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Marshfield, WI, United States

McKiernan F.E.,Center for Bone Disease
Journal of Clinical Densitometry | Year: 2016

Had Violet's abdominal MR not been performed, or its findings not appreciated, the cause of her clinical event might never have been known because our current concept of osteoporotic vertebral fracture (VF) is substantially predicated on a change in either vertebral height or shape on lateral or sagittal spine imaging. The intention of this commentary is to stimulate a multidisciplinary conversation of osteoporotic VFs from an integrated clinical, physiological, and imaging perspective. For research and epidemiological purposes, osteoporotic VFs have been defined as a reduction in anterior, middle, or posterior vertebral height although the required minimum height reduction (e.g., 15% or 20%) varies among definition schemes. We further classify osteoporotic VFs to be "clinical" when they are accompanied by back pain and "morphometric" when they are not, and we have generally accepted the assertion that most of the osteoporotic VFs are painless, that is, morphometric. This dichotomous VF definition scheme has been the foundation of osteoporosis epidemiology and the primary endpoint in most pivotal osteoporosis pharmaceutical trials. Although, having served the osteoporosis community well, our clinical experience, refined by recent insights into vertebral anatomy and spinal biomechanics, advances in vertebral imaging, and 2 decades of vertebral augmentation suggest that the spectrum of osteoporotic VFs is more complicated than this scheme suggests. © 2016 The International Society for Clinical Densitometry. Source


Epperla N.,Marshfield Clinic | McKiernan F.E.,Center for Bone Disease
Skeletal Radiology | Year: 2014

Hepatitis C-associated osteosclerosis (HCAO) is a rare sclerosing bone condition characterized by debilitating, predominantly lower extremity bone pain, accelerated bone turnover, and a generalized increase in histologically normal trabecular and cortical bone tissue. Herein we report the clinical presentation and imaging results of the 19th case of HCAO. Clinicians, particularly those caring for a population at risk for HCV infection, should be aware of this uncommon condition. The etio-pathogenesis of HCAO remains obscure but may bear important lessons in bone biology that could lead to new treatment options for osteoporosis. © 2014 ISS. Source


Mckenna M.J.,St Vincents University Hospital | Mckenna M.J.,University College Dublin | Heffernan E.,University College Dublin | Heffernan E.,St Vincents University Hospital | And 3 more authors.
QJM | Year: 2014

Stress fractures are repetitive strain injuries that occur in normal bones and in abnormal bones. Stress fractures share many features in common but differences depend on the status of the underlying bone. This review article for clinicians addresses aspects about stress fractures with particular respect to fatigue fractures, Looser zones of osteomalacia, atypical Looser zones, atypical femoral fractures associated with bisphosphonate therapy and stress fractures in Paget's disease of bone. © The Author 2013. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. Source


Majewski J.,McGill University | Schwartzentruber J.A.,McGill University | Marcadier J.,Childrens Hospital of Eastern Ontario | Fryns J.-P.,University Hospitals Leuven | And 6 more authors.
Human Mutation | Year: 2011

Hajdu-Cheney syndrome (HCS) is a rare genetic disorder whose hallmark is acro-osteolysis, shortening of terminal phalanges, and generalized osteoporosis. We assembled a cohort of seven families with the condition and performed whole exome resequencing on a selected set of affected patients. One protein-coding gene, NOTCH2, carried heterozygous truncating variants in all patients and their affected family members. Our results replicate recently published studies of HCS and further support this as the causal gene for the disorder. In total, we identified five novel and one previously reported mutation, all clustered near the carboxyl terminus of the gene, suggesting an allele specific genotype-phenotype effect since other mutations in NOTCH2 have been reported to cause a form of Alagille syndrome. Notch-mediated signaling is known to play a role in bone metabolism. Our results support a potential therapeutic role for Notch pathways in treatment of osteoporosis. © 2011 Wiley-Liss, Inc. Source


Broskey N.T.,University of Lausanne | Greggio C.,University of Lausanne | Boss A.,University of Bern | Boutant M.,Nestle | And 10 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2014

Context: Sarcopenia is thought to be associated with mitochondrial (Mito) loss. It is unclear whether the decrease in Mito content is consequent to aging per se or to decreased physical activity. Objectives: The objective of the study was to examine the influence of fitness on Mito content and function and to assess whether exercise could improve Mito function in older adults. Design and subjects: Three distinct studies were conducted: 1) a cross-sectional observation comparing Mito content and fitness in a large heterogeneous cohort of older adults; 2) a case-control study comparing chronically endurance-trained older adultsandsedentary (S) subjects matched for age and gender; and 3) a 4-month exercise intervention in S. Setting: The study was conducted at a university-based clinical research center. Outcomes: Mito volume density (MitoVd) was assessed by electron microscopy from vastus lateralis biopsies, electron transport chain proteins by Western blotting, mRNAs for transcription factors involved in M biogenesis by quantitative RT-PCR, and in vivo oxidative capacity (ATPmax) by 31Pmagnetice resonance spectroscopy. Peak oxygen uptake was measured by graded exercise test. Results: Peak oxygen uptake was strongly correlated with MitoVd in 80 60- to 80-year-old adults. Comparison of chronically endurance-trained older adults vs S revealed differences in MitoVd, ATPmax, and some electron transport chain protein complexes. Finally, exercise intervention confirmed that S subjects are able to recover MitoVd, ATPmax, and specific transcription factors. Conclusions: These data suggest the following: 1) aging per se is not the primary culprit leading to Mito dysfunction; 2) an aerobic exercise program, even at an older age, can ameliorate the loss in skeletal muscle Mito content and may prevent aging muscle comorbidities; and 3) the improvement of Mito function is all about content. © 2014 by the Endocrine Society. Source

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