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Thomas D. Brown

Bio: Thomas D. Brown is an academic researcher from University of Iowa. The author has contributed to research in topics: Femoral head & Contact mechanics. The author has an hindex of 58, co-authored 221 publications receiving 12436 citations. Previous affiliations of Thomas D. Brown include University of Pittsburgh & St Mary's Hospital.


Papers
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Journal ArticleDOI
TL;DR: This newer evidence suggests that AFFs are stress or insufficiency fractures, and studies with radiographic review consistently report significant associations between A FFs and BP use, although the strength and magnitude of effect vary.
Abstract: Reports linking long-term use of bisphosphonates (BPs) with atypical fractures of the femur led the leadership of the American Society for Bone and Mineral Research (ASBMR) to appoint a task force to address key questions related to this problem. A multidisciplinary expert group reviewed pertinent published reports concerning atypical femur fractures, as well as preclinical studies that could provide insight into their pathogenesis. A case definition was developed so that subsequent studies report on the same condition. The task force defined major and minor features of complete and incomplete atypical femoral fractures and recommends that all major features, including their location in the subtrochanteric region and femoral shaft, transverse or short oblique orientation, minimal or no associated trauma, a medial spike when the fracture is complete, and absence of comminution, be present to designate a femoral fracture as atypical. Minor features include their association with cortical thickening, a periosteal reaction of the lateral cortex, prodromal pain, bilaterality, delayed healing, comorbid conditions, and concomitant drug exposures, including BPs, other antiresorptive agents, glucocorticoids, and proton pump inhibitors. Preclinical data evaluating the effects of BPs on collagen cross-linking and maturation, accumulation of microdamage and advanced glycation end products, mineralization, remodeling, vascularity, and angiogenesis lend biologic plausibility to a potential association with long-term BP use. Based on published and unpublished data and the widespread use of BPs, the incidence of atypical femoral fractures associated with BP therapy for osteoporosis appears to be very low, particularly compared with the number of vertebral, hip, and other fractures that are prevented by BPs. Moreover, a causal association between BPs and atypical fractures has not been established. However, recent observations suggest that the risk rises with increasing duration of exposure, and there is concern that lack of awareness and underreporting may mask the true incidence of the problem. Given the relative rarity of atypical femoral fractures, the task force recommends that specific diagnostic and procedural codes be created and that an international registry be established to facilitate studies of the clinical and genetic risk factors and optimal surgical and medical management of these fractures. Physicians and patients should be made aware of the possibility of atypical femoral fractures and of the potential for bilaterality through a change in labeling of BPs. Research directions should include development of animal models, increased surveillance, and additional epidemiologic and clinical data to establish the true incidence of and risk factors for this condition and to inform orthopedic and medical management. © 2010 American Society for Bone and Mineral Research.

1,820 citations

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TL;DR: A population-based estimate was formulated, based on one large institution's experience in terms of its fraction of patients with OA presenting to lower-extremity adult reconstructive clinics with Oa of posttraumatic origin, that approximately 12% of the overall prevalence of symptomatic OA is attributable to posttraumatic OA of the hip, knee, or ankle.
Abstract: Although posttraumatic osteoarthritis (OA) is a common and important entity in orthopedic practice, no data presently exist regarding its prevalence or its relative burden of disease. A population-based estimate was formulated, based on one large institution's experience in terms of its fraction of patients with OA presenting to lower-extremity adult reconstructive clinics with OA of posttraumatic origin. The relative proportion of these patients undergoing total joint replacement provided a basis for extrapolating institutional experience with posttraumatic OA to a populationwide estimate because the numbers of lower-extremity total joint arthroplasty procedures performed were reliably tabulated both within the institution and populationwide. By this methodology, approximately 12% of the overall prevalence of symptomatic OA is attributable to posttraumatic OA of the hip, knee, or ankle. This corresponds to approximately 5.6 million individuals in the United States being affected by posttraumatic OA sufficiently severe to have caused them to present for care by an orthopedic lower-extremity adult reconstructive surgeon. Further, based on the relative prevalence of OA versus rheumatoid arthritis, and their relative impacts as assessed by the SF-36 (Short-Form 36) lower-extremity physical composite scores, about 85.5% of the societal costs of arthritis are attributable to OA. The corresponding aggregate financial burden specifically of posttraumatic OA is Dollars 3.06 billion annually, or approximately 0.15% of the total U.S. health care direct cost outlay.

786 citations

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TL;DR: The functional attributes of several dozen systems developed for mechanical stimulation of cell and tissue cultures, including their major advantages and disadvantages, are reviewed.

564 citations

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TL;DR: The hypotheses that in osteoarthrosis substructural disorganization of the matrix proceeds chondrocytic enzyme production, that impulsive loading is an essential factor in the progressive cartilage destruction, and that tidemark advancement and horizontal cartilage splitting are the primary mechanisms ingressive cartilage loss are discussed are discussed.

330 citations

Journal ArticleDOI
TL;DR: The purpose of this study was to compare the structural properties of a new vs. established design of composite replicate femurs and tibias, and found the new SGFR bones were significantly less stiff than the FFR bones, although both bone designs reasonably approximated the structural stiffnesses of natural human bones.

295 citations


Cited by
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TL;DR: The Clinician’s Guide to Prevention and Treatment of Osteoporosis was developed by an expert committee of the National Osteiporosis Foundation in collaboration with a multispecialty council of medical experts in the field of bone health convened by NOF.
Abstract: The Clinician’s Guide to Prevention and Treatment of Osteoporosis was developed by an expert committee of the National Osteoporosis Foundation (NOF) in collaboration with a multispecialty council of medical experts in the field of bone health convened by NOF. Readers are urged to consult current prescribing information on any drug, device, or procedure discussed in this publication.

2,926 citations

Journal ArticleDOI
TL;DR: This article is part 1 of a two-part summary of an NIH conference, Stepping Away with OA: Prevention of Onset, Progression, and Disability of Osteoarthritis, which brought together experts in osteoarth arthritis from diverse backgrounds and provided a multidisciplinary and comprehensive summary of recent advances in the prevention.
Abstract: Osteoarthritis is the most common form of arthritis, affecting millions of people in the United States. It is a complex disease whose etiology bridges biomechanics and biochemistry. Evidence is growing for the role of systemic factors (such as genetics, dietary intake, estrogen use, and bone density) and of local biomechanical factors (such as muscle weakness, obesity, and joint laxity). These risk factors are particularly important in weightbearing joints, and modifying them may present opportunities for prevention of osteoarthritis-related pain and disability. Major advances in management to reduce pain and disability are yielding a panoply of available treatments ranging from nutriceuticals to chondrocyte transplantation, new oral anti-inflammatory medications, and health education. This article is part 1 of a two-part summary of a National Institutes of Health conference. The conference brought together experts on osteoarthritis from diverse backgrounds and provided a multidisciplinary and comprehensive summary of recent advances in the prevention of osteoarthritis onset, progression, and disability. Part 1 focuses on a new understanding of what osteoarthritis is and on risk factors that predispose to disease occurrence. It concludes with a discussion of the impact of osteoarthritis on disability. Ann Intern Med. 2000;133:635-646. www.annals.org For author affiliations and current addresses, see end of text.

2,313 citations

Journal ArticleDOI
TL;DR: In the coming years, a better definition of osteoarthritis is expected by delineating different phenotypes of the disease, and treatment targeted more specifically at these phenotypes might lead to improved outcomes.

1,743 citations

Journal ArticleDOI
TL;DR: Current knowledge on the role of disturbed flow in EC physiology and pathophysiology, as well as its clinical implications are summarized to contribute to the understanding of the etiology of lesion development in vascular niches with disturbed flow and help to generate new approaches for therapeutic interventions.
Abstract: Vascular endothelial cells (ECs) are exposed to hemodynamic forces, which modulate EC functions and vascular biology/pathobiology in health and disease. The flow patterns and hemodynamic forces are not uniform in the vascular system. In straight parts of the arterial tree, blood flow is generally laminar and wall shear stress is high and directed; in branches and curvatures, blood flow is disturbed with nonuniform and irregular distribution of low wall shear stress. Sustained laminar flow with high shear stress upregulates expressions of EC genes and proteins that are protective against atherosclerosis, whereas disturbed flow with associated reciprocating, low shear stress generally upregulates the EC genes and proteins that promote atherogenesis. These findings have led to the concept that the disturbed flow pattern in branch points and curvatures causes the preferential localization of atherosclerotic lesions. Disturbed flow also results in postsurgical neointimal hyperplasia and contributes to pathophysiology of clinical conditions such as in-stent restenosis, vein bypass graft failure, and transplant vasculopathy, as well as aortic valve calcification. In the venous system, disturbed flow resulting from reflux, outflow obstruction, and/or stasis leads to venous inflammation and thrombosis, and hence the development of chronic venous diseases. Understanding of the effects of disturbed flow on ECs can provide mechanistic insights into the role of complex flow patterns in pathogenesis of vascular diseases and can help to elucidate the phenotypic and functional differences between quiescent (nonatherogenic/nonthrombogenic) and activated (atherogenic/thrombogenic) ECs. This review summarizes the current knowledge on the role of disturbed flow in EC physiology and pathophysiology, as well as its clinical implications. Such information can contribute to our understanding of the etiology of lesion development in vascular niches with disturbed flow and help to generate new approaches for therapeutic interventions.

1,699 citations

Journal ArticleDOI
TL;DR: There has been a paradigm shift in the prevention and treatment of osteoporosis and fractures, and the focus now is on preventing fragility fractures and their negative effects.
Abstract: See related commentary by Kanis, page [1829][1] Since the publication of the Osteoporosis Canada guidelines in 2002, there has been a paradigm shift in the prevention and treatment of osteoporosis and fractures. [1][2],[2][3] The focus now is on preventing fragility fractures and their negative

1,691 citations