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Osteoporosis: HELP
Articles from Katholieke Universiteit Leuven
Based on 84 articles published since 2008

These are the 84 published articles about Osteoporosis that originated from Katholieke Universiteit Leuven during 2008-2019.
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4
1 Guideline EAA clinical guideline on management of bone health in the andrological outpatient clinic. 2018

Rochira, V / Antonio, L / Vanderschueren, D. ·Unit of Endocrinology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy. · Azienda Ospedaliero-Universitaria di Modena, Ospedale Civile di Baggiovara, Modena, Italy. · Department of Endocrinology, University Hospitals Leuven, Leuven, Belgium. · Department of Clinical and Experimental Medicine, Laboratory of Clinical and Experimental Endocrinology, KU Leuven, Leuven, Belgium. · Department of Laboratory Medicine, University Hospitals Leuven, Leuven, Belgium. ·Andrology · Pubmed #29499097.

ABSTRACT: Male osteoporosis is now a well-recognized medical disorder with established clinical guidelines for both diagnosis and management. Prevention as well as management of osteoporosis in men consulting the andrological outpatient clinic because of low testosterone, however, is not well established. This gap of knowledge is-at least partly-explained by the controversy with respect to the threshold of testosterone needed for skeletal maintenance. However, testosterone deficiency may be clearly associated with bone loss as well as frailty in men. If anything, andrologists should therefore be aware of the potential silent presence of osteoporosis in men with confirmed hypogonadism. Therefore, the management of patients with potential hypogonadism should include a complete bone health assessment, besides clinical and biochemical evaluation of gonadal status. Such bone health assessment should include specific items in medical history and physical examination related to fracture risk. Furthermore, dual-energy absorptiometry is indicated to evaluate fracture risk in men with confirmed clinical hypogonadism. Regarding treatment, besides general measures to prevent or manage male osteoporosis testosterone replacement can be initiated (as described in guidelines for hypogonadism), but data on its efficacy in preventing fractures are lacking. Thus, additional anti-osteoporotic may be needed, especially in men with very low testosterone who are at high risk of bone loss and/or in men not able to receive testosterone replacement.

2 Review Age-related bone loss and sarcopenia in men. 2019

Laurent, Michaël R / Dedeyne, Lenore / Dupont, Jolan / Mellaerts, Bea / Dejaeger, Marian / Gielen, Evelien. ·Gerontology and Geriatrics Unit, Department of Chronic Diseases, Metabolism and Ageing (CHROMETA), University of Leuven, Herestraat 49, PO box 7003, 3000 Leuven, Belgium; Centre for Metabolic Bone Diseases, University Hospitals Leuven, Herestraat 49, 3000 Leuven, Belgium; Imelda Hospital, Imeldalaan 9, 2820 Bonheiden, Belgium. Electronic address: michael.laurent@uzleuven.be. · Gerontology and Geriatrics Unit, Department of Chronic Diseases, Metabolism and Ageing (CHROMETA), University of Leuven, Herestraat 49, PO box 7003, 3000 Leuven, Belgium. Electronic address: lenore.dedeyne@kuleuven.be. · Gerontology and Geriatrics Unit, Department of Chronic Diseases, Metabolism and Ageing (CHROMETA), University of Leuven, Herestraat 49, PO box 7003, 3000 Leuven, Belgium. Electronic address: jolan.dupont@uzleuven.be. · Imelda Hospital, Imeldalaan 9, 2820 Bonheiden, Belgium. Electronic address: bea.mellaerts@imelda.be. · Gerontology and Geriatrics Unit, Department of Chronic Diseases, Metabolism and Ageing (CHROMETA), University of Leuven, Herestraat 49, PO box 7003, 3000 Leuven, Belgium; Centre for Metabolic Bone Diseases, University Hospitals Leuven, Herestraat 49, 3000 Leuven, Belgium. Electronic address: marian.dejaeger@uzleuven.be. · Gerontology and Geriatrics Unit, Department of Chronic Diseases, Metabolism and Ageing (CHROMETA), University of Leuven, Herestraat 49, PO box 7003, 3000 Leuven, Belgium; Centre for Metabolic Bone Diseases, University Hospitals Leuven, Herestraat 49, 3000 Leuven, Belgium. Electronic address: evelien.gielen@uzleuven.be. ·Maturitas · Pubmed #30797530.

ABSTRACT: Bone and muscle are required for mobility but they also have endocrine and metabolic functions. In ageing as well as in many chronic diseases, bone loss and muscle atrophy occur simultaneously, leading to concomitant osteoporosis and sarcopenia. This occurs in both genders but compared with postmenopausal women, men appear to be better protected against age-related bone and muscle decay. Sex steroids (both androgens like testosterone and oestrogens like estradiol) are mainly responsible for musculoskeletal sexual dimorphism. They stimulate peak bone and muscle mass accretion during puberty and midlife, and prevent subsequent loss in ageing men but not post-menopausal women. Still, recent studies have highlighted the importance of intrinsic ageing mechanisms such as cellular senescence and oxidative stress in both genders. Sarcopenia may predispose to dysmobility, frailty, falls and fractures, but whether so-called osteosarcopenia qualifies as a distinct entity remains debated. Although randomized clinical trials in male osteoporosis are smaller and therefore underpowered for some outcomes like hip fractures, the available evidence suggests that the clinical diagnostic and therapeutic approach to male osteoporosis is largely similar to that in postmenopausal women. There is a clear unmet medical need for effective and safe anabolic drugs to rebuild the ageing skeleton, muscle, and preferably both tissues simultaneously. The Wnt/sclerostin and myostatin/activin receptor signalling pathways appear particularly promising in this regard. In this narrative review, we aim to provide an overview of our current understanding of the pathophysiology and treatment of male osteoporosis and sarcopenia, and interactions between these two diseases.

3 Review Aging, Osteocytes, and Mechanotransduction. 2017

Hemmatian, Haniyeh / Bakker, Astrid D / Klein-Nulend, Jenneke / van Lenthe, G Harry. ·Biomechanics Section, Department of Mechanical Engineering, KU Leuven, Celestijnenlaan 300c, 3001, Leuven, Belgium. · Department of Oral Cell Biology, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and Vrije Universiteit Amsterdam, Amsterdam Movement Sciences, Amsterdam, The Netherlands. · Department of Oral Cell Biology, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and Vrije Universiteit Amsterdam, Amsterdam Movement Sciences, Amsterdam, The Netherlands. j.kleinnulend@acta.nl. ·Curr Osteoporos Rep · Pubmed #28891009.

ABSTRACT: PURPOSE OF REVIEW: The bone is able to adapt its structure to mechanical signals via the bone remodeling process governed by mechanosensitive osteocytes. With aging, an imbalance in bone remodeling results in osteoporosis. In this review, we hypothesized that changes in lacunar morphology underlie the decreased bone mechanoresponsiveness to mechanical loading with aging. RECENT FINDINGS: Several studies have reported considerable variations in the shape of osteocytes and their lacunae with aging. Since osteocytes can sense matrix strain directly via their cell bodies, the variations in osteocyte morphology may cause changes in osteocyte mechanosensitivity. As a consequence, the load-adaptive response of osteocytes may change with aging, even when mechanical loading would remain unchanged. Though extensive quantitative data is lacking, evidence exists that the osteocyte lacunae are becoming smaller and more spherical with aging. Future dedicated studies might reveal whether these changes would affect osteocyte mechanosensation and the subsequent biological response, and whether this is (one of) the pathways involved in age-related bone loss.

4 Review Pharmacological treatment of osteoporosis in the oldest old. 2017

Vandenbroucke, A / Luyten, F P / Flamaing, J / Gielen, E. ·Clinical Department of Internal Medicine, UZ Leuven. · Skeletal Biology and Engineering, Department of Development and Regeneration, KU Leuven. · Center for Metabolic Bone Disease, UZ Leuven. · Gerontology and Geriatrics, Department of Clinical and Experimental Medicine, KU Leuven, Leuven, Belgium. ·Clin Interv Aging · Pubmed #28740372.

ABSTRACT: The incidence of osteoporotic fractures increases with age. Consequently, the global prevalence of osteoporotic fractures will increase with the aging of the population. In old age, osteoporosis is associated with a substantial burden in terms of morbidity and mortality. Nevertheless, osteoporosis in old age continues to be underdiagnosed and undertreated. This may, at least partly, be explained by the fact that evidence of the antifracture efficacy of osteoporosis treatments comes mainly from randomized controlled trials in postmenopausal women with a mean age of 70-75 years. However, in the last years, subgroup analyses of these landmark trials have been published investigating the efficacy and safety of osteoporosis treatment in the very elderly. Based on this evidence, this narrative review discusses the pharmacological management of osteoporosis in the oldest old (≥80 years). Because of the high prevalence of calcium and/or vitamin D deficiency in old age, these supplements are essential in the management of osteoporosis in the elderly people. Adding antiresorptive or anabolic treatments or combinations, thereof, reduces the risk of vertebral fractures even more, at least in the elderly with documented osteoporosis. The reduction of hip fracture risk by antiresorptive treatments is less convincing, which may be explained by insufficient statistical power in some subanalyses and/or a higher impact of nonskeletal risk factors in the occurrence of hip fractures. Compared with younger individuals, a larger absolute risk reduction is observed in the elderly because of the higher baseline fracture risk. Therefore, the elderly will benefit more of treatment. In addition, current osteoporosis therapies also appear to be safe in the elderly. Although more research is required to further clarify the effect of osteoporosis drugs in the elderly, especially with respect to hip fractures, there is currently sufficient evidence to initiate appropriate treatment in the elderly with osteoporosis and osteoporotic fractures.

5 Review Osteoporosis in Frail Patients: A Consensus Paper of the Belgian Bone Club. 2017

Gielen, E / Bergmann, P / Bruyère, O / Cavalier, E / Delanaye, P / Goemaere, S / Kaufman, J-M / Locquet, M / Reginster, J-Y / Rozenberg, S / Vandenbroucke, A-M / Body, J-J. ·Gerontology and Geriatrics, Department of Clinical and Experimental Medicine, KU Leuven & Center for Metabolic Bone Diseases, UZ Leuven, Herestraat 49, 3000, Leuven, Belgium. evelien.gielen@uzleuven.be. · Department of Radioisotopes, CHU Brugmann, Université Libre de Bruxelles, Bruxelles, Belgium. · Department of Public Health, Epidemiology and Health Economics, University of Liège, CHU de Liège, Liège, Belgium. · Department of Clinical Chemistry, UnilabLg, CIRM, University of Liège, CHU de Liège, Liège, Belgium. · Department of Nephrology, Dialysis, Transplantation, University of Liège, CHU de Liège, Liège, Belgium. · Unit for Osteoporosis and Metabolic Bone Diseases, Ghent University Hospital, Ghent, Belgium. · Department of Endocrinology, Ghent University Hospital, Ghent, Belgium. · Department of Gynaecology-Obstetrics, Université Libre de Bruxelles, Bruxelles, Belgium. · Clinical Department of Internal Medicine, UZ Leuven, Leuven, Belgium. · Department of Medicine, CHU Brugmann, Université Libre de Bruxelles, Bruxelles, Belgium. ·Calcif Tissue Int · Pubmed #28324124.

ABSTRACT: In this consensus paper, the Belgian Bone Club aims to provide a state of the art on the epidemiology, diagnosis, and management of osteoporosis in frail individuals, including patients with anorexia nervosa, patients on dialysis, cancer patients, persons with sarcopenia, and the oldest old. All these conditions may indeed induce bone loss that is superimposed on physiological bone loss and often remains under-recognized and under-treated. This is of particular concern because of the major burden of osteoporotic fractures in terms of morbidity, mortality, and economic cost. Therefore, there is an urgent need to appreciate bone loss associated with these conditions, as this may improve diagnosis and management of bone loss and fracture risk in clinical practice.

6 Review Estrogens and Androgens in Skeletal Physiology and Pathophysiology. 2017

Almeida, Maria / Laurent, Michaël R / Dubois, Vanessa / Claessens, Frank / O'Brien, Charles A / Bouillon, Roger / Vanderschueren, Dirk / Manolagas, Stavros C. ·Division of Endocrinology and Metabolism, Center for Osteoporosis and Metabolic Bone Diseases, University of Arkansas for Medical Sciences and the Central Arkansas Veterans Healthcare System, Little Rock, Arkansas; Departments of Cellular and Molecular Medicine and Clinical and Experimental Medicine, KU Leuven, Leuven, Belgium; Center for Metabolic Bone Diseases, University Hospitals Leuven, Leuven, Belgium; and Institut National de la Santé et de la Recherche Médicale UMR1011, University of Lille and Institut Pasteur de Lille, Lille, France. ·Physiol Rev · Pubmed #27807202.

ABSTRACT: Estrogens and androgens influence the growth and maintenance of the mammalian skeleton and are responsible for its sexual dimorphism. Estrogen deficiency at menopause or loss of both estrogens and androgens in elderly men contribute to the development of osteoporosis, one of the most common and impactful metabolic diseases of old age. In the last 20 years, basic and clinical research advances, genetic insights from humans and rodents, and newer imaging technologies have changed considerably the landscape of our understanding of bone biology as well as the relationship between sex steroids and the physiology and pathophysiology of bone metabolism. Together with the appreciation of the side effects of estrogen-related therapies on breast cancer and cardiovascular diseases, these advances have also drastically altered the treatment of osteoporosis. In this article, we provide a comprehensive review of the molecular and cellular mechanisms of action of estrogens and androgens on bone, their influences on skeletal homeostasis during growth and adulthood, the pathogenetic mechanisms of the adverse effects of their deficiency on the female and male skeleton, as well as the role of natural and synthetic estrogenic or androgenic compounds in the pharmacotherapy of osteoporosis. We highlight latest advances on the crosstalk between hormonal and mechanical signals, the relevance of the antioxidant properties of estrogens and androgens, the difference of their cellular targets in different bone envelopes, the role of estrogen deficiency in male osteoporosis, and the contribution of estrogen or androgen deficiency to the monomorphic effects of aging on skeletal involution.

7 Review Lower Bone Mineral Density at the Hip and Lumbar Spine in People with Psychosis Versus Controls: a Comprehensive Review and Skeletal Site-Specific Meta-analysis. 2016

Gomez, Lucia / Stubbs, Brendon / Shirazi, Ayala / Vancampfort, Davy / Gaughran, Fiona / Lally, John. ·Kings College London School of Medical Education, Strand, London, WC2R 2LS, UK. · Health Service and Population Research Department, Institute of Psychiatry, Psychology and Neuroscience, King's College London, De Crespigny Park, London, Box SE5 8AF, UK. brendon.stubbs@kcl.ac.uk. · Physiotherapy Department, South London and Maudsley NHS Foundation Trust, Denmark Hill, London, SE5 8AZ, UK. brendon.stubbs@kcl.ac.uk. · Department of Rehabilitation Sciences, KU Leuven-University of Leuven, Leuven, Belgium. · University Psychiatric Centre KU Leuven, KU Leuven-University of Leuven, Leuven-Kortenberg, Belgium. · Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK. · National Psychosis Service, South London and Maudsley NHS Foundation Trust, London, BR3 3BX, UK. · Department of Psychiatry, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin, Ireland. ·Curr Osteoporos Rep · Pubmed #27696144.

ABSTRACT: It remains unclear if differences in bone mineral density (BMD) exist at different skeletal sites between people with schizophrenia and age- and sex-matched healthy controls (HCs). Major databases were searched from inception until February 2016 for studies measuring BMD using dual-energy X-ray absorptiometry (DXA) at any skeletal site in individuals with schizophrenia. Ten studies investigating 827 people with schizophrenia (55.4 % female, 33.8 ± 9.7 years) and 1379 HCs (58.7 % female, 34.7 ± 9.1 years) were included. People with schizophrenia had significantly reduced BMD at the lumbar spine (standardised mean difference adjusted for publication bias (SMD) = -0.950 (95 % CI = -1.23 to -0.66, fail-safe number = 825) and hip (SMD = -0.534, 95 % CI = -0.876 to -0.192, fail-safe number = 186). A higher proportion of hyperprolactinaemia (β = -0.0102, p < 0.0001) and smokers (β = -0.0099, p = 0.02) moderated a larger reduced BMD at the lumbar spine. Further research is required to investigate if low bone mass and fractures can be prevented in people with schizophrenia.

8 Review Relationship between antipsychotic medication, serum prolactin levels and osteoporosis/osteoporotic fractures in patients with schizophrenia: a critical literature review. 2016

De Hert, Marc / Detraux, Johan / Stubbs, Brendon. ·a Department of Neurosciences , KU Leuven - University Psychiatric Centre , Kortenberg , Belgium. · b Physiotherapy Department , South London and Maudsley NHS Foundation Trust , Denmark Hill, London , United Kingdom. · c Health Service and Population Research Department , Institute of Psychiatry, King's College London , London , United Kingdom. ·Expert Opin Drug Saf · Pubmed #26986209.

ABSTRACT: INTRODUCTION: Using an antipsychotic medication can increase prolactin (PRL) levels, causing hyperprolactinemia (HPRL). Although the occurrence of osteoporosis within the population of patients with schizophrenia has been recognized, the precise nature of the association between antipsychotic treatment, PRL, osteoporosis, and the disease itself seems to be elusive. AREAS COVERED: The aim of this review is to critically review the literature regarding the association between osteoporosis and PRL and to summarize the available evidence with respect to the impact of PRL-elevating antipsychotics on bone mineral density (BMD) and fractures in non-elderly patients with schizophrenia. EXPERT OPINION: Although long-standing HPRL can have an impact on the rate of bone metabolism and, when associated with hypogonadism, may lead to decreased bone density in both female and male subjects, the relative contribution of antipsychotic-induced HPRL in bone mineral loss in patients with schizophrenia remains unclear. Methodological shortcomings of existing studies, including the lack of prospective data and the focus on measurements of BMD instead of bone turnover markers, preclude definitive conclusions regarding the relationship between PRL-raising antipsychotics and BMD loss in patients with schizophrenia. Therefore, more well conducted prospective trials of these biomarkers are necessary to establish the precise relationship between antipsychotics, PRL levels and osteoporosis/osteoporotic risk.

9 Review Bone mineral density, osteoporosis, and fractures among people with eating disorders: a systematic review and meta-analysis. 2016

Solmi, M / Veronese, N / Correll, C U / Favaro, A / Santonastaso, P / Caregaro, L / Vancampfort, D / Luchini, C / De Hert, M / Stubbs, B. ·Department of Neurosciences, University of Padova, Padova, Italy. · Department of Medicine, Geriatrics Section, University of Padova, Italy. · The Zucker Hillside Hospital, Department of Psychiatry, North Shore-Long Island Jewish Health System, Glen Oaks, NY, USA. · Feinstein Institute for Medical Research, Manhasset, NY, USA. · Department of Medicine, DIMED, University of Padova, Padova, Italy. · Department of Rehabilitation Sciences, Leuven - University of Leuven, Leuven, Belgium. · Z.org Leuven, KU Leuven - University of Leuven, Kortenberg, Belgium. · Department of Pathology and Diagnostics, University and Hospital Trust of Verona, Verona, Italy. · Physiotherapy Department, South London and Maudsley NHS Foundation Trust, London, UK. · Health Service and Population Research Department, Institute of Psychiatry King's College London, London, UK. ·Acta Psychiatr Scand · Pubmed #26763350.

ABSTRACT: OBJECTIVE: To provide meta-analytical evidence of bone mineral density (BMD), fractures, and osteoporosis rates in eating disorders (ED) vs. healthy controls (HCs). METHOD: Three independent authors searched major electronic databases from inception till August 2015 for cross-sectional studies reporting BMD in people with ED (anorexia nervosa, (AN); bulimia nervosa, (BN); eating disorders not otherwise specified, (EDNOS)) vs. HCs. Standardized mean differences (SMDs) ±95% and confidence intervals (CIs) were calculated for BMD, and odds ratios (ORs) for osteopenia, osteoporosis, and fractures. RESULTS: Overall, 57 studies were eligible, including 21 607 participants (ED = 6485, HCs = 15 122). Compared to HC, AN subjects had significantly lower BMD values at lumbar spine (SMD = -1.51, 95% CI = -1.75, -1.27, studies = 42), total hip (SMD = -1.56, 95%CI = -1.84, -1.28, studies = 23), intertrochanteric region (SMD = -1.80, 95%CI = -2.46, -1.14, studies = 7), trochanteric region (SMD = -1.05, 95%CI = -1.44, -0.66, studies = 7), and femoral neck (SMD = -0.98, 95%CI = -1.12, -0.77, studies = 20). Reduced BMD was moderated by ED illness duration and amenorrhea (P < 0.05). AN was associated with an increased likelihood of osteoporosis (OR = 12.59, 95%CI = 3.30-47.9, P < 0.001, studies = 4) and fractures (OR = 1.84, 95% CI = 1.17-2.89, I(2) = 56, studies = 6). No difference in BMD was found between BN and EDNOS vs. HC. CONCLUSION: People with AN have reduced BMD, increased odds of osteoporosis and risk of fractures. Proactive monitoring and interventions are required to ameliorate bone loss in AN.

10 Review Effects of Dairy Products Consumption on Health: Benefits and Beliefs--A Commentary from the Belgian Bone Club and the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases. 2016

Rozenberg, Serge / Body, Jean-Jacques / Bruyère, Olivier / Bergmann, Pierre / Brandi, Maria Luisa / Cooper, Cyrus / Devogelaer, Jean-Pierre / Gielen, Evelien / Goemaere, Stefan / Kaufman, Jean-Marc / Rizzoli, René / Reginster, Jean-Yves. ·Department of Gynaecology-Obstetrics, Université Libre de Bruxelles, Brussels, Belgium. · Department of Medicine, CHU Brugmann, Université Libre de Bruxelles, Brussels, Belgium. · Department of Public Health, Epidemiology and Health Economics, University of Liège, Liège, Belgium. · Department of Radioisotopes, CHU Brugmann, Université Libre de Bruxelles, Brussels, Belgium. · Metabolic Bone Unit, Department of Internal Medicine, University of Florence, Florence, Italy. · MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK. · University of Oxford, Oxford, UK. · Department of Rheumatology, Saint Luc University Hospital, Université Catholique de Louvain, Louvain-la-Neuve, Belgium. · Gerontology and Geriatrics Section, Department of Experimental Medicine, Katholiek Universiteit Leuven, Leuven, Belgium. · Department of Rheumatology and Endocrinology, State University of Ghent, Ghent, Belgium. · Department of Endocrinology, State University of Ghent, Ghent, Belgium. · Division of Bones Diseases, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland. · Department of Public Health, Epidemiology and Health Economics, University of Liège, Liège, Belgium. jyreginster@ulg.ac.be. ·Calcif Tissue Int · Pubmed #26445771.

ABSTRACT: Dairy products provide a package of essential nutrients that is difficult to obtain in low-dairy or dairy-free diets, and for many people it is not possible to achieve recommended daily calcium intakes with a dairy-free diet. Despite the established benefits for bone health, some people avoid dairy in their diet due to beliefs that dairy may be detrimental to health, especially in those with weight management issues, lactose intolerance, osteoarthritis, rheumatoid arthritis, or trying to avoid cardiovascular disease. This review provides information for health professionals to enable them to help their patients make informed decisions about consuming dairy products as part of a balanced diet. There may be a weak association between dairy consumption and a possible small weight reduction, with decreases in fat mass and waist circumference and increases in lean body mass. Lactose intolerant individuals may not need to completely eliminate dairy products from their diet, as both yogurt and hard cheese are well tolerated. Among people with arthritis, there is no evidence for a benefit to avoid dairy consumption. Dairy products do not increase the risk of cardiovascular disease, particularly if low fat. Intake of up to three servings of dairy products per day appears to be safe and may confer a favourable benefit with regard to bone health.

11 Review Sex steroid actions in male bone. 2014

Vanderschueren, Dirk / Laurent, Michaël R / Claessens, Frank / Gielen, Evelien / Lagerquist, Marie K / Vandenput, Liesbeth / Börjesson, Anna E / Ohlsson, Claes. ·Clinical and Experimental Endocrinology (D.V.) and Gerontology and Geriatrics (M.R.L., E.G.), Department of Clinical and Experimental Medicine · Laboratory of Molecular Endocrinology, Department of Cellular and Molecular Medicine (M.R.L., F.C.) · and Centre for Metabolic Bone Diseases (D.V., M.R.L., E.G.), KU Leuven, B-3000 Leuven, Belgium · and Center for Bone and Arthritis Research (M.K.L., L.V., A.E.B., C.O.), Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 413 45 Gothenburg, Sweden. ·Endocr Rev · Pubmed #25202834.

ABSTRACT: Sex steroids are chief regulators of gender differences in the skeleton, and male gender is one of the strongest protective factors against osteoporotic fractures. This advantage in bone strength relies mainly on greater cortical bone expansion during pubertal peak bone mass acquisition and superior skeletal maintenance during aging. During both these phases, estrogens acting via estrogen receptor-α in osteoblast lineage cells are crucial for male cortical and trabecular bone, as evident from conditional genetic mouse models, epidemiological studies, rare genetic conditions, genome-wide meta-analyses, and recent interventional trials. Genetic mouse models have also demonstrated a direct role for androgens independent of aromatization on trabecular bone via the androgen receptor in osteoblasts and osteocytes, although the target cell for their key effects on periosteal bone formation remains elusive. Low serum estradiol predicts incident fractures, but the highest risk occurs in men with additionally low T and high SHBG. Still, the possible clinical utility of serum sex steroids for fracture prediction is unknown. It is likely that sex steroid actions on male bone metabolism rely also on extraskeletal mechanisms and cross talk with other signaling pathways. We propose that estrogens influence fracture risk in aging men via direct effects on bone, whereas androgens exert an additional antifracture effect mainly via extraskeletal parameters such as muscle mass and propensity to fall. Given the demographic trends of increased longevity and consequent rise of osteoporosis, an increased understanding of how sex steroids influence male bone health remains a high research priority.

12 Review Osteoporosis in older men: recent advances in pathophysiology and treatment. 2013

Laurent, Michaël / Gielen, Evelien / Claessens, Frank / Boonen, Steven / Vanderschueren, Dirk. ·Geriatric Medicine, University Hospitals Leuven, Herestraat 49, 3000 Leuven, Belgium; Gerontology and Geriatrics, Department of Clinical and Experimental Medicine, KU Leuven, Herestraat 49, 3000 Leuven, Belgium; Laboratory of Molecular Endocrinology, Department of Cellular and Molecular Medicine, KU Leuven, Herestraat 49, 3000 Leuven, Belgium. Electronic address: michael.laurent@med.kuleuven.be. ·Best Pract Res Clin Endocrinol Metab · Pubmed #24054929.

ABSTRACT: Osteoporosis remains underrecognized and undertreated but more so in men, adding considerably to fracture burden and costs. Fracture-related morbidity and mortality is higher in men, partly due to greater frailty. Improved peak bone mass, geometry and turn-over contribute to lower fracture incidence in men. Bioavailable androgens and oestrogens regulate these aspects of musculoskeletal sexual dimorphism, yet the direct cellular and molecular targets of sex steroids in bone remain incompletely understood. Screening with clinical risk factors and dual energy X-ray absorptiometry are advised in men from age 70 (or 50 with additional risk factors). We now have compelling evidence that osteoporosis drugs are equally effective in men and women, not only to increase bone density but also to prevent osteoporotic fractures. The use of testosterone or selective androgen receptor modulators for osteoporosis, sarcopenia, frailty and falls in men with late-onset hypogonadism requires further investigation.

13 Review Novel insights in the regulation and mechanism of androgen action on bone. 2013

Sinnesael, Mieke / Claessens, Frank / Boonen, Steven / Vanderschueren, Dirk. ·Clinical and Experimental Endocrinology, Department of Experimental Medicine, KU Leuven, Leuven, Belgium. ·Curr Opin Endocrinol Diabetes Obes · Pubmed #23449008.

ABSTRACT: PURPOSE OF REVIEW: This review provides an update on the associations of testosterone, estrogens, sex hormone binding globulin, GH-IGF-I, osteocalcin and mechanical loading with relevance to skeletal health. RECENT FINDINGS: The simple concept of a dual model of action of androgens, i.e. either directly via the androgen receptor or indirectly by estrogens, is proving more complicated because of novel interactions of these hormones and their receptors with other hormonal as well as mechanical signals. SUMMARY: Testosterone - in contrast with estrogen - is not uniformly associated with fracture risk in men. However, androgen receptor mediated action is clearly important for trabecular bone maintenance in male mice whereas both estrogens and androgens regulate cortical bone growth. The osteoblast and osteocyte appear to be involved in such androgen receptor mediated action on bone in male mice. Studies in mice also showed an unexpected interaction between osteocalcin and testosterone production in males and, vice versa, between ovarian production of follicle-stimulating hormone with testosterone and potentially bone formation.

14 Review [The impact of bisphosphonates on orthodontic treatment]. 2012

Poelmans, S / Carels, C E L. ·Uit de afdeling Orthodontie van de Katholieke Universiteit Leuven. simon.poelmans@uzleuven.be ·Ned Tijdschr Tandheelkd · Pubmed #22567815.

ABSTRACT: Bisphosphonates are used in the treatment of various diseases which are associated with a disturbance of the balance between bone apposition and degradation. The most important complication of bisphosphonate use is osteonecrosis of the jaw. Certain components of an orthodontic treatment plan, such as the extraction of 1 or more teeth, are important risk factors in developing this complication. In addition to the desired effects on the bone metabolism, bisphosphonates may delay tooth eruption and inhibit or block orthodontic tooth movement. Nevertheless, case studies suggest that orthodontic treatment is possible despite the use of bisphosphonates. However, it is recommended to avoid orthodontic treatment unless this is strictly indicated.

15 Review Postmenopausal osteoporosis treatment with antiresorptives: effects of discontinuation or long-term continuation on bone turnover and fracture risk--a perspective. 2012

Boonen, Steven / Ferrari, Serge / Miller, Paul D / Eriksen, Erik F / Sambrook, Philip N / Compston, Juliet / Reid, Ian R / Vanderschueren, Dirk / Cosman, Felicia. ·Leuven University Center for Metabolic Bone Diseases, Katholieke Universiteit Leuven, Leuven, Belgium. ·J Bone Miner Res · Pubmed #22467094.

ABSTRACT: Osteoporosis may be a lifelong condition. Robust data regarding the efficacy and safety of both long-term osteoporosis therapy and therapy discontinuation are therefore important. A paucity of clinical trial data regarding the long-term antifracture efficacy of osteoporosis therapies necessitates the use of surrogate endpoints in discussions surrounding long-term use and/or discontinuation. Long-term treatment (beyond 3-4 years) may produce further increases in bone mineral density (BMD) or BMD stability, depending on the specific treatment and the skeletal site. Bisphosphonates, when discontinued, are associated with a prolonged reduction in bone turnover markers (BTMs), with a very gradual increase to pretreatment levels within 3 to 60 months of treatment cessation, depending on the bisphosphonate used and the prior duration of therapy. In contrast, with nonbisphosphonate antiresorptive agents, such as estrogen and denosumab, BTMs rebound to above pretreatment values within months of discontinuation. The pattern of BTM change is generally mirrored by a more or less rapid decrease in BMD. Although the prolonged effect of some bisphosphonates on BTMs and BMD may contribute to residual benefit on bone strength, it may also raise safety concerns. Adequately powered postdiscontinuation fracture studies and conclusive evidence on maintenance or loss of fracture benefit is lacking for bisphosphonates. Similarly, the effects of rapid reversal of bone turnover upon discontinuation of denosumab on fracture risk remain unknown. Ideally, studies evaluating the effects of long-term treatment and treatment discontinuation should be designed to provide head-to-head "offset" data between bisphosphonates and nonbisphosphonate antiresorptive agents. In the absence of this, a clinical recommendation for physicians may be to periodically assess the benefits/risks of continuation versus discontinuation versus alternative management strategies.

16 Review Inhibition of cathepsin K for treatment of osteoporosis. 2012

Boonen, Steven / Rosenberg, Elizabeth / Claessens, Frank / Vanderschueren, Dirk / Papapoulos, Socrates. ·Leuven University Division of Geriatric Medicine and Centre for Metabolic Bone Diseases, UZ Leuven campus Gasthuisberg, Herestraat 49, B-3000 Leuven, Belgium. steven.boonen@uzleuven.be ·Curr Osteoporos Rep · Pubmed #22228398.

ABSTRACT: Cathepsin K is the protease that is primarily responsible for the degradation of bone matrix by osteoclasts. Inhibitors of cathepsin K are in development for treatment of osteoporosis. Currently available antiresorptive drugs interfere with osteoclast function. They inhibit both bone resorption and formation, due to the coupling between these processes. Cathepsin K inhibitors, conversely, target the resorption process itself and may not interfere with osteoclast stimulation of bone formation. In fact, when cathepsin K is absent or inhibited in mice, rabbits, or monkeys, bone formation is maintained or increased. In humans, inhibition of cathepsin K is associated with sustained reductions in bone resorption markers but with smaller and transient reductions in bone formation markers. The usefulness of cathepsin K inhibitors in osteoporosis is now being examined in phase 2 and phase 3 clinical trials of postmenopausal osteoporotic women.

17 Review Sequential therapy in the treatment of osteoporosis. 2011

Boonen, Steven / Milisen, Koen / Gielen, Evelien / Vanderschueren, Dirk. ·Katholieke Universiteit Leuven, Centre for Metabolic Bone Diseases, and Division of Geriatric Medicine, Leuven, Belgium. steven.boonen@uz.kuleuven.ac.be ·Curr Med Res Opin · Pubmed #21466276.

ABSTRACT: OBJECTIVE: To review the clinical data in the sequential use of antiresorptive and anabolic agents for the treatment of osteoporosis. METHODS: The US National Library of Medicine was used to obtain the relevant information on osteoporosis management involving antiresorptive and anabolic bone agents. RESULTS: Antiresorptive and anabolic therapies are the two main types of medications approved for osteoporosis treatment. The efficacy of these agents in fracture risk reduction is well established. Many patients with osteoporosis are first treated with an antiresorptive agent, most commonly a bisphosphonate. Osteoporotic patients who fail to respond to antiresorptive therapy or patients with severe osteoporosis may require anabolic therapy at some point during their disease. Recombinant human parathyroid hormone (PTH) is an anabolic agent with proven benefits on bone strength. Sequential therapy using PTH after antiresorptive agents has been found beneficial for bone health. Recent research suggests that the speed and magnitude of PTH effect can differ, depending on the previous antiresorptive therapy. Upon PTH cessation, subsequent antiresorptive therapy may help maintain or increase gains in bone mass. CONCLUSIONS: Although further research is needed to determine the long-term significance of prior antiresorptive therapies and their differing effects on fracture risk reduction with subsequent PTH therapy, patients with severe osteoporosis should be considered for this treatment option, regardless of prior osteoporosis treatment.

18 Review Vitamin D deficiency and chronic obstructive pulmonary disease: a vicious circle. 2011

Janssens, Wim / Mathieu, Chantal / Boonen, Steven / Decramer, Marc. ·Respiratory Division, University of Leuven, Leuven, Belgium. ·Vitam Horm · Pubmed #21419281.

ABSTRACT: Vitamin D and vitamin D deficiency strongly interact with different pathogenic mechanisms in COPD. Prevalence of vitamin D deficiency is particularly high in COPD patients, increases with the severity of COPD, and is closely associated with osteoporosis prevalence. Adequate calcium and vitamin D supplementation in COPD patients with documented deficiencies reduces the risk for falling and osteoporotic fractures, may indirectly reduce morbidity, and may potentially prevent the further deterioration of pulmonary function. Apart from the proven beneficial effects of vitamin D supplements on bone and muscle tissue, many epidemiological studies have putatively linked vitamin D deficiency with a higher risk for cardiovascular, inflammatory and infectious diseases, and cancer, diseases known to be associated with and to contribute significantly to the phenotypic presentation of COPD patients. Different animal and human studies have provided considerable evidence on how vitamin D may affect these processes. The burning question in COPD is whether prevention of vitamin D deficiency or adequate supplementation may reverse the natural course of the disease.

19 Review Osteoporosis in men. 2011

Gielen, Evelien / Vanderschueren, Dirk / Callewaert, Filip / Boonen, Steven. ·Leuven University, Division of Geriatric Medicine, Leuven, Belgium. ·Best Pract Res Clin Endocrinol Metab · Pubmed #21397201.

ABSTRACT: Male osteoporosis is an increasingly important public health problem: from age 50 onward, one in three osteoporotic fractures occurs in men and fracture-related morbidity and mortality are even higher than in women. In 50% of osteoporotic men, an underlying cause can be identified (secondary osteoporosis). In the absence of an identifiable etiology, male osteoporosis is referred to as 'idiopathic osteoporosis' in men aged 30-70 years and as 'age-related osteoporosis' in older men. As in women, estrogen, not testosterone, appears the most important sex steroid regulating male skeletal status. Diagnosis and treatment recommendations are still largely based on bone mineral density (BMD), with osteoporosis defined as a T-score of 2.5 standard deviations below young adult values. However, there is ongoing discussion as to whether male or female reference ranges should be used and, like in women, treatment decisions are increasingly based on absolute fracture risk estimations rather than on BMD alone. In men, evidence-based data on the efficacy of pharmacologic interventions in reducing fracture risk are convincing but not conclusive. In particular, bisphosphonates and teriparatide seem to be as effective in men as in women.

20 Review [COPD and bone metabolism: a clinical update]. 2010

Lehouck, A / van Remoortel, H / Troosters, T / Decramer, M / Janssens, W. ·Service de Pneumologie, Hôpital Universitaire Gasthuisberg, Katholieke Universiteit, 3000 Leuven, Belgique. ·Rev Mal Respir · Pubmed #21163399.

ABSTRACT: Increasing evidence indicates that COPD and osteoporosis are strongly linked. Both diseases share common risk factors like age, smoking and inactivity but the typical presence in COPD of systemic inflammation, vitamin D deficiency and the frequent use of corticosteroids catalyse ongoing bone resorption. Osteoporosis in its turn may lead to vertebral compression fractures with a consequent further decline of forced vital capacity and forced expiratory volume in one second. In addition, fragility fractures in disabled COPD patients may cause further immobility and increased morbidity. Prevention and treatment of osteoporosis in COPD should therefore be based on population specific risk assessments which combine measures of bone mineral density and clinical factors. Unfortunately, intervention studies specifically designed for patients with COPD are currently lacking and no specific guidelines have yet been established. Hence, a rigorous application of the current treatment guidelines with respect to osteoporosis in general would already be a major step forward in the treatment of COPD.

21 Review Addressing the age-related needs of osteoporotic patients with strontium ranelate. 2010

Boonen, S. ·Leuven University Centre for Metabolic Bone Diseases and Division of Geriatric Medicine, Leuven, Belgium. steven.boonen@med.kuleuven.be ·Osteoporos Int · Pubmed #20464375.

ABSTRACT: Osteoporotic fractures are associated with significant morbidity and mortality with an enormous impact on society and the lives of affected individuals. Age and menopause are the two main risk factors for osteoporosis, and women therefore need to be particularly concerned about bone loss at this time. In addition to suffering fracture-associated morbidity, women with prior fractures have an increased risk of future fractures. Young postmenopausal women who have experienced a fragility fracture therefore face a lifetime of fracture risk. The burden of fractures increases with advancing age, and bone mineral density declines, with women over the age of 80 years having the highest risk of fracture because of their high prevalence of osteoporosis and an increased likelihood of falls. A number of antiosteoporotic agents are available for the treatment of postmenopausal women including bisphosphonates, raloxifene, teriparatide, and strontium ranelate. For osteoporotic drugs to be beneficial in reducing the burden of fractures, they need to be effective against fracture in all age groups of postmenopausal women. With its dual mode of action, strontium ranelate is the first agent with proven early and sustained antifracture efficacy in all age groups including young postmenopausal women and those over 80 years. Evidence is now available to show that all women, including the elderly, can benefit from treatment to prevent further bone loss and restore lost bone to decrease the risk of further fractures. By implementing procedures to identify those at greatest risk and initiate safe and effective treatments, physicians can significantly improve patients' quality of life.

22 Review Osteoporosis management: a perspective based on bisphosphonate data from randomised clinical trials and observational databases. 2009

Boonen, S / Kay, R / Cooper, C / Haentjens, P / Vanderschueren, D / Callewaert, F / Milisen, K / Ferrari, S. ·Division of Gerontology and Geriatrics & Center for Musculoskeletal Research, Leuven University Department of Experimental Medicine, Leuven, Belgium. steven.boonen@uz.kuleuven.ac.be ·Int J Clin Pract · Pubmed #19845802.

ABSTRACT: AIMS: The efficacy of treatments for osteoporosis can be evaluated using a variety of study designs. This article aims to comprehensively review the evidence for bisphosphonate anti-fracture efficacy in postmenopausal women, discussing the strengths and limitations associated with each study method. METHODS: Literature analysis included English-language publications reporting results of randomised controlled trials (RCTs), post hoc analyses, meta analyses and observational studies evaluating the efficacy of alendronate (ALN), ibandronate (IBN), risedronate (RIS) and zoledronate (ZOL), with an initial sample size > or = 100 patients, and follow-up data for at least 1 year. RESULTS: Primary and secondary analyses of RCT data suggest differences among bisphosphonates with regard to site-specific anti-fracture efficacy and onset of fracture risk reduction. While some observational studies indicate differences in clinical outcomes among these agents, others report similar effectiveness. ALN and RIS data demonstrate sustained fracture protection for up to 10 and 7 years of treatment respectively. The efficacy of IBN and ZOL has been evaluated for up to 3 and 5 years respectively. CONCLUSIONS: Understanding of the benefits of bisphosphonate treatment can be maximised by evaluating complementary data from RCTs and observational database studies. Fracture risk reduction with bisphosphonates is shown in RCTs and in real-world clinical settings.

23 Review Impact of treatment efficacy and dosing frequency on cost-effectiveness of bisphosphonate treatment for osteoporosis: a perspective. 2009

Boonen, Steven. ·Leuven University Center for Metabolic Bone Diseases and Division of Geriatric Medicine, Herestraat 49, B-3000 Leuven, Belgium. steven.boonen@uz.kuleuven.ac.be ·Curr Med Res Opin · Pubmed #19650755.

ABSTRACT: BACKGROUND: Osteoporosis is a chronic disease that presents a large economic burden both on the affected individual and on society. Osteoporotic fractures are a cause of significant morbidity and mortality. Given the high prevalence of osteoporosis and related costs, understanding the factors that determine the cost-effectiveness of osteoporosis therapy is important for physicians and managed-care organizations. Bisphosphonates are considered first-line therapy for osteoporosis, and pharmacological differences between them relate not only to differences in efficacy and safety, but also have an impact on health economics. Efficacy and persistence with therapy influence fracture risk-reduction and should be considered when determining the best osteoporosis therapy for each patient. SCOPE: This article synthesizes recent health economic data, assessing the impact of drug efficacy and persistence or dosing frequency on the cost-effectiveness of bisphosphonates as therapeutic agents for osteoporosis treatment. The author's interpretation of the available evidence is also discussed, from the perspective of a 'Commentary' article. FINDINGS: Although treatment persistence is an important factor in reducing fracture risk, when comparing the health economic data of several treatment options, studies have shown that the cost-effectiveness of bisphosphonate therapy is mainly dependent on drug efficacy rather than persistence or dosing frequency. It should also be noted that fractures at different skeletal sites have different economic impacts. Non-vertebral fractures (and particularly those of the hip) are more costly than vertebral fractures. CONCLUSIONS: Although persistence with osteoporosis therapy is an important factor in reducing fracture risk, it has less of an impact on cost-effectiveness than treatment efficacy, in particular efficacy at non-vertebral sites.

24 Review Multi-level patient-specific modelling of the proximal femur. A promising tool to quantify the effect of osteoporosis treatment. 2009

Lenaerts, Leen / van Lenthe, G Harry. ·Division of Biomechanics and Engineering Design, Katholieke Universiteit Leuven, Celestijnenlaan 300C, PB 2419, 3001 Leuven, Belgium. Leen.Lenaerts@mech.kuleuven.be ·Philos Trans A Math Phys Eng Sci · Pubmed #19380326.

ABSTRACT: Preventing femoral fractures is an important goal in osteoporosis research. In order to evaluate a person's fracture risk and to quantify response to treatment, bone competence is best assessed by bone strength. Finite-element (FE) modelling based on medical imaging is considered a very promising technique for the assessment of in vivo femoral bone strength. Over the past decades, a number of different FE models have been presented focusing on the effect of several methodological aspects, such as mesh type, material properties and loading conditions, on the precision and accuracy of these models. In this paper, a review of this work is presented. We conclude that moderate to good predictions can be made, especially when the models are tuned to specific loading scenarios. However, there is room for improvement when multiple loading conditions need to be evaluated. We hypothesize that including anisotropic material properties is the first target. As a proof of the concept, we demonstrate that the main orientation of the femoral bone structure can be calculated from clinical computed tomography scans. We hypothesize that this structural information can be used to estimate the anisotropic bone material properties, and that in the future this could potentially lead to a greater predictive value of FE models for femoral bone strength.

25 Review WNT Signaling in osteoarthritis and osteoporosis: what is the biological significance for the clinician? 2009

Lodewyckx, Liesbet / Lories, Rik J U. ·Department of Musculoskeletal Sciences, Division of Rheumatology, Laboratory for Skeletal Development and Joint Disorders, Katholieke Universiteit Leuven, Leuven, Belgium. ·Curr Rheumatol Rep · Pubmed #19171108.

ABSTRACT: Osteoporosis and osteoarthritis are common musculoskeletal disorders in which cause and outcome are determined by genetic and environmental factors. The WNT signaling pathway plays an important role in skeletal development and growth. Polymorphisms in a number of genes that belong to this pathway are associated with osteoarthritis and/or osteoporosis. This suggests a role for this molecular signaling pathway in postnatal joint and bone homeostasis and pathology. Increased activity of WNT signaling strengthens the bone but may have adverse effects on the articular cartilage. Frizzled related protein (FRZB) plays a role in both bone and cartilage. Better understanding of the WNT pathway and its modulators may lead to specific therapeutics for both osteoarthritis and osteoporosis. This review focuses on recent studies in human genetics and animal models and highlights the potential clinical relevance of this rapidly evolving field of research.