Use and efficacy of bone morphogenetic proteins in fracture healing

Signal transduction in aging related disease

Evaluation of a new immunoassay for cystatin C, based on a double monoclonal principle, in men with normal and impaired renal function.

BACKGROUND: Elevated cystatin C in blood reflects impaired glomerular filtration rate (GFR), but current cystatin C assays, based on polyclonal antibodies and immunoturbidimetric or nephelometric detection, have several limitations. We evaluated a new immunoassay based on monoclonal antibodies in samples from patients with and without chronic kidney disease (CKD). METHODS: The study enrolled 170 men without known CKD (Group A) and 104 men with CKD (Group B). All patients were assessed with iohexol clearance, plasma creatinine and plasma cystatin C by a conventional particle-enhanced immunoturbidimetric assay (PETIA) and by the new double monoclonal assay. In Group A, three serial blood draws were performed at median intervals of 4 h and 12 days between samples, to also allow assessments of the variability in cystatin C values with the new assay. Concordance correlation coefficients and the 95% limits of agreement were used to estimate the agreement of reciprocal cystatin C and reciprocal creatinine with iohexol clearance. RESULTS: Median iohexol clearance (mL/min/1.73 m(2)) was 81 [interquartile range (IQR) 70, 92] in Group A and 23 (IQR 16, 34) in Group B. The concordance correlation with GFR for the new cystatin C assay compared to the established assay was similar in Group A (0.441 versus 0.465) but higher in Group B (0.680 versus 0.593). Cystatin C measured by both assays exhibited closer agreement with GFR than creatinine. The agreement between the two cystatin C assays was high, with concordance correlations of 0.815 in Group A and 0.935 in Group B. Compared to the conventional assay, the new assay tended to yield lower values of cystatin C at the low end of the range in Group A. The new cystatin C assay exhibited small intraindividual variability across serial samples (coefficient of variation ≤ 6%). CONCLUSIONS: In this first clinical evaluation, the new cystatin C assay performed similarly to the established PETIA in patients with normal GFR and better in patients with CKD. The new assay may offer an alternative to current commercial assays to detect and monitor impaired kidney function

Application of BMP-7 to tibial non-unions: a 3-year multicenter experience.

SUMMARY: The effective treatment of the often debilitating, longlasting and large-asset-consuming complication of fracture non-unions has been in the centre of scientific interest the last decades. The use of alternative bone substitutes to the gold standard of autologous graft includes the osteoinductive molecules named bone morphogenetic proteins (BMPs). A multicenter registry and database (bmpusergroup.co.uk) focused on the application of BMP-7/OP-1 was created in December 2005. We present the preliminary results, using the prospective case-series of aseptic tibial non-unions as an example. Sixty-eight patients fulfilled the inclusion criteria for this observational study, with a minimum follow-up of 12 months. The median duration of tibial non-union prior to BMP-7 application was 23 months (range 9-317 mo). Patients had undergone a median of 2 (range 0-11) revision procedures prior to the administration of BMP-7. In 41\% the application of BMP-7 was combined with revision of the fixation at the non-union site. Non-union healing was verified in 61 (89.7\%) in a median period of 6.5 months (range 3-15 mo). No adverse events or complications were associated with BMP-7 application. The safety and efficacy of BMP-7 was verified in our case series, and was comparable to the existing evidence. The establishment of multicenter networks and the systematic and long-term follow- up of these patients are expected to provide further information and significantly improve our understanding of this promising osteoinductive bone substitute

Serum cystatin C and prediabetes in non-obese US adults

10.1007/s10654-013-9781-3European Journal of Epidemiology284311-316EJEP

RhBMP-7 for the Treatment of nonunion of fractures of long bones

We report the outcome of 84 nonunions involving long bones which were treated with rhBMP-7, in 84 patients (60 men: 24 women) with a mean age 46 years (18 to 81) between 2003 and 2011. The patients had undergone a mean of three previous operations (one to 11) for nonunion which had been present for a mean of 17 months (4 months to 20 years). The nonunions involved the lower limb in 71 patients and the remainder involved the upper limb. A total of 30 nonunions were septic. Treatment was considered successful when the nonunion healed without additional procedures. The relationship between successful union and the time to union was investigated and various factors including age and gender, the nature of the nonunion (location, size, type, chronicity, previous procedures, infection, the condition of the soft tissues) and type of index procedure (revision of fixation, type of graft, amount of rhBMP-7) were analysed. The improvement of the patients' quality of life was estimated using the Short Form (SF) 12 score. A total of 68 nonunions (80.9%) healed with no need for further procedures at a mean of 5.4 months (3 to 10) post-operatively. Multivariate logistic regression analysis of the factors affecting union suggested that only infection significantly affected the rate of union (p = 0.004).Time to union was only affected by the number of previous failed procedures (p = 0.006). An improvement of 79% and 32.2% in SF-12 physical and mental score, respectively, was noted within the first post-operative year. Rh-BMP-7 combined with bone grafts, enabled healing of the nonunion and improved quality of life in about 80% of patients. Aseptic nonunions were much more likely to unite than septic ones. The number of previous failed operations significantly delayed the time to union. © 2015 The British Editorial Society of Bone & Joint Surgery