did not receive advice from their physician and the 65.2% were dissuaded from playing sports after ATC. The recommended sports were swimming (44%) and the static bicycle (17.5%), correlating with the most practiced sports after the operation. CONCLUSION: The patients modified their sport activity after having undergone a total hip arthroplasty. The surgery and the physician's advice were the ones that influenced the choice of the sports activity performed after being operated on.

Clinical characteristics of patients with sustained ventricular arrhythmias after sacubitril/valsartan initiation.

Our aim was to describe the clinical profile of patients presenting sustained ventricular arrhythmias after sacubitril/valsartan (SV) initiation. All cases of sustained ventricular arrhythmias in patients receiving SV were consecutively recorded in two centers. Nineteen patients had sustained ventricular arrhythmias after SV. All were men and were previously receiving angiotensin-converting enzyme inhibitors, or angiotensin II receptor blockers before SV initiation. Fifteen patients (78.9%) had electrical stability in the previous 6 months. Nine patients (47.4%) initiated SV at the lowest available dose (24/26 mg). Globally, in all but five patients alive at discharge, SV was discontinued after the event. Six patients presented new arrhythmic events after discontinuation of SV. Two deaths and three heart transplants occurred (one due to heart failure and the other two due to persistent ventricular arrhythmias). All patients had a high arrhythmic risk, and 17 (89.5%) had an implanted cardioverter defibrillator. No specific triggers for the arrhythmic event were found. Male sex and previous episodes of ventricular arrhythmias could be associated with an increased risk of sustained ventricular tachycardia after SV initiation. Discontinuation of the drug might be an additional approach to enable a better control of ventricular arrhythmias in some patients.

Structure-composition relationships in ternary solvents containing methylbenzoate.

Thermophysical properties of the hexane+1-chlorohexane (or hexanoic acid or diisopropylether)+methylbenzoate ternary systems and their binary constituents are reported at 298.15 K and 0.1 MPa over the whole composition range. The properties and the optimized geometry of the gas-phase components were appraised from the density functional theory. To find out the causal link between the thermophysical measurements and the molecular level features, the derived mixing and excess functions of the ternary systems were looked into according to the scaled particle and Kirkwood-Buff analyses. The hydrogen bonding and dipole interactions along with the geometry effects brought about by the very different size and shape of the components give rise to complex mixed structures. Application of semiempirical models and use of simple cubic equations of state combined with a one-parameter van der Waals mixing rule has led to prediction of the ternary properties with variable degree of precision.

Techniques used to identify the Brazilian variant of HIV-1 subtype B.

The purpose of the present study was to compare the sensitivity and specificity of V3 enzyme immunoassay (solid phase EIA and EIA inhibition) and restriction fragment length polymorphism (RFLP) with the DNA sequencing "gold standard" to identify the Brazilian HIV-1 variants of subtype B and B"-GWGR. Peripheral blood mononuclear cells were collected from 61 HIV-1-infected individuals attending a clinic in São Paulo. Proviral DNA was amplified and sequentially cleaved with the Fok I restriction enzyme. Plasma samples were submitted to a V3-loop biotinylated synthetic peptide EIA. Direct partial DNA sequencing of the env gene was performed on all samples. Based on EIA results, the sensitivity for detecting B-GPGR was 70%, compared to 64% for the Brazilian variant B"-GWGR while, the specificity of B-GPGR detection was 85%, compared to 88% for GWGR. The assessment of RFLP revealed 68% sensitivity and 94% specificity for the B-GPGR strain compared to 84 and 90% for the B"-GWGR variant. Moreover, direct DNA sequencing was able to detect different base sequences corresponding to amino acid sequences at the tip of the V3 loop in 22 patients. These results show a similar performance of V3 serology and RLFP in identifying the Brazilian variant GWGR. However, V3 peptide serology may give indeterminate results. Therefore, we suggest that V3 serology be used instead of DNA sequencing where resources are limited. Samples giving indeterminate results by V3 peptide serology should be analyzed by direct DNA sequencing to distinguish between B-GPGR and the Brazilian variant B"-GWGR.

Techniques used to identify the Brazilian variant of HIV-1 subtype B

The purpose of the present study was to compare the sensitivity and specificity of V3 enzyme immunoassay (solid phase EIA and EIA inhibition) and restriction fragment length polymorphism (RFLP) with the DNA sequencing "gold standard" to identify the Brazilian HIV-1 variants of subtype B and B"-GWGR. Peripheral blood mononuclear cells were collected from 61 HIV-1-infected individuals attending a clinic in São Paulo. Proviral DNA was amplified and sequentially cleaved with the Fok I restriction enzyme. Plasma samples were submitted to a V3-loop biotinylated synthetic peptide EIA. Direct partial DNA sequencing of the env gene was performed on all samples. Based on EIA results, the sensitivity for detecting B-GPGR was 70 percent, compared to 64 percent for the Brazilian variant B"-GWGR while, the specificity of B-GPGR detection was 85 percent, compared to 88 percent for GWGR. The assessment of RFLP revealed 68 percent sensitivity and 94 percent specificity for the B-GPGR strain compared to 84 and 90 percent for the B"-GWGR variant. Moreover, direct DNA sequencing was able to detect different base sequences corresponding to amino acid sequences at the tip of the V3 loop in 22 patients. These results show a similar performance of V3 serology and RLFP in identifying the Brazilian variant GWGR. However, V3 peptide serology may give indeterminate results. Therefore, we suggest that V3 serology be used instead of DNA sequencing where resources are limited. Samples giving indeterminate results by V3 peptide serology should be analyzed by direct DNA sequencing to distinguish between B-GPGR and the Brazilian variant B"-GWGR.

Characterization and preferential solvation of the hexane/hexan-1-ol/methylbenzoate ternary solvent.

The thermophysical properties of the hexane/hexan-1-ol/methylbenzoate ternary system and its binary constituents were studied at 298.15 K over the whole composition range. The excess and mixing properties calculated from the experimental values combined with the mixture activity coefficients deduced from the UNIFAC group contribution method were used to calculate the integrals of the Kirkwood-Buff fluctuation theory for the ternary system and the binary constituents. Also the local composition and the excess or deficit number of molecules around a central molecule have been determined. The volumetric properties for the ternary system and its binary constituents were correlated and predicted successfully with several cubic equations of state combined with two simple mixing rules. The structural and intermolecular interactions of the mixtures were analyzed on the basis of the measured and derived properties.

Heavy metals in the vicinity of a chlor-alkali factory in the Upper Negro River ecosystem, Northern Patagonia, Argentina.

A study on heavy metal contents was performed in sediments and biota of the Upper Negro River (Alto Valle) aquatic system, Northern Patagonia, Argentina. The irrigation system of the Neuquén and Negro Rivers runs alongside these rivers for 150 km, supporting intensive agricultural and economical activities, mainly related to fruit production. A mercury cell chlor-alkali factory operated between 1951 and 1995. Close attention was given to the surroundings of the plant, located next to the Main Irrigation Channel, and to the PII drainage channel which received the plant's effluents between 1951 and 1979. From 1979 until its closure, the effluents were pumped above a ravine to a series of evaporation and decantation pools. Mercury and other heavy metals and metalloids (Ag, As, Ba, Co, Cr, Cs, Ni, Sb, Se, U and Zn) contents were measured for bottom sediments of the river and irrigation and drainage channels, for two widespread species of macrophytes (Potamogeton pectinatus and Myriophyllum brasiliensi), and for liver and muscle of native fish Odontesthes microlepidotus. River bed sediments show no evidence of heavy metal accumulation, however, biota might indicate that contaminants are entering the rivers. Mercury was the only element accumulated in the Main Irrigation channel sediments, the highest contents occurring in the surroundings of the nowadays shut-down chlor-alkali plant, returning to background values approximately 40 km downstream the plant. At the plant site, sediments from the center of the channel showed a decrease in Hg content in the upper 10 cm layer, ranging from 0.8 to 3.4 microg g(-1), and from 2.8 to 13.7 microg g(-1) in the next 10 cm lower layer. Conversely, the PII drainage channel sediments showed accumulation of Hg (2-4 microg g(-1)), distributed uniformly at different depths and along the channel, until its mouth at Negro river. Mercury contents of macrophytes downstream the chlor-alkali plant are higher than the baseline for the area, and macrophytes and fish liver from the PII drainage channel present the highest content in this element. The drainage channel system showed different degrees of impact, those channels flowing through densely populated areas being the most affected.

The E-cadherin gene is silenced by CpG methylation in human oral squamous cell carcinomas.

Reduction of E-cadherin strongly relates to invasiveness and metastasis in vitro. To clarify CpG methylation around the promoter region of the E-cadherin gene in oral squamous cell carcinoma (SCC), we examined the DNA samples of various human SCC cell lines and primary oral SCC tissues by methylation-specific polymerase chain reaction (MSP). CpG methylation of the E-cadherin gene markedly correlated to the reduction of E-cadherin expression in human oral SCC cell lines. In primary oral SCC tissues, only 1 of 5 preserved E-cadherin-expressing tissues was methylated, whereas methylation was found in 17 (94.4%) of 18 E-cadherin-reduced tissues. Our results suggest that reduction of E-cadherin expression is associated with CpG methylation of the E-cadherin gene promoter. We recently established two cell lines with high and low metastatic potential, UM1 and UM2, from SCC primary tongue tissue of a patient. E-cadherin expression of high-metastatic UM1 was clearly lower than that of low-metastatic UM2, and MSP results showed CpG methylation in the UM1 but not the UM2 cell line. To investigate whether demethylation of CpG methylation of the E-cadherin gene could restore expression and function of E-cadherin, we treated UM1 with the demethylating agent 5-azacytidine (5-aza) and found that E-cadherin expression was indeed restored by demethylation. Moreover, in the demethylated UM1, invasion of the collagen gel was clearly suppressed compared with the untreated UM1. These results suggested that inactivation of E-cadherin expression resulted from CpG methylation of the gene promoter; a correlation between CpG methylation of the E-cadherin gene promoter and invasive potential was also suggested.

The influence of blood arterial oxygen condition on the tumor response to preoperative radiation therapy in oral cancer patients.

The relationship between clinicopathological factors and response of radiation therapy in oral squamous cell carcinoma has been studied. It has been suggested that factors such as tumor site, extent and tumor differentiation determine the response to radiation therapy. It is known that oxygenation is related to the therapeutic effects of radiation therapy. However, there are few reports on the relationship between oxygen condition and the response to radiation therapy. The present study was carried out to assess whether any clinicopathological factors, including an evaluation of the oxygen condition can be used to predict the effects of preoperative radiation therapy in oral squamous cell carcinomas. Forty-seven patients with oral cancer treated with external radiation therapy preoperatively were evaluated. There were no significant differences in response to the radiation with respect to age, sex, tumor site, stage, macroscopic shape of tumors, and the histological factors. The hemoglobin (Hb) and arterial oxygen content (CaO(2)) levels of favorable cases (Hb: 14.4 g/dl, CaO(2) 19.1 ml/dl) were significantly higher than those of unfavorable cases (Hb: 11.0 g/dl, CaO(2): 16.1 ml/dl). These findings suggest that oxygen conditions of oral cancer patients predict tumor response to preoperative radiation therapy.

The role of caspase family protease, caspase-3 on cisplatin-induced apoptosis in cisplatin-resistant A431 cell line.

PURPOSE: Cisplatin (cis-diamminedichloro-platinum(II), CDDP) has been reported to induce apoptosis in cancer cells. the mechanism of the apoptosis in cancer cells induced by CDDP is still unclear. Recent studies have revealed that caspase family of cystine proteases play an important role in the regulation of several apoptotic processes. In this study, whether apoptosis induced by CDDP could be mediated by the activation of caspase-3, a caspase family protease, was investigated. METHODS: The CDDP-resistant subline A431/CDDP2 from the previously established human epidermoid carcinoma cell line A431 was used. The parent A431 cells (A431/P) and the A431/CDDP2 were exposed to CDDP with or without a caspase family protease inhibitor (Z-Asp-CH2-DCB), and cellular sensitivity to CDDP was determined. DNA fragmentation was then analyzed, and the caspase-3 protein levels determined by Western blotting following exposure of the cells to CDDP with or without Z-Asp-CH2-DCB. RESULTS: In the A431/P cells, the cytotoxicity of CDDP was clearly reduced by Z-Asp-CH2-DCB compared with its cytotoxicity in A431/CDDP2 cells. Furthermore, quantitative analysis of DNA fragmentation revealed that Z-Asp-CH2-DCB inhibited DNA fragmentation induced by CDDP in A431/P cells, but not in A431/CDDP2 cells. Western blotting analysis demonstrated a marked reduction in procaspase-3 protein levels in A431/P cells treated with Z-Asp-CH2-DCB. In the A431/CDDP2 cells, procaspase-3 protein levels were no different with and without Z-Asp-CH2-DCB. CONCLUSIONS: These findings suggest that caspase-3 may mediate apoptosis induced by CDDP, and its induction could represent a novel approach to the effective treatment of malignant tumors.

Soft tissue cephalometric norms in Japanese adults.

Lateral soft tissue cephalometric standards of Japanese normal adults were developed with the use of Ricketts, Epker, Holdaway, and Legan cephalometric analyses. Cephalometric radiographs of 211 Japanese normal adults were analyzed, and the soft tissue measurements were compared with those of an esthetically pleasant Japanese subgroup and white adult sample. Statistically significant differences were found in the Japanese sample when compared with the white norms. On the other hand, the soft tissue mean values of the Japanese supernormal group were similar to the white norms, with the exception of the nasolabial angle and the lip prominence. Soft tissue cephalometric norms are specific for ethnic groups, but these values should not be interpreted as treatment goals. Normative data represent an aid for the diagnosis and planning of orthodontic treatment and orthognathic surgery.

Regulation of apoptosis reduction in the cisplatin-resistant A431 cell line by Bcl-2 and CPP32.

Cisplatin (cis-diamminedichloroplatinum(II), CDDP) is one of the most important chemotherapeutic agents; however, the mechanisms of resistance to this drug are still unknown. Recent reports have demonstrated that chemotherapy can induce apoptosis in some cancer cells, indicating that apoptosis may play a very important role in cancer therapy. Therefore, we used a CDDP-resistant cell line from the human epidermoid carcinoma cell line A431 to investigate whether the modulation of apoptosis influences CDDP resistance. In the CDDP-resistant cell, the cell cycle was not perturbed after CDDP treatment. DNA gel electrophoresis and ELISA of the CDDP-resistant cell showed reduced apoptosis when compared with A431 cells treated with CDDP. We determined the p53, Bcl-2, Bax and CPP32 protein levels by Western blotting. This analysis demonstrated a marked increase in Bcl-2 protein levels and a reduction in CPP32 protein levels in CDDP-resistant cells. Our results indicate that the reduction of apoptosis was one of the CDDP-resistant mechanisms, and that reduced apoptosis in CDDP-resistant cells was influenced by Bcl-2 and CPP32 proteins.

Zinc accumulation and metallothionein gene expression in the proliferating epidermis during wound healing in mouse skin.

Metallothionein (MT), a low molecular weight metal-binding protein, has been related to zinc and copper metabolism, the acute-phase response, and cellular proliferation. In this study, we investigated changes in zinc metabolism and MT gene expression occurring in tissue damage and repair during wound healing in mouse skin. Northern blot analysis revealed that a significant increase of MT mRNA was observed in the liver for 18 h after wounding, and serum zinc downfall and hepatic zinc uptake were observed. In situ hybridization analysis showed that no significant expression of MT mRNA was detected within the first 9 h after wounding. However, it was expressed restrictively in the proliferating epidermis of the wound margin after 12 h. Zinc began to accumulate in wounded skin after MT gene expressed. Northern blotting and immunocytochemical staining revealed that MT has been synthesized actively during the growth phase compared with the stationary phase in normal human epidermal keratinocytes in vitro. Intracellular zinc accumulation was observed in the proliferating cells. We concluded that hepatic MT plays an important role as an acute phase protein against host damage, and epidermal MT contributes in the supply of zinc to wounded tissue and activates proliferation for the regeneration of epidermis.

Effects of bisphosphonate on experimental jaw metastasis model in nude mice.

The mechanism of osteolysis associated with metastatic cancer of the jaws is essentially osteoclast-mediated. Therefore, it is likely that potent osteoclastic bone resorption inhibitors such as bisphosphonates would be efficacious for the treatment of jaw metastasis. We examined the effects of a third generation bisphosphonate, YM175, in a nude mice jaw metastasis model with intracardiac injection of a human breast cancer cell line, MDA-MB-231. The metastatic lesions in untreated mice were radiographically observed at the body and angle of the mandible. Histology of the mandible of untreated mice revealed that most of the bone marrow cavities had been occupied by the metastatic tumor with active osteoclasts along the trabecular bone. The experimental group showed that YM175 markedly reduced the size of tumor and the number of osteoclasts. These results suggest that YM175 may suppress metastasis formation and tumor growth in jaw through inhibition of osteoclastic bone resorption.

Establishment and characterization of cisplatin-resistant human epidermoid carcinoma cell line, A431 cell.

Cisplatin, cis-diamminedichloroplatinum(II) (CDDP) is one of the most important anticancer agents, initially producing good responses in various tumors. However, resistance to this drug often develops in various tumors, and additional administration decreases its chemotherapeutic efficacy. The precise mechanism of acquisition of resistance to this drug is still uncertain. However in the present study, we established two CDDP-resistant sublines A431/CDDP1 and A431/CDDP2 from human epidermoid carcinoma cell line A431. These resistant sublines were constituted by exposing A431 cells to a gradually increasing dose of CDDP (A431/CDDP1), and by mutagenic induction with mutagen (A431/CDDP2). A431/CDDP1 and A431/CDDP2 have developed 3.1 and 2.7 times more resistance to CDDP than the original A431 cell in terms of IC50. The two CDDP-resistant sublines showed cross-resistance to the CDDP analogue, carboplatin (CBDCA), but not to other chemotherapeutic drugs such as Adriamycin (ADR) and 5-fluorouracil (5-FU). These CDDP-resistant sublines were transplanted into nude mice to demonstrate the resistance to CDDP treatment in vivo. According to the in vitro assay, the mechanism of resistance in A431/CDDP1 and A431/CDDP2 seems to be based on a reduction of intracellular accumulation of CDDP, because their platinum concentration, which is the major component of CDDP, significantly declined. The established CDDP-resistant sublines may be used in further trials to improve the understanding of the mechanisms of resistance to CDDP.

Experimental bone metastasis model of the oral and maxillofacial region.

Metastasis of the oral and maxillofacial region frequently causes serious morbidity. Despite the importance of the clinical problem, little is known about the pathophysiological mechanisms of this metastatic process. Therefore, we examined whether the intracardiac injection of human breast cancer cells reproductively leads to jaw metastases developing an adequate experimental model. Human breast cancer MDA-MB-231 (MDA-231) cells (1 x 10(5)) were injected into the left heart ventricle of 4-week-old, female nude mice. Jaw metastases were examined radiographically and histologically 4 weeks after the cancer cell inoculation. At this time, the nude mice showed a marked body weight loss and cachexia. Osteolytic bone metastases were commonly observed in limbs, vertebral bone, pelvis and scapulae. In maxillofacial bones, breast cancer cells metastasized in 11 of 12 nude mice (91.7%). The lesions were radiographically determined at the mandible (11/12), maxilla (8/12) and zygomatic arch (2/12). Metastasis frequently occurred at the molar and angle regions of the mandible and at the palatal suture as well as around the root of the incisal teeth of the maxilla respectively. Histological examination revealed that numerous osteoclasts were present along the trabecular bone surfaces with aggressive bone resorption. This experimental model may be useful not only for the investigation of the mechanism of jaw metastasis formation but also for the screening of potential therapeutic agents for osteolytic bone metastasis.

Effect of a newly developed bisphosphonate, YH529, on osteolytic bone metastases in nude mice.

YH529, [1-hydroxy-2-(imidazo [1,2-a] pyridin-3-yl) ethylidene]-bisphosphonic acid monohydrate, is a newly developed third-generation bisphosphonate with a potent inhibitory activity toward osteoclastic bone resorption. The primary cellular mechanism of osteolysis associated with metastatic cancer is osteoclast-mediated. It is likely that bisphosphonates would be efficacious in this situation. In the present study, we examined the effect of YH529 in a nude mice bone metastasis model, in which the intracardiac injection of a human breast cancer cell line, MDA-MB-231 (MDA-231), leads to osteolytic bone metastases. To examine whether YH529 would prevent such bone metastasis, we administered YH529 s.c. to nude mice simultaneously with cancer cell inoculation through the entire experimental period (protocol 1) or performed short-term prophylactic administration before inoculation of the MDA-231 cells (protocol 2). In addition, to examine the possible therapeutic effects of the drug on established bone metastases, we injected YH529 after radiographically small but distinct osteolytic bone metastases had been detected (protocol 3). In all protocols, YH529 (2 microg/mouse/day) markedly inhibited bone metastases as well as the progression of established metastatic foci that were quantified on the radiographs. Histological examination and histomorphometrical analysis revealed that YH529 markedly reduced the number of osteoclasts and the size of the tumor at the metastatic bone sites. Our results suggest that YH529 may suppress metastasis formation and tumor growth in bone through inhibition of osteoclastic bone resorption.