Nuclear factor erythroid 2–related factor 2 (Nrf2) is a crucial transcription factor to maintain cellular redox homeostasis, but is also affecting bone metabolism. As the association between Nrf2 and osteoporosis in elderly females is not fully elucidated, our aim was to shed light on the potential contribution of Nrf2 to the development of age-dependent osteoporosis using a mouse model. Female wild-type (WT, n=18) and Nrf2-knockout (KO, n=12) mice were sacrificed at different ages (12 weeks=young mature adult, and 90 weeks=old), morphological cortical and trabecular properties of femoral bone analyzed by micro-computed tomography (µCT), and compared to histochemistry. Mechanical properties were derived from quasi-static compression tests and digital image correlation (DIC) used to analyze full-field strain distribution. Bone resorbing cells and aromatase expression by osteocytes were evaluated immunohistochemically and empty osteocyte lacunae counted in cortical bone. Wilcoxon rank sum test was used for data comparison and differences considered statistically significant at p<0.05. When compared to old WT mice, old Nrf2-KO mice revealed a significantly reduced trabecular bone mineral density (BMD), cortical thickness (Ct.Th), cortical area (Ct.Ar), and cortical bone fraction (Ct.Ar/Tt.Ar). Surprisingly, these parameters were not different in skeletally mature young adult mice. Metaphyseal trabeculae were thin but present in all old WT mice, while no trabecular bone was detectable in 60% of old KO mice. Occurrence of empty osteocyte lacunae did not differ between both groups, but a significantly higher number of osteoclast-like cells and fewer aromatase-positive osteocytes were found in old KO mice. Furthermore, female Nrf2-KO mice showed an age-dependently reduced fracture resilience when compared to age-matched WT mice. Our results confirmed lower bone quantity and quality as well as an increased number of bone resorbing cells in old female Nrf2-KO mice. Additionally, aromatase expression in osteocytes of old Nrf2-KO mice was compromised, which may indicate a chronic lack of estrogen in bones of old Nrf2-deficient mice. Thus, chronic Nrf2 loss seems to contribute to age-dependent progression of female osteoporosis.
As the population continues to grow and age, the incidence of revision total knee replacement (RTKR) is expected to rise significantly. Modularity within revision total knee systems is common, and recognition of modular junctions as an important source adverse local tissue reaction (ALTR) has not yet been fully described in the literature. In both hips and knees, ALTR may be caused by wear debris from articulating surfaces, stress shielding, and other classic areas of focus, but now attention is shifting towards the role of corrosion products from modular junctions. In severe cases, junctions can become welded together creating significant hurdles in revisions and potentially altered biomechanics in vivo. In view of these issues, the present study was undertaken: (i) to examine the level of damage observed in modular junctions of total knee prostheses obtained at revision, (ii) to correlate the severity of surface damage to the design and composition of the mating components, and (iii) to associate patient demographics and comorbidities with the spectrum of corrosion and fretting seen in retrieved implants. 117 TKR components from 76 patients were examined after retrieval from revision procedures performed at a single institution. Patient demographics and clinical data were compiled. The retrievals consisted of 57 femoral components and 60 tibial components from a diverse range of manufacturers. The implants were disassembled manually, or in a mechanical testing machine if cold welded, and separated into groups based on mating material type. Modular junctions were then examined using stereomicroscopy (Wild) at magnifications of X6 to X31. Upon inspection, damage on the male component was graded using modified Goldberg scales for corrosion and fretting (Table 1). Factors associated with trunnions having damage scores of 3 or higher were evaluated using standard statistical procedures to determine the susceptibility for corrosion of each junction type and location.Introduction
Methods
Corrosion products from modular taper junctions of hip prostheses have been implicated in adverse local tissue reactions after THR. Numerous factors have been proposed as the root causes of this phenomenon, including implant design and materials, manufacturing variables, intraoperative assembly, and patient lifestyle. As significant taper damage only occurs in a few percent of cases of THR, we have addressed this complication using a “forensic” examination of retrieval specimens to gain insight into the factors initiating the cascade leading to irreversible damage of the modular interface. In this study we report the categorization of over 380 retrievals into groups having shared damage patterns, metallic composition, and interface surface geometries to isolate the genesis of mechanically-assisted corrosion and its relation to intraoperative assembly, manufacturing, and postoperative loading. A total of 384 femoral components were examined after retrieval at revision THR. The implants were produced by a diverse range of manufacturers, 271 in CoCr, and 113 in TiAlV, with both smooth (253) and machined (131) tapers. Initially, the implants were sorted into groups based on composition and taper roughness. Each trunnion was then cleaned to remove organic deposits and examined by stereomicroscopy at X6-X31. After an initial pilot study, we developed a classification system consisting of 8 basic patterns of damage (Table 1). We then classified all 384 trunnions according to this 8-group system. The prevalence of each pattern was calculated on the basis of both composition and surface texture of the trunnion.Introduction
Methods
With the rising demand for primary total hip arthroplasty (THA), there has been an emphasis on reducing the revision burden and improving patient outcomes. Although studies have shown that primary THA effectively minimizes pain and restores normal hip function for activities of daily living, many younger patients want to participate in more demanding activities after their operation. With IRB approval, 2 groups of subjects were enrolled in this study: (i) 143 patients at an average of 25 months (range 10–69 months) post-primary THA, and (ii) 165 control subjects with no history of hip surgery or hip pathology. All subjects were assigned to one of four categories according to their age and gender: Group A: 40–60 year old males (31 THA; 42 Controls), Group B: 40–60 year old females (25 THA; 53 Controls), Group C: 60–80 year old males (35 THA; 25 Controls), and Group D: 60–80 year old females (36 THA; 23 Controls). Each patient completed a self-administered Hip Function Questionnaire (HFQ) which assessed each subject's satisfaction, expectations, symptoms and ability to perform a series of 94 exercise, recreational and daily living activities. These included participation in work-out activities, adventure and water sports, running and biking, and contact and team sports. Each participant was also asked their activity frequency, symptom prevalence and satisfaction with their hip in performing each activity.Background
Methods
This work was aimed at study the role of paraspinal muscles on spinal tensegrity. Four different models of spinal tensegrity breakage with and without injury of the posterior spinal muscle were investigated. Fifteen minipigs (mean age 6-week) underwent costotransversectomy (CTT) at 5 consecutive vertebral segments. In 4 animals ribs and transverse processes (T7–T11) were removed through a posterior midline approach with complete desinsertion of paraspinal muscles. In other 3 animals, CTT was performed by a posterolateral approach (T6–T10) without detachment of paraspinal muscles. Other 4 minipigs underwent rib resection (T7-T11) throughout a thoracoscopic approach avoiding damage of posterior spinal muscles. A final group of 4 animals, a complete detachment of the paraspinal muscles was performed from T7 to T11 without removing bony structures and leaving in deep surgical wax attached to the spinous and transverse processes to avoid reinsertion of the muscles after surgery. Anatomic specimens were radiologically and macroscopically studied just at sacrifice 5 months after surgery All 4 animals operated on of CTT by midline posterior approach developed structural spinal deformity with curve convexity at the side of rib removal (mean Cobb angle 34,6°). Animals undergoing CTT by posterolateral approach without paraspinal muscle detachment did not develop any significant spinal deformity. Absence of spinal deformity was also found in those animals in which rib resection was performed by thoracoscopy without injury of the posterior spinal muscles. All 4 animals undergoing detachment of the paraspinal muscles without CTT and application of the surgical wax developed scoliotic curves (mean Cobb angle of 28°). In conclusion, a new insight on the underlying pathogenic mechanisms of scoliotic curves is given by using this spinal tensegrity model. Isolated damage of the posterior muscle-ligamentous structures around the costotransverse joints breaking muscles spine tensegrity seems to be mandatory to induce scoliotic deformity. Rib removal alone appeared to have less scoliotic inductive implication. The finding questions previous knowledge on scoliosis etiopathogeny.
