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Osteoporosis: HELP
Articles from Karolinska Institutions
Based on 93 articles published since 2008
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These are the 93 published articles about Osteoporosis that originated from Karolinska Institutions during 2008-2019.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4
1 Guideline EMAS position statement: The ten point guide to the integral management of menopausal health. 2015

Neves-E-Castro, Manuel / Birkhauser, Martin / Samsioe, Goran / Lambrinoudaki, Irene / Palacios, Santiago / Borrego, Rafael Sanchez / Llaneza, Placido / Ceausu, Iuliana / Depypere, Herman / Erel, C Tamer / Pérez-López, Faustino R / Schenck-Gustafsson, Karin / van der Schouw, Yvonne T / Simoncini, Tommaso / Tremollieres, Florence / Rees, Margaret. ·Clinica da Menopausa, Av. Luis Bivar, 93c-1 Dt, Lisboa 1050-143, Portugal. · Gynaecological Endocrinology and Reproductive Medicine, University of Berne, Gartenstrasse 67, CH-4052 Basel, Switzerland. · Department of Clinical Sciences, SUS University Hospital Lund, Lund University, SE-221 85 Lund, Sweden. · Second Department of Obstetrics and Gynecology, National and Capodestrian University of Athens, Greece. · Instituto Palacios, Salud y Medicina de la Mujer, C/Antonio Acuña, 9, 28009 Madrid, Spain. · DIATROS, Clínica de Atención a la Mujer, Barcelona, Spain. · Department of Obstetrics and Gynecology, University Central Hospital of Asturias, University of Oviedo, 33011 Oviedo, Spain. · Department of Obstetrics and Gynecology, 'Carol Davila' University of Medicine and Pharmacy, Bucharest, Romania; Department of Obstetrics and Gynecology, 'Dr. I. Cantacuzino' Hospital, Bucharest, Romania. · Breast Clinic and Menopause Clinic, University Hospital, De Pintelaan 185, 9000 Gent, Belgium. · Department of Obstetrics and Gynecology, Istanbul University, Cerrahpasa School of Medicine, Valikonagi Cad. No: 93/4, Nisantasi, 34365 Istanbul, Turkey. · Department of Obstetrics and Gynecology, Zaragoza University Facultad de Medicina, Hospital Clínico, Zaragoza 50009, Spain. · Department of Medicine, Cardiology Unit, Centre for Gender Medicine, Karolinska Institutet and Karolinska University Hospital, Thorax N3:05, SE 17176 Stockholm, Sweden. · Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands. · Department of Clinical and Experimental Medicine, University of Pisa, Via Roma, 67, 56100 Pisa, Italy. · Menopause and Metabolic Bone Disease Unit, Hôpital Paule de Viguier, F-31059 Toulouse cedex 09, France. · Women's Centre, John Radcliffe Hospital, Oxford OX3 9DU, UK. Electronic address: margaret.rees@st-hildas.ox.ac.uk. ·Maturitas · Pubmed #25757366.

ABSTRACT: With increased longevity and more women becoming centenarians, management of the menopause and postreproductive health is of growing importance as it has the potential to help promote health over several decades. Women have individual needs and the approach needs to be personalised. The position statement provides a short integral guide for all those involved in menopausal health. It covers diagnosis, screening for diseases in later life, treatment and follow-up.

2 Guideline EMAS position statement: The management of postmenopausal women with vertebral osteoporotic fracture. 2014

Triantafyllopoulos, Ioannis K / Lambropoulou-Adamidou, Kalliopi / Nacopoulos, Cleopatra C / Papaioannou, Nikolaos A / Ceausu, Iuliana / Depypere, Herman / Erel, C Tamer / Pérez-López, Faustino R / Schenck-Gustafsson, Karin / van der Schouw, Yvonne T / Simoncini, Tommaso / Tremollieres, Florence / Rees, Margaret / Lambrinoudaki, Irene / Anonymous4640789. ·Laboratory of Research for the Musculoskeletal System (LRMS), School of Medicine, University of Athens, 10 Athinas Street, 14561 Kifissia, Greece. Electronic address: sportdoc@otenet.gr. · Medical School, University of Athens, KAT General Hospital, 2 Nikis Street, 14561 Kifissia, Greece. · Medical School, University of Athens, 10 Athinas Street, 14561 Kifissia, Greece. · Laboratory of Research for the Musculoskeletal System (LRMS), School of Medicine, University of Athens, 10 Athinas Street, 14561 Kifissia, Greece. · Department of Obstetrics and Gynecology, 'Carol Davila' University of Medicine and Pharmacy, Bucharest, Romania; Department of Obstetrics and Gynecology, 'Dr. I. Cantacuzino' Hospital, Bucharest, Romania. · Breast Clinic and Menopause Clinic, University Hospital, De Pintelaan 185, 9000 Gent, Belgium. · Department of Obstetrics and Gynecology, Istanbul University, Cerrahpasa School of Medicine, Valikonagi Cad. No. 93/4, Nisantasi, 34365 Istanbul, Turkey. · Department of Obstetrics and Gynecology, Zaragoza University Facultad de Medicina, Hospital Clínico, Zaragoza 50009, Spain. · Department of Medicine, Cardiology Unit and Head Centre for Gender Medicine, Karolinska Institutet and Karolinska University Hospital, Thorax N3:06, SE 17176 Stockholm, Sweden. · Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands. · Department of Clinical and Experimental Medicine, University of Pisa, Via Roma, 67, 56100 Pisa, Italy. · Menopause and Metabolic Bone Disease Unit, Hôpital Paule de Viguier, F-31059 Toulouse cedex 09, France. · Women's Centre, John Radcliffe Hospital, Oxford OX3 9DU, UK. · Second Department of Obstetrics and Gynecology, National and Capodestrian University of Athens, Greece. ·Maturitas · Pubmed #24679890.

ABSTRACT: INTRODUCTION: Osteoporotic vertebral fractures are associated with significant morbidity, excess mortality as well as health and social service expenditure. Additionally, women with a prevalent osteoporotic vertebral fracture have a high risk of experiencing a further one within one year. It is therefore important for the physician to use a diagnostic and therapeutic algorithm for early detection and effective treatment of vertebral fractures. AIMS: The aim of this position statement is to provide and critically appraise evidence on the management of women with a vertebral osteoporotic fracture. MATERIALS AND METHODS: Literature review and consensus of expert opinion. RESULTS AND CONCLUSIONS: The management of women with osteoporotic vertebral fractures includes measures to reduce pain providing early mobility, to support the affected spine ensuring fracture healing, as well as starting treatment for osteoporosis itself. Any other underlying pathology should be sought and treated. Early detection and treatment is essential as there is an increased risk of further fractures in patients with vertebral fractures. Treatment will depend on the underlying causes of bone loss, efficacy in any particular situation, cost and patient preference.

3 Guideline EMAS position statement: Menopause for medical students. 2014

Brockie, Janet / Lambrinoudaki, Irene / Ceausu, Iuliana / Depypere, Herman / Erel, C Tamer / Pérez-López, Faustino R / Schenck-Gustafsson, Karin / van der Schouw, Yvonne T / Simoncini, Tommaso / Tremollieres, Florence / Rees, Margaret / Anonymous1280788. ·Women's Centre, John Radcliffe Hospital, Oxford OX3 9DU, UK. Electronic address: janet.brockie@ouh.nhs.uk. · Second Department of Obstetrics and Gynecology, National and Capodestrian University of Athens, Greece. · Department of Obstetrics and Gynecology, 'Carol Davila' University of Medicine and Pharmacy, Romania; Department of Obstetrics and Gynecology, 'Dr. I. Cantacuzino' Hospital, Bucharest, Romania. · Breast Clinic and Menopause Clinic, University Hospital, De Pintelaan 185, 9000 Gent, Belgium. · Department of Obstetrics and Gynecology, Istanbul University, Cerrahpasa School of Medicine, Valikonagi Cad. No. 93/4, Nisantasi, 34365 Istanbul, Turkey. · Department of Obstetrics and Gynecology, Zaragoza University Facultad de Medicina, Hospital Clínico, Zaragoza 50009, Spain. · Department of Medicine, Cardiology Unit and Head Centre for Gender Medicine, Karolinska Institutet and Karolinska University Hospital, Thorax N3:06, SE 17176 Stockholm, Sweden. · Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands. · Department of Clinical and Experimental Medicine, University of Pisa, Via Roma, 67, 56100 Pisa, Italy. · Menopause and Metabolic Bone Disease Unit, Hôpital Paule de Viguier, F-31059 Toulouse cedex 09, France. · Women's Centre, John Radcliffe Hospital, Oxford OX3 9DU, UK. ·Maturitas · Pubmed #24630127.

ABSTRACT: -- No abstract --

4 Review Animal models to explore the effects of glucocorticoids on skeletal growth and structure. 2018

Wood, Claire L / Soucek, Ondrej / Wong, Sze C / Zaman, Farasat / Farquharson, Colin / Savendahl, Lars / Ahmed, S Faisal. ·Division of Developmental BiologyRoslin Institute, University of Edinburgh, Edinburgh, UK. · Department of Paediatrics2nd Faculty of Medicine, Charles University in Prague and Motol University Hospital, Prague, Czech Republic. · Department of Women's and Children's HealthKarolinska Institutet and Pediatric Endocrinology Unit, Karolinska University Hospital, Stockholm, Sweden. · Developmental Endocrinology Research GroupSchool of Medicine, University of Glasgow, Glasgow, UK. · Developmental Endocrinology Research GroupSchool of Medicine, University of Glasgow, Glasgow, UK Faisal.ahmed@glasgow.ac.uk. ·J Endocrinol · Pubmed #29051192.

ABSTRACT: Glucocorticoids (GCs) are effective for the treatment of many chronic conditions, but their use is associated with frequent and wide-ranging adverse effects including osteoporosis and growth retardation. The mechanisms that underlie the undesirable effects of GCs on skeletal development are unclear, and there is no proven effective treatment to combat them. An

5 Review Recent Discoveries in Monogenic Disorders of Childhood Bone Fragility. 2017

Mäkitie, Riikka E / Kämpe, Anders J / Taylan, Fulya / Mäkitie, Outi. ·Folkhälsan Institute of Genetics, University of Helsinki, P. O. Box 63, FIN-00014, Helsinki, Finland. · Department of Molecular Medicine and Surgery, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden. · Folkhälsan Institute of Genetics, University of Helsinki, P. O. Box 63, FIN-00014, Helsinki, Finland. outi.makitie@helsinki.fi. · Department of Molecular Medicine and Surgery, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden. outi.makitie@helsinki.fi. · Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden. outi.makitie@helsinki.fi. · Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland. outi.makitie@helsinki.fi. ·Curr Osteoporos Rep · Pubmed #28646443.

ABSTRACT: PURPOSE OF REVIEW: This review summarizes our current knowledge on primary osteoporosis in children with focus on recent genetic findings. RECENT FINDINGS: Advances in genetic research, particularly next-generation sequencing, have found several genetic loci that associate with monogenic forms of inherited osteoporosis, widening the scope of primary osteoporosis beyond classical osteogenesis imperfecta. New forms of primary osteoporosis, such as those related to WNT1, PLS3, and XYLT2, have identified defects outside the extracellular matrix components and collagen-related pathways, in intracellular cascades directly affecting bone cell function. Primary osteoporosis can lead to severe skeletal morbidity, including abnormal longitudinal growth, compromised bone mass gain, and noticeable fracture tendency beginning at childhood. Early diagnosis and timely care are warranted to ensure the best achievable bone health. Future research will most likely broaden the spectrum of primary osteoporosis, hopefully provide more insight into the genetics governing bone health, and offer new targets for treatment.

6 Review [Bisphosphonates first-line pharmacological treatment]. 2016

Wallander, Märit / Ljunggren, Östen / Lorentzon, Mattias. ·Karolinska University Hospital - Department of Endocrinology Stockholm, Sweden Karolinska University Hospital - Department of Endocrinology Stockholm, Sweden. · Uppsala universitet - institutionen för medicinska vetenskaper Uppsala, Sweden - , Sweden. · Osteoporosmottagningen - Geriatriska kliniken, Sahlgrenska universitetssjukhset, Mölndal Mölndal, Sweden Geriatric Medicine - Institute of Medicine Mölndal, Sweden. ·Lakartidningen · Pubmed #27824394.

ABSTRACT: -- No abstract --

7 Review Osteoporosis and Bone Mass Disorders: From Gene Pathways to Treatments. 2016

Rivadeneira, Fernando / Mäkitie, Outi. ·Musculoskeletal Genomics, Health and Metabolism, Departments of Internal Medicine and Epidemiology, Erasmus University Medical Center, 3000CA Rotterdam, The Netherlands. Electronic address: f.rivadeneira@erasmusmc.nl. · Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Department of Molecular Medicine and Surgery, Karolinska Institutet, and Clinical Genetics, Karolinska University Hospital, 171 76 Stockholm, Sweden. ·Trends Endocrinol Metab · Pubmed #27079517.

ABSTRACT: Genomic technologies have evolved rapidly contributing to the understanding of diseases. Genome-wide association studies (GWAS) and whole-exome sequencing have aided the identification of the genetic determinants of monogenic and complex conditions including osteoporosis and bone mass disorders. Overlap exists between the genes implicated in monogenic and complex forms of bone mass disorders, largely explained by the clustering of genes encoding factors in signaling pathways crucial for mesenchymal cell differentiation, skeletal development, and bone remodeling and metabolism. Numerous of the remaining discovered genes merit functional follow-up studies to elucidate their role in bone biology. The insight provided by genetic studies is serving the identification of biomarkers predictive of disease, redefining disease, response to treatment, and discovery of novel drug targets for skeletal disorders.

8 Review Adjuvant bisphosphonates in early breast cancer: consensus guidance for clinical practice from a European Panel. 2016

Hadji, P / Coleman, R E / Wilson, C / Powles, T J / Clézardin, P / Aapro, M / Costa, L / Body, J-J / Markopoulos, C / Santini, D / Diel, I / Di Leo, A / Cameron, D / Dodwell, D / Smith, I / Gnant, M / Gray, R / Harbeck, N / Thurlimann, B / Untch, M / Cortes, J / Martin, M / Albert, U-S / Conte, P-F / Ejlertsen, B / Bergh, J / Kaufmann, M / Holen, I. ·Department of Bone Oncology, Endocrinology and Reproductive Medicine, Philipps-University of Marburg, Frankfurt, Germany. · Academic Unit of Clinical Oncology, Weston Park Hospital, University of Sheffield, Sheffield r.e.coleman@sheffield.ac.uk. · Academic Unit of Clinical Oncology, Weston Park Hospital, University of Sheffield, Sheffield. · Cancer Centre London, Wimbledon, UK. · INSERM, Research Unit UMR403, University of Lyon, School of Medicine Lyon-Est, Lyon, France. · Breast Center of the Multidisciplinary Oncology Institute, Genolier, Switzerland. · Hospital de Santa Maria & Lisbon School of Medicine, Institute of Molecular Biology, Lisbon, Potugal. · CHU Brugmann, Université Libre de Bruxelles (ULB), Brussels, Belgium. · Medical School, National University of Athens, Athens, Greece. · Medical Oncology, University Campus Bio-medico, Rome, Italy. · Institute for Gynaecological Oncology, Centre for Comprehensive Gynecology, Mannheim, Germany. · Sandro Pitigliani Medical Oncology Unit, Department of Oncology, Hospital of Prato, Prato, Italy. · University of Edinburgh Cancer Research Centre, Western General Hospital, Edinburgh. · Institute of Oncology, Bexley Wing, St James Hospital Leeds, Leeds. · The Royal Marsden Hospital and Institute of Cancer Research, London, UK. · Department of Surgery and Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria. · Clinical Trials and Epidemiological Unit, University of Oxford, Oxford, UK. · Breast Center, Department of Obstetrics and Gynaecology, University of Munich, Munich, Germany. · Kantonsspital St Gallen, Breast Center, St Gallen, Switzerland. · Interdisciplinary Breast Cancer Center HELIOS Klinikum Berlin-Buch Germany, Gynecologic Oncology and Obstetrics, Berlin, Germany. · Department of Oncology, Vall d'Hebron Institute of Oncology (VHIO), Barcelona. · Department of Medical Oncology, Institute of Investigation Sanitaria Gregorio Marañón, University Complutense, Madrid, Spain. · Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy. · Danish Breast Cancer Cooperative Group Statistical Center Department of Oncology Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. · Karolinska Institute and University Hospital, Stockholm, Sweden. · Institute for Obstetrics and Gynaecology, Goethe University, Frankfurt, Germany. ·Ann Oncol · Pubmed #26681681.

ABSTRACT: Bisphosphonates have been studied in randomised trials in early breast cancer to investigate their ability to prevent cancer treatment-induced bone loss (CTIBL) and reduce the risk of disease recurrence and metastasis. Treatment benefits have been reported but bisphosphonates do not currently have regulatory approval for either of these potential indications. This consensus paper provides a review of the evidence and offers guidance to breast cancer clinicians on the use of bisphosphonates in early breast cancer. Using the nominal group methodology for consensus, a systematic review of the literature was augmented by a workshop held in October 2014 for breast cancer and bone specialists to present and debate the available pre-clinical and clinical evidence for the use of adjuvant bisphosphonates. This was followed by a questionnaire to all members of the writing committee to identify areas of consensus. The panel recommended that bisphosphonates should be considered as part of routine clinical practice for the prevention of CTIBL in all patients with a T score of <-2.0 or ≥2 clinical risk factors for fracture. Compelling evidence from a meta-analysis of trial data of >18,000 patients supports clinically significant benefits of bisphosphonates on the development of bone metastases and breast cancer mortality in post-menopausal women or those receiving ovarian suppression therapy. Therefore, the panel recommends that bisphosphonates (either intravenous zoledronic acid or oral clodronate) are considered as part of the adjuvant breast cancer treatment in this population and the potential benefits and risks discussed with relevant patients.

9 Review New Genetic Forms of Childhood-Onset Primary Osteoporosis. 2015

Kämpe, Anders J / Mäkitie, Riikka E / Mäkitie, Outi. ·Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden. ·Horm Res Paediatr · Pubmed #26517534.

ABSTRACT: Recent developments in genetic technology have given us the opportunity to look at diseases in a new and more detailed way. This Mini Review discusses monogenetic forms of childhood-onset primary osteoporosis, with the main focus on osteoporosis caused by mutations in WNT1 and PLS3, two of the most recently discovered genes underlying early-onset osteoporosis. The importance of WNT1 in the accrual and maintenance of bone mass through activation of canonical WNT signaling was recognized in 2013. WNT1 was shown to be a key ligand for the WNT-signaling pathway, which is of major importance in the regulation of bone formation. More recently, mutations in PLS3, located on the X chromosome, were shown to be the cause of X-linked childhood-onset primary osteoporosis affecting mainly males. The function of PLS3 in bone metabolism is still not completely understood, but it has been speculated to have an important role in mechanosensing by osteocytes and in matrix mineralization. In this new era of genetics, our knowledge on genetic causes of childhood-onset osteoporosis expands constantly. These discoveries bring new possibilities, but also new challenges. Guidelines are needed to implement this new genetic knowledge to clinical patient care and to guide genetic investigations in affected families.

10 Review Osteoporosis in neurodegeneration. 2014

Roos, Per M. ·Department of Neurology, Division of Clinical Neurophysiology, Oslo University Hospital, Oslo, Norway; Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. Electronic address: per.roos@ki.se. ·J Trace Elem Med Biol · Pubmed #25220531.

ABSTRACT: Osteoporosis affects bone microarchitecture and reduces bone mass. There are more than 200 million people with osteoporosis worldwide, and the prevalence is slowly increasing. The highest prevalences are found in Scandinavia and USA, also slowly increasing. A parallel increase in neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, Amyotrophic lateral sclerosis, and multiple sclerosis has been noted since the middle of this century. Osteoporosis is more common in patients with each of these neurodegenerative conditions than in the general population. Several metals with neurotoxic properties accumulate in bone and can substitute for calcium in hydroxyapatite, the main mineral component of bone. Especially cadmium, but also lead, aluminum and arsenic affect bone mineral density negatively. Metals with neurotoxic properties have also been found in brain and cerebrospinal fluid from patients with Alzheimer's disease, Parkinson's disease, Amyotrophic lateral sclerosis, and multiple sclerosis, and markers for neurodegeneration such as amyloid beta peptide and amyloid precursor protein have been detected in bone tissue from patients with osteoporosis. A common mechanism contributing to the pathogenesis of both neurodegeneration and osteoporosis can be suspected. The hypothesis that neurodegenerative disorders are associated with osteoporosis is presented and discussed.

11 Review Hibernating bears (Ursidae): metabolic magicians of definite interest for the nephrologist. 2013

Stenvinkel, Peter / Jani, Alkesh H / Johnson, Richard J. ·Division of Renal Medicine, Department of Clinical Science Intervention and Technology, Karolinska University Hospital, Stockholm, Sweden. peter.stenvinkel@ki.se ·Kidney Int · Pubmed #23254895.

ABSTRACT: Muscle loss, osteoporosis, and vascular disease are common in subjects with reduced renal function. Despite intensive research of the underlying risk factors and mechanisms driving these phenotypes, we still lack effective treatment strategies for this underserved patient group. Thus, new approaches are needed to identify effective treatments. We believe that nephrologists could learn much from biomimicry; i.e., studies of nature's models to solve complicated physiological problems and then imitate these fascinating solutions to develop novel interventions. The hibernating bear (Ursidae) should be of specific interest to the nephrologist as they ingest no food or water for months, remaining anuric and immobile, only to awaken with low blood urea nitrogen levels, healthy lean body mass, strong bones, and without evidence for thrombotic complications. Identifying the mechanisms by which bears prevent the development of azotemia, sarcopenia, osteoporosis, and atherosclerosis despite being inactive and anuric could lead to novel interventions for both prevention and treatment of patients with chronic kidney disease.

12 Review Health economics of osteoporosis. 2008

Borgström, Fredrik / Kanis, John A. ·Medical Management Centre, Karolinska Institutet, 171 77 Stockholm, Sweden. fredrik.borgstrom@i3innovus.com ·Best Pract Res Clin Endocrinol Metab · Pubmed #19028362.

ABSTRACT: Rather than reviewing the many studies of cost effectiveness in osteoporosis, this paper reviews the principles of cost-effectiveness analysis and the gaps in our knowledge that are required to improve such analyses in osteoporosis. These include more information on the cost of fractures and their consequences on health states, particularly on an international basis. New developments include the incorporation of adherence into models, the use of the FRAX tool to assess cost-effectiveness in individuals with any combination of risk factors for fracture, and the setting of intervention thresholds based on cost-effectiveness.

13 Review Late effects following hematopoietic cell transplantation for children. 2008

Dahllöf, Göran / Hingorani, Sangeeta R / Sanders, Jean E. ·Department of Pediatric Dentistry, Karolinska Institutet, P.O. Box 4064, SE-141 04, Huddinge, Sweden. Goran.Dahllof@ofa.ki.se ·Biol Blood Marrow Transplant · Pubmed #18162227.

ABSTRACT: High-dose chemotherapy or chemoradiotherapy followed by hematopoietic cell transplantation (HCT) is being used for an ever increasing number of children with malignant or nonmalignant disorders, and improved results are leading to an ever increasing number of long-term survivors. Understanding the delayed effects that may occur after HCT is important in determining the evaluations to perform for this unique group of patients. The articles that follow detail what has been observed to date regarding the oral cavity and dental late effects, the kidney after HCT, and the evaluations to perform to determine late effects when patients return to the centers after their HCT.

14 Clinical Trial Further reductions in nonvertebral fracture rate with long-term denosumab treatment in the FREEDOM open-label extension and influence of hip bone mineral density after 3 years. 2015

Ferrari, S / Adachi, J D / Lippuner, K / Zapalowski, C / Miller, P D / Reginster, J-Y / Törring, O / Kendler, D L / Daizadeh, N S / Wang, A / O'Malley, C D / Wagman, R B / Libanati, C / Lewiecki, E M. ·Geneva University Hospital, Geneva, Switzerland. Serge.Ferrari@unige.ch. · McMaster University, Hamilton, ON, Canada. · Bern University Hospital, Bern, Switzerland. · Amgen Inc., Thousand Oaks, CA, USA. · Colorado Center for Bone Research, Lakewood, CO, USA. · University of Liège, Liège, Belgium. · Karolinska Institutet, Södersjukhuset, Stockholm, Sweden. · University of British Columbia, Vancouver, BC, Canada. · New Mexico Clinical Research & Osteoporosis Center, Albuquerque, NM, USA. ·Osteoporos Int · Pubmed #26068295.

ABSTRACT: INTRODUCTION: This study aimed to evaluate whether denosumab treatment continued beyond 3 years is associated with a further reduction in nonvertebral fracture rates. METHODS: Participants who completed the 3-year placebo-controlled Fracture REduction Evaluation of Denosumab in Osteoporosis every 6 Months (FREEDOM) study were invited to participate in an open-label extension. The present analysis includes 4,074 postmenopausal women with osteoporosis (n = 2,343 long-term; n = 1,731 cross-over) who enrolled in the extension, missed ≤1 dose during their first 3 years of denosumab treatment, and continued into the fourth year of treatment. Comparison of nonvertebral fracture rates during years 1-3 of denosumab with that of the fourth year and with the rate during years 4-7 was evaluated. RESULTS: For the combined group, the nonvertebral fracture rate per 100 participant-years was 2.15 for the first 3 years of denosumab treatment (referent) and 1.36 in the fourth year (rate ratio [RR] = 0.64; 95 % confidence interval (CI) = 0.48 to 0.85, p = 0.003). Comparable findings were observed in the groups separately and when nonvertebral fracture rates during years 1-3 were compared to years 4-7 in the long-term group (RR = 0.79; 95 % CI = 0.62 to 1.00, p = 0.046). Fracture rate reductions in year 4 were most prominent in subjects with persisting low hip bone mineral density (BMD). CONCLUSIONS: Denosumab treatment beyond 3 years was associated with a further reduction in nonvertebral fracture rate that persisted through 7 years of continuous denosumab administration. The degree to which denosumab further reduces nonvertebral fracture risk appears influenced by the hip bone density achieved with initial therapy.

15 Clinical Trial Ablation of the pro-apoptotic protein Bax protects mice from glucocorticoid-induced bone growth impairment. 2012

Zaman, Farasat / Chrysis, Dionisios / Huntjens, Kirsten / Fadeel, Bengt / Sävendahl, Lars. ·Pediatric Endocrinology Unit, Department of Women's and Children's Health, Astrid Lindgren Children's Hospital, Karolinska Institutet, Stockholm, Sweden. Farasat.Zaman@ki.se ·PLoS One · Pubmed #22442678.

ABSTRACT: Dexamethasone (Dexa) is a widely used glucocorticoid to treat inflammatory diseases; however, a multitude of undesired effects have been reported to arise from this treatment including osteoporosis, obesity, and in children decreased longitudinal bone growth. We and others have previously shown that glucocorticoids induce apoptosis in growth plate chondrocytes. Here, we hypothesized that Bax, a pro-apoptotic member of the Bcl-2 family, plays a key role in Dexa-induced chondrocyte apoptosis and bone growth impairment. Indeed, experiments in the human HCS-2/8 chondrocytic cell line demonstrated that silencing of Bax expression using small-interfering (si) RNA efficiently blocked Dexa-induced apoptosis. Furthermore, ablation of Bax in female mice protected against Dexa-induced bone growth impairment. Finally, Bax activation by Dexa was confirmed in human growth plate cartilage specimens cultured ex vivo. Our findings could therefore open the door for new therapeutic approaches to prevent glucocorticoid-induced bone growth impairment through specific targeting of Bax.

16 Clinical Trial Effects of physical training on bone mineral density in fertile women with idiopathic osteoporosis. 2008

Bergström, Ingrid / Brinck, Jonas / Sääf, Maria. ·Department of Endocrinology, Metabolism and Diabetes, Karolinska University Hospital, Huddinge, M52, Stockholm, 141 86, Sweden. ingrid.b.bergstrom@karolinska.se ·Clin Rheumatol · Pubmed #18443738.

ABSTRACT: The aim of this study was to investigate whether moderate physical training can improve the bone mineral density (BMD) in women with idiopathic osteoporosis. Ten pre-menopausal women aged 24-44 years diagnosed with idiopathic osteoporosis were included in the study. The physical training program consisted of three fast 30-min walks plus one or two sessions of 1-h training per week during 1 year at a training centre separate from the hospital. All patients were given supplements of vitamin D and calcium. Bone mineral density was measured in the femoral neck area and the lumbar spine by dual energy X-ray absorptiometry. The measurements were performed at baseline and after 12 months of training and compared with the measurements at the time of diagnosis, 1-3 years before the study. Eight women fulfilled the 12-month training period, and their mean (SD) BMD at start was 0.88 (0.08) g/cm(2) in the spine and 0.76 (0.13) g/cm(2) in the femoral neck. The mean spine BMD increase was 0.031 g/cm(2) (3.5%) after 1 year of training, which was significant (Wilcoxon's non-parametric test, p = 0.018). The mean increment in BMD in the femoral neck was insignificant, 0.007 g/cm(2) (0.9%) after the intervention (p = 0.74). However, the bone loss during the 1- to 3-year period from diagnosis to study start was, on average, 0.045 g/cm(2) or 5.0% in the femoral neck (p = 0.042), thus indicating a positive indirect effect of the intervention. There is no evidence-based therapy for women with idiopathic osteoporosis. It is therefore of importance to elucidate the impact of moderate physical activity in this group of patients. A 1-year training program was sufficient to induce a small but significant change in the spine BMD.

17 Article The effects of dual-task balance training on gait in older women with osteoporosis: A randomized controlled trial. 2019

Conradsson, David / Halvarsson, Alexandra. ·Karolinska Institutet, Department of Neurobiology, Care Sciences and Society, Division of Physiotherapy, Stockholm, Sweden; Karolinska University Hospital, Allied Health Professionals Function, Function Area Occupational Therapy & Physiotherapy, Stockholm, Sweden. Electronic address: David.Conradsson.1@ki.se. · Karolinska Institutet, Department of Neurobiology, Care Sciences and Society, Division of Physiotherapy, Stockholm, Sweden; Karolinska University Hospital, Allied Health Professionals Function, Function Area Occupational Therapy & Physiotherapy, Stockholm, Sweden. Electronic address: Alexandra.Halvarsson@ki.se. ·Gait Posture · Pubmed #30640156.

ABSTRACT: BACKGROUND: Although there is a growing body of literature showing promising effects of balance training on gait in older adults, little is known about the effects of dual-task training on varying domains of spatial and temporal gait parameters. RESEARCH QUESTION: Does the short-term effects of dual-task balance training differ between single and dual-task gait in older women with osteoporosis with regards to different gait domains (pace, rhythm, variability, asymmetry and postural control)? METHODS: Elderly women with osteoporosis who experienced fear of falling and/or ≥1 fall the last 12 months were recruited. Ninety-five participants were randomized to 12 weeks of balance training or to a control group. The participants in the training group (n = 65) received 12 weeks (3 times/week) of balance and gait exercises including dual-tasks, and the control group (n = 30) received care as usual. Single- and dual-task gait were assessed before and after the intervention with an electronic walkway system and analyzed using non-parametric statistics and effect sizes. RESULTS: 68 participants completed the study. The training group walked faster for single- and dual-task gait following training (P ≤ .044) by increasing their cadence (P ≤ .012) and reducing step and swing time (P ≤ .045) compared with the control group. Significant between-group differences in favor of the training group were found for gait variability during dual-task gait (P ≤ .041). The improvement in speed were greater for dual- than single-task gait (0.10 vs. 0.05 m/s) and the effect sizes revealed small to medium effects for dual-task gait, and either non-existent or small for single-task gait. SIGNIFICANCE: Greater training effects found on a variety of domains of dual-task gait compared to single-task gait support the role of cognitively demanding exercises for the maintenance of safe ambulation in older women with osteoporosis.

18 Article Is sleep apnea underdiagnosed in adult patients with osteogenesis imperfecta? -a single-center cross-sectional study. 2018

Arponen, Heidi / Bachour, Adel / Bäck, Leif / Valta, Helena / Mäkitie, Antti / Waltimo-Sirén, Janna / Mäkitie, Outi. ·Department of Oral and Maxillofacial Diseases, University of Helsinki, P.O. Box 41, FI-00014, Helsinki, Finland. heidi.arponen@helsinki.fi. · Sleep Unit, Heart and Lung Center, Helsinki University Hospital and University of Helsinki, Helsinki, Finland. · Department of Otorhinolaryngology - Head and Neck Surgery, Helsinki University Hospital and University of Helsinki, Helsinki, Finland. · Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland. · Department of Oral and Maxillofacial Diseases, University of Helsinki, P.O. Box 41, FI-00014, Helsinki, Finland. · Folkhälsan Institute of Genetics, University of Helsinki, Helsinki, Finland. · Center for Molecular Medicine, Karolinska Institutet and Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden. ·Orphanet J Rare Dis · Pubmed #30594215.

ABSTRACT: BACKGROUND: Patients with Osteogenesis imperfecta (OI) suffer from increased bone fracture tendency generally caused by a mutation in genes coding for type I collagen. OI is also characterized by numerous co-morbidities, and recent data from questionnaire studies suggest that these may include increased risk for sleep apnea, a finding that lacks clinical evidence from cohort studies. In this cross-sectional study, 25 adults with OI underwent clinical otorhinolaryngology examination as well as overnight polysomnography to address the question. The participants were aged between 19 and 77 years, and ten of them had mild clinical OI phenotype, seven had a moderately severe phenotype, and eight had a severe phenotype. RESULTS: We found obstructive sleep apnea (apnea hypopnea index ≥5/h) in as many as 52% of the OI patients in the cohort. Unexpectedly, however, no correlation was present between sleep apnea and daytime sleepiness, experienced bodily pain, severity of OI, Mallampati score, or neck circumference. CONCLUSIONS: Seeing that the usual predictors showed no association with occurrence of sleep apnea, we conclude that obstructive sleep apnea may easily be left as an undetected disorder in individuals with OI. Recurrent nocturnal hypoxia due to episodes of apneas can even affect bone metabolism, thereby further aggravating bone fragility in patients with OI.

19 Article Low BMD and high alcohol consumption predict a major re-operation in patients younger than 70 years of age with a displaced femoral neck fracture-A two -year follow up study in 120 patients. 2018

Campenfeldt, Pierre / Al-Ani, Amer / Hedström, Margareta / Ekström, Wilhelmina. ·Karolinska Institutet, Department of Clinical Science Intervention and Technology, Sweden; Swedish Armed Forces, Defence Inspector for Medicine and Environmental Health, Tegeluddsvägen 100 SE-107 85, Stockholm, Sweden. Electronic address: pierre.campenfeldt@ki.se. · Karolinska Institutet, Department of Clinical Science Intervention and Technology, Sweden; Orthopedic Clinic, Vällingby-Läkarhuset, Praktikertjänst AB, Sweden. · Karolinska Institutet, Department of Clinical Science Intervention and Technology, Sweden; Department of Orthopaedics, Karolinska University Hospital, Sweden. · Department of Orthopaedics, Karolinska University Hospital, Sweden; Karolinska Institutet, Department of Molecular Medicine and Surgery, Section of Orthopaedics and Sport Medicine, Sweden. ·Injury · Pubmed #30243652.

ABSTRACT: BACKGROUND AND PURPOSE: The recommended treatment of displaced femoral neck fractures (FNF) in patients younger than 70 years of age is fracture reduction and internal fixation (IF). The incidence of re-operation due to nonunion (NU) or avascular necrosis (AVN) has been reported to be between 20-30%. Knowledge of possible predisposing factors needs to be elucidated. The primary aim of this study was to identify factors associated with a major re-operation due to NU or AVN in patients <70 years with a displaced FNF treated with IF. PATIENTS AND METHODS: 128 patients, 20-69 years with a FNF treated with IF. Follow up included radiographic and clinical examination at 4, 12 and 24 months. Logistic regression analysis was used to identify factors associated with re-operation due to NU or AVN. RESULTS: The re-operation rate due to NU or AVN was 6%, 16% and 28% at 4, 12 and 24 months respectively. Patients with low BMD was more likely to be re-operated than those with normal BMD, OR 5.5, CI (95%) 1.15-26.8, and those with a high alcohol consumption had 3.2 times higher odds to be re-operated due to NU or AVN, CI (95%) 1.16-8.76. INTERPRETATION: In more than two thirds (83/120) of the patients the fracture healed after one operation. Moreover, a low BMD and high alcohol consumption were related to a major re-operation. These results suggest that only age as a sole variable for choosing the type of surgical treatment may not be rational.

20 Article Osteoporosis and osteopenia in the distal forearm predict all-cause mortality independent of grip strength: 22-year follow-up in the population-based Tromsø Study. 2018

Hauger, A V / Bergland, A / Holvik, K / Ståhle, A / Emaus, N / Strand, B H. ·Department of Physiotherapy, Faculty of Health Sciences, Oslo Metropolitan University, OsloMet - storbyuniversitetet Postboks 4 St. Olavs plass, 0130, Oslo, Norway. anvoha@oslomet.no. · Department of Physiotherapy, Faculty of Health Sciences, Oslo Metropolitan University, OsloMet - storbyuniversitetet Postboks 4 St. Olavs plass, 0130, Oslo, Norway. · Norwegian Institute of Public Health, Marcus Thranes gate 6, 0473, Oslo, Norway. · Department of Neurobiology, Care Sciences and Society, Division of Physiotherapy, Karolinska Institutet, Alfred Nobels Allé 23, 14183, Huddinge, Sweden. · Function Area Occupational Therapy & Physiotherapy, Allied Health Professionals Function, Karolinska University Hospital, Stockholm, Sweden. · Department of Health and Care Sciences, Faculty of Health Sciences, UiT The Arctic University of Norway, 9037, Tromsø, Norway. · Norwegian National Advisory Unit on Aging and Health, Vestfold Hospital Trust, Tønsberg, Norway. · Faculty of Medicine, University of Oslo, Oslo, Norway. ·Osteoporos Int · Pubmed #30094609.

ABSTRACT: Low bone mineral density (BMD) gives an increased risk of fractures, which can lead to premature death. Can BMD of the wrist predict mortality? BMD consistent with osteopenia and osteoporosis gave a significantly increased risk of death for both men and women in a general population in Tromsø, Norway. INTRODUCTION: To investigate if bone mineral density (BMD) levels of the distal forearm, consistent with osteopenia and osteoporosis, can predict mortality and if grip strength is an effect modifier. METHODS: The study population constituted 6565 participants aged 50-79 years at baseline in the Tromsø Study wave 4 conducted in 1994-1995. Forearm BMD measured by SXA was categorized as "normal," "osteopenia," or "osteoporosis" following WHO's definition. Cox regression with all-cause mortality as the outcome over 22 years of follow-up was performed for men and women separately, adjusting for health-related factors, as well as BMD by grip strength interaction. A secondary analysis with a 15-year follow-up also adjusted for hip fractures and osteoporotic fractures. RESULTS: During follow-up, 3176 of participants died (47%). Those categorized as osteoporotic had higher mortality hazard ratio (HR) compared to those with normal BMD; men HR = 1.37 (95% confidence interval (CI) 1.19, 1.58) and women HR = 1.32 (1.14, 1.53) were adjusted for age, body mass index, physical activity, smoking habits, education, health status, chronic diseases, and grip strength. Corresponding HRs for osteopenia were men HR = 1.13 (1.00, 1.27) and women HR = 1.17 (1.01, 1.35). Further adjustments for fractures did only marginally attenuate the results, and HRs were still significant. There was no grip strength by BMD interaction. CONCLUSION: Men and women with low distal forearm BMD values, consistent with osteoporosis or osteopenia, had an increased mortality compared to normal BMD participants. High grip strength did not modify this association, and the association remained after adjustment for a range of health-related factors.

21 Article A novel frameshift deletion in PLS3 causing severe primary osteoporosis. 2018

Costantini, Alice / Krallis, Panagiotis Ν / Kämpe, Anders / Karavitakis, Emmanouil M / Taylan, Fulya / Mäkitie, Outi / Doulgeraki, Artemis. ·Department of Molecular Medicine and Surgery and Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden. alice.costantini@ki.se. · Department of Orthopaedics, "Aghia Sophia" Children's Hospital, Athens, Greece. · Department of Molecular Medicine and Surgery and Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden. · Neonatal Special Care Unit General Hospital of Chania, Crete, Greece. · Folkhälsan Institute of Genetics and University of Helsinki, Helsinki, Finland. · Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland. · Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden. · Department of Bone and Mineral Metabolism, Institute of Child Health, "Aghia Sophia" Children's Hospital, Athens, Greece. ·J Hum Genet · Pubmed #29884797.

ABSTRACT: Mutations in the gene encoding plastin-3, PLS3, have recently been associated to severe primary osteoporosis. The molecular function of plastin-3 is not fully understood. Since PLS3 is located on the X chromosome, males are usually more severely affected than females. PLS3 mutations have thus far been reported in approximately 20 young patients with low bone mineral density (BMD). We describe an 8-year-old Greek boy with severe primary osteoporosis with multiple vertebral compression fractures and one low-energy long bone fracture. His clinical manifestations were consistent with osteogenesis imperfecta, including blue sclerae, joint hypermobility, low bone mineral density, kyphosis, bilateral conductive hearing loss, and mild dysmorphic features. The family history was negative for primary osteoporosis. COL1A1 and COL1A2 mutations were excluded by Sanger sequencing. However, Sanger sequencing of PLS3 led to the identification of a de novo frameshift deletion, NM_005032: c.1096_1100delAACTT, p.(Asn366Serfs*5), in exon 10 confirming the diagnosis of PLS3 osteoporosis. In conclusion, we describe a novel frameshift deletion in PLS3 causing severe primary osteoporosis in a boy. Our finding highlights the clinical overlap between type I collagen and PLS3-related skeletal fragility and underscores the importance of PLS3 screening in patients with multiple fractures to enable proper genetic counseling.

22 Article Altered MicroRNA Profile in Osteoporosis Caused by Impaired WNT Signaling. 2018

Mäkitie, Riikka E / Hackl, Matthias / Niinimäki, Riitta / Kakko, Sakari / Grillari, Johannes / Mäkitie, Outi. ·Folkhälsan Institute of Genetics and University of Helsinki, Helsinki, Finland. · TAmiRNA GmbH, Vienna, Austria. · Department of Children and Adolescents, Oulu University Hospital, and PEDEGO Research Unit, University of Oulu, Oulu, Finland. · Internal Medicine and Clinical Research Center, University of Oulu, Oulu, Finland. · Christian Doppler Laboratory on Biotechnology of Skin Aging, Department of Biotechnology, University of Natural Resources and Life Sciences Vienna, Vienna, Austria. · Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland. · Center for Molecular Medicine, Karolinska Institutet and Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden. ·J Clin Endocrinol Metab · Pubmed #29506076.

ABSTRACT: Context: WNT signaling is fundamental to bone health, and its aberrant activation leads to skeletal pathologies. The heterozygous missense mutation p.C218G in WNT1, a key WNT pathway ligand, leads to severe early-onset and progressive osteoporosis with multiple peripheral and spinal fractures. Despite the severe skeletal manifestations, conventional bone turnover markers are normal in mutation-positive patients. Objective: This study sought to explore the circulating microRNA (miRNA) pattern in patients with impaired WNT signaling. Design and Setting: A cross-sectional cohort study at a university hospital. Participants: Altogether, 12 mutation-positive (MP) subjects (median age, 39 years; range, 11 to 76 years) and 12 mutation-negative (MN) subjects (35 years; range, 9 to 59 years) from two Finnish families with WNT1 osteoporosis due to the heterozygous p.C218G WNT1 mutation. Methods and Main Outcome Measure: Serum samples were screened for 192 miRNAs using quantitative polymerase chain reaction. Findings were compared between WNT1 MP and MN subjects. Results: The pattern of circulating miRNAs was significantly different in the MP subjects compared with the MN subjects, with two upregulated (miR-18a-3p and miR-223-3p) and six downregulated miRNAs (miR-22-3p, miR-31-5p, miR-34a-5p, miR-143-5p, miR-423-5p, and miR-423-3p). Three of these (miR-22-3p, miR-34a-5p, and miR-31-5p) are known inhibitors of WNT signaling: miR-22-3p and miR-34a-5p target WNT1 messenger RNA, and miR-31-5p is predicted to bind to WNT1 3'UTR. Conclusions: The circulating miRNA pattern reflects WNT1 mutation status. The findings suggest that the WNT1 mutation disrupts feedback regulation between these miRNAs and WNT1, providing insights into the pathogenesis of WNT-related bone disorders. These miRNAs may have potential in the diagnosis and treatment of osteoporosis.

23 Article A health economic simulation model for the clinical management of osteoporosis. 2018

Jonsson, E / Hansson-Hedblom, A / Ljunggren, Ö / Åkesson, K / Spångeus, A / Kanis, J A / Borgström, F. ·Quantify Research, Hantverkargatan 8, 112 21, Stockholm, SE, Sweden. emma.jonsson@quantifyresearch.com. · Quantify Research, Hantverkargatan 8, 112 21, Stockholm, SE, Sweden. · Department of Medical Sciences, Uppsala University Hospital, Uppsala, Sweden. · Department of Clinical Sciences, Clinical and Molecular Osteoporosis Unit, Lund University, Malmö, Sweden. · Department of Endocrinology, Medicine and Health, Linköping University, Linköping, Sweden. · University of Sheffield, Sheffield, UK. · Catholic University of Australia, Melbourne, Australia. · LIME/MMC, Karolinska Institutet, Stockholm, Sweden. ·Osteoporos Int · Pubmed #29196775.

ABSTRACT: The objective was to estimate the burden of osteoporosis in Sweden based on current clinical practice and the cost-effectiveness of improvements in the management of osteoporosis over the clinical management compared to current clinical practice. Results showed that better compliance to treatment guidelines is associated with better projected outcomes and cost-savings. INTRODUCTION: The purpose of this study is to estimate the burden of osteoporosis in Sweden based on current clinical practice and the cost-effectiveness of improvements in the management of osteoporosis over the clinical management compared to current clinical practice. METHODS: The analysis was carried out using a model that simulates the individual patients considered for pharmacological treatment during 1 year and their projected osteoporosis treatment pathway, quality-adjusted life years (QALYs) and costs over their remaining lifetime. All patients regardless of treatment or no treatment were simulated. Information on current management of osteoporosis in terms of patient characteristics and treatment patterns were derived from a Swedish osteoporosis research database based on national registers and patient records. Current (standard) clinical management was compared with alternative scenarios mirroring Swedish treatment guidelines. RESULTS: The national burden in terms of lost QALYs was estimated at 14,993 QALYs and the total economic cost at €776M. Scenario analyses showed that 382-3864 QALYs could be gained at a cost/QALY ranging from cost-saving to €31368, depending on the scenario. The margin of investment, i.e. the maximum amount that could be invested in the healthcare system to achieve these improvements up to the limit of the willingness to pay/QALY, was estimated at €199M on a population level (€3,634/patient). CONCLUSIONS: The analysis showed that better compliance to treatment guidelines is associated with better projected outcomes and cost-savings. From a cost-effectiveness perspective, there is also considerable room for investment to achieve these improvements in the management of osteoporosis.

24 Article Defective WNT signaling associates with bone marrow fibrosis-a cross-sectional cohort study in a family with WNT1 osteoporosis. 2018

Mäkitie, R E / Niinimäki, R / Kakko, S / Honkanen, T / Kovanen, P E / Mäkitie, O. ·Folkhälsan Institute of Genetics, University of Helsinki, P.O. Box 63, FIN-00014, Helsinki, Finland. riikka.makitie@helsinki.fi. · Department of Children and Adolescents, Oulu University Hospital and Oulu University, Oulu, Finland. · Internal Medicine and Clinical Research Center, University of Oulu, Oulu, Finland. · Department of Hematology, Päijät-Häme Central Hospital, Lahti, Finland. · HUSLAB, Helsinki University Hospital and Department of Pathology, University of Helsinki, Helsinki, Finland. · Folkhälsan Institute of Genetics, University of Helsinki, P.O. Box 63, FIN-00014, Helsinki, Finland. · Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland. · Center for Molecular Medicine, Karolinska Institutet and Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden. ·Osteoporos Int · Pubmed #29147753.

ABSTRACT: This study explores bone marrow function in patients with defective WNT1 signaling. Bone marrow samples showed increased reticulin and altered granulopoiesis while overall hematopoiesis was normal. Findings did not associate with severity of osteoporosis. These observations provide new insight into the role of WNT signaling in bone marrow homeostasis. INTRODUCTION: WNT signaling regulates bone homeostasis and survival and self-renewal of hematopoietic stem cells. Aberrant activation may lead to osteoporosis and bone marrow pathology. We aimed to explore bone marrow findings in a large family with early-onset osteoporosis due to a heterozygous WNT1 mutation. METHODS: We analyzed peripheral blood samples, and bone marrow aspirates and biopsies from 10 subjects with WNT1 mutation p.C218G. One subject was previously diagnosed with idiopathic myelofibrosis and others had no previously diagnosed hematologic disorders. The findings were correlated with the skeletal phenotype, as evaluated by number of peripheral and spinal fractures and bone mineral density. RESULTS: Peripheral blood samples showed no abnormalities in cell counts, morphology or distributions but mild increase in platelet count. Bone marrow aspirates (from 8/10 subjects) showed mild decrease in bone marrow iron storages in 6 and variation in cell distributions in 5 subjects. Bone marrow biopsies (from 6/10 subjects) showed increased bone marrow reticulin (grade MF-2 in the myelofibrosis subject and grade MF-1 in 4 others), and an increase in overall, and a shift towards early-phase, granulopoiesis. The bone marrow findings did not associate with the severity of skeletal phenotype. CONCLUSIONS: Defective WNT signaling associates with a mild increase in bone marrow reticulin and may predispose to myelofibrosis, while overall hematopoiesis and peripheral blood values are unaltered in individuals with a WNT1 mutation. In this family with WNT1 osteoporosis, bone marrow findings were not related to the severity of osteoporosis.

25 Article Psychometric properties of the Swedish version of the Falls Efficacy Scale-International for older adults with osteoporosis, self-reported balance deficits and fear of falling. 2018

Halvarsson, Alexandra / Ståhle, Agneta. ·a Department of Neurobiology Health Care Sciences and Society (NVS) Division of Physiotherapy , Karolinska Institutet , Stockholm , Sweden. · b Allied Health Professionals Function , Karolinska University Hospital , Stockholm , Sweden. ·Disabil Rehabil · Pubmed #28687055.

ABSTRACT: PURPOSE: Investigate the psychometric properties of the Swedish version of the Falls Efficacy Scale-International (FES-I). METHOD: Cross-sectional study. Community-dwelling older adults with self-reported balance deficits and fear of falling were recruited from an ongoing randomised controlled study to evaluate the psychometric properties of the FES-I using Rasch model analysis. RESULTS: The Rasch model analysis revealed good category function, the questionnaire measured one dimension with an explained variance of 68.6% and item goodness-of-fit with mean square values (MnSq) 0.7-1.44. The item map showed that all items are spread over the scale, which indicates different difficulties in the items. Non-satisfactory person goodness-of-fit was shown with seven persons and showed person misfit according to both the MnSq-value and the z-value, 38 persons (40%) showed a person misfit when only following the threshold for MnSq. CONCLUSIONS: The Swedish version of FES-I shows good psychometric properties with unidimensionality and item goodness-of-fit. Lower person goodness-of-fit was shown probably because of confounding factors that may influence the answers. The transformed values of the FES-I make it possible to use parametric statistics preferable for this population in future research. Implications for rehabilitation The Falls Efficacy Scale-International (FES-I) shows good psychometric properties with unidimensionality, item goodness-of-fit and good item reliability, which means that FES-I is a valuable tool when measuring concerns about falling in an older population with osteoporosis and could be useful in clinical settings. Confounding factors such as pain, high number of falls, low fall self-efficacy, experience of previous falls, and vertigo may influence the answers and result in low person goodness-of-fit.

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