Bone alterations in inflammatory bowel diseases

Inflammatory bowel diseases(IBDs)are characterized by a multifactorial partially unknown etiology that involves genetic,immunological and environmental factors.Up to 50%of IBD patients experience at least one extraintestinal manifestation;among them is the involvement of bone density which is referred to as metabolic bone disease(MBD),including osteopenia and osteoporosis.Bone alterations in IBDs population appear to have a multifactorial etiology:Decreased physical activity,inflammation-related bone resorption,multiple intestinal resections,dietary malabsorption of minerals and vitamin D deficiency,genetic factors,gut-bone immune signaling interaction,steroid treatment,microbiota and pathogenic micro-organisms interaction,and dietary malabsorption of minerals,that,all together or individually,may contribute to the alteration of bone mineral density.This review aims to summarize the prevalence and pathophysiology of metabolic bone alterations in IBD subjects outlining the main risk factors of bone fragility.We also want to underline the role of the screening and prophylaxis of bone alterations in Crohn’s disease and ulcerative colitis patients and the importance of treating appropriately MBD.

Roles and regulation of bone morphogenetic protein-7 in kidney development and diseases

The gene encoding bone morphogenetic protein-7(BMP7) is expressed in the developing kidney in embryos and also in the mature organ in adults. During kidney development, expression of BMP7 is essential to determine the final number of nephrons in and proper size of the organ. The secreted BMP7 acts on the nephron progenitor cells to exert its dual functions: To maintain and expand the progenitor population and to provide them with competence to respond to differentiation cues, each relying on distinct signaling pathways. Intriguingly, in the adult organ, BMP7 has been implicated in protection against and regeneration from injury. Exogenous administration of recombinant BMP7 to animal models of kidney diseases has shown promising effects in counteracting inflammation, apoptosis and fibrosis evoked upon injury. Although the expression pattern of BMP7 has been well described, the mechanisms by which it is regulated have remained elusive and the processes by which the secretion sites of BMP7 impinge upon its functions in kidney development and diseases have not yet been assessed. Understanding the regulatory mechanisms will pave the way towards gaining better insight into the roles of BMP7, and to achieving desired control of the gene expression as a therapeutic strategy for kidney diseases.

Non-alcoholic fatty liver disease connections with fat-free tissues: A focus on bone and skeletal muscle

The estimates of global incidence and prevalence of non-alcoholic fatty liver disease(NAFLD) are worrisome, due to the parallel burden of obesity and its metabolic complications. Indeed, excess adiposity and insulin resistance represent two of the major risk factors for NAFLD; interestingly, in the last years a growing body of evidence tended to support a novel mechanistic perspective, in which the liver is at the center of a complex interplay involving organs and systems, other than adipose tissue and glucose homeostasis. Bone and the skeletal muscle are fat- free tissues which appeared to be independently associated with NAFLD in several cross-sectional studies. The deterioration of bone mineral density and lean body mass, leading to osteoporosis and sarcopenia, respectively, are age-related processes. The prevalence of NAFLD also increases with age. Beyond physiological aging, the three conditions share some common underlying mechanisms, and their elucidations could be of paramount importance to design more effective treatment strategies for the management of NAFLD. In this review, we provide an overview on epidemiological data as well as on potential contributors to the connections of NAFLD with bone and skeletal muscle.

Bone loss in chronic liver diseases:Could healthy liver be a requirement for good bone health?

Given that the liver is involved in many metabolic mechanisms,it is not surprising that chronic liver disease(CLD)could have numerous complications.Secondary osteoporosis and increased bone fragility are frequently overlooked complications in CLD patients.Previous studies implied that up to one-third of these individuals meet diagnostic criteria for osteopenia or osteoporosis.Recent publications indicated that CLD-induced bone fragility depends on the etiology,duration,and stage of liver disease.Therefore,the increased fracture risk in CLD patients puts a severe socioeconomic burden on the health system and urgently requires more effective prevention,diagnosis,and treatment measures.The pathogenesis of CLD-induced bone loss is multifactorial and still insufficiently understood,especially considering the relative impact of increased bone resorption and reduced bone formation in these individuals.It is essential to note that inconsistent findings regarding bone mineral density measurement were previously reported in these individuals.Bone mineral density is widely used as the“golden standard”in the clinical assessment of bone fragility although it is not adequate to predict individual fracture risk.Therefore,microscale bone alterations(bone microstructure,mechanical properties,and cellular indices)were analyzed in CLD individuals.These studies further support the thesis that bone strength could be compromised in CLD individuals,implying that an individualized approach to fracture risk assessment and subsequent therapy is necessary for CLD patients.However,more well-designed studies are required to solve the bone fragility puzzle in CLD patients.

Growth and bone health in paediatric patients with Crohn's disease receiving subcutaneous tumor necrosis factor antibody

AIM:To study whether adalimumab(ADA) was associated with improvement in growth,bone mineraldensity(BMD) and bone metabolism.METHODS:In children with Crohn's disease(CD) there is a high prevalence of growth failure and reduced BMD.Treatment with infliximab is associated with an improvement in growth.Anthropometry,paediatric CD activity index(PCDAI),bone markers and BMD was measured in 18 patients(72% females) one year before and after start of ADA with a median age of 14.4 years(range:5-19 years) at treatment start.Outcomes were indicators of growth with treatment as well as interval growth.RESULTS:Eleven(61%) children experienced catchup growth after ADA.PCDAI significantly decreased from 52.1 ± 16 to 30.4 ± 23(P ≤ 0.001).Post ADA,body mass index(BMI) standard deviation score(SDS) 0.1[range:2.7-(-0.8)] vs-1 [range:0.1-(-3.6)],P = 0.04 and △BMI SDS in children 0.3 [range:0.7-(-0.2)] vs-1.1 [range:1.2-(-2.3)],P = 0.01 in remission were significantly higher compared to those with moderate to severe inflammation.The main predictors for growth were 25-hydroxycholecalciferol and for bone mineralisation weight and height SDS.ADA had no significant influence on bone markers and BMD.CONCLUSION:Next to improvement of PCDAI,half of the children achieved a positive catch-up growth.A better nutritional status with improvement in BMI and weight is positive predictor for improved growth and bone mineralisation.

Clinical benefits of biochemical markers of bone turnover in Egyptian children with chronic liver diseases

AIM： To investigate the association between serum insulin-like growth factor 1 （IGF-1）, osteocalcin, and parathyroid hormone （PTH） levels with the etiology and clinical condition of patients with chronic liver disease. METHODS： Eighty children with hepatocellular damage were divided into 3 groups according to the etiology of disease infection： bilharziasis （9 patients）, hepatitis B virus （HBV, 12 patients） and hepatitis C virus （HCV, 29 patients）. The Child score index was found as A in 24 patients, B in 22 patients, C in 4 patients. Thirty healthy children served as control group.HBsAg, HBcAbIgM, HBcAbIgG, and anti-HCV were detected using ELISA technique. HCV-RNA was measured by reverse transcription polymerase chain reaction （RT-PCR）. Antibllharzial antibodies were detected by indirect haemagglutination test. Liver function tests were performed using autoanalyser. Serum IGF-1, osteocalcin and PTH levels were measured by ELISA technique. Abdominal ultrasonography was also conducted. RESULTS： Serum IGF-1 level was significantly lower in all patient groups with liver diseases, while serum osteocalcin and PTH levels were significantly elevated in patients with HBV and HCV infections compared with the control group. Serum osteocalcin and PTH concentrations were measured with the severity of liver disease from Child A to C. Child A patients unexpectedly showed significantly reduced IGF-1 levels in comparison to patients staged as Child B or C. Serum osteocalcin level was negatively correlated with albumin （14.7 ± 0.54 vs 3.6 ± 0.10, P 〈 0.05）, while that for PTH was positively correlated with total protein （70.1 ± 2.17 vs 6.7 ± 0.10, P 〈 0.05） in patients with HCV infection.

Epigenetic regulation by long noncoding RNAs in osteo-/adipogenic differentiation of mesenchymal stromal cells and degenerative bone diseases

Bone is a complex tissue that undergoes constant remodeling to maintain homeostasis,which requires coordinated multilineage differentiation and proper proliferation of mesenchymal stromal cells(MSCs).Mounting evidence indicates that a disturbance of bone homeostasis can trigger degenerative bone diseases,including osteoporosis and osteoarthritis.In addition to conventional genetic modifications,epigenetic modifications(i.e.,DNA methylation,histone modifications,and the expression of noncoding RNAs)are considered to be contributing factors that affect bone homeostasis.Long noncoding RNAs(lncRNAs)were previously regarded as‘transcriptional noise’with no biological functions.However,substantial evidence suggests that lncRNAs have roles in the epigenetic regulation of biological processes in MSCs and related diseases.In this review,we summarized the interactions between lncRNAs and epigenetic modifiers associated with osteo-/adipogenic differentiation of MSCs and the pathogenesis of degenerative bone diseases and highlighted promising lncRNA-based diagnostic and therapeutic targets for bone diseases.

Glucagon-like peptide-1 receptor agonists:Exploring the mechanisms from glycemic control to treatment of multisystemic diseases

This editorial takes a deeper look at the insights provided by Soresi and Giannitrapani,which examined the therapeutic potential of glucagon-like peptide-1 receptor agonists(GLP-1RAs)for metabolic dysfunction-associated fatty liver disease.We provide supplementary insights to their research,highlighting the broader systemic implications of GLP-1RAs,synthesizing the current understanding of their mechanisms and the trajectory of research in this field.GLP-1RAs are revolutionizing the treatment of type 2 diabetes mellitus and beyond.Beyond glycemic control,GLP-1RAs demonstrate cardiovascular and renal protective effects,offering potential in managing diabetic kidney disease alongside renin–angiotensin–aldosterone system inhibitors.Their role in bone metabolism hints at benefits for diabetic osteoporosis,while the neuroprotective properties of GLP-1RAs show promise in Alzheimer's disease treatment by modulating neuronal insulin signaling.Additionally,they improve hormonal and metabolic profiles in polycystic ovary syndrome.This editorial highlights the multifaceted mechanisms of GLP-1RAs,emphasizing the need for ongoing research to fully realize their therapeutic potential across a range of multisystemic diseases.

Role of fibroblast growth factor receptor 1 in the bone development and skeletal diseases

Accumulating data suggest that FGFs/FGFR1 plays essential roles in the bone development and human skeletal diseases. Conditional inactivation of fgfrl caused different phenotypes displaying in different cells or specific organs and revealed some novel functions of FGFR1 in bone development. Fgfrl mutation mainly induced 2 types of human skeletal diseases, craniosynostosis syndrome and dysplasias. Similar mutation of fgfrl in mouse model just mimicked the phenotype that happened in human. These fa- cilitate the investigation on the underlying mechanism of the diseases. Here we mainly focused on the ad- vance of FGFR1 function in the bone development and its mutation caused skeletal diseases.

Surgical treatment of metastatic bone disease of the distal extremities

Metastatic bone disease of the distal extremities,also known as acrometastasis,is very rare.Thus,there is very limited information regarding the clinical manifestations and methods of surgical treatment.The current available literature shows that acrometastases are often encountered in the context of advanced disease and are thus associated with poor patient survival.As metastatic bone disease is generally uncurable,the goal of surgical treatment is to provide the patient with good function with as few complications as possible.In this article,we discuss the clinical manifestation of acrometastases,the methods of surgical intervention,and the expected clinical outcome.Non-surgically managed pathological fractures generally remain ununited;therefore,conservative treatment is reserved for patients with poor general condition or dismal prognosis.The current evidence suggests that in lesions of the lower arm and leg,osteosynthesis(plate and screw fixation or intramedullary nail)is the most common method of reconstruction,whereas local excision or amputation are more commonly used in cases of more distal lesions(such as ankle,foot and hand).Following surgery most patients receive adjuvant radiotherapy,even though its role is poorly documented.Close collaboration between orthopedic surgeons and medical oncologists is necessary to improve patient care and treatment outcome.Further studies are needed in order to provide stronger clinical evidence and improve decision-making,in an effort to optimize the patients’quality of life and avoid the need for revision surgery.

Intracerebroventricular transplanted bone marrow stem cells survive and migrate into the brain of rats with Parkinson's disease

In this study, 6-hydroxydopamine was stereotaxically injected into the right substantia nigra compact and ventral tegmental area of rats to establish Parkinson＇s disease models. The rats then received a transplantation of bone marrow stromal cells that were previously isolated, cultured and labeled with 5-bromo-2＇-deoxyuridine in vitro. Transplantation of the bone marrow stromal cells significantly decreased apomorphine-induced rotation time and the escape latency in the Morris water maze test as compared with rats with untreated Parkinson＇s disease. Immunohistochemical staining showed that, 5-bromo-2＇-deoxyuridine-immunoreactive cells were present in the lateral ventricular wall and the choroid plexus 1 day after transplantation. These immunoreactive cells migrated to the surrounding areas of the lateral cerebral ventricle along the corpus callosum. The results indicated that bone marrow stromal cells could migrate to tissues surround the cerebral ventricle via the cerebrospinal fluid circulation and fuse with cells in the brain, thus altering the phenotype of cells or forming neuron-like cells or astrocytes capable of expressing neuron-specific proteins. Taken together, the present findings indicate that bone marrow stromal cells transplanted intracerebroventricularly could survive, migrate and significantly improve the rotational behavior and cognitive function of rats with experimentally induced Parkinson＇s disease.

Association Between Knee Alignment,Disease Severity and Subchondral Trabecular Bone Microarchitecture in Patients with Knee Osteoarthritis

Objective Most patients with knee osteoarthritis(OA)have alignment deformity with the change of Hip-knee-ankle(HKA)angle.The knee alignment influences load distribution at the tibial plateau.Meanwhile,change of subchondral trabecular bone microstructure is related to load bearing and OA progression.However,the relationship between knee alignment on the changes of subchondral trabecular bone microstructure and OA severity have been poorly investigated.The main goal of this work was to investigate variation in tibial plateaus subchondral trabecular bone microstructure in knee OA patients and their association with the severity of OA with the change of knee alignment.Methods Seventy-one knee OA patients planning to undergo total knee arthroplasty were enrolled in this study.The HKA angle and OA disease severity(OARSI score,compartment-specific Kellgren-Lawrence(K-L)grade and OARSI Atlas grade)based on full-leg standing posteroanterior radiographs were evaluated preoperatively in all patients.The tibial plateau collected during surgery was first used for micro-computed tomography(μCT)to analyze the subchondral trabecular bone microstructures,and then used for pathological sections to analyze cartilage degeneration(OARSI score).Pearson and spearman correlations were used to examine linear relationships between knee alignment,OA disease severity and subchondral trabecular bone microstructure.Patients were then divided into group I(HKA angle exceeds 0°in the valgus direction),group II(varus angle<10°)and group III(varus angle≥10°).The differences in subchondral trabecular bone microstructural parameters between the three groups were analyzed by the one-way ANOVA with a post hoc Tukey test.Results HKA angle was significantly correlated with all tibial plateau subchondral trabecular bone microstructure parameters.Regardless of the medial or lateral tibia,HKA angle was most strongly correlated with bone volume fraction(BV/TV),M:(r=0. 613,P<0.01);L:(r=-0.490,P<0.01).In addition,for the media-to-lateral ratios(M:L)of the subchondral trabecular bone microstructure parameters,the HKA angle is positively correlated with M:L BV/TV(r=0.658,P<0.01),M:L trabecular number(Tb.N)(r=0.525,,P<0.01),M:L trabecular thickness(Tb.Th)(r=0.636,P<0.01),and negatively correlated with M:L trabecular separation(Tb.Sp)(r=-0.636,P<0.01)and M:L Specific Bone Surface(BS/BV)(r=-0.792,P<0.01).The BV/TV,Tb.N,and Tb.Th of the medial tibia were sequentially incremented in the order of groupⅠ,Ⅱ,Ⅲof knee alignment,while the Tb.Sp and BS/BV were decreased in this order.The lateral tibia is the opposite.In addition,most of the severity indices of OA are associated with subchondral trabecular bone microstructures,of which OARSI score and BV/TV in medial tibia are the most relevant(r=0.787,P<0.01).HKA angle is significantly correlated with all OA severity grades in medial compartment,but only with OARSI score and Bone sclerosis grade in lateral compartment.Conclusions Tibial plateau subchondral trabecular bone microarchitecture is associated with the HKA angle and OA severity.With the increase of varus angle and the severity of OA,the subchondral trabecular bone in medial tibia has more obvious sclerosis changes and vice versa,suggesting that knee malalignment may promote abnormal subchondral trabecular bone remodeling by altering joint load distribution,thereby affecting the progression of OA.

Bone Mineral Density in Patients with Newly Diagnosed Inflammatory Bowel Disease: Frequency and Risk Factors in Tunisian Population. Results of a Prospective Study

Background and Aims: Osteopenia and osteoporosis are frequently encountered with Inflammatory Bowel Disease (IBD). Our aims were to determine the prevalence of low bone mineral density (BMD) in patients with recently diagnosed IBD, and to assess predictive factors of reduced BMD. Patients and Methods: Prospective study conducted from January 2008 to December 2012 and involved patients with IBD treated in the Department of Gastroenterology of the Internal Security Forces Hospital. The data collected included: age, gender, body mass index (BMI), diagnostic delay, disease activity, and disease localization. Laboratory findings included serum calcium, phosphate, albumin, hemoglobin, and C-reactive protein. BMD was assessed by dual energy X-ray absorptiometry (DEXA) of the lumber spine and femoral neck. According to WHO criteria, osteopenia was defined as a T-score between -1 and -2 SD, and osteoporosis as a T-score less than -2 SD. Results: A total of 34 patients (17 men, 17 women) were enrolled. Mean age was 37.1 ± 13.8 years (range 16 - 62). Twenty-two patients (65%) had Crohn’s disease (CD) and 12 patients (35%) had ulcerative colitis (UC). Mean BMI was 20.5 ± 4 kg/m2. Low BMD occurred in 50% of patients (12 CD, 5 UC). Thirteen patients (38.2%) exhibited osteopenia and 4 patients (10.8%) showed osteoporosis. Mean vertebral T-score was -0.933 ± 1.41 (range -4.1 to 1.7) and BMD in this site was 1.079 ± 0.17 g/cm2 (range 0.674 to 1.380). Mean femoral T-score was -0.398 ± 1.2 (range -3.1 to 2.4) and BMD in this site was 0.990 ± 0.173 g/cm2 (range 0.633 to 1.600). There was a positive correlation between T-score and albuminemia. Low BMI was found to be predictive factor of reduced BMD at the moment of IBD diagnosis. However, no correlation was found between BMD and the other studied variables (age, gender, smoking, history of fracture, disease location, duration of disease, activity, small bowel resection, serum calcium level, phosphate, C-reactive protein and hemoglobin). Conclusion: Our study showed that the half of patients with IBD had a low BMD in newly diagnosed IBD patients. Low BMI and hypoalbuminemia were the major factors affecting BMD in these patients. Bone density measurement should be performed in all patients with IBD in an early stage of the disease.

Significance of preoperative peripheral blood neutrophil-lymphocyte ratio in predicting postoperative survival in patients with multiple myeloma bone disease

BACKGROUND The neutrophil-lymphocyte ratio(NLR)is often used to predict a poor prognosis in patients with tumors.This study investigated the preoperative peripheral blood NLR in predicting postoperative survival(POS)in patients with multiple myeloma bone disease(MMBD).AIM To evaluate whether NLR can be used to predict the prognosis of MMBD patients after surgery.METHODS The clinical data of 82 MMBD patients who underwent surgical treatments in Beijing Chao-yang Hospital were collected.The NLR was obtained from the absolute number of neutrophils and lymphocytes,calculated by the number of neutrophils and divided by the number of lymphocytes.The peripheral blood lymphocyte percentage was used as the major marker to analyze the change in characteristics of the immune statuses of multiple myeloma patients.RESULTS The NLR cut-off values of NLR≥3 patients and NLR≥4 patients were significantly correlated with POS.The 3-and 5-year cumulative survival rates of the high NLR group(NLR≥3 patients)were 19.1%and 0.0%,respectively,which were lower than those of the low NLR group(NLR<3 patients)(67.2%and 48.3%)(P=0.000).In the high NLR group,POS(14.86±14.28)was significantly shorter than that in the low NLR group(32.68±21.76).Univariate analysis showed that the lymphocyte percentage 1 wk after the operation(19.33±9.08)was significantly lower than that before the operation(25.72±11.02).Survival analysis showed that postoperative chemotherapy,preoperative performance status and preoperative peripheral blood NLR≥3 were independent risk factors for POS.CONCLUSION The preoperative peripheral blood NLR can predict POS in MMBD patients.MMBD patients with a high preoperative NLR(NLR≥3)showed poor prognosis.

Experimental study of G-CSF alleviating graft-versus-host disease after mixed bone marrow transplantation in mice

Objective： How to reduce the incidence and severity of acute graft-versus-host disease （aGVHD） is a crucial step to improve the overall survival of allogeneic bone marrow transplantation （allo-BMT）. The low incidence of severe aGVHD observed in allogeneic peripheral blood stem cell transplantation （allo-PBSCT）, which may be related to modulating immune function of T lymphocytes by granulocyte colony-stimulating factor （G-CSF） primed donors. The study aimed to explore whether aGVHD could be alleviated by syngeneic bone marrow mixed with G-CSF-mobilized H-2 haploidentical marrow grafting. Methods： Female BALB/c mice and neonatal BALB/c mice were recipients and male （BALB/c × C57BL/6）F1（BCF1） mice were donor mice respectively. Donor mice were injected subcutaneously with G-CSF daily at 0.01 μg/g body weight or saline for 6 days, and splenocytes were harvested on day 6. Spleen index （SI） represented GVHD in neonatal mice after the intraperitoneal injection of mixed spleen cells. Lethally irradiated （^60Co, 8.5 Gy） adult mice were transplanted with a mixture of syngeneic plus G-CSF-mobilized （control diluents） H-2 haploidentical marrow cells. Survival time and survival rate of the recipients were observed after mixed marrow transplantation （MBMT）. GVHD was assessed by observing signs of weight loss, ruffled fur, diarrhea and histological change of skin, liver and small intestines. Enzyme-linked immunosorbent assay （ELISA） method was used to detect cytokines （IL-2, IL-4 and INF-γ）. Fluorescence-activated cell sorting （FACS） analysis was used to detect T cells phenotype. Results： （1） The neonatal mice subject to injection of 2：1 and 1：1 mixed spleen cells and H-2 haploidentical spleen cells all suffered from aGVHD. The severity of aGVHD in recipient mice receiving G-CSF-mobilized splenocytes was dramatically reduced. （2） The aGVHD signs and histological change were observed in most mice of 2：1 and 1：1 MBMT groups. However, the survival time of G-CSF-mobilized MBMT was longer than in control groups and these mice had signs of moderate GVHD. （3） L3T4^＋ cells and relative ratio in both subsets was significantly reduced in G-CSF-treated donor mice. The total number of Thyl.2 and lyt2^＋ cells was increased after G-CSF pretreatment of donors, but no statistical difference. （4） The supernatants from a primary MLR were collected at 48 h for cytokine measurement. The results showed an increased production of IL-4 and a decreased production of IL-2 and INF-γ after stimulating with concanavalin A for 48 h. Conclusion： The GVHD could be reduced using syngeneic bone marrow mixed with H-2 haploidentical marrow cells. The severity of aGVHD in recipient mice receiving G-CSF-mobilized splenocytes or marrow cells could be further moderated, which is associated with increased IL-4 production and decreased IL-2 and INF-y production.

Advances and perspectives on cellular therapy in acquired bone marrow failure diseases

Acquired bone marrow failure diseases(ABMFD) are a class of hematopoietic stem cell diseases with a commonality of non-inherited disruption of hematopoiesis that results in pancytopenia. ABMFDs also are a group of heterogeneous diseases with different etiologies and treatment options. The three most common ABMFDs are aplastic anemia, myelodysplastic syndrome, and paroxysmal nocturnal hemoglobinuria. Stem cell transplantation is the only treatment that can cure these diseases. However, due to high therapy-related mortality, stem cell transplantation has rarely been used as a first line treatment in treating ABMFD. With the advance of personalized medicine and precision medicine, various novel cellular therapy strategies are in trial to increase the efficiency and efficacy of ABMFD treatment. This article aims to review current available stem cell transplantation protocols and promising cellular therapy research in treating ABMFD.

Surgical management of metastatic disease of long bone

Objective To improve the life quality of cancer patients with metastasis to long bone and to long bone and to select suitable surgical treatment. Methods Fifty-two patients with metastasis 27 men and 25 women, were June 2003 Vol12 No2 treated from 1990 to 1999. Their average age was 56. 8 years (33 - 74). In 16 patients with multiple lesions, underwent surgery at bone shaft (29 patients) and bone epiphysis (26). Thirty patients were treated for pathologic fracture and the rest for impending fracture. Operations included limb-salvage (51 patients) and amputation (4) Limb salvage consisted of intralesional curettage (3 patients ), intramedullary nailing reconstruction (29 ), endoprosthesis ( 18 ), and temporary spacer ( 1 ). 21 patients accepted postoperative chemotherapy or radiotherapy. Results Follow-up of 52 patients for a mean of 28. 2 months (2 - 122 months) showed pain relief (41 patients), (75%) and full or part weight-bearing stability ( 36 ) 69 % . Local tumor recurrence occurred in 11 patients.

Bone mineral density and disorders of mineral metabolism in chronic liver disease

AIM： To estimate the prevalence and identify the risk factors for metabolic bone disease in patients with cirrhosis. METHODS： The study was performed on 72 Indian patients with cirrhosis （63 male, 9 female; aged 〈 50 years）. Etiology of cirrhosis was alcoholism （n = 37）, hepatitis B （n = 25） and hepatitis C （n = 10）. Twenty-three patients belonged to Child class A, while 39 were in class B and 10 in class C. Secondary causes for metabolic bone disease and osteoporosis were ruled out. Sunlight exposure, physical activity and dietary constituents were calculated. Complete metabolic profiles were derived, and bone mineral density （BMD） was measured using dual energy X ray absorptiometry. Low BMD was defined as a Z score below -2. RESULTS： Low BMD was found in 68% of patients. Lumbar spine was the most frequently and severely affected site. Risk factors for low BMD included low physical activity, decreased sunlight exposure, and low lean body mass. Calcium intake was adequate, with unfavorable calcium： protein ratio and calcium： phosphorus ratio. Vitamin D deficiency was highly prevalent （92%）. There was a high incidence of hypogonadism （41%）. Serum estradiol level was elevated significantly in patients with normal BMD. Insulin-like growth factor （IGF） 1 and IGF binding protein 3 levels were below the age-related normal range in both groups. IGF-1 was significantly lower in patients with low BMD. Serum osteocalcin level was low （68%） and urinary deoxypyridinoline to creatinine ratio was high （79%）, which demonstrated low bone formation with high resorption. CONCLUSION： Patients with cirrhosis have low BMD. Contributory factors are reduced physical activity, low lean body mass, vitamin D deficiency and hypogonadism and low IGF-1 level.

Vanishing bone disease(Gorham-Stout syndrome): A review of a rare entity

Vanishing bone disease(Gorham-Stout syndrome) is a rare entity of unknown etiology, characterized by de struction of osseous matrix and proliferation of vascula structures, resulting in destruction and absorption o bone. Despite the extensive investigation of the patho genetic mechanisms of the disease, its etiology hasn'been clarified and several theories exist. The syndrome can affect one or multiple bones of the patient, includ ing the skull, the upper and lower extremities, the spine and pelvis. The clinical presentation of a patient suffer ing from vanishing bone disease includes, pain, func tional impairment and swelling of the affected region although asymptomatic cases have been reported, as well as cases in which the diagnosis was made after a pathologic fracture. In this short review we summarize the theories regarding the etiology as well as the clini cal presentation, the diagnostic approach and treat ment options of this rare disease.

TGF-β and BMP signaling in osteoblast,skeletal development,and bone formation,homeostasis and disease

INTRODUCTIONThe transforming growth factor-β （TGF-β） superfamily com- prises TGF-βs, Activin, bone morphogenetic proteins （BMPs） and other related proteins. TGF-β superfamily members act through a heteromeric receptor complex,, comprised of type I and type II receptors at the cell surface that transduce intracellular signals via Smad complex or mitogen-activated protein kinase （MAPK） cascade.