Isolated olecranon fractures in children affected by osteogenesis imperfecta type I treated with single screw or tension band wiring system: outcomes and pitfalls in relation to bone mineral density

The purpose of this study is to compare the results of 2 techniques, tension band wiring (TBW) and fixation with screws, in olecranon fractures in children affected with osteogenesis imperfecta (OI) type I. Between 2010 and 2014, 21 olecranon fractures in 18 children with OI (average age: 12 years old) were treated surgically. Ten patients were treated with the screw fixation and 11 with TBW. A total of 65% of olecranon fractures occurred as a result of a spontaneous avulsion of the olecranon during the contraction of the triceps muscle. The average follow-up was 36 months. Among the children treated with 1 screw, 5 patients needed a surgical revision with TBW due to a mobilization of the screw. In this group, the satisfactory results were 50%. In patients treated with TBW, the satisfactory results were 100% of the cases. The average Z-score, the last one recorded in the patients before the trauma, was -2.53 in patients treated with screw fixation and -2.04 in those treated with TBW. TBW represents the safest surgical treatment for patients suffering from OI type I, as it helps to prevent the rigidity of the elbow through an earlier recovery of the range of motion, and there was no loosening of the implant. In analyzing the average Z-score before any fracture, the fixation with screws has an increased risk of failure in combination with low bone mineral density

Genotype-phenotype correlation study in 364 osteogenesis imperfecta Italian patients

Osteogenesis imperfecta (OI) is a rare genetic disorder of the connective tissue and 90% of cases are due to dominant mutations in COL1A1 and COL1A2 genes. To increase OI disease knowledge and contribute to patient follow-up management, a homogeneous Italian cohort of 364 subjects affected by OI types I-IV was evaluated. The study population was composed of 262 OI type I, 24 type II, 39 type III, and 39 type IV patients. Three hundred and nine subjects had a type I collagen affecting function mutations (230 in α1(I) and 79 in α2(I)); no disease-causing changes were noticed in 55 patients. Compared with previous genotype-phenotype OI correlation studies, additional observations arose: a new effect for α1- and α2-serine substitutions has been pointed out and heart defects, never considered before, resulted associated to quantitative mutations (P = 0.043). Moreover, some different findings emerged if compared with previous literature; especially, focusing the attention on the lethal form, no association with specific collagen regions was found and most of variants localized in the previously reported "lethal clusters" were causative of OI types I-IV. Some discrepancies have been highlighted also considering the "50-55 nucleotides rule," as well as the relationship between specific collagen I mutated region and the presence of dentinogenesis imperfecta and/or blue sclera. Despite difficulties still present in defining clear rules to predict the clinical outcome in OI patients, this study provides new pieces for completing the puzzle, also thanks to the inclusion of clinical signs never considered before and to the large number of OI Italian patients

Osteogenesis imperfecta: the audiological phenotype lacks correlation with the genotype

Contains fulltext : 97190.pdf (publisher's version ) (Open Access)ABSTRACT: BACKGROUND: Osteogenesis Imperfecta (OI) is a heritable connective tissue disorder mainly caused by mutations in the genes COL1A1 and COL1A2 and is associated with hearing loss in approximately half of the cases. The hearing impairment usually starts between the second and fourth decade of life as a conductive hearing loss, frequently evolving to mixed hearing loss thereafter. A minority of patients develop pure sensorineural hearing loss. The interindividual variability in the audiological characteristics of the hearing loss is unexplained. METHODS: With the purpose of evaluating inter- and intrafamilial variability, hearing was thorougly examined in 184 OI patients (type I: 154; type III: 4; type IV: 26), aged 3-89 years, with a mutation in either COL1A1 or COL1A2 and originating from 89 different families. Due to the adult onset of hearing loss in OI, correlations between the presence and/or characteristics of the hearing loss and the underlying mutation were investigated in a subsample of 114 OI patients from 64 different families who were older than 40 years of age or had developed hearing loss before the age of 40. RESULTS: Hearing loss was diagnosed in 48.4% of the total sample of OI ears with increasing prevalence in the older age groups. The predominant type was a mixed hearing loss (27.5%). A minority presented a pure conductive (8.4%) or pure sensorineural (12.5%) loss. In the subsample of 114 OI subjects, no association was found between the nature of the mutation in COL1A1 or COL1A2 genes and the occurrence, type or severity of hearing loss. Relatives originating from the same family differed in audiological features, which may partially be attributed to their dissimilar age. CONCLUSIONS: Our study confirms that hearing loss in OI shows a strong intrafamilial variability. Additional modifications in other genes are assumed to be responsible for the expression of hearing loss in OI

Intraoperative bleeding in patients with osteogenesis imperfecta type III treated by Fassier-Duval femoral rodding: analysis of risk factors

The surgical treatment of osteogenesis imperfecta (OI) is negatively influenced by clinical features such as osteoporosis, limb deformities and bone changes caused by bisphosphonate therapy. Blood loss during femoral nailing surgeries in patients with OI is a serious problem. Platelet anomalies have been associated with an elevation of the serum pyrophosphate originating from the platelets during clotting, even if the causality with the platelet dysfunction has not yet been established. To identify predictive risk factors regarding intraoperative bleeding, a retrospective analysis was conducted on 23 patients aged between 6 and 13 years, affected by OI type III, who were treated to correct femoral deformities or to perform an osteosynthesis for femoral shaft fractures, using the Fassier-Duval telescopic nail. Osteotomies were performed in 14 cases of deformities and in two out of seven cases of fractures. A survey about the bleeding had been obtained by calculating the sum of the blood aspirated and that lost with the gauzes or present on the surgical drapes. To obtain an estimate of the intraoperative blood losses, one must resort to a calculation based on an algorithm that evaluates the ratio between the effective blood loss divided by the total blood volume expected as per age and weight (γ distribution). The average blood loss was 237.4 ml (0.12 γ). In seven cases, it was necessary to perform postoperative transfusions, owing to an average blood loss of 502.8 ml (0.27 γ). Patients aged less than 10 years had a minor blood loss. A greater number of osteotomies was associated with a significant increase of average bleeding (P=0.046). Patients who were never treated with bisphosphonates showed a significantly greater bleeding rate (P=0.048). Patients affected by OI type III have a high risk of severe blood loss during surgery, even caused by the platelet disfunction, which characterizes this OI type. In addition to this predisposing factor, there are other risk factors to consider in preoperative surgical planning. In patients who were never treated with bisphosphonates, the bleeding was higher than in the ones treated with bisphosphonates since at least 1 year. The effects of bisphosphonates on bone tissue (such as the medullar canal narrowing and the bone cortex thickening) could reduce the spongious bone amount and the bleeding. Inhibiting the farnesyl pyrophosphate synthase enzyme and reducing the prenylation of many plasma proteins, including the methylene tetrahydrofolate reductase, the bisphosphonates could lead to an alteration of the coagulation cascade. The correlation found with the intake of bisphosphonates, capable of inhibiting the action of the farnesyl pyrophosphate synthase enzyme, thus influencing coagulation, requires further prospective studies with research of the methylene tetrahydrofolate reductase mutation in patients with OI type III undergoing surgical procedures. The number of osteotomies, the patient's age and the intake of bisphosphonates for at least 1 year seem to be the best predictive factors for blood loss

Scavenging properties of neutrophil 4-hydroxyphenylpyruvate dioxygenase are based on a hypothesis that does not stand up to scrutiny

It was previously reported by D’Eufemia et al. that neutrophil preparations from a patient with tyrosinemia type III, i.e. with inherited deficiency of 4-hydroxyphenylpyruvate dioxygenase (HPPD), exhibited a far higher NO release than controls, when NO was estimated in terms of nitrite content in the suspending media. It was hypothesized that HPPD might participate to NO sequestration in neutrophils and that excessive NO release might reflect the lack of the scavenging action in defective cells. In recent control experiments, we found that HPPD activity in neutrophils preparations from healthy subjects is below the detection limit of the enzymatic assay (less than 3 nmol product/h per mg protein). This indicates that HPPD concentration in neutrophils is very low, if any, confirming what was already suggested in literature, and rules out the possibility of a prominent role of HPPD as NO scavenger in these cells. Moreover, we found that 500 microM L-tyrosine increases nitrite release and accumulation in suspending media of U-937 cells, a human monoblast-like lymphoma cell line which displays many characteristics of macrophages, including the expression of inducible and endothelial nitric oxide synthases. We hypothesize that the increase of nitrite release by patient’s neutrophils might be related to the presence of high L-tyrosine concentrations in the blood samples (426 micromol/L instead of 52.1 +/- 10.9 micromol/L as healthy subjects), rather than to HPPD deficiency of in these cells