Introduction. Mechanical properties of irradiated Ultra High Molecular Weight Polyethylene (UHMWPE) after aging have been well documented. However there was no sufficient data for the dimensional change due to irradiation and aging. This change may have adverse effects to the implant modular locking mechanism. The purpose of this study was to characterize the dimensional change of UHMWPE after irradiation and aging. Materials and Method. Total (30) ø15mm × 50mm virgin GUR 1050 UHMWPE rods were cleaned, dried, inspected, vacuum packaged and stored in 20°C environment for 2 days. Among them, (20) samples were measured along the 50mm length at 20°C +/-2°C before and after two conditions: 1, (10) were submerged in 40°C DI water for 2 hours and dried in 40°C to simulate the cleaning process and 2, (10) were soaked in 37°C saline for 14 days to simulate initial in-vivo environment. Remaining (10) samples were measured in the same way after irradiation of 30KGy dosage and then measured again after soaking in 37°C saline for 14 days to simulate the actual radiation sterilization and in-vivo soaking conditions. Same samples were measured once more after accelerated aging per ASTM-1980-07 for 80 days to simulate the 3 year in vivo life. The differences in measurements between virgin and end conditions were documented as the percentage dimensional change. After the measurements, in the groups of DI water, saline soaking and radiation + aging, (3) samples were randomly selected for DSC measurements. The results were compared with dimensional measurements. Statistical analysis was performed by the student t test to compare virgin condition and the conditions after each treatment. 95% significance level was assumed. Results. As shown in Table 1, after water wash and saline soaking, the average dimensions increased but not statistically significant. Radiation alone caused the net decrease in sample dimensions and remained in negative after a saline soaking. Further significant dimensional decrease (P<0.05) occurred after aging. Increased DSC % crystallinity was found in the aged samples. Discussion. Study showed the net dimensional change of UHMWPE was shrinkage under simulated in-vivo enviroment. Aging caused further significant shrinkage which was likely related to the elevation of crytallinity. Significance. With this shrinkage factor, the design of modular poly components may need to be compensated to avoid the loosening of modular components in-vivo condition

Highly cross linked polyethylenes have been shown to be substantially wear resistant. Typically, crosslinking is achieved by radiation in a low oxygen environment. While the early wear-simulation data is encouraging, concerns remain about the potential for aging and oxidative damage on exposure to oxygen during storage or in the body. This study measured wear rates in highly crosslinked liners that had been exposed to room air for up to 4 years. Polyethylene liners were divided into four groups: two groups of highly crosslinked liners, XL (freshly opened) and XL-Aged (aged); and two groups of nominally crosslinked liners, N (freshly opened) and N-Aged (aged). The highly crosslinked liners were crosslinked with 9.5 Mrad of warm electron-beam irradiation, treated to a post-cross linking heat treatment to quench free radicals (WIAM), followed by ethylene oxide sterilization. The nominally cross linked liners were sterilized with 2.5 Mrad. The aged liners (XL-Aged and N-Aged) were stored in saline (at 37°C) exposed to room air for 4 years. Three liners from each group were tested in a hip-wear simulator (90% bovine serum) for 5 million cycles. Gravimetric wear measurements were made at 500,000 cycle intervals. The N and N-Aged groups wore at rates of 14.76 ±3.1 and 15.58 ±1.21 mg/million cycles, respectively. The wear in both XL and XL-Aged groups was not measurable, resulting in weight gains of 2.73±0.5 and 2.17 ±1.1 mg/million cycles, respectively. WIAM cross linked polyethylene has been reported to generate the least free radicals and has the least potential for oxidative damage. There have been concerns regarding the validity of artificial aging by the high-temperature oxidation. Aging in saline at body temperature while exposed to room air is more representative of in vivo aging. This data supports the results of artificial aging and the long-term durability of WIAM polyethylene

Aims

The escalating demand for medical resources to address spinal diseases as society ages is an issue that requires careful evaluation. However, few studies have examined trends in spinal surgery, especially unscheduled hospitalizations or surgeries performed after hours, through large databases. Our study aimed to determine national trends in the number of spine surgeries in Japan. We also aimed to identify trends in after-hours surgeries and unscheduled hospitalizations and their impact on complications and costs.

Introduction

The in vivo evolution of surface material properties is important in determining the longevity of bioceramics. Fracture toughness is particularly relevant because of its role in wear resistance. Some bioceramics, such as zirconia (ZrO2) undergo in vivo phase transformation, resulting in a marked reduction in toughness and commensurate increased wear. Here, we investigated the effect of accelerated aging on the surface toughness of alumina (Al2O3), zirconia-toughened alumina (ZTA), and silicon nitride (Si3N4) femoral heads, in order to identify the optimal ceramic material for in vivo implantation and long-term durability.

31 consecutive patients (mean 54.7 years) were examined mean follow-up time of 47 months. Patients were evaluated clinically; using Lysholm, Cincinnati, IKDC and Tegner Activities Scores. Objective assessments were made with KT1000 Arthrometer and Isokinetic strength testing.

Lysholm scores improved from 62 preoperatively to 93 at review; Cincinnati 48 to 89; Tegner 3.6 to 5.2. 81 percent of knees were considered normal or nearly normal to IKDC, 6 abnormal, none severely abnormal. KT1000 manual max difference 2.9mm; Isokinetic flexion strength 102 percent; extension strength 95 percent. Poor results were mainly associated with advanced articular cartilage degenerative changes at time of surgery. This also correlated with increased time from injury to surgery, and increased preoperative injury rates.

This study demonstrates that the anterior cruciate ligament can be reliably reconstructed in patients over the age of 50 years with good symptomatic relief, restoration of function and return to activity.

The suggestion of a meniscal tear produces a pavlovian response in the orthopaedic surgeon. However, meniscal signal anomalies and associated changes become common with age in symptom free knees. T he issue for the IME requested to assess workers with painful knees is to determine if the MRI changes represent a painful injury and if the treatment planned (usually arthroscopy) may, in fact, be harmful.

MRI signal changes are assessed on the likelihood they predict for unstable meniscal tears. Some patterns of meniscal tears are benign. Associated changes such as baker's cyst and ligament thickening are also common but are poor predictors of symptomatic tears. Preclinical osteoarthritis has a high incidence of associated meniscal change and arthroscopic menisectomy may accelerate osteoarthritis progression.

Clinical tests have variable specificity and sensitivity but in combination with an understanding of the patterns of MRI signal can be combined to predict which meniscal tears would benefit from arthroscopic surgery, which injuries would do as well with non-operative treatment and which patterns predict deterioration after surgery.

As the views of the IME are often contrary to the surgeon, a comprehensive bibliography is provided for any who need to argue their case. As the topic is information and image dense, a CD ROM will be distributed.

Vitamin E (alpha-tocopherol) is a free-radical stabilizing agent used to maintain oxidative stability in radiation crosslinked UHMWPE for total joint replacements. Diffusion of vitamin E into UHMWPE after irradiation is one method of incorporation, while an alternative is blending vitamin E with UHMWPE resin powder and subsequently irradiating the consolidated mixture. With the latter method, it is possible for the antioxidant properties of Vitamin E to be exhausted in blends during irradiation, leading to oxidation.

We report on the relative oxidative resistance of both irradiated (100kGy, 150kGy, 200kGy) vitamin E blends (0.02 wt%, 0.05 wt% and 0.1wt%) and post-irradiation vitamin E-diffused UHMWPE after three years of real-time aging in an aqueous environment at 40°C. Blocks of each type, including irradiated virgin UHMWPE, were also accelerated aged per ASTM F2003. Oxidation was measured with FTIR per ASTM F2102. Oxidation potential was determined through nitric oxide staining of hexane extracted thin sections, FTIR analysis and calculated using the height of the nitrate peak (1630 cm^-1).

Our results showed that unstabilized samples exhibited substantial oxidation and oxidation potential throughout the surface and bulk with both types of aging. Post-irradiation diffused UHMWPE showed no detectable oxidation and decreasing oxidation potential with both aging methods. The vitamin E concentration at the surface of the diffused blocks decreased and the initial non-uniform profile with high surface concentration (3.4 wt%) shifted towards a uniform profile, equilibrating at an index of 0.1 or 0.7 wt% vitamin E. Samples showed a reduction in their initial vitamin E content by 47%– 61% over 36 months, but oxidative stability was not compromised. The non-uniform profile presumably created a driving force for elution into the aqueous environment, while the difference in solubility of vitamin E at 40°C, compared to the initial diffusion temperature at 120°C, may have also contributed. After six months of real-time aging, all irradiated blends showed surface oxidation, while 0.02 wt% blends additionally showed subsurface oxidation potential. However, oxidation was not induced by accelerated aging Methods: in any blended, irradiated samples.

In conclusion, real-time aging resulted in greater differentiation in the relative oxidative stability of vitamin E-stabilized, radiation crosslinked UHMWPEs than accelerated aging. Irradiated blends with vitamin E concentrations as high as 0.1 wt% showed surface oxidation after 3 years; higher vitamin E concentrations cannot address this shelf oxidation as that will also reduce the crosslinking efficiency and increase wear. Post-irradiation diffused UHMWPE, which was not limited by the amount of incorporated vitamin E, showed oxidative resistance up to 3 years with a reduction in oxidative potential.

Purpose: Previous gait studies in community ambulatory older adults show reduced walking velocity, shorter steps, ankle stiffness, and increased duration of double-limb support. A description of gait in very active older adults is needed.

Methods: Subjects: 13 senior athletes (age 65±4 years) and 13 young athletes (age 24±3 years). Inclusion criteria: running plus other activity, body mass index < 26, no systemic disease, no lower leg pathology. Outcome measures: Subjects were evaluated barefoot (walking 1.5 m/s) using a force platform, motion analysis (frontal, medial and plantar videography), and electromyography (EMG) of tibialis anterior (ta), peroneus longus (pl), gastrocnemius (gc), soleus (so), vastus medialis (vm), vastus lateralis (vl), rectus femoris (rf), biceps femoris (bf). Questionnaires were completed (Short Form 36 Health Survey (SF-36), Foot Function Index) and physical examination findings of the lower leg were documented.

Results: Senior subjects, compared to young subjects, had decreased passive ankle dorsiflexion (14° vs. 18°). Senior subjects had a higher incidence of hallux valgus deformity (43% vs. 8%), and dynamic clawing of the toes (29% vs. 8%). Other physical findings were similar between groups. Questionnaire scores were similar for both groups. |There was no difference between groups in duration of single- and double-limbed stance. Seniors, compared to young subjects, had increased muscle activity (normalized EMG signal, stance phase) in seven of eight muscles. The percentage difference was greatest in the lower leg muscles (gc=50% more active in seniors, so=30%, pl=30%, ta=15%). Upper leg activity was moderately increased: vm=15%, rf=6%, vl=6%. Only biceps femoris had decreased activity (−15%). Further analysis of EMG intensity, kinematics and kinetics are pending.

Conclusions: This study shows that even in healthy, active subjects, the foot and ankle is subtly altered with increasing age. Increased muscle activity may be a compensatory mechanism (i.e., to maintain overall performance). While our findings require further explanation, the characteristics documented in this study are in contrast to the shuffling gait often ascribed to older persons.

Background: Continuous bone “creep” under constant load can cause measurable deformity in cadaveric vertebrae, but the phenomenon is extremely variable.

Purpose: We test the hypothesis that vertebral micro-damage accelerates creep deformity.

Methods: Twenty-six thoracolumbar “motion segments” were tested from cadavers aged 42–92 yrs. Bone mineral density (BMD) of each vertebral body was measured using DXA. A 1.0 kN compressive force was applied for 30 mins, while the height of each vertebral body was measured using a MacReflex optical tracking system. After 30 mins recovery, one vertebral body from each specimen was subjected to controlled micro-damage (< 5mm height loss) by compressive overload, and the creep test was repeated. Load-sharing between the vertebral body and neural arch was evaluated from stress measurements made by pulling a pressure transducer through the intervertebral disc.

Results: Creep was inversely proportional to BMD (P=0.041) and did not recover substantially after unloading. Creep was greater in the anterior vertebral body cortex compared to the posterior (p=0.002). Vertebral micro-damage usually affected a single endplate, causing creep of that vertebra to increase in proportion to the severity of damage. Anterior wedging of the vertebral bodies during creep increased by 0.10o (STD 0.20o) for intact vertebrae, and by 0.68o (STD 1.34o) for damaged vertebrae.

Conclusion: Creep is substantial in elderly vertebrae with low BMD, and is accelerated by micro-damage. Preferential loss of trabeculae from the anterior vertebral body could explain why creep is greater there, and so causes wedging deformity, even in the absence of fracture.

Conflicts of Interest: none

Source of Funding: Action Medical Research

Irradiation cross-linking of UHMWPE has been shown to reduce wear while generating free radicals that oxidise in the presence of oxygen or oxidising species. Various methods have been used to minimise or eliminate the effect of these free radicals including below-melt annealing, remelting, Vitamin E infusion, or the use of other antioxidants. Each method has benefits and drawbacks with respect to wear properties, mechanical properties, and chemical properties. Accelerated aging techniques are used to evaluate the efficacy of new methods in stabilising free radicals in highly cross-linked UHMWPE.

Various procedures have been described for aging standard gamma-air sterilised UHMWPE to produce oxidation levels that represent shelf-aged bearings. An important factor in evaluating and comparing these aging techniques is validating that they reproduce the profile of oxidation (depth and magnitude) seen both in gamma-air, shelfaged polyethylene and in clinical retrievals. Moreover, the resulting oxidation level in the aged UHMWPE should predict the fatigue and/or wear damage seen in retrieved gamma-air inserts and liners.

The present study compared clinically relevant UHMWPE samples aged with ASTM 2003-00, (Method B: 70°C, 5 atm O2, 14 days) and a published lower temperature, lower oxygen-pressure environment (63° C, 3 atm O2, 28 days). Longer aging times (35 to 42 days) were also tested to examine oxidation rate and time to onset of mechanical degradation.

Both published methods result in oxidation of gamma-air and gamma-barrier sterilised polyethylene, but have little effect on remelted or antioxidant stabilised crosslinked polyethylene. These aging protocols, however, did not bring standard polyethylene to the critical oxidation level necessary for the fatigue damage that is seen in retrieved inserts and liners.

Oxidation of gamma-air and gamma-barrier sterilised UHMWPE increases exponentially with time on the shelf or in the two aging environments. Of note, longer aging times (35 to 42 days) that bring standard UHMWPE to sufficiently high oxidation levels for fatigue to occur also cause increased oxidation levels in remelted UHMWPE.

Oxidation increases were the smallest in antioxidant UHMWPE, though still detectable.

While this oxidation is not high enough in remelted material or antioxidant material to cause the fatigue damage seen in gamma-air sterilised UHMWPE, it does raise concerns about the published aging techniques and the long term stability of the new materials in vivo.

Relying on artificial aging techniques that do not adequately challenge even gamma-air polyethylene may conceal unforeseen weaknesses of new materials. Using longer aging times for existing techniques or novel aging approaches may be necessary to effectively evaluate the long term stability of new bearing materials.

The purpose of this study was to examine the interactive effects of diet and the aging process on the mechanical and material properties of bone. We investigated how an ad libitum (AL) diet and 40% caloric restriction (CR) with nutrient supplementation, beginning at 3.5 months of age, interacted with the aging process to influence bone development. Diet effects were determined by measuring changes in bone geometry and bone mechanics of the tibia in young adult and senescent Fischer 344 X Brown-Norway Rats (F344 BN) rats.

Male F344 BN rats were divided into two dietary groups, AL or CR. CR commenced at 14 weeks of age, with 40% restriction and micronutrient supplementation. The AL group represented young adult (8 mo) and senescent (30–35 mo) rats. The CR group represented 8 mo and 35–40 mo rats. AL and CR groups were matched together for comparison based on the percentage survival rate. Tibiae were assessed using microcomputed tomography, mechanical testing, and ash analysis.

The results showed that a CR diet resulted in a significant decrease in total body mass when compared to the AL diet group across all ages. With aging, both AL and CR diet groups showed a general increase in structural properties and a decrease in material properties. Furthermore, material and structural properties changed proportionately between both diet groups. Comparisons between diet groups based on percentage survival rate revealed a significant decrease in most structural properties, but no significant changes in material properties with CR. After normalization to body mass, structural properties were significantly greater in the CR group when compared to the AL group.

The significantly greater CR structural properties over the AL diet group after normalization, with no significant changes in material properties, indicated that CR did not adversely affect the appendicular skeleton in F344 BN rats. Therefore, a CR diet with 40% restriction at fourteen weeks, with nutrient supplementation did not negatively impact tibial geometrical and mechanical properties in young and senescent male F344 BN rats.

Introduction: Two second generation highly crosslinked UHMWPEs have been cleared by the FDA for clinical use in the United States: sequentially crosslinked UHMWPE (X3™ UHMWPE, Stryker Inc., Mahwah, NJ, USA) and α-tocopherol stabilized UHMWPE (E-Poly™ UHMWPE, Biomet, Inc., Warsaw, IN, USA). Both have been shown to be oxidatively stable under standardized aging methods (ASTM F2003); however, these conventional aging methods did not consider the effect of mechanical loading on the oxidative behavior of the materials. By coupling the adverse effects of thermal aging and mechanical stress, we sought to investigate if either material was prone to environmental stress cracking (ESC). We hypothesize that the residual free radicals remaining in sequentially crosslinked PE will lead to oxidative degradation in this adverse test; furthermore, we hypothesized that the α-tocopherol infused in E-Poly™ will continue to protect the highly crosslinked PE even under such unfavorable conditions.

Materials and Methods: Three materials were tested:

Conventional: UHMWPE gamma sterilized in inert,

Four specimens from each group were subjected to a reciprocating mechanical stress of 10 MPa at a frequency of 0.5 Hz in an environmental chamber maintained at 80°C. Control samples were placed in the chamber but not subjected to cyclic mechanical stress. When a visible crack was observed on a sample’s surface or when a sample fractured, it and its corresponding control sample were analyzed by FTIR to quantify oxidation.

Results: All conventional specimens, half (2 of 4) of the SXL specimens, and none of the E-Poly specimens failed prior to the completion of 1,530,000 cycles (5 weeks of testing at 0.5 Hz). Cyclic loading had an adverse effect on the oxidation of the conventional and the SXL groups; the peak oxidation levels were higher in the cyclically loaded samples as compared to the control samples removed at the same time which were not loaded, likely due to an increase in chain scission induced by the mechanical load. The E-Poly specimens did not fail during the 5 weeks of testing, and FTIR did not reveal detectable oxidation in either control or loaded samples.

Discusssion and conclusion: Though the sequential processing of SXL creates a material with a lower free radical content compared to once-annealed material, it still yields a material prone to oxidation under extreme conditions, raising questions about its long-term oxidative stability. E-Poly™, protected by α-tocopherol, continues to exhibit high oxidation resistance even under adverse conditions.

Introduction: The purpose of this study was to determine whether regional blood flow (microspheres) in the femur is diminished with aging, and whether a reduction in flow is associated with impaired endothelium-dependent vasodilation.

Materials and Methods: Blood flow and PNA endothelium-dependent vasodilation was measured in young (4–6 months old) and aged (24–26 months old) male Fischer-344 rats.

Results: Blood flow in the aged rats was ~25% lower in femoral bone and 45% lower in diaphyseal marrow. Endothelium-dependent vasodilation was lower with old age (young: 83 ± 6% maximal relaxation; aged: 62 ± 5% maximal relaxation) and was mediated through impairment of the NOS signaling pathway, which resulted in a lower nitric oxide bioavailability (young: 168 ± 56 nM nitric oxide; aged: 50 ± 7 nM nitric oxide).

Discussion: Such age-related changes in bone perfusion and nitric oxide signaling could impact clinical bone loss, increase risk of fracture, and impair fracture healing in the elderly.

Aim of study: ‘Dark discs’ (intervertebral discs with normal shape and height but low signal intensity on T2-weighted MRI) are believed by some authors to represent an early stage in the degenerative process although other authors have suggested that they are simply an appearance of the normal aging process. This study addresses the above question by investigating the correlation between disc morphology on MRI of the lumbar spine (‘dark disc’ or obviously degenerative signs such as annular tear, loss of disc height and shape and end plate changes) and the distribution of lower back pain.

Background: It is generally accepted that spinal levels appearing degenerate on MRI may act as ‘pain generators’ either directly or indirectly (by affecting adjacent structures or levels). Furthermore, histopathologic and discographic studies have shown transmition of specific patterns of somatic pain from degenerate spinal levels.

Methods: 231 consecutive patients (mean age: 45 years, SD:15.9) presenting with mechanical lower back pain of more than six months duration completed topographic graphs of the distribution of their back pain (categorised for this study as upper-, mid-, low-lumbar and sacroiliac area pain) and underwent an MRI of the lumbar spine. Chi-square test was used to investigate the association between presence of abnormalities at any spinal level and pain at any of the considered body areas. Two sets of analyses were performed: one including ‘dark discs’ in the ‘pain generators’ group and the other excluding the ‘dark discs’ from this group.

Results: When the ‘dark discs’ were not considered as ‘pain generators’ the only association to reach statistical significance was that between L5/S1 abnormalities and mid-lumbar pain (P=0.02). However, inclusion of the ‘dark discs’ in the ‘pain generators’ group increased the strength of the association between L5/S1 abnormalities and mid-lumbar pain (P< 0.01) and also resulted in the associations between L3/4 and L4/5 level abnormalities and sacroiliac area pain reaching statistical significance (P=0.02 and P< 0.01 respectively).

Conclusion: The significant statistical effect of considering ‘dark discs’ as ‘pain generators’ on the association between specific spinal level abnormalities and presence of back pain in well-defined areas suggests that the MRI appearance of a ‘dark disc’ should be considered an early stage in the degenerative process and not simply an effect of normal aging.

Exercise deters systemic diseases such as osteoporosis, sarcopenia, diabetes and obesity. Brief daily periods of low intensity vibration (LIV; <0.4g) is anabolic to bone and muscle, an adaptive response achieved in part by biasing mesenchymal stem cell (MSC) fate selection towards forming higher order connective tissues. In the clinic, LIV has protected the musculoskeletal system even under severe challenges such as Crohn Disease, Cerebral Palsy, and end-stage renal disease.

Low magnitude mechanical signals also suppress adipogenesis in the mouse, with reductions in subcutaneous and visceral fat. The starkly distinct response of these tissues (augment bone & muscle; suppress fat) suggests that LIV influences the differentiation pathway of MSCs. Extending this diet induced obesity model to 7 months increased total adiposity, accelerated age-related loss of trabecular bone and severely reduced B & T-cell number in the marrow and blood, shifting hematopoietic stem cells (HSC) towards the myeloid lineage. LIV introduced at 4 months rescued bone and B-cells to those levels measured in regular diet controls.

These data emphasise why inactivity can promote osteoporosis, diabetes and obesity, and why a sedentary individual is predisposed to disease sequelae. Protection of MSC and HSC populations by mechanical signals may represent a unique strategy by which adiposity can be suppressed, the immune system protected, and a musculoskeletal system enhanced.

Aging impairs the regenerative capacity of musculoskeletal tissues and is associated with poor healing outcomes. PolgA. D257A/D257A. (PolgA) mice present a premature aging phenotype due to the accumulation of mitochondrial DNA (mtDNA) point mutations at rates 3 – 5 fold higher compared to wild type mice. Consequently, PolgA mice exhibit the premature onset of clinically-relevant musculoskeletal aging characteristics including frailty, osteo-sarcopenia, and kyphosis. I will present our recent findings on the use of PolgA mice to investigate the effects of aging on the regenerative capacity of bone. In particular, I will focus on the mechano-sensitivity of the regenerative process in aged bone environments and the opportunities it presents for clinical translation of mechanical intervention therapies

Both total joint arthroplasty (TJA) and Alzheimer's Disease (AD) are prevalent in elderly populations. It is the goal of this study to determine if the presence of implant metals originating from TJA correlates with the onset with higher implant metal content in the brain and AD pathology. Tissue samples from four brain regions of 701 (229 with TJA) participants from an ongoing longitudinal cohort study (Rush Memory and Aging Project) was analyzed including the inferior-temporal-cortex (ITC), which is associated with early onset of AD. Implant metal (Co, Cr, Mo, Ti, Al) content was determined by ICP-MS. Comparisons were conducted between the no-TJA-group and a TJA group. Due to the higher likelihood of Co release the TJA group was further differentiated in a THA (N=146) and a TKA/TSA (N=83) group. Diffuse and neuritic amyloid plaques and phosphorylated tau were assessed and summarized as standard measures of AD pathology. We used separate linear regression models adjusted for age, sex, education, and APOɛ4-status for the associations of all metals (log-transformed) with global AD pathology, amyloid plaques, and phosphorylated tau. The THA group had higher cobalt content across all brain regions (p=0.003) and within the ITC (p=0.051) compared to the no-TJA group, whereas the TKA/TSA group did not. Across all tissue samples, Co was associated with higher amyloid load (β=0.35, p=0.027), phosphorylated tau (β=0.47, p=0.011), and global AD pathology (β=0.19, 0.0004) in the ITC. The presence of TJA itself was not associated with AD pathology. We showed that only Co content was higher within the ITC in persons with THA. We found among all tested metals that Co was consistently associated with AD pathology. Although we found an association of cobalt with AD pathology, the cross-sectional nature of this study does not allow the determination of cause and effect

Osteoporosis accounts for a leading cause of degenerative skeletal disease in the elderly. Osteoblast dysfunction is a prominent feature of age-induced bone loss. While microRNAs regulate osteogenic cell behavior and bone mineral acquisition, however, their function to osteoblast senescence during age-mediated osteoporosis remains elusive. This study aims to utilize osteoblast-specific microRNA-29a (miR-29a) transgenic mice to characterize its role in bone cell aging and bone mass. Young (3 months old) and aged (9 months old) transgenic mice overexpressing miR-29a (miR-29aTg) driven by osteocalcin promoter and wild-type (WT) mice were bred for study. Bone mineral density, trabecular morphometry, and biomechanical properties were quantified using μCT imaging, material testing system and histomorphometry. Aged osteoblasts and senescence markers were probed using immunofluorescence, flow cytometry for apoptotic maker annexin V, and RT-PCR. Significantly decreased bone mineral density, sparse trabecular morphometry (trabecular volume, thickness, and number), and poor biomechanical properties (maximum force and breaking force) along with low miR-29a expression occurred in aged WT mice. Aging significantly upregulated the expression of senescence markers p16INK4a, p21Waf/Cip1, and p53 in osteoporotic bone in WT mice. Of note, the severity of bone mass and biomechanical strength loss, as well as bone cell senescence, was remarkably compromised in aged miR-29aTg mice. In vitro, knocking down miR-29a accelerated senescent (β-galactosidase activity and senescence markers) and apoptotic reactions (capsas3 activation and TUNEL staining), but reduced mineralized matrix accumulation in osteoblasts. Forced miR-29a expression attenuated inflammatory cytokine-induced aging process and retained osteogenic differentiation capacity. Mechanistically, miR-29a dragged osteoblast senescence through targeting 3′-untranslated region of anti-aging regulator FoxO3 to upregulate that of expression as evident from luciferase activity assessment. Low miR-29a signaling speeds up aging-induced osteoblast dysfunction and osteoporosis development. Gain of miR-29a function interrupts osteoblast senescence and shields bone tissue from age-induced osteoporosis. The robust analysis sheds light to the protective actions of miR-29a to skeletal metabolism and conveys a perspective of miR-29a signaling enhancement beneficial for aged skeletons

Purpose. Back pain is the primary cause of disability worldwide yet surprisingly little is known of the underlying pathobiology. We conducted a genome-wide association study (GWAS) meta-analysis of chronic back pain (CBP). Adults of European ancestry from 15 cohorts in the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, and UK Biobank were studied. Methods. CBP cases were defined as reporting back pain present for ≥3–6 months; non-cases were included as comparisons (“controls”). Each cohort conducted genotyping followed by imputation. GWAS used logistic regression with additive genetic effects adjusting for age, sex, study-specific covariates, and population substructure. Suggestive (p<5×10. –7. ) & genome-wide significant (p<5×10. –8. ) variants were carried forward for replication in an independent sample of UK Biobank participants. Discovery sample n = 158,025 individuals, including 29,531 CBP cases. Results. Genome-wide significant association was found for intron variant rs12310519 in SOX5 (OR=1.08, p=7.2×10. −10. ). This was replicated in the independent sample n = 283,752, comprising 50,915 cases (OR 1.06, p=5.3×10. −11. ); in joint meta-analysis OR=1.07, p=4.5×10. −19. exceeding genome-wide significance. We found three other suggestive associations in discovery, two of which exceeded genome-wide significance in joint meta-analysis: an intergenic variant rs7833174 located between CCDC26 and GSDMC (OR 1.05, p=4.4×10. −13. ), and an intron variant, rs4384683, in DCC (OR 0.97, p=2.4×10. −10. ). Conclusion. We have identified and replicated a genetic locus associated with CBP (SOX5). We also identified 2 other loci that reached genome-wide significance in a 2-stage joint meta-analysis (CCDC26/GSDMC and DCC) which will shed light on the pathogenic mechanisms underlying CBP. Conflicts of interest: YA and LK are owners of Maatschap PolyOmica. This study was supported by the European Community's Seventh Framework Programme funded project PainOmics (Grant agreement n. 602736) and conducted using the UK Biobank Resource (project # 18219). CHARGE and other cohort-specific funding sources to be submitted- see below

Aging has been associated with decreases in muscle strength and bone quality. In elderly patients, paravertebral muscle atrophy is accompanied by vertebral osteoporosis. The purpose of this study was to use paravertebral injection of botulinum toxin-A (BTX) to investigate the effects of paravertebral muscle atrophy on lumbar vertebral bone quality. Forty 16-week-old female SD rats were randomly divided into four groups: (1) a control group (CNT); (2) a resection of erector spinae muscles group (RESM); (3) a botulinum toxin-A group (BTX) that was treated with local injection of 5U BTX into the paravertebral muscles bilaterally; and (4) a positive control group (OVX) that underwent bilateral ovariectomy. At 3 months post-surgery the lumbar vertebrae (L3 – L6) were collected. The BMDs of the RESM and BTX groups were significantly lower than that of the CNT group (P < 0.01). Micro-CT scans showed that rats in the three experimental groups had fewer trabeculae and trabecular connections than rats in the CNT group. The bone loss trend of the trabecular networks was most obvious in the OVX rats. Vertebral compression testing revealed that the three experimental groups had significantly lower maximum load, energy absorption, maximum stress, and elastic modulus values than the CNT group (P < 0.01), and these parameters were lowest in the OVX group (P < 0.05). Our results demonstrate that the new paravertebral muscle atrophy model using local BTX injection causes sufficient muscle atrophy and dysfunction to result in local lumbar vertebral bone loss and quality deterioration