Extracellular matrix (ECM) remodeling is important during bone development and repair. Because matrix metalloproteinase 13 (MMP13, collagenase-3) plays a role in long bone development, we have examined its role during adult skeletal repair. In this study we find that MMP13 is expressed by hypertrophic chondrocytes and osteoblasts in the fracture callus. We demonstrate that MMP13 is required for proper resorption of hypertrophic cartilage and for normal bone remodeling during non-stabilized fracture healing, which occurs via endochondral ossification. However, no difference in callus strength was detected in the absence of MMP13. Transplant of wild-type bone marrow, which reconstitutes cells only of the hematopoietic lineage, did not rescue the endochondral repair defect, indicating that impaired healing in Mmp13−/− mice is intrinsic to cartilage and bone. Mmp13−/− mice also exhibited altered bone remodeling during healing of stabilized fractures and cortical defects via intramembranous ossification. This indicates that the bone phenotype occurs independently from the cartilage phenotype. Taken together, our findings demonstrate that MMP13 is involved in normal remodeling of bone and cartilage during adult skeletal repair, and that MMP13 may act directly in the initial stages of ECM degradation in these tissues prior to invasion of blood vessels and osteoclasts.
Patient-specific measures derived from quantitative computed tomography (QCT) scans are currently being developed as a clinical tool for vertebral strength prediction. QCT-based measurement techniques vary greatly in structural complexity and generally fall into one of three categories: 1) bone mineral density (BMD), 2) "mechanics of solids" (MOS) models, such as minimum axial rigidity (the product of axial stiffness and vertebral height), or 3) three dimensional finite element (FE) models. There is no clear consensus as to the relative performance of these measures due to differences in experimental protocols, sample sizes and demographics, and outcome metrics. The goal of this study was to directly compare the performance of QCT-based assessment techniques of varying degrees of structural sophistication in predicting experimental vertebral compressive strength. Eighty-one human thoracic vertebrae (T6 -T10) from 44 donors cadavers (F = 32, M = 12; 85 + 8 y.o., max = 97 y.o., min = 54 y.o.) were QCT scanned and destructively tested in uniaxial compression. The QCT scans were processed to generate FE models and various BMD and MOS measures, including trabecular bone mineral density (tBMD), integral bone mineral density (iBMD), and axial rigidity. Bone mineral density was weakly to moderately predictive of compressive strength (R 2 = 0.16 and 0.62 for tBMD and iBMD, respectively). Ex vivo vertebral strength was strongly correlated with both axial rigidity (R 2 = 0.81) and FE strength measurements (R 2 = 0.80), and the predictive capabilities of these two metrics were statistically equivalent (p > 0.05 for differences between FE and axial rigidity). The results of this study indicate that non-invasive predictive measures of vertebral strength should include some level of structural sophistication, specifically, gross geometric and material property distribution information. However, for uniaxial compression of isolated vertebrae, which is the current biomechanical testing paradigm for new non-invasive strength assessment techniques, QCT-based FE and axial rigidity measures are equivalent predictors of experimental strength. However, before abandoning the FE method in favor of more simplistic techniques, future work should investigate the performance of the FE method versus MOS measures for more physiologically representative loading conditions, e.g., anterior bending or in situ loading with intervertebral discs intact.
In the setting of ankle fractures with syndesmosis disruption, fixing the fibula in as much as 30 degrees of external rotation may go undetected using intraoperative fluoroscopy alone.
Background Orthopaedic surgery lags behind other surgical specialties in terms of gender diversity. The percentage of women entering orthopaedic residency persistently remains at 14% despite near equal ratios of women to men in medical school classes. This trend has been attributed to negative perceptions among women medical students of workplace culture and lifestyle in orthopaedics as well as lack of exposure, particularly during medical school when most women decide to enter the field. Since 2012, The Perry Initiative, a nonprofit organization that is focused on recruiting and retaining women in orthopaedics, had conducted extracurricular outreach programs for first-and second-year female medical students to provide exposure and mentoring opportunities specific to orthopaedics. This program, called the Medical Student Outreach Program (MSOP), is ongoing at medical centers nationwide and has reached over 300 medical students in its first 3 program years (2012)(2013)(2014). Questions/purposes (1) What percentage of MSOP participants eventually match into orthopaedic surgery residency? (2) Does MSOP impact participants' perceptions of the orthopaedics profession as well as intellectual interest in the field? Methods The percentage of program alumnae who matched into orthopaedics was determined by annual followup for our first two cohorts who graduated from medical school. All program participants completed a survey immediately before and after the program that assessed the impact of MSOP on the student's intention to pursue orthopaedics as well as perceptions of the field and intellectual interest in the discipline. 123Clin Orthop Relat Res (2016) 474:1962-1966 DOI 10.1007 Clinical Orthopaedics and Related Research ® A Publication of The Association of Bone and Joint Surgeons®Results The orthopaedic surgery match rate for program participants was 31% in our first graduating class (five of 16 participants in 2015) and 28% in our second class (20 of 72 participants in 2016). Pre/post program comparisons showed that the MSOP influenced students' perceptions of the orthopaedics profession as well as overall intellectual interest in the field. Conclusions The results of our study suggest that The Perry Initiative's MSOP positively influences women to choose orthopaedic surgery as a profession. The match rate for program alumnae is twice the percentage of females in current orthopaedic residency classes. Given these positive results, MSOP can serve as a model, both in its curricular content and logistic framework, for other diversity initiatives in the field.
Intraoperative contouring of posterior rods in lumbar arthrodesis constructs introduces stress concentrations that can substantially reduce fatigue life. The sensitivity of titanium (Ti) and stainless steel (SS) to intraoperative contouring has been established in the literature; however, notch sensitivity has yet to be quantified for cobalt chrome (CoCr), which is now being advocated for use in posterior arthrodesis constructs. The goal of this study is to evaluate the sensitivity of CoCr rods to intraoperative contouring for posterior lumbar screwrod arthrodesis constructs. In this paper lumbar bilateral vertebrectomy models are constructed based on ASTM F1717-01 with curved rods (26-30 degrees total curvature) and poly-axial pedicle screws. Three types of constructs are assembled: first, 5.5 mm SS rods with SS screws (6.5 x 35 mm), second, 6.0 mm Ti rods with Ti screws (7.5 x 35 mm), and third, 6.0 mm CoCr rods with Ti screws (7.5 x 35 mm). All specimens are tested at 4 Hz in dynamic axial compression-bending with a load ratio of ten and maximum load levels of 250, 400, and 700 N until run-out at 2 000 000 cycles. Results are presented that show that the fatigue life of CoCr constructs tend to be greater than Ti constructs at all levels. At the 400 N maximum loading, CoCr lasts an average of 350 000 cycles longer than the Ti constructs. The CoCr constructs are able to sustain the 250 N load until run-out at 2 000 000 cycles but they fail at high load levels (maximum 700 N). The CoCr constructs fail at the neck of the Ti screw at high loads whereas Ti screws fail at the notch induced by contouring. Since CoCr is compatible with magnetic resonance imaging and has high static strength characteristics, the results of this study suggest that it may be an appropriate substitute for Ti.
Tissue mechanical properties reflect extracellular matrix composition and organization, and as such, their changes can be a signature of disease. Examples of such diseases include intervertebral disk degeneration, cancer, atherosclerosis, osteoarthritis, osteoporosis, and tooth decay. Here we introduce the tissue diagnostic instrument (TDI), a device designed to probe the mechanical properties of normal and diseased soft and hard tissues not only in the laboratory but also in patients. The TDI can distinguish between the nucleus and the annulus of spinal disks, between young and degenerated cartilage, and between normal and cancerous mammary glands. It can quantify the elastic modulus and hardness of the wet dentin left in a cavity after excavation. It can perform an indentation test of bone tissue, quantifying the indentation depth increase and other mechanical parameters. With local anesthesia and disposable, sterile, probe assemblies, there has been neither pain nor complications in tests on patients. We anticipate that this unique device will facilitate research on many tissue systems in living organisms, including plants, leading to new insights into disease mechanisms and methods for their early detection.
Our results suggest that the poor clinical performance of noninvasive structural measures may be due to their inability to predict vertebral strength under bending loads. While their performance was not statistically better than MOS bending rigidities, QCT-based FE models were moderate predictors of both compressive and bending loads at failure, suggesting that this technique has the potential for strength prediction under nonuniform loads. The current FE modeling strategy is insufficient, however, and significant modifications must be made to better mimic whole bone elastic and inelastic material behavior.
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