Aging is associated with impaired tissue regeneration. Stem cell number and function have been identified as potential culprits. We first demonstrate a direct correlation between stem cell number and time to bone fracture union in a human patient cohort. We then devised an animal model recapitulating this age-associated decline in bone healing and identified increased cellular senescence caused by a systemic and local proinflammatory environment as the major contributor to the decline in skeletal stem/progenitor cell (SSPC) number and function. Decoupling age-associated systemic inflammation from chronological aging by using transgenic Nfkb1KO mice, we determined that the elevated inflammatory environment, and not chronological age, was responsible for the decrease in SSPC number and function. By using a pharmacological approach inhibiting NF-κB activation, we demonstrate a functional rejuvenation of aged SSPCs with decreased senescence, increased SSPC number, and increased osteogenic function. Unbiased, whole-genome RNA sequencing confirmed the reversal of the aging phenotype. Finally, in an ectopic model of bone healing, we demonstrate a functional restoration of regenerative potential in aged SSPCs. These data identify aging-associated inflammation as the cause of SSPC dysfunction and provide mechanistic insights into its reversal. regeneration | skeletal stem cell | senescence | inflammation | bone healing
Background:Basketball players are at risk for foot injuries, including Jones fractures. It is unknown how this injury affects the future play and performance of athletes.Hypothesis:National Basketball Association (NBA) players who sustain Jones fractures of the base of the fifth metatarsal have high rates of return to play and do not experience a decrease in performance on return to competition when compared with preinjury and with control-matched peers.Study Design:Retrospective cohort study.Level of Evidence:Level 5.Methods:Data on 26 elite basketball players with Jones fractures over 19 NBA seasons (1994-1995 to 2012-2013) were obtained from injury reports, press releases, player profiles, and online public databases. Variables included age, body mass index (BMI), player position, experience, and surgical treatment. Individual season statistics pre- and postinjury were collected. Twenty-six controls were identified by matched player position, age, and performance statistics.Results:The mean age at the time of injury was 24.8 years, mean BMI was 24.7 kg/m2, and the mean experience prior to injury was 4.1 NBA seasons. Return to previous level of competition was achieved by 85% of athletes. There was no change in player efficiency rating (PER) when pre- and postinjury performance was compared. When compared with controls, no decline in PER measured performance was identified.Conclusion:The majority of NBA players sustaining a Jones fracture return to their preinjury level of competition. These elite athletes demonstrate no decrease in performance on their return to play.Clinical Relevance:Jones fractures are well-studied injuries in terms of etiology, diagnosis, and management. However, the effect of these injuries on future performance of athletes is unknown. Using the findings of our study, orthopaedic surgeons may be better prepared to counsel and educate elite athletes who sustain a Jones fracture.
This study shows that our novel model can be used to study subchondral microdamage after ACL-rupture, and its association with localized remodeling. Cartilage degeneration, on a similar time-scale to other models, is also a feature of this system.
This study demonstrates that surgeons do not currently uniformly agree on ideal single-bundle tunnel placement and that the TT technique may yield more poorly placed tunnels.
Purpose To describe a nonlinear finite element analysis method by using magnetic resonance (MR) images for the assessment of the mechanical competence of the hip and to demonstrate the reproducibility of the tool. Materials and Methods This prospective study received institutional review board approval and fully complied with HIPAA regulations for patient data. Written informed consent was obtained from all subjects. A nonlinear finite element analysis method was developed to estimate mechanical parameters that relate to hip fracture resistance by using MR images. Twenty-three women (mean age ± standard deviation, 61.7 years ± 13.8) were recruited from a single osteoporosis center. To thoroughly assess the reproducibility of the finite element method, three separate analyses were performed: a test-retest reproducibility analysis, where each of the first 13 subjects underwent MR imaging on three separate occasions to determine longitudinal variability, and an intra- and interoperator reproducibility analysis, where a single examination was performed in each of the next 10 subjects and four operators independently performed the analysis two times in each of the subjects. Reproducibility of parameters that reflect fracture resistance was assessed by using the intraclass correlation coefficient and the coefficient of variation. Results For test-retest reproducibility analysis and inter- and intraoperator analyses for proximal femur stiffness, yield strain, yield load, ultimate strain, ultimate load, resilience, and toughness in both stance and sideways-fall loading configurations each had an individual median coefficient of variation of less than 10%. Additionally, all measures had an intraclass correlation coefficient higher than 0.99. Conclusion This experiment demonstrates that the finite element analysis model can consistently and reliably provide fracture risk information on correctly segmented bone images. RSNA, 2016 Online supplemental material is available for this article.
Background: Rotator cuff disease is a major medical and economic burden due to a growing aging population, but management of rotator cuff tears remains controversial. We hypothesized that there is no difference in outcomes between patients who undergo rotator cuff repair and matched patients treated nonoperatively. Methods: After institutional review board approval, a prospective cohort of patients over 18 years of age who had a full-thickness rotator cuff tear seen on magnetic resonance imaging (MRI) were retrospectively evaluated. After clinical evaluation, each patient elected to undergo either rotator cuff repair or nonsurgical treatment. Demographic information was collected at enrollment, and self-reported outcome measures (the Normalized Western Ontario Rotator Cuff Index [WORCnorm], American Shoulder and Elbow Surgeons score [ASES], Single Assessment Numerical Evaluation [SANE], and pain score on a visual analog scale [VAS]) were collected at baseline and at 6, 12, and >24 months. The Functional Comorbidity Index (FCI) was used to assess health status at enrollment. The size and degree of atrophy of the rotator cuff tear were classified on MRI. Propensity score analysis was used to create rotator cuff repair and nonsurgical groups matched by age, sex, symptom duration, FCI, tear size, injury mechanism, and atrophy. The Student t test, chi-square test, and regression analysis were used to compare the treatment groups. Results: One hundred and seven patients in each group were available for analysis after propensity score matching. There were no differences between the groups with regard to demographics or rotator cuff tear characteristics. For all outcome measures at the time of final follow-up, the rotator cuff repair group had significantly better outcomes than the nonsurgical treatment group (p < 0.001). At the time of final follow-up, the mean outcome scores (and 95% confidence interval) for the surgical repair and nonsurgical treatment groups were, respectively, 81.4 (76.9, 85.9) and 68.8 (63.7, 74.0) for the WORCnorm, 86.1 (82.4, 90.3) and 76.2 (72.4, 80.9) for the ASES, 77.5 (70.6, 82.5) and 66.9 (61.0, 72.2) for the SANE, and 14.4 (10.2, 20.2) and 27.8 (22.5, 33.5) for the pain VAS. In the longitudinal regression analysis, better outcomes were independently associated with younger age, shorter symptom duration, and rotator cuff repair. Conclusions: Patients with a full-thickness rotator cuff tear reported improvement in pain and functional outcome scores with nonoperative treatment or surgical repair. However, patients who were offered and chose rotator cuff repair reported greater improvement in outcome scores and reduced pain compared with those who chose nonoperative treatment. Level of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
Purpose To investigate whether assessment of bone strength with quantitative computed tomography (CT) in combination with dual-energy x-ray absorptiometry (DXA) is cost-effective as a screening tool for osteoporosis in postmenopausal women. Materials and Methods A state-transition microsimulation model of osteoporosis for postmenopausal women aged 55 years or older was developed with a lifetime horizon and U.S. societal perspective. All model inputs were derived from published literature. Three strategies were compared: no screening, DXA with T score–dependent rescreening intervals, and a combination of DXA and quantitative CT with different intervals (3, 5, and 10 years) at different screening initiation ages (55–65 years). Oral bisphosphonate therapy was started if DXA hip T scores were less than or equal to −2.5, 10-year risk for hip fracture was greater than 3% (World Health Organization Fracture Risk Assessment Tool score, or FRAX), 10-year risk for major osteoporotic fracture was greater than 20% (FRAX), quantitative CT femur bone strength was less than 3000 N, or occurrence of first fracture (eg, hip, vertebral body, wrist). Outcome measures were incremental cost-effectiveness ratios (ICERs) in 2015 U.S. dollars per quality-adjusted life year (QALY) gained and number of fragility fractures. Probabilistic sensitivity analysis was also performed. Results The most cost-effective strategy was combined DXA and quantitative CT screening starting at age 55 with quantitative CT screening every 5 years (ICER, $2000 per QALY). With this strategy, 12.8% of postmenopausal women sustained hip fractures in their remaining life (no screening, 18.7%; DXA screening, 15.8%). The corresponding percentages of vertebral fractures for DXA and quantitative CT with a 5-year interval, was 7.5%; no screening, 11.1%; DXA screening, 9%; for wrist fractures, 14%, 17.8%, and 16.4%, respectively; for other fractures, 22.6%, 30.8%, and 27.3%, respectively. In probabilistic sensitivity analysis, DXA and quantitative CT at age 55 years with quantitative CT screening every 5 years was the best strategy in more than 90% of all 1000 simulations (for thresholds of $50 000 per QALY and $100 000 per QALY). Conclusion Combined assessment of bone strength and bone mineral density is a cost-effective strategy for osteoporosis screening in postmenopausal women and has the potential to prevent a substantial number of fragility fractures.
Background:The aim was to determine whether players in the National Basketball Association (NBA) who sustain metacarpal fractures demonstrate decreased performance upon return to competition when compared with their performance before injury and that of their control-matched peers. Methods: Data for 32 NBA players with metacarpal fractures incurred over 11 seasons (2002-2003 to 2012-2013) were obtained from injury reports, press releases, and player profiles (www.nba.com and www.basketballreference.com). Player age, body mass index (BMI), position, shooting hand, number of years in the league, and treatment (surgical vs nonsurgical) were recorded. Individual season statistics for the 2 seasons immediately prior to injury and the 2 seasons after injury, including player efficiency rating (PER), were obtained. Thirty-two controls matched by player position, age, and performance statistics were identified. A performance comparison of the cohorts was performed. Results: Mean age at the time of injury was 27 years with an average player BMI of 24. Players had a mean 5.6 seasons of NBA experience prior to injury. There was no significant change in PER when preinjury and postinjury performances were compared. Neither injury to their shooting hand nor operative management of the fracture led to a decrease in performance during the 2 seasons after injury. When compared with matched controls, no significant decline in performance in PER the first season and second season after injury was found. Conclusion: NBA players sustaining metacarpal fractures can reasonably expect to return to their preinjury performance levels following appropriate treatment.
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