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Dive into the research topics where Natalie H. Kelly is active.

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Featured researches published by Natalie H. Kelly.


Journal of Bone and Joint Surgery, American Volume | 2010

Dynamic Contact Mechanics of the Medial Meniscus as a Function of Radial Tear, Repair, and Partial Meniscectomy

Asheesh Bedi; Natalie H. Kelly; Michael Baad; Alice J.S. Fox; Robert H. Brophy; Russell F. Warren; Suzanne A. Maher

BACKGROUND The menisci are integral to normal knee function. The purpose of this study was to measure the contact pressures transmitted to the medial tibial plateau under physiological loads as a function of the percentage of the meniscus involved by the radial tear or repair. Our hypotheses were that (1) there is a threshold size of radial tears above which contact mechanics are adversely affected, and (2) partial meniscectomy results in increased contact pressure compared with that found after meniscal repair. METHODS A knee simulator was used to apply physiological multidirectional dynamic gait loads across human cadaver knees. A sensor inserted below the medial meniscus recorded contact pressures in association with (1) an intact meniscus, (2) a radial tear involving 30% of the meniscal rim width, (3) a radial tear involving 60% of the width, (4) a radial tear involving 90% of the width, (5) an inside-out repair with horizontal mattress sutures, and (6) a partial meniscectomy. The effects of these different types of meniscal manipulation on the magnitude and location of the peak contact pressure were assessed at 14% and 45% of the gait cycle. RESULTS The peak tibial contact pressure in the intact knees was 6 +/- 0.5 MPa and 7.4 +/- 0.6 MPa at 14% and 45% of the gait cycle, respectively. The magnitude and location of the peak contact pressure were not affected by radial tears involving up to 60% of the meniscal rim width. Radial tears involving 90% resulted in a posterocentral shift in peak-pressure location manifested by an increase in pressure in that quadrant of 1.3 +/- 0.5 MPa at 14% of the gait cycle relative to the intact condition. Inside-out mattress suture repair of a 90% tear did not restore the location of the pressure peak to that of the intact knee. Partial meniscectomy led to a further increase in contact pressure in the posterocentral quadrant of 1.4 +/- 0.7 MPa at 14% of the gait cycle. CONCLUSIONS Large radial tears of the medial meniscus are not functionally equivalent to meniscectomies; the residual meniscus continues to provide some load transmission and distribution functions across the joint.


Journal of Bone and Mineral Research | 2014

Female mice lacking estrogen receptor-alpha in osteoblasts have compromised bone mass and strength.

Katherine M Melville; Natalie H. Kelly; Sohaib A. Khan; John C. Schimenti; F. Patrick Ross; Russell P. Main; Marjolein C. H. van der Meulen

Reduced bioavailability of estrogen increases skeletal fracture risk in postmenopausal women, but the mechanisms by which estrogen regulates bone mass are incompletely understood. Because estrogen signaling in bone acts, in part, through estrogen receptor alpha (ERα), mice with global deletion of ERα (ERαKO) have been used to determine the role of estrogen signaling in bone biology. These animals, however, have confounding systemic effects arising from other organs, such as increased estrogen and decreased insulin‐like growth factor 1 (IGF‐1) serum levels, which may independently affect bone. Mice with tissue‐specific ERα deletion in chondrocytes, osteoblasts, osteocytes, or osteoclasts lack the systemic effects seen in the global knockout, but show that presence of the receptor is important for the function of each cell type. Although bone mass is reduced when ERα is deleted from osteoblasts, no study has determined if this approach reduces whole bone strength. To address this issue, we generated female osteoblast‐specific ERαKO mice (pOC‐ERαKO) by crossing mice expressing a floxed ERα gene (ERαfl/fl) with mice transgenic for the osteocalcin‐Cre promoter (OC‐Cre). Having confirmed that serum levels of estrogen and IGF‐1 were unaltered, we focused on relating bone mechanics to skeletal phenotype using whole bone mechanical testing, microcomputed tomography, histology, and dynamic histomorphometry. At 12 and 18 weeks of age, pOC‐ERαKO mice had decreased cancellous bone mass in the proximal tibia, vertebra, and distal femur, and decreased cortical bone mass in the tibial midshaft, distal femoral cortex, and L5 vertebral cortex. Osteoblast activity was reduced in cancellous bone of the proximal tibia, but osteoclast number was unaffected. Both femora and vertebrae had decreased whole bone strength in mechanical tests to failure, indicating that ERα in osteoblasts is required for appropriate bone mass and strength accrual in female mice. This pOC‐ERαKO mouse is an important animal model that could enhance our understanding of estrogen signaling in bone cells in vivo.


Arthroscopy | 2012

Dynamic Contact Mechanics of Radial Tears of the Lateral Meniscus: Implications for Treatment

Asheesh Bedi; Natalie H. Kelly; Michael Baad; Alice J.S. Fox; Yan Ma; Russell F. Warren; Suzanne A. Maher

PURPOSE To characterize the effect of radial tears (RTs) of the lateral meniscus and their subsequent treatment (inside-out repair, partial meniscectomy) on joint contact mechanics during simulated gait. METHODS Six human cadaveric knees were mounted on a simulator programmed to mimic human gait. A sensor was inserted below the lateral meniscus to measure peak joint contact pressure location, magnitude, and contact area. The following conditions were compared: intact meniscus, 30% RT (at the popliteal hiatus), 60% RT, 90% RT, repair, and partial meniscectomy. Data were analyzed in the midstance phase of gait (14% and 45%) when axial force was at its highest (2,100 N). RESULTS Intact knees had peak contact pressures of 5.9 ± 0.9 MPa and 6.4 ± 1.1 MPa at 14% and 45% of gait, respectively. RTs of up to and including 60% had no effect on pressure magnitude or location. RTs of 90% resulted in significantly increased peak pressure (8.4 ± 1.1 MPa) in the postero-peripheral aspect of the tibial plateau and reduced contact area versus the intact knee, at 45% of gait. Repair resulted in a significant decrease in peak pressure (7.7 ± 1.0 MPa) relative to 90% RT but had no effect on contact area. Partial lateral meniscectomy resulted in areas and pressures that were not significantly different from 90% tears (8.7 ± 1.5 MPa). CONCLUSIONS Simulated large RTs of the lateral meniscus in the region of the popliteal hiatus show unfavorable dynamic contact mechanics that are not significantly different from those resulting from a partial lateral meniscectomy. Pressure was significantly reduced with inside-out repair but was not affected by partial meniscectomy; contact area was not restored to that of the intact condition for either procedure. CLINICAL RELEVANCE Large RTs in the region of the popliteal hiatus show unfavorable dynamic contact mechanics.


Journal of Bone and Mineral Research | 2014

Mechanical Load Increases in Bone Formation via a Sclerostin‐Independent Pathway

Alyson Morse; Michelle M. McDonald; Natalie H. Kelly; Katherine M Melville; Aaron Schindeler; Ina Kramer; Michaela Kneissel; Marjolein C. H. van der Meulen; David G. Little

Sclerostin, encoded by the Sost gene, is an important negative regulator of bone formation that has been proposed to have a key role in regulating the response to mechanical loading. To investigate the effect of long‐term Sclerostin deficiency on mechanotransduction in bone, we performed experiments on unloaded or loaded tibiae of 10 week old female Sost−/− and wild type mice. Unloading was induced via 0.5U botulinum toxin (BTX) injections into the right quadriceps and calf muscles, causing muscle paralysis and limb disuse. On a separate group of mice, increased loading was performed on the left tibiae through unilateral cyclic axial compression of equivalent strains (+1200 µe) at 1200 cycles/day, 5 days/week. Another cohort of mice receiving equivalent loads (−9.0 N) also were assessed. Contralateral tibiae served as normal load controls. Loaded/unloaded and normal load tibiae were assessed at day 14 for bone volume (BV) and formation changes. Loss of BV was seen in the unloaded tibiae of wild type mice, but BV was not different between normal load and unloaded Sost−/− tibiae. An increase in BV was seen in the loaded tibiae of wild type and Sost−/− mice over their normal load controls. The increased BV was associated with significantly increased mid‐shaft periosteal mineralizing surface/bone surface (MS/BS), mineral apposition rate (MAR), and bone formation rate/bone surface (BFR/BS), and endosteal MAR and BFR/BS. Notably, loading induced a greater increase in periosteal MAR and BFR/BS in Sost−/− mice than in wild type controls. Thus, long‐term Sclerostin deficiency inhibits the bone loss normally induced with decreased mechanical load, but it can augment the increase in bone formation with increased load.


Clinical Orthopaedics and Related Research | 2011

Retrieved Highly Crosslinked UHMWPE Acetabular Liners Have Similar Wear Damage as Conventional UHMWPE

David T. Schroder; Natalie H. Kelly; Timothy M. Wright; Michael L. Parks

BackgroundHighly crosslinked UHMWPE is associated with increased wear resistance in hip simulator and clinical studies. Laboratory and case studies, however, have described rim fracture in crosslinked acetabular liners. Controversy exists, therefore, on the relative merits of crosslinked liners over conventional liners in terms of wear performance versus resistance to fatigue cracking.Questions/purposesWe asked whether crosslinked liners would show less surface damage than conventional liners but would be more susceptible to fatigue damage.MethodsWe examined 36 conventional UHMWPE and 39 crosslinked UHMWPE retrieved implants with similar patient demographics and identical design for evidence of wear damage, including articular surface damage, impingement, screw-hole creep, and rim cracks.ResultsWe observed no difference in wear damage scores for the two liners. Conventional liners more frequently impinged but were more often elevated with smaller head sizes. We observed creep in approximately 70% of both types of liners. Incipient rim cracks were found in five crosslinked liners, and one liner had a rim fracture. Only one conventional liner had an incipient rim crack.ConclusionsContrary to our expectation, damage was similar between crosslinked and conventional UHMWPE liners. Moreover, the 15% occurrence (six of 39) of incipient or complete fractures in crosslinked liners as compared with a 3% occurrence (one of 36) in conventional liners may have implications for the long-term performance of crosslinked liners. Longer-term studies will be necessary to establish the fate of rim cracks and thus the overall clinical fatigue performance of crosslinked liners.


Clinical Orthopaedics and Related Research | 2011

Wear Damage in Mobile-bearing TKA is as Severe as That in Fixed-bearing TKA

Natalie H. Kelly; Rose H. Fu; Timothy M. Wright; Douglas E. Padgett

BackgroundMobile-bearing TKAs reportedly have no clinical superiority over fixed-bearing TKAs, but a potential benefit is improved polyethylene wear behavior.Questions/purposesWe asked whether extent of damage and wear patterns would be less severe on retrieved mobile-bearing TKAs than on fixed-bearing TKAs and if correlations with patient demographics could explain differences in extent or locations of damage.MethodsWe performed damage grading and mapping of 48 mobile-bearing TKAs retrieved due to osteolysis/loosening, infection, stiffness, instability or malpositioning. Visual grading used stereomicroscopy to identify damage, and a grade was assigned based on extent and severity. Each damage mode was then mapped onto a photograph of the implant surface, and the area affected was calculated.ResultsMarked wear damage occurred on both surfaces, with burnishing, scratching, and pitting the dominant modes. Damage occurred over a large portion of both surfaces, exceeding the available articular borders in nearly 30% of implants. Wear of mobile-bearing surfaces included marked third-body debris. Damage on tibiofemoral and mobile-bearing surfaces was not correlated with patient BMI or component alignment. Damage on mobile-bearing surfaces was positively correlated with length of implantation and was greater in implants removed for osteolysis or instability than in those removed for stiffness or infection.ConclusionsEach bearing surface in mobile-bearing implants was damaged to an extent similar to that in fixed-bearing implants, making the combined damage score higher than that for fixed-bearing implants. Mobile-bearing TKAs did not improve wear damage, providing another argument against the superiority of these implants over fixed-bearing implants.


Knee | 2011

Matched-pair total knee arthroplasty retrieval analysis: Oxidized zirconium vs. CoCrMo

Thomas J. Heyse; Dan X. Chen; Natalie H. Kelly; Friedrich Boettner; Timothy M. Wright; Steven B. Haas

Oxidized zirconium (OxZr) was introduced to serve as a ceramic surface for femoral components in TKA. The aim of this study was to compare retrieved OxZr components and corresponding PE inserts in matched comparison with conventional cobalt/chrome/molybdenum alloy (CoCrMo). Eleven retrieved posterior stabilized TKA with an OxZr femoral component were included. This included 6 implants from an earlier preliminary study. From a cohort of 56 retrieved TKA with conventional CoCrMo femoral components, pairs were matched according to duration of implantation, patient age, reason for revision, and BMI. Polyethylene inlays and femoral components were optically scored for in vivo damage. The average damage score of the tibial PE inserts was significantly lower with OxZr components (p=0.01). Mainly burnishing and scratches were found. The average wear score in the visual analysis of the femoral components was significantly lower for the OxZr as well (p=0.005). Femoral components made of OxZr were less sensitive to in vivo damage and corresponding PE inlays also showed less damage than CoCrMo components.


Journal of Arthroplasty | 2010

Unicondylar Knee Retrieval Analysis

Theodore T. Manson; Natalie H. Kelly; Joseph D. Lipman; Timothy M. Wright; Geoffrey H. Westrich

Unicondylar knee arthroplasty (UKA) is considered an alternative to total knee arthroplasty for patients who have arthritis limited to one compartment of the knee. This study examined surface damage of 3 contemporary UKA designs that were retrieved at revision surgery. Two of the UKA designs were fixed bearing and one was mobile bearing. Demographic information was collected, as well as information about the implants used at revision surgery. Articular surface damage was greater in the fixed-bearing designs as compared to the mobile bearing, although the mobile-bearing implants had significantly shorter length of implantation. Backside damage was also graded for the mobile bearing and when combined with articular wear resulted in overall damage scores higher than both fixed-bearing designs. The fixed-bearing designs showed delamination and surface deformation, whereas the mobile bearing had no evidence of these damage modes. However, mobile-bearing components showed other types of wear, and significant wear damage was present on the bearing surfaces of the mobile-bearing implants despite a short time of implantation. At the time of conversion to a total knee arthroplasty, more than 50% of cases required the use of stems, augments, or constrained inserts for the tibial reconstruction. In conclusion, wear modes differed among UKA prosthesis designs. Revision of a UKA to a total knee arthroplasty remains complex with the tibial preparation more complicated than in the primary setting.


Proceedings of the Institution of Mechanical Engineers, Part H: Journal of Engineering in Medicine | 2013

Changes in dynamic medial tibiofemoral contact mechanics and kinematics after injury of the anterior cruciate ligament: A cadaveric model

Asheesh Bedi; Tony Chen; Thomas J. Santner; Saadiq F. El-Amin; Natalie H. Kelly; Russell F. Warren; Suzanne A. Maher

The effects of tears of the anterior cruciate ligament on knee kinematics and contact mechanics during dynamic everyday activities, such as gait, remains unclear. The objective of this study was to characterize anterior cruciate ligament–deficient knee contact mechanics and kinematics during simulated gait. Nine human cadaveric knees were each augmented with a sensor capable of measuring dynamic normal contact stresses on the tibial plateau, mounted on a load-controlled simulator, and subjected to physiological, multidirectional, dynamic loads to mimic gait. Using a mixed model with random knee identifiers, confidence intervals were constructed for contact stress before and after anterior cruciate ligament transection at two points in the gait cycle at which axial force peaked (14% and 45% of the gait cycle). Kinematic and contact mechanics changes after anterior cruciate ligament transection were highly variable across knees. Nonetheless, a statistically significant increase in contact stress in the posterior–central aspect of the medial tibial plateau at 45% of the gait cycle was identified, the location of which corresponds to the location of degenerative changes that are frequently found in patients with chronic anterior cruciate ligament injury. The variability in the contact stress in other regions of the medial plateau at 45% of the gait cycle was partly explained by the variations in osseous geometry across the nine knees tested. At 14% of gait, there was no significant change in peak contact stress after anterior cruciate ligament transection in any of the four quadrants, and none of the possible explanatory variables showed statistical significance. Understanding the variable effect of anterior cruciate ligament injury on contact mechanics based on geometric differences in osseous anatomy is of paramount clinical importance and may be invaluable to select the best reconstruction techniques and counsel patients on their individual risk of subsequent chondral degeneration.


Journal of Bone and Mineral Research | 2015

Effects of Deletion of ERα in Osteoblast-Lineage Cells on Bone Mass and Adaptation to Mechanical Loading Differ in Female and Male Mice

Katherine M Melville; Natalie H. Kelly; Gina Surita; Daniel B Buchalter; John C. Schimenti; Russell P. Main; F. Patrick Ross; Marjolein C. H. van der Meulen

Estrogen receptor alpha (ERα) has been implicated in bones response to mechanical loading in both males and females. ERα in osteoblast lineage cells is important for determining bone mass, but results depend on animal sex and the cellular stage at which ERα is deleted. We demonstrated previously that when ERα is deleted from mature osteoblasts and osteocytes in mixed‐background female mice, bone mass and strength are decreased. However, few studies exist examining the skeletal response to loading in bone cell–specific ERαKO mice. Therefore, we crossed ERα floxed (ERαfl/fl) and osteocalcin‐Cre (OC‐Cre) mice to generate animals lacking ERα in mature osteoblasts and osteocytes (pOC‐ERαKO) and littermate controls (LC). At 10 weeks of age, the left tibia was loaded in vivo for 2 weeks. We analyzed bone mass through micro‐CT, bone formation rate by dynamic histomorphometry, bone strength from mechanical testing, and osteoblast and osteoclast activity by serum chemistry and immunohistochemistry. ERα in mature osteoblasts differentially regulated bone mass in males and females. Compared with LC, female pOC‐ERαKO mice had decreased cortical and cancellous bone mass, whereas male pOC‐ERαKO mice had equal or greater bone mass than LC. Bone mass results correlated with decreased compressive strength in pOC‐ERαKO female L5 vertebrae and with increased maximum moment in pOC‐ERαKO male femora. Female pOC‐ERαKO mice responded more to mechanical loading, whereas the response of pOC‐ERαKO male animals was similar to their littermate controls.

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Timothy M. Wright

Hospital for Special Surgery

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Suzanne A. Maher

Hospital for Special Surgery

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Douglas E. Padgett

Hospital for Special Surgery

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F. Patrick Ross

Hospital for Special Surgery

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Geoffrey H. Westrich

Hospital for Special Surgery

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Mathias Bostrom

Hospital for Special Surgery

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