Consensus Statement on the Use of Bone Turnover Markers for Short-Term Monitoring of Osteoporosis Treatment in the Asia-Pacific Region

Osteoporosis is a major health issue. By 2050, a greater than 2-fold increase in patients number with hip fractures will occur in Asia representing 50% of all hip fractures worldwide. For the Asia-Pacific (AP) region, more efforts on controlling osteoporosis and the subsequent fractures are crucial. Bone mineral density (BMD) by dual energy X-ray absorptiometry (DXA) is commonly used to diagnose osteoporosis and monitor osteoporosis treatment. However, the inconvenience, cost, limited availability of DXA and the delay in detection of BMD changes after treatment initiation support an important role for bone turnover markers (BTMs), as short-term tools to monitor therapy. With regards to low adherence rates of medical treatment of osteoporosis, the experts reached consensus on the use of BTMs for both raising awareness and short-term monitoring of osteoporosis treatment in the AP region. The experts endorse the use of BTMs, especially serum C-terminal telopeptide of type 1 collagen (CTX) and serum procollagen type 1 N propeptide (P1NP), as short-term monitoring tools to help clinicians assess the responses to osteoporosis therapies and appropriately adjust treatment regimens earlier than BMD. Either the absolute values or the degree of change from baseline in BTMs can be used to monitor the potential efficacy of osteoporosis therapies. The use of BTMs can be incorporated in osteoporosis care programs, such as fracture liaison service (FLS), to improve patient adherence and treatment outcomes. Encouraging sufficient reimbursement from health care systems may facilitate widespread use of BTMs in clinical practice in the AP region.     

Relationships between anthropometric adiposity indexes and bone mineral density in a cross-sectional Chinese study

Background ContextPrevious studies have reported conflicting results for the relationships between anthropometric adiposity indexes and bone mineral density, based on dual-energy X-ray absorptiometry (DXA). However, few studies were published based on quantitative computed tomography (QCT), especially for Chinese population.PurposeTo evaluate the associations of spine bone mineral density (BMD) with body mass index (BMI), waist circumstance (WC), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR) and a body shape index (ABSI) using QCT.Study Design/SettingA Cross-sectional study.Patient SampleAround 3,457 participants in multiple communities across 7 administrative regions of China.Outcome MeasuresSpine BMD was measured using QCT, and the classification of osteoporosis was defined as follows: 1) osteoporosis if BMD <80mg/cm³, 2) osteopenia if BMD 80–119 mg/cm³, and 3) normal bone mass if BMD≥120 mg/cm³.MethodsThis study was conducted using convenient sampling between 2013 and 2017. Multivariable linear regression model and logistic regression models were used for the associations of continuous and categorical BMD, respectively.ResultsAround 3,405 participants were included in the final analyses, including 1,272 males and 2,133 females, with spine BMD of 111.00±35.47 mg/cm³ and 99.38±40.60 mg/cm³, respectively. Spine BMD decreased significantly with the increase of ABSI in females (adjusted β, ?5.74; 95% confidence interval [CI], ?8.50 to ?2.98), and this trend also was kept in females aged at less than 60 years (adjusted β, ?14.54; 95% CI, ?20.40 to ?8.68), and females with age ≥60 years (adjusted β, ?7.59; 95% CI, ?10.91 to ?4.28). However, this inverse association was observed only in males with age ≥ 60 years (adjusted β, ?5.19; 95% CI, ?10.08 to ?0.29). Except ABSI, negative associations of Spine BMD with WC (adjusted β, ?0.46; 95% CI, ?0.77 to ?0.15), WHR (adjusted β, ?6.25; 95% CI, ?10.63 to ?1.86), WHtR (adjusted β, ?6.80; 95% CI, ?11.63 to ?1.97) were shown in females aged at <60 years, and positive association with BMI in males with age ≥60 years (adjusted β, 0.92; 95% CI, 0.29–1.55).ConclusionsABSI had more remarkable association with spine BMD, compared with the other four indexes.     

Anterior tibial artery injury is not the contraindication of medial plantar flap: digital subtraction angiography evidence and clinical application

The medial plantar artery (MPA) is often sacrificed as the vascular pedicle of the medial plantar flap (MPF). However, for patients with ankle soft tissue defect caused by traffic accident, the anterior tibial artery (ATA) could be damaged and the blood supply of the distal foot would only come from the MPA and the lateral plantar artery (LPA). In this case, sacrificing the MPA for the MPF means that the LPA will become the mainly source of blood supply of the distal foot. Whether the blood supply of the distal foot is adequately guaranteed remains to be discussed. A total of seven patients with ankle soft tissue defect and ATA injury were enrolled in the study. The digital subtraction angiography (DSA) was performed to observe the hemodynamics of the ipsilateral foot. The MPF was harvested only when the foot arterial network consisting of the MPA, the LPA, the deep plantar arch, and the deep plantar artery of DPA, and the blood redistribution existed. DSA results showed the blood from the posterior tibial artery was redistributed to the ipsilateral foot and the MPA is not the dominant artery in the foot. Seven MPFs were harvested, and all flaps survived completely. No complications, such as pain, ulcer, and necrosis, occurred in the ipsilateral toes. The DSA could accurately and intuitively evaluate the hemodynamics of foot in patients with ATA injury. The DSA data and clinical practice proved that the ATA injury is not the contraindication of the MPF.     

Potential lack of “standardized” processing techniques for production of allogeneic and xenogeneic bone blocks for application in humans

In the present study, the structure of two allogeneic and three xenogeneic bone blocks, which are used in dental and orthopedic surgery, were histologically analyzed. The ultimate goal was to assess whether the components postulated by the manufacturer can be identified after applying conventional histological and histochemical staining techniques. Three samples of each material, i.e. allogeneic material-1 and -2 as well as xenogeneic material-1, -2 and -3, were obtained commercially. After decalcification and standardized embedding processes, conventional histological staining was performed in order to detect inorganic matrix, cellular or organic matrix components. Allogeneic material-1 showed trabecular bone-like structures, which were free of cellular components as well as of organic matrix. The allogeneic material-2 showed trabecular bone structures, in which connective tissue and cellular remnants were embedded. Additionally, some connective tissue, which resembled fat-like tissue, was found within this material. The xenogeneic material-1 showed trabecular bone-like structures and contained organic components comparable to that demonstrated for the allogeneic material-2. The xenogeneic material-2 showed trabecular bone structures with single cells located in lacunae. The xenogeneic material-3 also showed trabecular structures. Neither cellular nor organic matrix components were found within this material. According to the data of the present study, the allogeneic material-1 and the xenogeneic material-3 were the only investigated materials for which the obtained histological data were in accordance with the manufactureŕs advertised information. The remaining three materials showed discrepancies—although the manufacturers of all five bone substitute materials stated that their blocks were free of organic/cellular remnants. These data are of great clinical and material science interest. It seems that even patented processing techniques are not always able to deliver reproducible materials. Although the manufacturers of all five bone blocks stated that their blocks were free of organic/cellular remnants, our histological analysis revealed that three out of five bone blocks did contain such remnants. Such specimens might be able to induce an immune response within the recipient.     

Reactive oxygen at the heart of metabolism

During heart development, the progression from a pluripotent, undifferentiated embryonic stem cell to a functional cardiomyocyte in the adult mammalian heart is characterised by profound changes in gene expression, cell structure, proliferative capacity and metabolism. Whilst the precise causal relationships between these processes are not fully understood, it is clear that the availability and cellular ability to utilise oxygen are critical effectors of cardiomyocyte differentiation and function during development. In particular, cardiomyocytes switch from a largely glycolytic-based production of ATP to predominantly β-oxidation of long-chain fatty acids to generate the cellular energy requirements. Whilst this transition occurs progressively during embryonic and foetal development, it is particularly abrupt over the period of birth. In the adult heart, many cardiopathologies are accompanied by a reversal to a more foetal-like metabolic profile. Understanding the mechanistic causes and consequences of the normal metabolic changes that occur during heart development and those in the pathological heart setting is crucial to inform future potential therapeutic interventions. It is becoming clear that reactive oxygen species (ROS) play critical roles in the regulation of redox-mediated molecular mechanisms that control cellular homoeostasis and function. ROS are generated as a consequence of metabolic processes in aerobic organisms. An overproduction of ROS, when not balanced by the cell's antioxidant defence mechanisms (termed “oxidative stress”), results in non-specific oxidation of proteins, lipids and DNA and is cytotoxic. However, the tightly regulated temporal and spatial production of ROS such as H₂O₂ acts to control the activity of proteins through specific post-translational oxidative modifications and is crucial to cellular function. We describe here the metabolic changes that occur in the developing heart and how they can revert in cardiopathologies. They are discussed in the light of what is currently known about the regulation of these processes by changes in the cellular redox state and levels of ROS production.     

Protective effect of gastrodin on bile duct ligation-induced hepatic fibrosis in rats

Gastrodin has been showed to possess many beneficial physiological functions, including protection against inflammation and oxidation and apoptosis. Studies showed inflammation and oxidation play important roles in producing liver damage and initiating hepatic fibrogenesis. However, it has not been reported whether gastrodin has a protective effect against hepatic fibrosis or not. This is first ever made attempts to test gastrodin against liver fibrosis in bile duct ligation (BDL) rats. The aim of the present study is to evaluate the effect of gastrodin on BDL-induced hepatic fibrosis in rats. BDL rats were divided into two groups, BDL alone group, and BDL-gastrodin group treated with gastrodin (5 mg/ml in drinking water). The effects of gastrodin on BDL-induced hepatic injury and fibrosis in rats were estimated by assessing serum, urine, bile and liver tissue biochemistry followed by liver histopathology (using hematoxylin & eosin and sirius red stain) and hydroxyproline content measurement. The results showed that gastrodin treatment significantly reduced collagen content, bile duct proliferation and parenchymal necrosis after BDL. The serum alanine aminotransferase (ALT) and serum aspartate aminotransferase (AST) decreased with gastrodin treatment by 15.1 and 23.6 percent respectively in comparison to BDL group did not receive gastrodin. Gastrodin also significantly increased the level of serum high density lipoprotein (HDL) by 62.5 percent and down-regulated the elevated urine total bilirubin (TBIL) by 56.5 percent, but had no effect on total bile acid (TBA) in serum, bile and liver tissues. The immunohistochemical assay showed gastrodin remarkably reduced the expressions of CD68 and NF-κB in BDL rats. Hepatic SOD levels, depressed by BDL, were also increased by gastrodin by 8.4 percent. In addition, the increases of hepatic MDA and NO levels in BDL rats were attenuated by gastrodin by 31.3 and 38.7 percent separately. Our results indicate that gastrodin significantly attenuated the severity of BDL-induced hepatic injury and fibrosis by attenuating oxidative stress and inflammation. Taken together, these findings suggest that gastrodin might be an effective antifibrotic drug in cholestatic liver disease.     

A new look at osteomyelitis development – Focus on CCR5delta32. Study in patients from Northeast Brazil

IntroductionCCR5 receptor exerts an important role in the host immune response. Osteomyelitis is an inflammatory process and Staphylococcus aureus is the principal causative agent of this bone injury complication. A deletion of 32 bp (CCR5Δ32) in the CCR5 gene seems to protect against HIV-1, S. aureus and other infections. However, the CCR5Δ32 allele has been associated with an increased risk for other diseases.ObjectiveTo investigate the function of CCR5 and to gather data about the relationship of the CCR5Δ32 mutation and the risk of developing osteomyelitis as a complication in patients with bone traumas.MethodsIn a study of 153 patients with bone traumas the presence of the CCRΔ32 mutation was determined by PCR.ResultsIn this study, the CCR5Δ32 allele was present only in the heterozygous form. Osteomyelitis was more frequent in the wild type carriers (94.87%; 37/39) and most of the CCR5Δ32 carriers (87.5%; 14/16) did not present with osteomyelitis.ConclusionThe CCR5Δ32 could be associated with protection against osteomyelitis caused by S. aureus, corroborating the data from Alonzo & Torres study, in which CCR5 receptor is required for S. aureus leukotoxin ED (LukED) cytotoxicity.     

CD146 as a new marker for an increased chondroprogenitor cell sub‐population in the later stages of osteoarthritis

Cartilage‐derived mesenchymal stem cells (MSCs) have been isolated with different methods. In this study lateral and medial femoral condyles were respectively collected from patients with late‐stage osteoarthritis during the total knee arthroplasty. After digestion of the cartilage tissues with type II collagenase and analysis by fluorescence‐activated cell sorting (FACS) with CD146, a chondroprogenitor cell sub‐population were isolated and purified. The expression of other MSC‐associated markers in the CD146⁺ chondroprogenitors was analyzed by flow cytometry. Multi‐lineage differentiation capacity of CD146⁺ chondroprogenitors was compared with that of unsorted chondrocytes and adipose‐derived MSCs (ADMSCs). Higher percentage of CD146⁺ chondroprogenitors isolated from the medial femoral condyles was observed than that from the lateral. CD146⁺ chondroprogenitors expressed high levels of MSC‐specific surface antigens, and showed higher chondrogenesis capacity than ADMSCs and unsorted chondrocytes in a 3D cell pellet culture model. Thus CD146 might be a new cell surface marker for cartilage progenitor cell population in the late‐stage osteoarthritis. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:84–91, 2015.