Bone mineral density measurement and osteoporosis treatment after a fragility fracture in older adults: regional variation and determinants of use in Quebec

Affiliation: Pierre Dagenais : Hôpital Maisonneuve-Rosemont, Faculté de médecine, Université de Montréal

Évolution de la gestion pharmacologique de la polyarthrite rhumatoïde et impact sur le risque de fracture ostéoporotique non vertébrale

Au cours des dernières années, le développement des connaissances au niveau de l’étiologie de la maladie ainsi que l’arrivée de nouveaux médicaments et de lignes directrices guidant la pratique clinique sont susceptibles d’avoir entraîné une meilleure gestion de la polyarthrite rhumatoïde (PAR) et de l’ostéoporose, une comorbidité fréquente chez ces patients. Dans cette thèse, trois questions de recherche sont étudiées à l’aide des banques de données administratives québécoises (RAMQ, MED-ÉCHO). Une première étude documente l’utilisation des médicaments pour la PAR au Québec. À ce jour, il s’agit de la seule étude canadienne à rapporter les tendances d’utilisation des DMARD (disease-modifying antirheumatic drug) biologiques depuis leur introduction dans la pratique clinique. Au cours de la période à l’étude (2002-2008), l’utilisation de DMARD (synthétiques et biologiques) a augmenté légèrement dans la population atteinte de PAR (1,9%, 95% CI : 1,1 - 2,8). Cependant, malgré la présence de recommandations cliniques soulignant l’importance de commencer un traitement rapidement, et la couverture de ces traitements par le régime général d’assurance médicaments, les résultats démontrent une initiation sous-optimale des DMARD chez les patients nouvellement diagnostiqués (probabilité d’initiation à 12 mois : 38,5%). L’initiation de DMARD était beaucoup plus fréquente lorsqu’un rhumatologue était impliqué dans la provision des soins (OR : 4,31, 95% CI : 3,73 - 4,97). Concernant les DMARD biologiques, le facteur le plus fortement associé avec leur initiation était l’année calendrier. Chez les sujets diagnostiqués en 2002, 1,2 sur 1 000 ont initié un DMARD biologique moins d’un an après leur diagnostic. Pour ceux qui ont été diagnostiqués en 2007, le taux était de 13 sur 1 000. Les résultats démontrent que si la gestion pharmacologique de la PAR s’est améliorée au cours de la période à l’étude, elle demeure tout de même sous-optimale. Assurer un meilleur accès aux rhumatologues pourrait, semble-t-il, être une stratégie efficace pour améliorer la qualité des soins chez les patients atteints de PAR. Dans une deuxième étude, l’association entre l’utilisation des DMARD biologiques et le risque de fractures ostéoporotiques non vertébrales chez des patients PAR âgés de 50 ans et plus a été rapportée. Puisque l’inflammation chronique résultant de la PAR interfère avec le remodelage osseux et que les DMARD biologiques, en plus de leur effet anti-inflammatoire et immunosuppresseur, sont des modulateurs de l’activité cellulaire des ostéoclastes et des ostéoblastes pouvant possiblement mener à la prévention des pertes de densité minérale osseuse (DMO), il était attendu que leur utilisation réduirait le risque de fracture. Une étude de cas-témoin intra-cohorte a été conduite. Bien qu’aucune réduction du risque de fracture suivant l’utilisation de DMARD biologiques n’ait pu être démontrée (OR : 1,03, 95% CI : 0,42 - 2,53), l’étude établit le taux d’incidence de fractures ostéoporotiques non vertébrales dans une population canadienne atteinte de PAR (11/1 000 personnes - années) et souligne le rôle d’importants facteurs de risque. La prévalence élevée de l’ostéoporose dans la population atteinte de PAR justifie que l’on accorde plus d’attention à la prévention des fractures. Finalement, une troisième étude explore l’impact de la dissémination massive, en 2002, des lignes directrices du traitement de l’ostéoporose au Canada sur la gestion pharmacologique de l’ostéoporose et sur les taux d’incidence de fractures ostéoporotiques non vertébrales chez une population de patients PAR âgés de 50 ans et plus entre 1998 et 2008. Étant donné la disponibilité des traitements efficaces pour l’ostéoporose depuis le milieu des années 1990 et l’évolution des lignes directrices de traitement, une réduction du taux de fractures était attendue. Quelques études canadiennes ont démontré une réduction des fractures suivant une utilisation étendue des médicaments contre l’ostéoporose et de l’ostéodensitométrie dans une population générale, mais aucune ne s’est attardée plus particulièrement sur une population adulte atteinte de PAR. Dans cette étude observationnelle utilisant une approche de série chronologique, aucune réduction du taux de fracture après 2002 (période suivant la dissémination des lignes directrices) n’a pu être démontrée. Cependant, l’utilisation des médicaments pour l’ostéoporose, le passage d’ostéodensitométrie, ainsi que la provision de soins pour l’ostéoporose en post-fracture ont augmenté. Cette étude démontre que malgré des années de disponibilité de traitements efficaces et d’investissement dans le développement et la promotion de lignes directrices de traitement, l’effet bénéfique au niveau de la réduction des fractures ne s’est toujours pas concrétisé dans la population atteinte de PAR, au cours de la période à l’étude. Ces travaux sont les premiers à examiner, à l’aide d’une banque de données administratives, des sujets atteints de PAR sur une période s’étalant sur 11 ans, permettant non seulement l’étude des changements de pratique clinique suivant l’apparition de nouveaux traitements ou bien de nouvelles lignes directrices, mais également de leur impact sur la santé. De plus, via l’étude des déterminants de traitement, les résultats offrent des pistes de solution afin de combler l’écart entre la pratique observée et les recommandations cliniques. Enfin, les résultats de ces études bonifient la littérature concernant la qualité des soins pharmacologiques chez les patients PAR et de la prévention des fractures.

Studies on the fracture behaviour of polymer blends with special reference to PP/HDPE and PS/HIPS blends

Investigations on the fracture behaviour of polymer blends is the topic of this thesis. The blends selected are PP/HDPE and PS/HIPS. PP/HDPE blend is chosen due to its commercial importance and PS/HIPS blend is selected to study the transition from brittle fracture to ductile fracture.PP/HDPE blends were prepared at different compositions by melt blending at 180°C and fracture failure process was investigated by conducting notch sensitivity test and tensile test at different strain rates. The effects of two types of modifiers (particulate and elastomer) on the fracture behaviour and notch sensitivity of PP/HDPE blends were studied. The modifiers used are calcium carbonate, a hard particulate filler commonly used in plastics and Ethylene Propylene Diene Monomer (EPDM). They were added in 2%, 4% and 6% by weight of the blends.The study shows that the mechanical properties of PP/HDPE blends can be optimized by selecting proper blend compositions. The selected modifiers are found to alter and improve the fracture behaviour and notch sensitivity of the blends. Particulate fillers like calcium carbonate can be used for making the mechanical behaviour more stable at the various blend compositions. The resistance to notch sensitivity of the blends is found to be marginally lower in the presence of calcium carbonate. The elastomeric modifier EPDM produces a better stability of the mechanical behaviour. A low concentration of EPDM is sufficient to effect such a change. EPDM significantly improves the resistance to notch sensitivity of the blends. The study shows that judicious selection of modifiers can improve the fracture behaviour and notch sensitivity of PP/HDPE blends and help these materials to be used for critical applications.For investigating the transition in fracture behaviour and failure modes, PS/HIPS blends were selected. The blends were prepared by melt mixing followed by injection moulding to prepare the specimens for conducting tensile, impact and flexure tests. These tests were used to simulate the various conditions which promote failure.The tensile behaviour of unnotched and notched PS/HIPS blend samples were evaluated at slow speeds. Tensile strengths and moduli were found to increase at the higher testing speed for all the blend combinations whereas maximum strain at break was found to decrease. For a particular speed of testing, the tensile strength and modulus show only a very slight decrease as HIPS content is increased up to about 40%. However, there is a drastic decrease on increasing the HIPS content thereafter.The maximum strain at break shows only a very slight change up to about 40% HIPS content and thereafter shows a remarkable increase. The notched specimens also follow a comparable trend even though the notch sensitivity is seen high for PS rich blends containing up to 40% HIPS. The notch sensitivity marginally decreases with increase in HIPS content. At the same time, it is found to increase with the increase in strain rate. It is observed that blends containing more than 40% HIPS fail in ductile mode.The impact characteristics of PSIHIPS blends studied were impact strength, the energy absorbed by the test specimen and impact toughness. Remarkable increase in impact strength is observed as HIPS content in the blend exceeds 40%. The energy absorbed by the test specimens and the impact toughness also show a comparable trend.Flexural testing which helps to characterize the load bearing capacity was conducted on PS/HIPS blend samples at the two different testing speeds of 5mmlmin and 10 mm/min. The flexural strength increases with increase in testing speed for all the blend compositions. At both the speeds, remarkable reduction in flexural strength is observed as HIPS content in the blend exceeds 40%. The flexural strain and flexural energy absorbed by the specimens are found to increase with increase in HIPS content. At both the testing speeds, brittle fracture is observed for PS rich blends whereas HIPS rich blends show ductile mode of failure.Photoelastic investigations were conducted on PS/HIPS blend samples to analyze their failure modes. A plane polariscope with a broad source of light was utilized for the study. The coloured isochromatic fringes formed indicate the presence of residual stress concentration in the blend samples. The coverage made by the fringes on the test specimens varies with the blend composition and it shows a reducing trend with the increase in HIPS content. This indicates that the presence of residual stress is a contributing factor leading to brittle fracture in PS rich blends and this tendency gradually falls with increase in HIPS content and leads to their ductile mode of failure.

Modelling metal cutting using modern ductile fracture mechanics: Quantitative explanations for some longstanding problems

The assumption that negligible work is involved in the formation of new surfaces in the machining of ductile metals, is re-examined in the light of both current Finite Element Method (FEM) simulations of cutting and modern ductile fracture mechanics. The work associated with separation criteria in FEM models is shown to be in the kJ/m2 range rather than the few J/m2 of the surface energy (surface tension) employed by Shaw in his pioneering study of 1954 following which consideration of surface work has been omitted from analyses of metal cutting. The much greater values of surface specific work are not surprising in terms of ductile fracture mechanics where kJ/m2 values of fracture toughness are typical of the ductile metals involved in machining studies. This paper shows that when even the simple Ernst–Merchant analysis is generalised to include significant surface work, many of the experimental observations for which traditional ‘plasticity and friction only’ analyses seem to have no quantitative explanation, are now given meaning. In particular, the primary shear plane angle φ becomes material-dependent. The experimental increase of φ up to a saturated level, as the uncut chip thickness is increased, is predicted. The positive intercepts found in plots of cutting force vs. depth of cut, and in plots of force resolved along the primary shear plane vs. area of shear plane, are shown to be measures of the specific surface work. It is demonstrated that neglect of these intercepts in cutting analyses is the reason why anomalously high values of shear yield stress are derived at those very small uncut chip thicknesses at which the so-called size effect becomes evident. The material toughness/strength ratio, combined with the depth of cut to form a non-dimensional parameter, is shown to control ductile cutting mechanics. The toughness/strength ratio of a given material will change with rate, temperature, and thermomechanical treatment and the influence of such changes, together with changes in depth of cut, on the character of machining is discussed. Strength or hardness alone is insufficient to describe machining. The failure of the Ernst–Merchant theory seems less to do with problems of uniqueness and the validity of minimum work, and more to do with the problem not being properly posed. The new analysis compares favourably and consistently with the wide body of experimental results available in the literature. Why considerable progress in the understanding of metal cutting has been achieved without reference to significant surface work is also discussed.

Effect of the manufacturing process on the interlaminar fracture toughness of 2/2 twill weave fabric carbon/epoxy composites

A 2/2 twill weave fabric carbon fibre reinforced epoxy matrix composite MTM56/CF0300 was used to investigate the effect of different manufacturing processes on the interlaminar fracture toughness. Double cantilever beam tests were performed on composites manufactured by hot press, autoclave and 'Quickstep' processes. The 'Quickstep' process was recently developed in Perth, Western Australia for the manufacture of advanced composite components. The values of the mode I critical strain energy release rate (G1d were compared and the results showed that the composite specimens manufactured by the autoclave and the 'Quickstep' process had much higher interlaminar fracture toughness than the specimen produced by the hot press. When compared to specimens manufactured by the hot press, the interlaminar fracture toughness values of the Quickstep and autoclave samples were 38% and 49% higher respectively. The 'Quickstep' process produced composite specimens that had comparable interlaminar fracture toughness to autoclave manufactured composites. Scanning electron microscopy (SEM) was employed to study the topography of the mode I interlaminar fracture surface and dynamic mechanical analysis (DMA) was performed to investigate the fibre/matrix interphase. SEM micrography and DMA spectra indicated that autoclave and 'Quickstep' produced composites with stronger fibre/matrix adhesion than hot press.

Characterization and analysis of delamination fracture and nanocreep properties in carbon epoxy composites manufactured by different processes

Delamination resistance and nanocreep properties of 2/2 twill weave carbon epoxy composites manufactured by hot press, autoclave, and Quickstep^TM process are characterized and analyzed. Quickstep is a fluid filled, balanced pressure heated floating mold technology, which is recently developed in Perth, Western Australia for the manufacture of advanced composite components. Mode I and Mode II interlaminar fracture toughness tests, and nanoindentation creep tests on matrix materials show that the fast ramp rate of the Quickstep process provides mechanical properties comparable to that of autoclave at a lower cost for composite manufacturing. Low viscosity during ramping process and good fiber wetting are believed to be the reasons that this process produces composites with high delamination and creep-resistant properties. Nanocreep properties are analyzed using a Kelvin–Voigt model.

Manufacturing influence on the delamination fracture behavior of the T800H/3900-2 carbon fiber reinforced polymer composites

'Torayca' T800H/3900-2 is the first material qualified on Boeing Material Specification (BMS 8-276) which utilizes the thermoplastic-particulate interlayer toughening technology. Two manufacturing processes, the autoclave process and the fast heating rated Quickstep™ process, were employed to cure this material. The Quickstep process is a unique composite production technology which utilizes the fast heat transfer rate of fluid to heat and cure polymer composite components. The manufacturing influence on the mode I delamination fracture toughness of laminates was investigated by performing double cantilever beam tests. The composite specimens fabricated by two processes exhibited dissimilar delamination resistance curves (R-curves) under mode I loading. The initial value of fracture toughness GIC-INIT was 564 J/m2 for the autoclave specimens and 527 J/m2 for the Quickstep specimens. However, the average propagation fracture toughness GIC-PROP was 783 J/m2 for the Quickstep specimens, which was 2.6 times of that for the autoclave specimens. The mechanism of fracture occurred during delamination was studied under scanning electron microscope (SEM). Three types of fracture were observed: the interlayer fracture, the interface fracture, and the intralaminar fracture. These three types of fracture played different roles in affecting the delamination resistance curves during the crack growth. More fiber bridging was found in the process of delamination for the Quickstep specimens. Better fiber/matrix adhesion was found in the Quickstep specimens by conducting indentation-debond tests.

Experimental study on effect of loading rate on mode I delamination of z-pin reinforced laminates

This paper presents an experimental investigation on mode I delamination of z-pinned double-cantilever-beams (DCB) and associate z-pin bridging mechanisms. Tests were performed with three types of samples: big-pin with an areal density of 2%, small-pin with an areal density of 2% and small-pin with an areal density of 0.5%. The loading rates for each type of samples were set at 1 mm/min and 100 mm/min. Comparison of fracture load under different loading rates shows the rate effects on delamination crack opening and delamination growth. Optical micrographs of z-pins after pullout were also presented to identify the bridging mechanisms of z-pins under different loading rates.

The effect of cure cycle heating rate on the fibre/matrix interface

Development of civil aerospace composites is key to future “greener” aircraft. Aircraft manufacturers must improve efficiency of their product and manufacturing processes to remain viable. The aerospace industry is undergoing a materials revolution in the design and manufacture of composite airframes. The Airbus A350 and Boeing 787 (both due to enter service in the latter part of this decade) will push utilisation levels of  composite materials beyond 50% of the total airframe by weight. This  change requires massive investment in materials technology, manufacturing capability and skills development. The Quickstep process provides the ability to rapidly cure aerospace standard composite materials whilst providing enhanced mechanical properties. Utilising fluid to transfer heat to the   composite component during the curing process allows far higher heat rates than with conventional cure techniques. The rapid heat-up rates reduce the viscosity of the resin system greatly to provide a longer processing window introducing greater flexibility and removing the need for high pressure during cure. Interlaminar fracture toughness (Mode I) and Interfacial Shear Strength of aerospace standard materials cured using Quickstep have been    compared to autoclave cured laminates. Results suggest an improvement in fibre-matrix adhesion.

Study on thermoplastic-modified multifunctional epoxies : influence of heating rate on cure behaviour and phase separation

The effect of heating rate on the cure behaviour and phase separation of thermoplastic-modified epoxy systems was investigated. Polyethersulphone (PES) modified multifunctional epoxies, triglycidyl-aminophenol (TGAP) and tetraglycidyldiaminodiphenylmethane (TGDDM), as well T300/914 prepreg were used. It was shown that heating rate had a significant influence on the cure kinetics and phase structures of investigated systems. Greater heating rate causes higher epoxy conversion. The domain size of the macrophases formed from phase separation increases with the increase of heating rate. A more complete phase separation is achieved by fast heated thermoplastic-modified epoxy blends.

High strain rate tensile properties of rapidly cured woven carbon fibre composites

Tensile tests at high speeds corresponding to automotive crash events were conducted to understand the dynamic properties of rapidly cured woven carbon fiber composites. The High Strain Rate (HSR) experiments were conducted on a servo-hydraulic machine at constant velocities up to a maximum of 25 m/s (82 ft/s). Results from HSR tests were compared with the static results to determine the rate sensitivity of the composite. A high speed camera was used to capture the failure at HSR. The tensile properties of rapidly cured laminate were compared to oven cured laminate to justify its productivity while maintaining the desired properties. The methodology used to achieve constant velocity during HSR tests is discussed in detail. The specimen geometry was specially designed to suit the test rig and to achieve high speeds during tests. All the specimens failed with linear elasticity until sudden brittle fracture. The Scanning Electron Microscopy (SEM) images of the fracture zone were used to identify the failure modes observed at static and high strain rates.

Rheumatoid arthritis and incident fracture in women: a case-control study

Background:
To examine fracture incidence in women with rheumatoid arthritis (RA) for an entire geographical region of south-eastern Australia.

Methods:
Women aged 35 years and older, resident in the Barwon Statistical Division (BSD) and clinically diagnosed with RA 1994–2001 were eligible for inclusion as cases (n =1,008). The control population (n = 172,422) comprised the entire female BSD population aged 35 years and older, excluding those individuals identified as cases. Incident fractures were extracted from the prospective Geelong Osteoporosis Study Fracture Grid. We calculated rate ratios (RR) and 95% confidence intervals (CI) to compare the age- adjusted rate of fracture between the RA and non-RA populations, and used a chi-square test to compare proportions of fractures between women with and without RA, and a two-sided Mann–Whitney U-test to examine age-differences.

Results:
Among 1,008 women with RA, 19 (1.9%) sustained a fracture, compared to 1,981 fractures sustained by the 172,422 women without RA (1.2%). Fracture rates showed a trend for being greater among women diagnosed with RA (age-adjusted RR 1.43, 95%CI 0.98-2.09, p= 0.08). Women with RA sustained vertebral fractures at twice the expected frequency, whereas hip fractures were underrepresented in the RA population (p< 0.001). RA status was not associated with the likelihood of sustaining a fracture at sites adjacent to joints most commonly affected by RA (p= 0.22).

Conclusion:
Given that women with RA have a greater risk of fracture compared to women without RA, these patients may be a suitable target population for anti-resorptive agents; however, larger studies are warranted.

Investigating the predictive ability of gait speed and quadriceps strength for incident falls in community-dwelling older women at high risk of fracture

Gait speed is a recommended geriatric assessment of physical performance, but may not be regularly examined in clinical settings. We aimed to investigate whether quadriceps strength tests demonstrate similar predictive ability for incident falls as gait speed in older women. We investigated 135 female volunteers aged mean±SD 76.7±5.0 years (range 70-92) at high risk of fracture. Participants completed gait speed assessments using the GAITRite Electronic Walkway System, and quadriceps strength assessments using a hand-held dynamometer (HHD). Participants reported incident falls monthly for 3.7±1.2 years. N=99 (73%) participants fell 355 times during the follow-up period (mean fall rate 83 per 100 person years). We observed a reduced odds ratio for multiple falls (0.83, 95% CI 0.70-0.98) and a reduced hazard ratio for time to first fall (0.90, 95% CI 0.83-0.98), according to quadriceps strength. There was also a significantly shorter time to first fall for those with low quadriceps strength (<7.0 kg; lowest tertile) compared with those with normal quadriceps strength (estimated means [95% CI] 1.54 [1.02, 2.06] vs. 2.23 [1.82, 2.64] years; P=0.019), but not for those with low (<1.0 m/s) vs. normal gait speed (P=0.15). Quadriceps strength is a significant predictor of incident falls over three years amongst community-dwelling older women at high risk of fracture. Quadriceps strength tests may be an acceptable alternative to gait speed for geriatric assessments of falls risk.

Modeling of shear ductile fracture considering a changeable cut-off value for stress triaxiality

 A macroscopic ductile fracture criterion is proposed based on micro-mechanism analysis of nucleation, growth and shear coalescence of voids from experimental observation of fracture surfaces. The proposed ductile fracture model endows a changeable cut-off value for the stress triaxiality to represent effect of micro-structures, the Lode parameter, temperature, and strain rate on ductility of metals. The proposed model is used to construct fracture loci of AA 2024- T351. The constructed fracture loci are compared with experimental data covering wide stress triaxiality ranging between –0.5 and 1.0. The comparison suggests that the proposed model can provide a satisfactory prediction of ductile fracture for metals from compressive upsetting tests to plane strain tension with slanted fracture surfaces. Moreover, it is expected that the proposed model reasonably describes ductile fracture behavior in high velocity perforation simulation since a reasonable cut-off value for the stress triaxiality is coupled with the proposed ductile fracture criterion.

Investigation of hydraulic fracture propagation using a post-peak control system coupled with acoustic emission

This study investigates the fracture mechanism of fluid coupled with a solid resulting from hydraulic fracture. A new loading machine was designed to improve upon conventional laboratory hydraulic fracture testing and to provide a means of better understanding fracture behavior of solid media. Test specimens were made of cement mortar. An extensometer and acoustic emission (AE) monitoring system recorded the circumferential deformation and crack growth location/number during the test. To control the crack growth at the post-peak stage the input fluid rate can be adjusted automatically according to feedback from the extensometer. The complete stress-deformation curve, including pre- and post-peak stages, was therefore obtained. The crack extension/growth developed intensively after the applied stress reached the breakdown pressure. The number of cracks recorded by the AE monitoring system was in good agreement with the amount of deformation (expansion) recorded by the extensometer. The results obtained in this paper provide a better understanding of the hydraulic fracture mechanism which is useful for underground injection projects. © 2014 Springer-Verlag Wien.