Increasing bone screw anchoring in the femur head by cement administration via the implant--a biomechanical study

PURPOSE: Osteoporosis reveals a higher risk of fractures. Due to the lack of possibilities to anchor fixation elements, fracture treatment often turns out to be complicated. An experimental study served to investigate the extent to which the application of bone cement through a modified gliding screw (Dynamic Hip Screw DHS) would improve the screw anchoring in osteoporotic femoral heads. METHODS: Quasi-static compressive and torsional load tests were used to assess the desired improvement of the screw anchoring. Cadaver femur pairs served to compare the cement augmentation to the uncemented contralateral control. RESULTS: The improvement of the holding strength of the screw under static compressive and torsional load depended on the cement flow into the adjacent bone tissue. The filling with additional cement was only successful after having created a small hollow space at the screw tip with a special instrument. Consequently, under compression as well as torsion, the cement application yielded improvements from 17% up to several times as much. CONCLUSION: In the application of gliding screws in osteoporotic femoral heads, the locally limited cement application through the implant has been shown to be a biomechanical possibility to improve screw fixation.     

About composite materials and their use in bone surgery

Composite materials consist of two or even more different material components or phases, which are combined with the aim to improve physical, mechanical and/or biological properties. Such structures are designed to fulfil very specific requirements with respect to a selected device application making full use of their higher weight-specific strength and/or stiffness. Furthermore, these materials offer an opportunity for constructing radiolucent devices. In medical technology, composite materials mainly consist of a polymer matrix and fibres as a reinforcement phase. Composites similar to those known from technical applications reveal a number of specific biological problems. This is due to the materials and manufacturing processes available for the construction of such composites preventing their unrestricted use in direct bone contact. Nevertheless, an application potential for these materials in bone surgery exists and justifies further research and development efforts.     

Responsiveness of the generic EQ-5D summary measure compared to the disease-specific EORTC QLQ C-30

Introduction: We investigated whether the sensitivity of the generic health-related quality of life (HRQoL) EQ-5D summary measure (or index) to detect changes over time in a clinical setting is comparable with that of a disease-specific HRQoL questionnaire. Methods: Patients with liver metastases (n = 75) filled out the five domains of the EQ-5D self-classifier, the EQ VAS, and the EORTC QLQ C-30 (a disease-specific (cancer) HRQoL questionnaire). The HRQoL instruments were completed before intervention, and 1/2 month and 3 and 6 months after intervention. Three analyses were performed. First, the EQ-5D index (based on self-classification) was compared to the EQ VAS. Second, the EQ-5D domains were compared to corresponding EORTC QLQ C-30 scales. Third, EQ-5D index and EQ VAS were compared with the EORTC QLQ C-30 global health-status scale. Effect size was chosen as the metric of responsiveness. Results: The EQ-5D index was slightly less responsive than the EQ VAS. Overall, the responsiveness of the EQ-5D index and EQ VAS was equal to the EORTC QLQ C-30 global health-status scale. Conclusion: Despite its generic principle and the apparent crudeness of its framework, the responsiveness of the EQ-5D proved to be comparable to that of a disease-specific HRQoL questionnaire in this specific clinical setting.     

CYP1A2 and NAT2 genotype/phenotype relations and urinary excretion of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in a human dietary intervention study.

2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a mutagenic and carcinogenic heterocyclic amine formed during ordinary cooking, and is subsequently metabolically activated by cytochrome P4501A2 (CYP1A2) and N-acetyltransferase 2 (NAT2). Respective genes encoding for these enzymes, display polymorphic distribution in the human population and are thus believed to cause interindividual differences in cancer risk susceptibility. The present study investigated the influence of dietary exposure and CYP1A2 and NAT2 genotypes and phenotypes on differential urinary PhIP excretion levels in 71 human volunteers after consumption of either a high (7.4 ng/g) or low (1.7 ng/g) dose of PhIP. Urinary PhIP excretion levels were found to reflect recent dietary exposure levels, with average levels of 174% (high dose group) and 127% (low dose group), as compared to pre-feed levels. Urinary caffeine metabolite ratios were significantly different between the two NAT2 genotypes, whereas for CYP1A2, the apparent difference in metabolic ratios between the genotypes was statistically non-significant. Significant correlations were firstly found between the CYP1A2-164A-->C (CYP1A2*1F) polymorphism and differential urinary PhIP excretion levels. Although the found correlations are driven primarily by a small number of subjects possessing the homozygous variant constellation, the strong influence of this genotype indicates that the CYP1A2*1F polymorphism could play an important role in human cancer risk susceptibility.     

Contribution of growth phases to adult size

Based on the data of the First Zurich Longitudinal Growth Study we investigate how interindividual differences in adult size arise in the variables leg height, sitting height and standing height, arm length, biiliac width and bihumeral width. Specifically, we are also interested in the question of whether across sexes and variables the same growth phases and the same parameters are predictive for achieving a certain adult size. A rather complex pattern emerges, demonstrating that regulation of growth is not the same for boys and girls and moreover is not the same for the six anthropometric variables studied. Prepubertal growth is characterized by its intensity (average velocity) and by its duration. Whereas duration has by itself no appreciable influence on adult size, prepubertal intensity determines adult size to a high degree across all variables and both sexes. The intensity of prepubertal growth determines adult size to a larger degree for boys than for girls. For a given size at the end of the prepubertal period, a small duration enhances the chance of obtaining a large adult size. Compared with prepubertal growth, the amount of variance of adult size explained is small for pubertal parameters, and - with respect to linear measures - significant for girls only. A small duration of prepubertal growth is in the following mainly compensated by a stronger pubertal spurt (PS), to a varying degree across variables. The overall picture which emerges indicates that sitting height - and to a lesser extent bihumeral width - develop in a more irregular fashion than the variables biiliac width and leg height.     

Activity of Praziquantel Enantiomers and Main Metabolites against Schistosoma mansoni

A racemic mixture of R and S enantiomers of praziquantel (PZQ) is currently the treatment of choice for schistosomiasis. Though the S enantiomer and the metabolites are presumed to contribute only a little to the activity of the drug, in-depth side-by-side studies are lacking. The aim of this study was to investigate the in vitro activities of PZQ and its main metabolites, namely, R- and S-cis- and R- and S-trans-4′-hydroxypraziquantel, against adult worms and newly transformed schistosomula (NTS). Additionally, we explored the in vivo activity and hepatic shift (i.e., the migration of the worms to the liver) produced by each PZQ enantiomer in mice. Fifty percent inhibitory concentrations of R-PZQ, S-PZQ, and R-trans- and R-cis-4′-hydroxypraziquantel of 0.02, 5.85, 4.08, and 2.42 μg/ml, respectively, for adult S. mansoni were determined in vitro. S-trans- and S-cis-4′-hydroxypraziquantel were not active at 100 μg/ml. These results are consistent with microcalorimetry data and studies with NTS. In vivo, single 400-mg/kg oral doses of R-PZQ and S-PZQ achieved worm burden reductions of 100 and 19%, respectively. Moreover, worms treated in vivo with S-PZQ displayed an only transient hepatic shift and returned to the mesenteric veins within 24 h. Our data confirm that R-PZQ is the main effector molecule, while S-PZQ and the metabolites do not play a significant role in the antischistosomal properties of PZQ.     

Positionspapier zur medikamentenassoziierten Osteonekrose des Kiefers (MRONJ)

It is now 12 years since the first article on medication-related osteonecrosis of the jaw (MRONJ) was reported in 2003. The recognition of MRONJ is still inconsistent between physicians and dentists but it is without doubt a severe disease with impairment of oral health-related quality of life. This position paper was developed by three Austrian societies for dentists, oral surgeons and osteologists involved in this topic. This update contains amendments on the incidence, pathophysiology, diagnosis, staging and treatment and provides recommendations for management based on a multidisciplinary international consensus. The MRONJ can be a medication-related side effect of treatment of malignant and benign bone diseases with bisphosphonates (Bp), bevacizumab and denosumab (Dmab) as antiresorptive therapy. The incidence of MRONJ is highest in the oncology patient population (range 1–15?%), where high doses of these medications are used at frequent intervals. In the osteoporosis patient population, the incidence of MRONJ is estimated to be 0.001–0.01?%, marginally higher than the incidence in the general population (<?0.001?%). Other risk factors for MRONJ include glucocorticoid use, maxillary or mandibular bone surgery, poor oral hygiene, chronic inflammation, diabetes mellitus, ill-fitting dentures as well as other drugs, including antiangiogenic agents. Prevention strategies for MRONJ include elimination or stabilization of oral disease prior to initiation of antiresorptive agents, as well as maintenance of good oral hygiene. In those patients at high risk for the development of MRONJ, including cancer patients receiving high-dose BP or Dmab therapy, consideration should be given to withholding antiresorptive therapy following extensive oral surgery until the surgical site heals with mature mucosal coverage. Management of MRONJ is based on the stage of the disease, extent of the lesions and the presence of contributing drug therapy and comorbidity. Conservative therapy includes topical antibiotic oral rinses and systemic antibiotic therapy. Early data have suggested enhanced osseous wound healing with teriparatide in those patients without contraindications for its use. The MRONJ related to denosumab may resolve more quickly with a drug holiday than MRONJ related to bisphosphonates. Localized surgical debridement is indicated in advanced nonresponsive disease and has proven successful. More invasive surgical techniques are becoming increasingly more important. Prevention is the key for the management of MRONJ. This requires a close teamwork for the treating physician and the dentist. It is necessary that this information is disseminated to other relevant health care professionals and organizations.