Assessment of plasma BMP-2, BMP-7, BMP-10, vitamin D, and TGF ß1 in simple fractures among Sudanese patients.

BACKGROUND: Bone morphogenetic proteins (BMP) are multifunctional proteins. They work as cytokines regulating osteogenesis during fracture healing process. The objectives of this study were to assess changes in BMPs during fracture and their correlations to Fracture's healing. METHODS: Case-Control hospital-based study conducted from January 2018 to January 2019. Demographic data, anthropometric measurements, and blood samples were collected from patients and controls (18-65 years old). Plasma concentrations of selected BMPs and vitamin D were measured using quantitative enzyme linked immunosorbent assay (ELISA). SPSS version 25 was used to calculate frequencies, Pearson correlation tests, chi-square and unpaired t-test. RESULTS: Sixty-five patients with fractures and Sixty-five controls were studied. Means of plasma concentrations were (TGFß1 = 21.07 ng/ml ±8.49 and 19.8 ng/ml ±7.2) (BMP-2 = 76.3 pg/ml ± 156.6 and 55.5 ng/ml ± 127.9) (BMP-7 = 13.02 pg/ml ±43.5 and 64.6pg/ml ±250) (BMP-10 = 8.14 pg/ml ±12.7 and 5.48 pg/ml ±11.3) (Vitamin D mean was 24.94 ng/ml ±13.2 and 26.2 ng/ml ±11.6) in patients and controls, respectively. Forty-five subjects were enrolled into follow up study: 30 males, 15 females. Healing time mean was 4.13± 2.6 months. No significant correlation between BMP-2/BMP-7 with healing time. CONCLUSIONS: BMP-7 was significantly lowers in the plasma of patients that controls (P = 0.042). Low Vitamin D was observed among Sudanese participants.

Changes in bone formation regulator biomarkers in early axial spondyloarthritis.

OBJECTIVE: The hallmark of advanced axial SpA (axSpA) is spine ankylosis due to excessive ectopic bone formation. This prospective study aimed to describe the changes in serum levels of different regulators [sclerostin, dickkopf-1 (DKK-1)] and markers of bone formation [bone morphogenetic protein 7 (BMP-7)] over 5 years in early axSpA patients and to assess determinants of such changes. METHODS: The DEvenir des Spondyloarthropathies Indifférenciées Récentes cohort is a prospective, multicentre French study of 708 patients with early (>3 months-<3 years) inflammatory back pain suggestive of axSpA. Serum levels of BMP-7, sclerostin and DKK-1 were assessed at baseline and after 2 and 5 years. Changes in bone formation regulators over time were analysed using mixed linear models. RESULTS: Serum BMP-7 significantly increased over time, with a median relative change of 223.7% [interquartile range (IQR) 0-10 700 (0.17 pg/ml/month), P < 0.001]. Serum sclerostin significantly increased over time, with a median relative change of 14.8% [IQR -7.9-41.4% (0.001 ng/ml/month), P < 0.001]. Serum DKK-1 did not significantly change over time. Serum BMP-7 increased over time in active disease (Ankylosing Spondylitis Disease Activity Score with CRP ≥1.3, P = 0.01), but the increase was less pronounced with TNF inhibitor (TNFi) use (P < 0.001). No determinant was associated with serum sclerostin change. CONCLUSION: Serum BMP-7 change over 5 years was related with inflammation; it was increased in active disease, but the increase was low with TNFi use. Serum sclerostin levels significantly increased over time, but to a lesser degree than for serum BMP-7. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/, NCT01648907.

Efecto regulador de paricalcitol sobre parámetros inflamatorios, fibróticos y anticalcificantes en el paciente con enfermedad renal crónica. Más allá de la regulación de la enfermedad óseo-mineral / Paricalcitol regulatory effect on inflammatory, fibrotic and anticalcificating parameters in renal patiente. Far beyond mineral bone disease regulation

ANTECEDENTES: La principal causa de morbimortalidad en el paciente con enfermedad renal crónica (ERC) es la cardiovascular. La inflamación y las alteraciones en el metabolismo óseo-mineral en estos pacientes conllevan aumento del riesgo cardiovascular. OBJETIVOS: Valorar el papel de paricalcitol sobre distintos parámetros séricos relacionados con inflamación, fibrosis y enfermedad óseo-mineral en la ERC. MATERIAL Y MÉTODOS: Estudio prospectivo, no controlado en 46 pacientes con ERC estadios III-V sin diálisis, con niveles elevados de paratohormona, según su estadio de ERC, por lo que se introdujo tratamiento con el análogo de vitamina D paricalcitol. Durante 4 meses de tratamiento valoramos los parámetros clásicos y novedosos del metabolismo óseo-mineral en suero (calcio, fósforo, paratohormona, factor de crecimiento fibroblástico-23 [FGF-23], Klotho y calcidiol) y parámetros relacionados con el proceso de inflamación-fibrosis y anticalcificantes (interleucina-6 y 10, factor de necrosis tumoral alfa [TNF-a], factor de crecimiento transformante beta [TGF-b], proteína ósea morfogénica-7 [BMP-7], y fetuína-A). RESULTADOS: Tras el uso de paricalcitol los niveles de Klotho aumentaron (p = 0,001) y los de FGF-23 se mantuvieron estables al igual que los de calcio y fósforo; calcidiol aumentó de forma significativa (p = 0,010) y paratohormona descendió (p = 0,002). Los parámetros de inflamación, fibrosis y calcificación mostraron una regulación benigna con descenso significativo de interleucina-6 (p = 0,001), TNF-alfa (p = 0,005) y TGF-β (p = 0,001) y aumento de BMP-7 (p = 0,001), fetuína-A (p = 0,001) e interleucina-10 (p = 0,001). El filtrado glomerular y la proteinuria se mantuvieron estables. CONCLUSIONES: El tratamiento con paricalcitol en el paciente renal sin diálisis parece ser beneficioso en la regulación de los parámetros inflamatorios y anticalcificantes, preservando la función renal y el eje óseo-mineral. Los marcadores elegidos en nuestro estudio podrían indicarnos un efecto positivo de paricalcitol a nivel vascular

BACKWARD: Cardiovascular events are the major cause of morbidity and mortality in patients with chronic kidney disease (CKD). Inflammation and mineral-bone disorder are pathological conditions that have been associated with an increased cardiovascular risk. OBJECTIVE: Show paricalcitol regulation overinflammatory, fibrotic and mineral disorder parameters in CKD. MATERIAL AND METHODS: Prospective Study in 46 CKD stages III-V patients without dialysis patients whith elevated parathormone in which we introduced paricalcitol. We evaluated classic and newest mineral and bone metabolism serum parameters (calcium, phosphorus, parathormone, fibroblast growth factor-23 [FGF-23], Klotho, calcidiol), inflammatory-fibrosis and anticalcifying parameters (interleukin-6 and 10, tumor necrosis factor-a [TNF- alfa], transforming growth factor-b [TGF-β],bone morphogenic protein-7 [BMP-7] and fetuin-A) for four months. RESULTS: At the end of study soluble Klotho increased (p = .001), FGF-23 remained stable, calcium and phosphorus levels were not increased, calcidiol increased (p = .010) and PTH decreased (p = .002). Inflammation-fibrosis and calcification parameters showed positive regulation after paricalcitol treatment: interleukin-6 decreased significantly (p = .001) and also TNF-alfa did (p = .005), on the contrary, interleukin-10 and fetuin-A increased (p = .001 for both). Anti-fibrosis marker BMP-7 increased (p = .001) and TGF-b decreased (p = .001). We did not find significant changes in renal function. CONCLUSIONS: Paricalcitol treatment might be profitable in regulating inflammatory and anticalcificant parameters, unmodified calcium or phosphorus seric levels and preserving kidney function in renal patients with no dialysis. Our selected parameters could indicate paricalcitol effects in mineral and endothelial disorder related to renal disease

Paricalcitol regulatory effect on inflammatory, fibrotic and anticalcificating parameters in renal patiente. Far beyond mineral bone disease regulation. / Efecto regulador de paricalcitol sobre parámetros inflamatorios, fibróticos y anticalcificantes en el paciente con enfermedad renal crónica. Más allá de la regulación de la enfermedad óseo-mineral.

BACKWARD: Cardiovascular events are the major cause of morbidity and mortality in patients with chronic kidney disease (CKD). Inflammation and mineral-bone disorder are pathological conditions that have been associated with an increased cardiovascular risk. OBJECTIVE: Show paricalcitol regulation overinflammatory, fibrotic and mineral disorder parameters in CKD. MATERIAL AND METHODS: Prospective Study in 46 CKD stages III-V patients without dialysis patients whith elevated parathormone in which we introduced paricalcitol. We evaluated classic and newest mineral and bone metabolism serum parameters (calcium, phosphorus, parathormone, fibroblast growth factor-23 [FGF-23], Klotho, calcidiol), inflammatory-fibrosis and anticalcifying parameters (interleukin-6 and 10, tumor necrosis factor-a [TNF- α], transforming growth factor-b [TGF-ß],bone morphogenic protein-7 [BMP-7] and fetuin-A) for four months. RESULTS: At the end of study soluble Klotho increased (p=.001), FGF-23 remained stable, calcium and phosphorus levels were not increased, calcidiol increased (p=.010) and PTH decreased (p=.002). Inflammation-fibrosis and calcification parameters showed positive regulation after paricalcitol treatment: interleukin-6 decreased significantly (p=.001) and also TNF-α did (p=.005), on the contrary, interleukin-10 and fetuin-A increased (p=.001 for both). Anti-fibrosis marker BMP-7 increased (p=.001) and TGF-b decreased (p=.001). We did not find significant changes in renal function. CONCLUSIONS: Paricalcitol treatment might be profitable in regulating inflammatory and anticalcificant parameters, unmodified calcium or phosphorus seric levels and preserving kidney function in renal patients with no dialysis. Our selected parameters could indicate paricalcitol effects in mineral and endothelial disorder related to renal disease.

Noninvasive method of differentiating diabetic nephropathy and nondiabetic renal disease using serum bone morphogenetic protein-7 and transforming growth factor-beta 1 levels in patients with type-2 diabetes mellitus.

Diabetic nephropathy (DN), one of the major complications of diabetes mellitus, is diagnosed by the presence of pedal edema, 24-h proteinuria >300 mg/day, and retinopathy. However, in view of variable clinical presentations and deviation from the above-said clinical features, it has become difficult to diagnose DN or the presence of nondiabetic renal disease (NDRD). Many biomarkers have been identified which could predict the progression of DN. Despite such advancement in science, it is still difficult to differentiate between DN and NDRD. Diabetes is a state of chronic inflammation. Among the pro-inflammatory cytokines, it has been shown that transforming growth factor-beta (TGF-ß) and bone morphogenetic protein-7 (BMP-7) play a key role in the development and progression of DN. We assessed whether the levels of serum BMP-7 and TGF-ß can help differentiate between DN and NDRD, thus serving as surrogate markers of DN.

Comparison of Sofosbuvir Plus Ribavirin Treatment with Pegylated Interferon Plus Ribavirin Treatment for Chronic Hepatitis C Genotype 2.

BACKGROUND: Sofosbuvir plus ribavirin (RBV) therapy showed higher sustained virological response at 12 weeks after treatment (SVR12) than pegylated interferon (peg-IFN) plus RBV; however, liver function, fibrosis, and hepatocellular carcinoma markers have not been assessed so far. SUMMARY: Patients (n = 21) receiving Sofosbuvir plus RBV and those (n = 24) receiving peg-IFN plus RBV were enrolled in this study. Changes in alanine aminotransferase (ALT) and α-fetoprotein (AFP) levels, platelet (PLT) counts, FIB-4, and aspartate aminotransferase-to-platelet ratio index (APRI) in both groups were assessed in patients achieving SVR12. Also, fibrosis regression was assessed using pathophysiological biomarkers, such as hyaluronic acid, bone morphogenetic protein 7 (BMP-7), and connective tissue growth factor (CTGF) in the Sofosbuvir plus RBV group. In both groups, while the reduction in ALT levels was significant that of AFP was not. Compared with the baseline, although serum PLT count at the end of treatment (EOT) was significantly higher in the Sofosbuvir plus RBV group, it was significantly lower in the peg-IFN plus RBV group. Although a significant decline in fibrosis markers such as FIB-4 and APRI was observed between the baseline and at EOT in the Sofosbuvir plus RBV group, no significant change of these markers was observed in the peg-IFN plus RBV group. Moreover, BMP-7 and CTGF were significantly lower at EOT than the baseline in the Sofosbuvir plus RBV group. Key Message: The treatment with Sofosbuvir plus RBV results in not only a higher SVR, but also improves the liver function and the degree of fibrosis.

Synergic Impact of Vascular Calcification and Low Autonomic Tone in Mortality of Hemodialysis Patients.

BACKGROUND: Both cardiovascular calcification and autonomic dysfunction are frequently encountered in hemodialysis patients. We aimed to investigate the relationship between cardiovascular calcification and heart rate variability (HRV) and their influence on long-term outcome. METHODS: Seventy-eight hemodialysis patients underwent echocardiogram and radiography of the pelvis and hands to identify valvular and vascular calcification. HRV was evaluated using a commercial machine. RESULTS: Based on the average, the patients were divided into higher and lower subgroups of high frequency (HF) and low frequency (LF) respectively. Patients with higher LF were younger and were found to have a lower proportion of diabetes. Their hemoglobin, albumin, and bone morphogenic protein (BMP)-7 levels were significantly higher and both high-sensitive C-reactive protein (hs-CRP) and osteoprotegerin levels were lower (all p < 0.05). In patients of the higher HF group, the proportion of diabetes was lower but they were found to have higher levels of BMP-7 and lower levels of hs-CRP, interleukin-6 (all p < 0.05). Significantly higher LF and HF were noted in patients without vascular calcification, but only hand artery (HA) calcification was negatively correlated with both LF and HF in multivariate analysis. Low LF and high hs-CRP were the independent predictors of mortality. Coexistence of low LF band and HA calcification was associated with the worse outcome. CONCLUSIONS: Abnormal autonomic nervous function was closely related to inflammation and mortality in hemodialysis patients. Calcification of HA was associated with autonomic dysfunction and patients with lower autonomic tone and HA calcification had the highest mortality rate in this population.

Bone morphogenetic protein-7 (BMP-7) augments insulin sensitivity in mice with type II diabetes mellitus by potentiating PI3K/AKT pathway.

A direct link between development of insulin resistance and the presence of chronic inflammation, in case of obesity exists, with cytokines playing an important role in glucose metabolism. Members of TGF-ß superfamily, including bone morphogenetic proteins (BMPs), have been shown to be involved in islet morphogenesis, establishment of ß-cell mass and adipose cell fate determination. Here, we demonstrate a novel and direct role of BMP-4 and -7 in the regulation of glucose homeostasis and insulin resistance. An age-dependent increase in serum BMP-4 and decrease in serum BMP-7 levels was observed in animal models of type II diabetes. In this study, BMP-7 and -4 have been demonstrated to have antagonistic effects on insulin signaling and thereby on glucose homeostasis. BMP-7 augmented glucose uptake in the insulin sensitive tissues such as the adipose and muscle by increasing Glut4 translocation to the plasma membrane through phosphorylation and activation of PDK1 and Akt, and phosphorylation and translocation of FoxO1 to the cytoplasm in liver/HepG2 cells. Restoration of BMP-7 levels in serum of diabetic animals resulted in decreased blood glucose levels in contrast to age matched untreated control groups, opening up a new therapeutic avenue for diabetes. On the contrary, BMP-4 inhibited insulin signaling through activation of PKC-θ isoform, and resulted in insulin resistance through the attenuation of insulin signaling. BMP-7 therefore is an attractive candidate for tackling a multifaceted disease such as diabetes, since it not only reduces body fat, but also strengthens insulin signaling, causing improved glucose uptake and ameliorating peripheral insulin resistance. © 2017 BioFactors, 43(2):195-209, 2017.

Serum Heme Oxygenase-1 and BMP-7 Are Potential Biomarkers for Bone Metabolism in Patients with Rheumatoid Arthritis and Ankylosing Spondylitis.

Backgrounds. Heme oxygenase-1 (HO-1) has been reported to play a regulatory role in osteoclastogenesis. Bone morphogenetic protein (BMP) pathways induce osteoblastic differentiation and bone remodeling. Aims. To identify serum levels of HO-1, BMP-7, and Runt related-transcription factor 2 (Runx2) in patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS) and to investigate the relationships between HO-1, BMP-7, Runx2, and other common biomarkers for bone metabolism. Results. Serum levels of HO-1 and BMP-7 were revealed to be significantly higher in patients with RA or AS than in healthy controls (p < 0.01). In RA group, HO-1 was positively correlated with BMP-7, Runx2, and tartrate-resistant acid phosphatase-5b (TRAP-5b) (p < 0.05, resp.), BMP-7 was positively correlated with Runx2 and TRAP-5b (p < 0.05, resp.), and Runx2 was negatively correlated with N-terminal midfragment of osteocalcin (NMID) (p < 0.05). In AS group, we observed identical correlation between HO-1 and BMP-7, but opposite correlations between BMP-7 and TRAP-5b and between Runx2 and NMID, when comparing with the RA cohort. Conclusion. Our findings suggest that HO-1 and BMP-7 are potential biomarkers for bone metabolism in patients with RA and AS. The different correlations between the bone markers point to distinct differences in bone remodeling pathways in the two types of arthritis.

Elevated Levels of Circulating Bone Morphogenetic Protein 7 Predict Mortality in Pulmonary Arterial Hypertension.

BACKGROUND: This study aimed to show whether circulating bone morphogenetic proteins (BMPs) levels are associated with increased risk of mortality in patients with pulmonary arterial hypertension (PAH). METHODS: A total of 156 patients with PAH including 43 with heritable PAH (HPAH) and 113 with idiopathic PAH (IPAH) diagnosed by gene screening were enrolled in the study. Circulating BMPs were measured by ELISA in plasma samples from patients with HPAH (n = 43) and IPAH (n = 113) and from control subjects (n = 51). Clinical characteristics at baseline and long-term survival were compared according to the different BMP levels. RESULTS: Patients with HPAH had significantly higher BMP7 concentrations than patients with IPAH and control subjects (20.1 [interquartile range (IQR), 9.4, 55.2] vs 6.5 [IQR, 3.5, 11.7] and 2.5 [IQR, 0.9, 6.6] pg/mL, respectively; P < .001). Elevated plasma BMP7 were associated with a higher risk of mortality after adjustment for sex, 6-minute walk distance, mean right atrial pressure, mean pulmonary arterial pressure, pulmonary vascular resistance, and cardiac output (HR, 1.904; 95% CI, 1.021-3.551; P = .043). Patients with IPAH with a BMP7 level > 7.85 pg/mL had a higher risk of mortality than those with a low BMP7 concentration (P = .042, log-rank test). CONCLUSIONS: Levels of circulating BMP7 correlate with mortality in PAH, and may be a predictor of disease in patients with HPAH and IPAH.

[Expression profile of TGF-ß1 and BMP-7 in serum of preterm infants with respiratory distress syndrome].

OBJECTIVE: To study the expression profile and significance of serum transforming growth factor-beta 1 (TGF-ß1) and bone morphogenetic protein-7 (BMP-7) in preterm infants with respiratory distress syndrome (RDS). METHODS: Thirty-two preterm infants with RDS who were given pulmonary surfactant (PS) within 12 hours after birth were enrolled as the PS group. Twenty-eight preterm infants with RDS who were not given PS were selected as the non-PS group. Another 30 preterm infants without RDS were used as the control group. Serum levels of TGF-ß1 and BMP-7 in the three groups were measured using enzyme-linked immunosorbent assay at 0, 1, 3, and 7 days after birth. RESULTS: The PS group had higher serum levels of TGF-ß1 than the control group at 1 and 3 days after birth (P<0.05). The non-PS group had significantly higher serum levels of TGF-ß1 than the control group at 1, 3, and 7 days after birth (P<0.05), and serum levels of TGF-ß1 in the non-PS group were significantly higher than the PS group at 3 and 7 days after birth (P<0.05). The PS group had higher serum levels of BMP-7 than the control group at 1 and 3 days after birth (P<0.05). The non-PS group had higher serum levels of BMP-7 than the control group at 1, 3, and 7 days after birth (P<0.05). The levels of BMP-7 in the non-PS group at 7 days after birth were reduced than before, but were still higher than in the PS group (P<0.05). CONCLUSIONS: Both serum TGF-ß1 and BMP-7 levels increase in the early stage in preterm infants with RDS, however, in the late stage, the expression of BMP-7 decreases with the increase in TGF-ß1 expression, suggesting that administration of exogenous BMP-7 may reduce the expression of TGF-ß1, which might be a therapeutic approach for RDS in preterm infants.

Evaluation of shear wave velocity and human bone morphogenetic protein-7 for the diagnosis of diabetic kidney disease.

PURPOSE: The aim of this study was to determine the diagnostic values of kidney shear wave velocity (SWV) and bone morphogenetic protein-7 (BMP-7), and their correlation in the diagnosis of early diabetic kidney disease. METHODS: A total of 150 patients with type 2 diabetes mellitus were divided into three equal groups based on the urinary albumin-creatinine ratio (ACR): normal albuminuria (normo- group, ACR < 30 mg/g creatinine, n = 50), microalbuminuria (micro- group, 30 ≤ ACR < 300 mg/g creatinine, n = 50), and macroalbuminuria (macro- group, ACR ≥ 300 mg/g creatinine and estimated glomerular filtration rate (eGFR) ≥30 ml/min/1.73 m2, n = 50). Fifty healthy volunteers were recruited to serve as controls (control group). The levels of serum BMP-7 were detected, and virtual touch tissue quantification was used to detect the renal SWV value in all study subjects. Correlations between groups as well as SWV and BMP-7 were analyzed. RESULTS: Serum BMP-7 and SWV were significantly and progressively decreased and increased, respectively, during the development of renal disease, from the normo- to the micro- and to the macro- groups (all P < 0.01 between each other for BMP-7 and SWV). Moreover, no significant differences between the normo- and control groups were observed for either BMP-7 or SWV (both P > 0.05). In addition, a significant correlation was found between SWV and BMP-7, with a coefficient of -0.569 (P < 0.05). CONCLUSION: The determination of SWV together with serum BMP-7 may play an important role in the diagnosis of diabetic kidney disease.

Fetuin-A is related to syndesmophytes in patients with ankylosing spondylitis: a case control study.

OBJECTIVES: New bone formation is one of the hallmark characteristics of ankylosing spondylitis, which is thereby associated with syndesmophytes. Fetuin-A is a molecule that is abundantly found in calcified tissues and it shows high affinity for calcium phosphate minerals and related compounds. Considering the role of fetuin-A in the regulation of calcified matrix metabolism, we compared the fetuin-A levels in ankylosing spondylitis patients with syndesmophytes with those in patients without syndesmophytes and in healthy controls. We also studied other biomarkers that are thought to be related to syndesmophytes. METHODS: Ninety-four patients (49 patients without syndesmophytes, 67.3% male, 40.7±8.7 years; 45 patients with syndesmophytes, 71.1% M, 43.9±9.9 years) and 68 healthy controls (44.2±10.6 years and 70.6% male) were included in this study. Syndesmophytes were assessed on the lateral radiographs of the cervical and lumbar spine. The serum levels of fetuin-A, dickkopf-1, sclerostin, IL-6, high-sensitivity C-reactive protein and bone morphogenetic protein-7 were measured with an enzyme-linked immunosorbent assay. RESULTS: Patients with syndesmophytes had significantly higher levels of fetuin-A compared with patients without syndesmophytes and controls (1.16±0.13, 1.05±0.09 and 1.08±0.13 mg/ml, respectively). However, fetuin-A was not different between the patients without syndesmophytes and controls. Bone morphogenetic protein-7 was significantly lower; dickkopf-1 was significantly higher in patients with ankylosing spondylitis compared with controls. The sclerostin concentrations were not different between the groups. In regression analysis, fetuin-A was an independent, significant predictor of syndesmophytes. CONCLUSION: Our results suggest that fetuin-A may a role in the pathogenesis of bony proliferation in ankylosing spondylitis.

The importance and the differences of bone morphogenetic proteins for osteoporotic hip fractures.

Bone morphogenetic proteins (BMPs), major contributors to tissue repair, have become one of the most exciting fields in rheumatic and orthopaedic research. In our study we aimed to evaluate the relationship between osteoporotic hip fractures and the serum levels of BMPs to reveal their potential roles in the diagnosis of patients. The study group included 62 patients with osteoporotic hip fracture (Group 1; intertrochanteric fracture, Group 2; collum femoris fracture) and the control group. All fractures were due to low energy trauma, simple falls. For all subjects BMD measurements were in agreement for osteoporosis and no significant differences were observed between the two fracture groups. Biochemical markers; BMP-4 and BMP-7 (pg/mL) were determined by commercial Elisa kits from the serum samples. The mean and standard error values of serum samples for BMP-4 and BMP-7 in Group 1 (100.70 +/- 10.03, 74.41 +/- 6.31 respectively) and in Group 2 (112.34 +/- 11.52, 81.91 +/- 10.14 respectively) were not statistically different however for both groups only BMP-7 values increased statistically when compared to the control group. BMP-7 measurements may not only serve as potential biochemical markers for determining disease severity but also the increased levels, an osteogenic factor and bone stimulating agent in vivo, after trauma elevated levels are adaptive or protective and therefore may reduce the severity of the fracture.

Effect of tumour necrosis factor-α inhibitor on serum level of dickkopf-1 protein and bone morphogenetic protein-7 in ankylosing spondylitis patients with high disease activity.

OBJECTIVES: To examine changes in serum levels of the bone remodelling molecules dickkopf-1 (Dkk-1), sclerostin, wingless-type protein-3a (Wnt-3a), and bone morphogenetic protein-7 (BMP-7) during 6 months of anti-tumour necrosis factor (anti-TNF) treatment in ankylosing spondylitis (AS) patients with high disease activity. METHOD: We included 40 patients with axial AS: 20 patients with high disease activity were assigned to treatment with TNF inhibitor and 20 with low disease activity were assigned to non-steroidal anti-inflammatory drug (NSAID) treatment. Markers of bone remodelling and inflammation were assessed at baseline and after 6 months. RESULTS: In the TNF inhibitor-treated group Dkk-1 decreased significantly from 196.8 pg/mL [95% confidence interval (CI) 94.1-399.0] to 116.3 pg/mL (95% CI 38.0-301.6) and BMP-7 increased significantly from 1.4 pg/mL (95% CI 0-23.0) to 20.3 pg/mL (95% CI 4.9-41.3). There was a significant negative correlation between Dkk-1 and BMP-7 at 6 months (r = -0.64, p = 0.004) in this group. Non-parametric regression analysis adjusted for disease duration, age, sex, baseline modified Stoke's Ankylosing Spondylitis Spine Score (mSASSS), and baseline C-reactive protein (CRP) confirmed a statistically significant effect of treatment on time-related changes of Dkk-1 and BMP-7. Erythrocyte sedimentation rate (ESR), CRP, and also the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score decreased significantly in the anti-TNF-treated group. CONCLUSIONS: Among the potential biomarkers of bone remodelling in AS, Dkk-1 and BMP-7 displayed significant time alterations and correlative interactions during anti-TNF treatment.

Biomarkers of vascular calcification and mortality in patients with ESRD.

BACKGROUND: Vascular calcification is common among patients undergoing dialysis and is associated with mortality. Factors such as osteoprotegerin (OPG), osteopontin (OPN), bone morphogenic protein-7 (BMP-7), and fetuin-A are involved in vascular calcification. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: OPG, OPN, BMP-7, and fetuin-A were measured in blood samples from 602 incident dialysis patients recruited from United States dialysis centers between 1995 and 1998 as part of the Choices for Healthy Outcomes In Caring for ESRD Study. Their association with all-cause and cardiovascular mortality were assessed using Cox proportional hazards models adjusted for demographic characteristics, comorbidity, serum phosphate, and calcium. An interaction with diabetes was tested because of its known association with vascular calcification. Predictive accuracy of selected biomarkers was explored by C-statistics in nested models with training and validation subcohorts. RESULTS: Higher OPG and lower fetuin-A levels were associated with higher mortality over up to 13 years of follow-up (median, 3.4 years). The adjusted hazard ratios (HR) for highest versus lowest tertile were 1.49 (95% confidence interval [95% CI], 1.08 to 2.06) for OPG and 0.69 (95% CI, 0.52 to 0.92) for fetuin-A. In stratified models, the highest tertile of OPG was associated with higher mortality among patients without diabetes (HR, 2.42; 95% CI, 1.35 to 4.34), but not patients with diabetes (HR, 1.26; 95% CI, 0.82 to 1.93; P for interaction=0.001). In terms of cardiovascular mortality, higher fetuin-A was associated with lower risk (HR, 0.85 per 0.1 g/L: 95% CI, 0.75 to 0.96). In patients without diabetes, higher OPG was associated with greater risk (HR for highest versus lowest tertile, 2.91; 95% CI, 1.06 to 7.99), but not in patients with diabetes or overall. OPN and BMP-7 were not independently associated with outcomes overall. The addition of OPG and fetuin-A did not significantly improve predictive accuracy of mortality. CONCLUSIONS: OPG and fetuin-A may be risk factors for all-cause and cardiovascular mortality in patients undergoing dialysis, but do not improve risk prediction.

Bone morphogenetic protein-7 and disease progression in renal amyloidosis patients.

INTRODUCTION: Chronic kidney disease (CKD) is an important health care problem with increasing incidence. Early diagnosis, recognition and interventions to avoid the disease progression have great value. Even some risk factors for disease progression have been described; there are still some dark spots. Transforming growth factors (TGFs), particularly bone morphogenetic protein-7 (BMP7) take place in renal fibrosis. Our study aimed to evaluate the association between serum BMP7 levels and the progression of CKD. MATERIALS AND METHODS: Our study has been conducted between January 2008 and December 2010. Decrease in GFR by 10%, doubling of serum creatinine and need for renal replacement therapy have been set as progression end-points. Totally 93 patients (48 female, 45 male) have been included. Baseline and end of follow-up BMP7 levels have been measured. RESULTS: At the end of the follow-up, 46 of 93 patients have been considered as having progressive CKD. Higher levels of serum BMP7 levels have been found to be associated in progressive kidney disease. DISCUSSION: Our results showed that BMP7 levels were higher in patients with progressive CKD, and also BMP7 to be associated with CKD progression. But this relationship was not statistically significant. In patients with progressive CKD, higher levels of proteinuria and blood pressure have been previously described. The effect of BMP7 on kidneys is not still clear, it is hypothesized that TGF-beta1 inhibition may alter renal fibrosis.

Prediction of renal end points in chronic kidney disease.

Estimated glomerular filtration rate and albuminuria are dominant clinical predictors of renal outcomes in chronic kidney disease. Wong and collaborators report that BMP-7 and transforming growth factor-ß1 improve risk discrimination for renal end points in type 2 diabetes. However, to develop predictive models, clearly defined, clinically meaningful, validated end points must be used. End-stage renal disease and kidney transplantation remain the most definitive renal end points, whereas doubling of serum creatinine and death from renal disease lack rigor.

Serum levels of BMP-2, 4, 7 and AHSG in patients with degenerative joint disease requiring total arthroplasty of the hip and temporomandibular joints.

To date, there is no objective or reliable means of assessing the severity of degenerative joint disease (DJD) and need for joint replacement surgery. Hence, it is difficult to know when an individual with DJD has reached a point where total arthroplasty is indicated. The purpose of the present study is to determine whether serum levels of Alpha-2 HS-glycoprotein (AHSG) as well as bone morphogenetic proteins (BMP-2, 4, 7) can be used to predict the presence of severe DJD of the hip and/or temporomandibular joint (TMJ) (specifically: joints that require replacement). A total of 30 patients scheduled for arthroplasty (diseased) (15 HIP, 15 TMJ) and 120 age-matched controls (healthy/non-diseased) were included. Blood samples were collected from all patients ≥8 weeks after the last arthroplasty. Concentrations of serum analytes were measured using enzyme-linked immunosorbent assays, and these were compared between the Diseased and Healthy groups, utilizing the Mann-Whitney U-test. Patients with disease had significantly higher levels of BMP-2 and BMP-4 and lower levels of AHSG in serum compared to non-diseased humans (p < 0.01). Higher levels of BMP-2, 4 and reduced levels of AHSG appear to characterize patients who have DJD that is severe enough to require total joint replacement. Perhaps measurements of these proteins can be used to make objective decisions regarding the need for total arthroplasty as opposed to the current subjective approaches.

Circulating bone morphogenetic protein-7 and transforming growth factor-ß1 are better predictors of renal end points in patients with type 2 diabetes mellitus.

Albuminuria and a reduced glomerular filtration rate are conventional predictors of a future decline in kidney function in patients with type 2 diabetes mellitus. Using a nested case-control study we assessed whether circulating transforming growth factor-ß1 (TGF-ß1) and bone morphogenetic protein-7 (BMP-7) levels more accurately predict renal end points than the conventional markers. Cases were defined as those who developed a renal end point (doubling of serum creatinine to at least 200 µmol/l, the need for renal replacement therapy, or death due to renal disease) during the study. Using propensity scoring, two controls were selected for each of 281 cases. Participants who developed renal end points had significantly higher total TGF-ß1, lower BMP-7 levels, and a higher total TGF-ß1 to BMP-7 ratio at baseline. A graded increase in risk was found in individuals with lower BMP-7 levels (odds ratio 24.07, for the lowest to the highest tertile), or significantly higher TGF-ß1 levels (odds ratio for the highest to the lowest tertile, 8.43). The area under the receiver operating characteristic curve (c-statistic) for the conventional predictors was 0.73. Using BMP-7 and total and active TGF-ß1, the c-statistic was 0.94 (significantly higher to conventional predictors). Thus, our results suggest these novel kidney markers are better predictors of renal progression than the conventional predictors in patients with type 2 diabetes mellitus.