Bone metastasis in hepatocellular carcinoma (HCC) poses a significant clinical challenge, characterized by poor prognosis and severe skeletal complications. This study identifies the HMGB1/LCN2/JAK1/STAT3 axis as the central mechanism driving HCC bone metastasis through tumor-osteoclast crosstalk. High-mobility group box 1 (HMGB1) induces osteoclast activation and differentiation, promoting lipocalin-2 (LCN2) secretion by osteoclasts, which activates the JAK1/STAT3 pathway in HCC cells, forming a feedback loop that enhances osteolytic bone resorption and tumor dissemination. Integrated single-cell and bulk RNA sequencing reveal enriched osteoclast-related and pro-metastatic pathways in the tumor-bone microenvironment, while functional assays involving knockdown and overexpression demonstrate that modulating the HMGB1/LCN2/JAK1/STAT3 axis regulates osteoclast activity, tumor growth, and bone destruction in vitro and in vivo. These results suggest the HMGB1/LCN2/JAK1/STAT3 axis as a potential therapeutic target, offering a strategy to reduce skeletal damage and systemic tumor progression, thereby contributing to improved management of advanced HCC.

The aim of this study was to determine the rate of metastasis types in prostate cancer (PCa) patients with bone metastasis and to evaluate the relationship between volumetric parameters obtained from gallium-68 ( 68 Ga) prostate-specific membrane antigen (PSMA) PET/computed tomography (CT) and prostate-specific antigen (PSA) levels. We retrospectively reviewed the images of patients who underwent 68 Ga-PSMA PET/CT for restaging for recurrent PCa between 2014 and 2019. All detected bone lesions were manually grouped as 'osteoblastic (OB), osteolytic (OL), mixed (M), and radio-occult (RO) lesions' and the number and percentage were determined. Different volumetric values are obtained for each type of bone metastasis using the LIFEx v7.3.0 program. The relationship between PSA level and these volumetric values will be determined by the Spearman correlation test. The relationship between the International Society of Urological Pathology (ISUP) PCa grade group and volumetric values will be evaluated by the Kruskal-Wallis correlation test. Seventy-one patients had a total of 599 bone metastasis. Of these lesions, 268 were OB (44.7%), 39 were OL (6.5%), 72 were M (12.0%), and 220 were RO (36.7%). Total lesion volume (TLV) (P : 0.001), total lesion activity (TLA) (P : 0.001), and OB-TLA (P : 0.042) were significantly different between ISUP grades. In addition, the total number of lesions showed a statistically significant difference between ISUP grades (P : 0.019). PSA level correlated with RO lesion number ( r : 0.404, P : 0.016), RO-TLV ( r : 0.471, P : 0.004), and RO-TLA ( r : 0.528, P : 0.001). 68 Ga-PSMA PET/CT can identify the source of biochemical recurrence by detecting RO lesions at early stages when bone mineral density is not affected.

Multiple myeloma (MM) is a malignancy of terminally differentiated B-cells that is localized primarily in the bone marrow (BM) but also can be present in peripheral blood and tissue/organs [...].

Bone lengths of paired digits of front and hind limbs from 12 captive European bison (Bison bonasus) of different ages (from nine to 175 months) and sexes were measured on digital radiographs in palmarodorsal (PaD) and dorsoplantar (DPl) projections of each limb. All bone lengths were measured, and lateral/medial ratios calculated. The bone measurements included length of the canon bone condyle (LCBC), length of the first, second, and third phalanges (LP1, LP2, LP3), and overall digit length (OL). Furthermore, radiographic abnormalities such as new bone formation (NBF), soft tissue mineralization (SFT), osteolysis (OS), widened vascular channels (WVC), and soft tissue swelling (STS) were recorded using PaD, DPl, and oblique projections. NBF and SFT received a single combined grade as without radiographic changes (0), mild (one to 10 changes = 1), moderate (11 to 20 changes = 2), and severe (>20 changes = 3). OS, WVC, and STS were graded as 0 = absent and 1 = present. There were no significant differences (P > 0.1) of lateral to medial ratios for LCBC, LP1, LP2, and OL in front limbs as compared with hind limbs. Only LP3 was significantly longer (P = 0.004) in the lateral digit of the hind limbs as compared with the front limbs. For both the front and the hind limbs, the lateral LCBC, LP1, LP2, LP3 and OL were significantly longer than the respective measurements of the medial bones (P < 0.05), except for LP2 and LP3 of the hind limbs. Length measurement ratios did not vary significantly with age (P > 0.1). The most common radiographic changes were both NBF and SFT, observed in all animals from 39 months of age and older. This study provides baseline data on in vivo radiographic anatomy and evaluation of feet of European bison under field conditions.

Loss of bone is a common medical problem and, while it can be treated with available therapies, some of these therapies have critical side effects. We have previously demonstrated that CGS21680, a selective A2A adenosine receptor agonist, prevents bone loss, but its on-target toxicities (hypotension, tachycardia) and frequent dosing requirements make it unusable in the clinic. We therefore generated a novel alendronate-CGS21680 conjugate (MRS7216), to target the agonist to bone where it remains for long periods thereby diminishing the frequency of administration and curtailing side effects. MRS7216 was synthesized from CGS21680 by sequential activation of the carboxylic acid moiety and reacting with an appropriate amino acid (PEG, alendronic acid) under basic conditions. MRS7216 was tested on C57BL/6J (WT) mice with established osteoporosis (OP) and WT or A2A KO mice with wear particle-induced inflammatory osteolysis (OL). Mice were treated weekly with MRS7216 (10mg/kg). Bone formation was studied after in vivo labeling with calcein/Alizarin Red, and μCT and histology analyses were performed. In addition, human primary osteoblasts and osteoclasts were cultured using bone marrow discarded after hip replacement. Receptor binding studies demonstrate that MRS7216 efficiently binds the A2A adenosine receptor. MRS7216-treated OP and OL mice had significant new bone formation and reduced bone loss compared to vehicle or alendronate-treated mice. Histological analysis showed that MRS7216 treatment significantly reduced osteoclast number and increased osteoblast number in murine models. Interestingly, cultured human osteoclast differentiation was inhibited, and osteoblast differentiation was stimulated by the compound indicating that MRS7216 conjugates represent a novel therapeutic approach to treat osteoporosis and osteolysis.

Abnormal activation and overproliferation of osteoclast in inflammatory bone diseases lead to osteolysis and bone mass loss. Although current pharmacological treatments have made extensive advances, limitations still exist. N-[2-bromo-4-(phenylsulfonyl)-3-thienyl]-2-chlorobenzamide (BNTA) is an artificially synthesized molecule compound that has antioxidant and anti-inflammatory properties. In this study, we presented that BNTA can suppress intracellular ROS levels through increasing ROS scavenging enzymes SOD1 and SOD2, subsequently attenuating the MARK signaling pathway and the transcription of NFATc1, leading to the inhibition of osteoclast formation and osteolytic resorption. Moreover, the results also showed an obvious restrained effect of BNTA on RANKL-stimulated proinflammatory cytokines, which indirectly mediated osteoclastogenesis. In line with the in vitro results, BNTA protected LPS-induced severe bone loss in vivo by enhancing scavenging enzymes, reducing proinflammatory cytokines, and decreasing osteoclast formation. Taken together, all of the results demonstrate that BNTA effectively represses oxidation, regulates inflammatory activity, and inhibits osteolytic bone resorption, and it may be a potential and exploitable drug to prevent inflammatory osteolytic bone diseases.

BACKGROUNDMetastatic adenocarcinoma of the jaw (MAJ) is a rare disease that accounts for 1%-3% of all oral and maxillofacial malignant tumours. Oral and maxillofacial pain may be the first symptom of metastatic spread of an occult primary tumour. Therefore, early identification of oral and maxillofacial pain by dental professionals is critical.AIMTo explore the clinical and computerized tomography (CT) features of MAJ with oral and maxillofacial pain as the first symptom.METHODSThe medical records of all patients who were treated in our hospital between January 2006 and February 2020, and diagnosed with MAJ with oral and maxillofacial pain as the first symptom, were reviewed retrospectively. Clinical data were collected on age, sex, medical history, clinical manifestations, site of metastasis, and site of the primary lesion. CT features were analysed in detail, and a radiological classification scheme comprising five types: Osteolytic, osteoblastic, mixed, cystic, and alveolar bone resorption was proposed.RESULTSThe primary sites of MAJ were the lungs (n = 6), liver (n = 4), kidneys (n = 2), prostate (n = 1), and gastric cardia (n = 1). Five tumours were classified as the osteolytic type, all with a permeative margin (100%, P < 0.05), and three were classified as the mixed type, mostly with a moth-eaten margin (80%, P < 0.05). The cystic (n = 3) and alveolar bone resorption (n = 1) types had geographic margins, and the osteoblastic type (n = 1) had sclerotic margins. Moreover, nine tumours showed periosteal reaction and five showed a localised soft tissue mass, while the occurrence of jaw expansion was relatively rare.CONCLUSIONMAJ has complex clinical and CT features. Oral and maxillofacial pain may be the first sign of a primary tumour affecting other sites.

This study sought to investigate the characteristics of bone metastasis (BM) and the association of BM with clinicopathological factors in prostate cancer (PCa) patients presenting with BM on the initial staging gallium-68-prostate-specific membrane antigen (68Ga-PSMA) positron emission tomography/computed tomography (PET/CT). Patients with at least one BM in the initial staging 68Ga-PSMA PET/CT between January 2018 and December 2021 were reviewed retrospectively. Types of BM were classified according to 68Ga-PSMA PET/CT findings as osteoblastic (OB), osteolytic (OL), intramedullary (IM) and coexistence of these types. Patients were divided into two groups according to the number of BM: Oligo-BM for those with five or fewer BMs and poly-BM for those with more than five BM. Receiver-operating characteristic (ROC) curves were generated for serum bone-specific alkaline phosphatase (ALP) and prostate-specific antigen (PSA) levels to discriminate between oligo-BM and poly-BM groups. Univariate and multivariate logistic regression tests were performed to find independent predictors of poly-BM. A total of 53 patients with a median age of 70 (range: 49-88) were included in the study. The median Gleason score of the patients was 8 (range: 6-10). Among the patients, 23 had solely OB-type; 10 had solely IM type; 12 had OB and IM type; four had IM and OL type, two had OB and OL type; one had solely OL type, and one had IM and OB and OL type BM. Oligo-BM was detected in 25 patients (47.2%) and poly-BM was detected in 28 patients (52.8%). In multivariate analyses, serum ALP levels ≥122U/L and PSA levels ≥85.4ng/mL were found to be independent predictors of poly-BM. In characterizing BM of PCa, we found that OB-type metastases were the most common type, followed by IM-type and OL-type metastases, respectively. High ALP and PSA levels were found to be independent predictors of poly-BM.

Bone is the most preferred site for colonization of metastatic breast cancer cells for each subtype of the disease. The standard of therapeutic care for breast cancer patients with bone metastasis includes bisphosphonates (e.g., zoledronic acid), which have poor oral bioavailability, and a humanized antibody (denosumab). However, these therapies are palliative, and a subset of patients still develop new bone lesions and/or experience serious adverse effects. Therefore, a safe and orally bioavailable intervention for therapy of osteolytic bone resorption is still a clinically unmet need. This study demonstrates suppression of breast cancer-induced bone resorption by a small molecule (sulforaphane, SFN) that is safe clinically and orally bioavailable. In vitro osteoclast differentiation was inhibited in a dose-dependent manner upon addition of conditioned media from SFN-treated breast cancer cells representative of different subtypes. Targeted microarrays coupled with interrogation of The Cancer Genome Atlas data set revealed a novel SFN-regulated gene signature involving cross-regulation of runt-related transcription factor 2 (RUNX2) and nuclear factor-κB and their downstream effectors. Both RUNX2 and p65/p50 expression were higher in human breast cancer tissues compared with normal mammary tissues. RUNX2 was recruited at the promotor of NFKB1 Inhibition of osteoclast differentiation by SFN was augmented by doxycycline-inducible stable knockdown of RUNX2. Oral SFN administration significantly increased the percentage of bone volume/total volume of affected bones in the intracardiac MDA-MB-231-Luc model indicating in vivo suppression of osteolytic bone resorption by SFN. These results indicate that SFN is a novel inhibitor of breast cancer-induced osteolytic bone resorption in vitro and in vivo.

At present, total hip arthroplasty (THA) is the primary treatment for hip diseases such as femoral head necrosis and developmental dysplasia of the hip. It has good effects in reducing pain and improving joint function. The appearance of modular hip prosthesis facilitates adjustment of limb length and femoral offset. However, the wear between the interface of hip prosthesis can lead to inflammatory pseudotumor, osteolysis and other adverse reactions. To explore the risk factors of wear between hip prosthesis interface is helpful to improve the design and manufacturing concept of the product, improve the product performance, help surgeons optimize the operation technology and reduce the impact of human factors on the wear of the prosthesis. Many literatures have reported the mechanism of wear between the head-acetabula interface of prosthesis. The mechanism of wear between the interfaces has been described relatively clearly. In addition to the head-acetabula interface, the wear between the head-neck interface is another major cause of unexplained pain around the joint and prosthesis loosening after hip replacement. Many factors affect head-neck wear. The design of prosthesis (such as prosthesis material and prosthesis taper), surgical technology (such as impact strength and prosthesis mismatch) and patient factors (such as age, gender and activity) have important impact on head-neck wear. Adverse reactions caused by head-neck wear have also been widely concerned. However, there is no considerable solution for wear prevention. Thus, we should optimize the design of prosthesis, improve the surgical technology, and guide the rehabilitation of patients to prevent wear. In order to improve the attention of joint surgeons, the present paper reviews the literatures and analyzes the risk factors of head-neck interface wear and the clinical manifestations caused by head-neck wear.

Objective To evaluate the interrelationship between intervertebral osteolysis and inflammatory or osteoclastic gene expression. Methods Adipose derived stromal cells (ADSCs) were osteoinduced, conventioanl tissue-engineered (TE) and surface-modified TE cage constructs were establisehd. Anterior cervical fusion model of goat was established. Implantation was carried out according to following six group: surface-modified TE cage group [Nd: YAG+ RGD+ β- tricalcium phosphate (β-TCP)/chitosan (CS)/polycaprolactone (PCL) cage+ ADSCs], TE cage group (β-TCP/CS/PCL cage+ ADSCs), non-modified β-TCP/CS/PCL cage, hydroxyapatite (HA) cage, titanium and bone allograft cage. Three-dimensional CT was used to observe morphology changing, bone mineralization ratio, new bone mension and osteoblatic quantity, interleukin-6 (IL-6), metalloprotease-1 (MMP-1), tumor necrosis factor-α (TNF-α) and tartrate resistant acid phosphatase (TRAP), and osteoprotein (OPG) gene expression were detected at 2, 4, 8, 12, 16, 20, 24, 28 and 36 weeks. Biomechanical property was also detected at different interval. Results Compared with other groups, implant subsidence and migration were not found in surface-modified TE cage group. Meanwhile, new bone prolifreated remarkably with satisfactory data of bone mineralization ratio, and new bone mension or osteoblatic quantity [(63.9±1.3)%, (76.54±1.8)%, (73.8±2.3) cells]. IL-6, MMP-1, TNF-α and TRAP gene downregulated (0.09±0.01, 0.13±0.02, 0.08±0.01). Conversely, Runx2 and OPG gene upregulated (0.73±0.13, 0.57±0.16). In addition, data of bone strength and rang of motion in surface-modified TE cage group were significantly higher than those of other groups [(4.38±0.25) Nm/degree, (6.55±0.19)°]. Conclusion Invertebral osteolysis can be effectively controlled by surface-modified TE approach, and this provides a potential therapy for implant aseptic loosening. Key words: Osteolysis; Cage; Surface modification; Tissue engineering; Interface

Objective To analyze the radiological imagines and SPECT imaging features of primary leiomyosarcoma of bone and to improve the diagnostic level. Methods The imaging data of 16 patients in our hospital from January 2009 to May 2018 were retrospectively analyzed by two senior musculoskeletal radiologists, and they were all proved by surgery and pathology. The location of the lesions, type of bone destruction, size, soft tissue mass, mineralization, pathological fracture and periosteal reaction were detected by radiography and CT. The types of bone destruction are osteolytic, cystic and mixed. Periosteal reaction was divided into codman triangle, layered periosteal reaction and spiculate periosteal reaction. The signal intensity of lesions, size, distruction of the bony cortex, soft tissue mass and peritumoral edema were detected by MRI.Signal intensity was divided into low signal,iso-signal and high signal by taking surrounding normal muscles as reference. Enhancement scan was used to detect the form of enhancement. SPECT bone scan: compared with normal bone, SPECT bone scan signals were higher than normal bone, which was called concentrated radioactivity. Results Among the 16 cases, located in tibia(5 cases), femur (4 cases), sacrum(1 case), pubis(1 case), ilium(1 case), thoracic vertebra (2 cases) and humerus(2 cases). Radiography showed osteolytic, cystic and mixed bone destruction, among which 8 cases were osteolytic, 2 cases were cystic, 4 cases were mixed, and 1 case was normal. On CT images, 9 cases were osteolytic, 6 cases with soft tissue masses, among which 3 cases with partial sclerosis rim (2 cases with pathological fractare and obviously enhanced), 1 case with mild bone expansion and soft tissue, 2 cases with partial sclerosis rim. Four cases were mixed, all with cortical bone destruction, penetration, 1 case with soft tissue mass and periosteal reaction, 1 case which in the long bone of the extremity was central in location with periosteal reaction. Two cases were obviously and heterogeneously enhanced atter the enhanced CT scanning (1 case with bone expansion). Two cases were cystic,all with cortical destruction and penetration,1 case with soft tissue mass,1 case with partial sclerotic rim;after the enhanced CT scanning,2 case were obviously and heterogeneously enhanced. The most of the MR imagines showed the iso-intensity signal (10cases) and/or lightly lower signal (3cases), lightly higher sign (2cases) on T1WI, inhomogeneous hyperintensity on T2WI (15cases),after injected contrast medium,the tumor was inhomogeneous enhancement (14cases) with the cysts, necrosis and hemorrhage in it,11 cases with soft tissue masses,12 cases accompanied by peritumoral edema. On SPECT bone scan, 10 Cases showed significant concentrated radioactivity(1 case was circumferential) and 1 case was mild concentrated radioactivity. Conclusion PLB usually occurs in the lower extremities,more frequently at the distal end of the femur, the proximal end of the tibia. The mainly appearance are central situated and osteolytic destruction with mass of the soft tissue. Although PLB has some imaging features, it is difficult to differentiate it from malignant bone tumors. Multi-imaging modalities such as radiography, CT, MRI and SPECT may suggest the diagnosis. Key words: Leimyosarcoma; Bone; Magnetic resonance imaging; Tomography, X-Ray computed

Objective To explore the effects of tangeretin on osteoclastogenesis and bone resorption. Methods Primary bone marrow mononuclear macrophages were isolated and purified from C57BL/6 mice, and different concentrations of tangeretin were added for co-culture. Cell count kit (CCK-8) method was used to detect the cytotoxicity of tangeretin. Macrophage-colony stimulating factor (M-CSF) and receptor activator of nuclear factor-κB ligand (RANKL) were used to induce the differentiation of primary bone marrow mononuclear macrophages into osteoclasts. No tangeretin was given in the control group, and different concentrations of tangeretin (3.125, 6.250 μmol/L) were added in the experimental groups. The number of osteoclasts was counted by tartrate resistant acid phosphatase (TRAP) staining. Cells were planted on bone slices and treated with different concentrations of tangeretin until osteoclasts formed, and bone slices were imaged and analyzed using field-emission scanning electron microscopy. Twenty mice were randomly assigned to four groups (n=5 for each): sham PBS control (sham), Ti particles with PBS (vehicle), and Ti particles with low [10 mg/(kg·day)] or high [20 mg/(kg·day)] concentrations of tangeretin. After 14 days, the effects of tangeretin on osteoclasts in vivo were studied using the titanium particle-induced calvarial osteolysis model. Results Tangeretin cytotoxicity was concentration-dependent. Cell viabilities at 6.250, 12.500 and 25.000 μmol/L of tangeretin were not significantly different from those in the control group (P>0.05). The maximum concentration used in our study was 25.000 μmol/L, which was proven to have no cytotoxic effects on primary bone marrow mononuclear macrophages. Compared to the control group, the number of TRAP positive multinucleated osteoclasts in tangeretin 3.125 μmol/L group (P<0.01) and 6.250 μmol/L group (P<0.01) was significantly decreased. Similarly, the bone resorption area in tangeretin 3.125 μmol/L group (P<0.01) and 6.250 μmol/L group (P<0.01) was also significantly decreased. The In vivo results showed significant osteolysis of the skull in the control group compared to the sham group (P<0.01). As compared with the control group, the osteolysis was significantly inhibited in both the low-concentration tangeretin group (P<0.01) and the high-concentration tangeretin group (P<0.01), and the degree of osteolysis in the high-concentration tangeretin group was significantly lower than that in the low-concentration tangeretin group (P<0.01). Conclusion Tangeretin could inhibit the osteoclastogenesis and osteolysis. Key words: Tangeretin; Osteoclasts; Bone resorption; Osteoporosis

Abstract Bone is the preferred site for metastatic spread in women with advanced breast cancer, and skeletal complications is associated with high morbidity and mortality. Nearly 70% of luminal-type breast cancer patients with metastases to bone experience skeletal complications due to enhanced osteoclastogenesis (osteoclast activation) that increases bone resorption, pain, pathological fractures, spinal cord compression, and hypercalcemia. The present study was designed to determine the effect of a cruciferous vegetable component (Sulforaphane; SFN) on breast cancer-induced osteoclastogenesis. Osteoclast differentiation in mouse bone marrow monocytes (BMM) was inhibited significantly upon the addition of 10% conditioned-media (CM) from SFN-treated breast cancer cells belonging to different subtypes, including MDA-MB-231, MCF-7, and SK-BR-3, in comparison with corresponding control. PCR-based gene expression profiling identified a common set of genes downregulated by SFN treatment compared to vehicle-treated control in MDA-MB-231, MCF-7, and SK-BR-3 cells, including osteoclastogenesis promoting transcription factors (RUNX2, NF-κB, and SOX-9) and certain soluble molecules (MMP9, TNFα, and Cathepsin K). Many of these gene expression changes were confirmed in MDA-MB-231, MCF-7, and SK-BR-3 cells by RT-PCR or western blotting. To determine the in vivo efficacy, SFN was administrated orally (1 mg per mouse; three times/week) to athymic mice intracardially injected with MDA-MB-231-Luc cells. SFN administration significantly inhibited the multiplicity of bone metastases and increased the bone volume relative to total volume. SFN-mediated prevention of osteoclastogenesis was associated with a significant decrease in TRAP-positive osteoclasts in bones and the levels of Cathepsin K, IL-8, and RANKL in serum. Altogether, this study demonstrates, for the first time to the best of our knowledge, that SFN is a potent inhibitor of breast cancer-induced osteoclastogenesis and bone resorption in vitro and in vivo. This study was partly funded by a pilot project grant from the UPMC Hillman Cancer (NCI grant P30 CA047904; Robert L. Ferris- Principal Investigator) and RO1 CA142604 and CA129347 awarded by the National Cancer Institute (Shivendra Singh- Principal Investigator). Citation Format: Subrata K. Pore, Joseph D. Latoche, Carolyn J. Anderson, Juraj Adamik, Deborah L. Galson, Kurt R. Weiss, Boeun Lee, Rebecca J. Watters, Prashant N. Kumta, Shivendra V. Singh. Sulforaphane is a novel inhibitor of breast cancer-induced osteolytic bone resorption [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 5070.

Objective To investigate the expressions of CD28 and CD117 in patients with newly diagnosed multiple myeloma (MM) and their clinical significances. Methods The clinical data of 115 newly diagnosed MM patients in the First Affiliated Hospital of Zhengzhou University from May 2015 to December 2017 were retrospectively analyzed. The expressions of CD28 and CD117 were detected by using multiparameter flow cytometry. The relationship between the expressions of CD28 and CD117 and MM staging and clinical parameters was analyzed. The staging was performed according to the International Staging System (ISS). Results Among these 115 patients, there were 15 patients with CD117 positive and 30 patients with CD28 positive. Erythrocyte sedimentation rate (r = -0.481, P = 0.039), C-reactive protein level (r = -0.314, P = 0.015), the proportion of plasma cells detected by bone marrow cytology (r = -0.027, P = 0.001) were negatively correlated with CD117 positive expressions. CD28 positive expression was positively correlated with lactate dehydrogenase level (r = 0.249, P = 0.033) and ISS stage (r = 0.319, P = 0.017), while it was negatively correlated with hemoglobin level (r = -0.372, P = 0.026). CD28 positive was associated with light chain type, and non-secretory type mostly occurred (P = 0.016). The incidence of osteolytic lesions in CD28 positive group and CD117 positive group was high, but there was no statistical difference between CD28 positive group, CD117 positive group and CD28 negative group, CD117 negative group (P = 0.052, P = 0.479). Conclusions The positive expression of CD117 in the early stage of MM patients is higher than that in the advanced stage, and the expression of CD28 positive in the advanced stage of MM patients is higher than that in the early stage. CD28 and CD117 can be used as indicators of prognosis stratification in the patients with newly diagnosed MM. Key words: Multiple myeloma; Antigens, CD28; Antigens, CD117; Flow cytometry

Objective To investigate the impacts of acromion morphology on acromion osteolysis and fracture after clavicular hook plate fixation. Methods The clinical data were analyzed retrospectively of 255 patients who had been treated by clavicle hook plate from January 1st, 2011 through December 31th, 2012 at Department of Orthopedics, Shanghai Sixth People’s Hospital. They were 182 males and 73 females with an average age of 46.6 years (from 14 to 76 years). Of them, 130 were diagnosed with distal clavicular fracture, of which 126 were acute cases (within 14 days) and 4 chronic ones. The other 125 patients were diagnosed with acromioclavicular dislocation, of which 121 were acute cases and 4 chronic ones. Radiological data were reviewed to analyze the morphology and clinical outcome of acromion osteolysis. The hook-acromion (HA) angle was measured and the relationships between HA angles and different types of acromion osteolysis were statistically analyzed. Results The follow-up for the 255 patients averaged 6 months (from 1 to 24 months). Acromion osteolysis with different migrations of clavicular hook plate was observed in 175 cases (68.6%), of which 77 were type I (osteolysis with clavicular hook migration) and 98 type Ⅱ (osteolysis without clavicular hook migration). Acromion fractures were observed in the other 6 cases (2.35%). The HA angles in type Ⅰosteolysis (11.05°±11.69°) were significantly larger than that in type Ⅱ (6.36°±11.47°) (P<0.05) Conclusions An increased HA angle may be a risk factor for acromion osteolysis with clavicular hook migration and acromion fracture. Variation in acromion morphology may increase the HA angle. Stress localization may be one of the mechanisms of acromion osteolysis and fractures. Key words: Acromion; Acromioclavicular joint; Internal fixators; Stress; Complications

Multiple myeloma bone diseases (MMBD) is a series of osteolytic changes caused by plasma cells malignant proliferation, including bone pain, hypercalcemia, osteoporosis, pathological fracture, etc. MMBD has insidious onset, high misdiagnosis rate and poor prognosis. The broken-up bone homeostasis model due to the activated osteoclasts and inhibited osteoblasts is considered as the core mechanism. More and more studies suggest that osteocyte is the key to regulate the activity of osteoclasts and osteoblasts, and the occurrence of MMBD is regulated by some cytokines. This article reviews the mechanisms of MMBD. Key words: Multiple myeloma; Myeloma bone diseases; Prognosis

Objective To evaluate the short-term clinical efficacy of three dimension printed titanium augments for the reconstruction of acetabular bone defects in revision total hip arthroplasty. Methods The retrospective study was conducted. To retrospectively analyze clinical data of 21 patients who were underwent revision total hip arthroplasty with severe acetabular bone defects reconstructed by three dimension printed titanium augment from March 2016 to September 2017 from Department of Orthopaedics, Beijing Friendship Hospital, Capital Medical University. There were 9 males and 12 females, age (58.9±6.3) years, 51-67 years, body mass index (23.8±2.9) kg/m2. According preoperative CT scan of hip joints, three dimension printed titanium augments were designed for acetabular defects personality. The data including the vertical distance from centre of rotation to the interteardrop line in X-ray examination, preoperative Harris score, final follow-up Harris score of hip postoperatively, and complications were recorded. Outpatient visits ranged from 11.8 to 19.6 months. Measurement data were expressed as (Mean±SD), and t test was used before and after surgery. Results For X-ray examination, the average vertical distance from centre of rotation to the interteardrop line was (6.1±1.2) cm preoperatively and (2.8±0.7) cm postoperatively, and the difference was statistically significant(P<0.01). The hip Harris score increased from preoperative (47.5±6.4) scores to the last follow-up (84.6±5.9) scores, and the difference was statistically significant (P<0.01). The final follow-up data showed the acetabular prosthesis and augments were stable, while there were no hip joint dislocation, periprosthetic joint infection, loosening of acetabular components and other complications. Conclusion Three dimension printed augments can reconstruct severe acetabular bone defects and restore the hip rotation centre. Key words: Arthroplasty, replacement, hip; Prosthesis failure; Acetabulum; Osteolysis; Recovery of function

Objective To compare the efficacy between hook plate combined with coracoclavicular ligament functional reconstruction by conjoined tendon transfer and single hook plate surgery in the treatment of Rockwood type III and type V acute acromioclavicular joint dislocations. Methods A prospective cohort study was conducted to analyze the clinical data of 37 patients with Rockwood type III and V acute acromioclavicular dislocations admitted to Jiangning Hospital Affiliated to Nanjing Medical University from October 2011 to April 2016. According to the random number method, the patients were divided into combined tendon and ligament reconstruction group (ligament reconstruction group, 19 patients) and clavicular hook plate group (single plate group, 18 patients). In the ligament reconstruction group, there were 14 males and five females, aged (47.0±11.4)years, and there were 10 patients with type III and nine with type V. In the simple plate group, there were 12 males and six females, aged (45.0±11.2)years, and there were 11 patients with type III and seven with type V. In the ligament reconstruction group, the acromioclavicular joint was reduced by clavicular hook plate, and the oblique ligament and the conical ligament were reconstructed by lateral half-inversion of the short head tendon of biceps brachii combined with tendon. The double-bundle functional reconstruction of coracoclavicular ligament was performed. In single plate group, hook plate was used to reduce acromioclavicular joint. The intraoperative blood loss, incision length, operation time, and visual analogue score (VAS) before operation and after 1 year follow-up were compared. Constant-Murley score and Karlsson score were used to evaluate the effect of operation. X-ray films were taken regularly to observe the reduction and maintenance of acromioclavicular joint dislocation. The complications were recorded. Results All patients were followed up for 17-24 months [(20.0±1.7)months]. There was no significant difference in intraoperative blood loss between the two groups (P>0.05). In the ligament reconstruction group and single plate group, the incision length was (13.4±0.8)cm and (6.6±0.7)cm (P 0.05); the VAS at 1 year after operation was (2.1±0.9)points and (3.8±1.4)points (P<0.05). X-ray showed good reduction of acromioclavicular joint in ligament reconstruction group, with no loss of reduction occurred after removal of hook plate. In the simple plate group, loss of reduction, resorption of distal clavicle bone and bone fusion occurred after removal of hook plate. The Constant-Murley scores in the ligament reconstruction group and the single plate group were (89.5±2.9)points and (79.6±5.0)points respectively; the excellent and good rates of Karlsson score were 89.5% (17/19) and 61.1% (11/18) (bothP<0.05), respectively. In the ligament reconstruction group, one patient complained of pain and swelling at the tendon. In the single plate group, loss of reduction occurred in three patients after removal of internal fixator; obvious subacromial osteolysis was seen in seven patients at 1 year after operation; and impingement sign was positive in nine patients at 1 year after operation. Conclusion The overall surgical effect of hook plate combined with coracoclavicular ligament functional reconstruction by conjoined tendon transfer is superior to single hook plate surgery in the treatment of type Rockwood III and Rockwood V acute acromioclavicular joint dislocations, though with longer operation time and bigger incision. Key words: Acromioclavicular joint; Dislocations; Coracoclavicular ligament

Objective To explore the effect of salmon calcitonin on the receptor activator of NF-κB/receptor activator of NF-κB ligand/osteoprotegerin (RANK/RANKL/OPG) osteolysis pathway in human macrophages after particles induction. Methods The polyethylene wear particles were extracted from the periacetabular boundary membrane tissue of a patient with hip prosthesis loosening. The optimal reaction cell concentration of human macrophages to polyethylene wear particles (with a concentration of 0.1 mg/ml) was measured by methyl thiazolyl tetrazolium (MTT) assay. Particles were used to stimulate human macrophages, while salmon calcitonin with different drug concentrations was used for intervention. They were randomly divided into five groups, with six parts in each group: Group A, control group; Group B, particle group; Group C, particle+ salmon calcitonin (10-8 mol/L) group; Group D, particle+ salmon calcitonin (10-10 mol/L) group; Group E, particle+ salmon calcitonin (10-12 mol/L) group. After cocultured for 48 hours, quantitative polymerase chain reaction (qPCR) assay was used to detect the mRNA expression of RANK, RANKL and OPG in macrophages. Results After induction with particles, Group B had a higher expression in RANK and RANKL, and lower OPG expression than Group A. After salmon calcitonin intervention, the expression of RANK and RANKL were significantly decreased, and OPG expression was significantly increased. Group B had the highest RANKL/OPG rate. After drug intervention, the RANKL/OPG rate in C, D, E group were reduced. Conclusions The particles can induce the transformation of macrophages into osteoclasts. In addition to directly inhibiting osteoclast activity, salmon calcitonin prevents macrophage from differentiating into osteoclasts through modulating RANKL/RANK/OPG signaling pathway. Key words: Calcitonin; Macrophages; Receptor activator of nuclear factor-kappa B; RANK ligand; Osteoprotegerin; Osteolysis; In vitro