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Osteoporosis: HELP
Articles by Dirk Vanderschueren
Based on 28 articles published since 2008

Between 2008 and 2019, D. Vanderschueren wrote the following 28 articles about Osteoporosis.
+ Citations + Abstracts
Pages: 1 · 2
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 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.

3 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.

4 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.

5 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.

6 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.

7 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.

8 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.

9 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.

10 Review Reducing fracture risk with calcium and vitamin D. 2010

Lips, Paul / Bouillon, Roger / van Schoor, Natasja M / Vanderschueren, Dirk / Verschueren, Sabine / Kuchuk, Natalia / Milisen, Koen / Boonen, Steven. ·Department of Endocrinology and EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands. P.Lips@vumc.nl ·Clin Endocrinol (Oxf) · Pubmed #20796001.

ABSTRACT: Studies of vitamin D and calcium for fracture prevention have produced inconsistent results, as a result of different vitamin D status and calcium intake at baseline, different doses and poor to adequate compliance. This study tries to define the types of patients, both at risk of osteoporosis and with established disease, who may benefit from calcium and vitamin D supplementation. The importance of adequate compliance in these individuals is also discussed. Calcium and vitamin D therapy has been recommended for older persons, either frail and institutionalized or independent, with key risk factors including decreased bone mineral density (BMD), osteoporotic fractures, increased bone remodelling as a result of secondary hyperparathyroidism and increased propensity to falls. In addition, treatment of osteoporosis with a bisphosphonate was less effective in patients with vitamin D deficiency. Calcium and vitamin D supplementation is a key component of prevention and treatment of osteoporosis unless calcium intake and vitamin D status are optimal. For primary disease prevention, supplementation should be targeted to those with dietary insufficiencies. Several serum 25-hydroxyvitamin D (25(OH)D) cut-offs have been proposed to define vitamin D insufficiency (as opposed to adequate vitamin D status), ranging from 30 to 100 nmol/l. Based on the relationship between serum 25(OH)D, BMD, bone turnover, lower extremity function and falls, we suggest that 50 nmol/l is the appropriate serum 25(OH)D threshold to define vitamin D insufficiency. Supplementation should therefore generally aim to increase 25(OH)D levels within the 50-75 nmol/l range. This level can be achieved with a dose of 800 IU/day vitamin D, the dose that was used in successful fracture prevention studies to date; a randomized clinical trial assessing whether higher vitamin D doses achieve a greater reduction of fracture incidence would be of considerable interest. As calcium balance is not only affected by vitamin D status but also by calcium intake, recommendations for adequate calcium intake should also be met. The findings of community-based clinical trials with vitamin D and calcium supplementation in which compliance was moderate or less have often been negative, whereas studies in institutionalized patients in whom medication administration was supervised ensuring adequate compliance demonstrated significant benefits.

11 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.

12 Review Osteoporosis and osteoporotic fracture occurrence and prevention in the elderly: a geriatric perspective. 2008

Boonen, Steven / Dejaeger, Eddy / Vanderschueren, Dirk / Venken, Katrien / Bogaerts, An / Verschueren, Sabine / Milisen, Koen. ·Leuven University Centre for Metabolic Bone Disease and Division of Geriatric Medicine, UZ Leuven campus Gasthuisberg, Herestraat 49, B-3000 Leuven, Belgium. steven.boonen@uz.kuleuven.be ·Best Pract Res Clin Endocrinol Metab · Pubmed #19028356.

ABSTRACT: Age is a major determinant of osteoporosis, but the elderly are rarely assessed and often remain untreated for this condition. Falls, co-morbidities and co-medications compound the risk of fracture in senile osteoporosis. The prevalence of osteoporosis is expected to increase with increasing life expectancy, and the associated fractures - particularly hip fractures - will lead to significant demands on health resources. Treatment of senile osteoporosis can include pharmacological and non-pharmacological intervention. Calcium and vitamin D dietary supplementation is a relatively low-cost way of reducing the risk of fracture. Pharmacological interventions with risedronate, zoledronic acid, or teriparatide have been shown to reduce vertebral fracture risk in osteoporosis patients over the age of 75. Zoledronic acid has been shown to reduce fracture risk in frail patients with recent hip fracture. In the oldest old (patients over 80), strontium ranelate is the first agent with documented anti-fracture efficacy for both non-vertebral and vertebral fracture and documented sustained efficacy over 5 years. Falls prevention is an essential component of any strategy for decreasing fracture risk in old age. Currently, senile osteoporosis is under-diagnosed and under-treated, but age should not be a barrier to intervention.

13 Review Recent developments in the management of postmenopausal osteoporosis with bisphosphonates: enhanced efficacy by enhanced compliance. 2008

Boonen, S / Vanderschueren, D / Venken, K / Milisen, K / Delforge, M / Haentjens, P. ·Leuven University, Department of Experimental Medicine, Leuven, Belgium. steven.boonen@uz.kuleuven.ac.be ·J Intern Med · Pubmed #18823505.

ABSTRACT: Bisphosphonates are the current mainstay of treatment for postmenopausal osteoporosis. Although daily oral dosing is effective, it is associated with poor compliance, partly because of the pre and postdose fasting and posture requirements. This negatively impacts treatment outcomes, leading to a reduced clinical benefit. Improved, yet still suboptimal adherence has been noticed with less frequent bisphosphonate dosing e.g. once-weekly and once-monthly oral regimens. The recently approved quarterly intravenous (i.v.) injection regimen of ibandronate and yearly i.v. infusion of zoledronic acid are attractive options in the management of postmenopausal osteoporosis. These regimens may assure quarterly and year long compliance.

14 Review Sex hormones, their receptors and bone health. 2008

Venken, K / Callewaert, F / Boonen, S / Vanderschueren, D. ·Bone Research Unit, Laboratory for Experimental Medicine and Endocrinology, Department of Experimental Medicine, Katholieke Universiteit Leuven, Herestraat 49, Box 902, B-3000, Leuven, Belgium. ·Osteoporos Int · Pubmed #18392663.

ABSTRACT: Sex steroids regulate skeletal maturation and preservation in both men and women, as already recognized in the 1940s by Albright and Reifenstein. The impact of gonadal insufficiency on skeletal integrity has been widely recognized in adult men and women ever since. In the context of their skeletal actions, androgens and estrogens are no longer considered as just male and female hormones, respectively. Androgens can be converted into estrogens within the gonads and peripheral tissues and both are present in men and women, albeit in different concentrations. In the late 1980s, sex steroid receptors were discovered in bone cells. However, the understanding of sex steroid receptor activation and translation into biological skeletal actions is still incomplete. Due to the complex metabolism, sex steroids may have not only endocrine but also paracrine and/or autocrine actions. Also, circulating sex steroid concentrations do not necessarily reflect their biological activity due to strong binding to sex hormone binding globulin (SHBG). Finally, sex steroid signaling may include genomic and non-genomic effects in bone and non-bone cells. This review will focus on our current understanding of gonadal steroid metabolism, receptor activation, and their most relevant cellular and biological actions on bone.

15 Article Bone turnover predicts change in volumetric bone density and bone geometry at the radius in men. 2017

Pye, S R / Ward, K A / Cook, M J / Laurent, M R / Gielen, E / Borghs, H / Adams, J E / Boonen, S / Vanderschueren, D / Wu, F C / O'Neill, T W. ·Arthritis Research UK Centre for Epidemiology, Division of Musculoskeletal and Dermatological Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, The University of Manchester, Oxford Road, Manchester, M13 9PT, UK. · NIHR Manchester Musculoskeletal Biomedical Research Unit, Central Manchester NHS Foundation Trust, Manchester Academic Health Sciences Centre, Manchester, UK. · MRC Human Nutrition Research, Elsie Widdowson Laboratory, Cambridge, UK. · Gerontology and Geriatrics, Department of Clinical and Experimental Medicine, KU Leuven, Leuven, Belgium. · Center for Metabolic Bone Diseases, University Hospitals Leuven, Leuven, Belgium. · Radiology and Manchester Academic Health Science Centre, The Royal Infirmary, The University of Manchester, Manchester, UK. · Clinical and Experimental Endocrinology, Department of Clinical and Experimental Medicine, KU Leuven, Leuven, Belgium. · Andrology Research Unit, Centre for Endocrinology and Diabetes, University of Manchester, Manchester, UK. · Arthritis Research UK Centre for Epidemiology, Division of Musculoskeletal and Dermatological Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, The University of Manchester, Oxford Road, Manchester, M13 9PT, UK. terence.o'neill@manchester.ac.uk. · NIHR Manchester Musculoskeletal Biomedical Research Unit, Central Manchester NHS Foundation Trust, Manchester Academic Health Sciences Centre, Manchester, UK. terence.o'neill@manchester.ac.uk. ·Osteoporos Int · Pubmed #27815569.

ABSTRACT: Peripheral quantitative computed tomography scans of the distal and midshaft radius were performed in 514 European men aged 40-79 years at baseline and a median of 4.3 years later. Age-related changes in volumetric bone mineral density (vBMD) and bone geometry were greater in men with higher biochemical markers of bone turnover at baseline. INTRODUCTION: This study aimed to determine prospective change in bone density and geometry at the radius in men and examine the influence of bone turnover markers and sex hormones on that change. METHODS: Men aged 40-79 years were recruited from population registers in Manchester (UK) and Leuven (Belgium). At baseline, markers of bone formation (P1NP and osteocalcin) and resorption (β-cTX and ICTP) were assessed. Total and bioavailable testosterone and oestradiol were also measured. Peripheral quantitative computed tomography (pQCT) was used to scan the radius at distal and midshaft sites at the baseline assessment and a median of 4.3 years later. RESULTS: Five hundred fourteen men, mean (SD) age of 59.6 (10.5) years, contributed to the data. At the midshaft site, there was a significant decrease in mean cortical vBMD (-0.04 %/year), bone mineral content (BMC) (-0.1 %/year) and cortical thickness (-0.4 %/year), while total and medullary area increased (+0.5 and +2.4 %/year respectively). At the distal radius, total vBMD declined (-0.5 %/year) and radial area increased (+0.6 %/year). Greater plasma concentrations of bone resorption and formation markers were associated with greater decline in BMC and cortical area at the midshaft and total vBMD at the distal site. Increased bone resorption was linked with an increase in total and medullary area and decrease in cortical thickness at the midshaft. Sex hormone levels were unrelated to change in pQCT parameters. CONCLUSIONS: Age-related changes in vBMD and bone geometry are greater in men with higher biochemical markers of bone turnover at baseline. Sex hormones have little influence on change in pQCT parameters.

16 Article Bone turnover markers predict hip bone loss in elderly European men: results of the European Male Ageing Study (EMAS). 2015

Gielen, E / O'Neill, T / Pye, S / Adams, J / Ward, K / Wu, F / Laurent, M / Claessens, F / Boonen, S / Vanderschueren, D / Verschueren, S. ·Gerontology and Geriatrics, Department of Clinical and Experimental Medicine, KU Leuven, Leuven, Belgium, evelien.gielen@uzleuven.be. ·Osteoporos Int · Pubmed #25224294.

ABSTRACT: SUMMARY: The aim of this study was to determine whether bone turnover markers (BTMs) predict changes in areal bone mineral density (aBMD) in middle-aged and elderly European men. Older men with high bone turnover are at a higher risk of accelerated hip bone loss, but the clinical utility of BTMs in individuals is limited. INTRODUCTION: Prospective studies on the value of BTMs to predict changes in aBMD in men are few and conflicting. The aim of this study was to determine whether BTMs predict changes in aBMD in middle-aged and elderly European men. METHODS: In 487 men aged 40-79 years from the European Male Ageing Study (EMAS), BTMs were assessed at baseline and dual-energy X-ray absorptiometry (DXA) at the lumbar spine (LS), femoral neck (FN) and total hip (TH) was performed at baseline and after a mean follow-up of 4.3 years. RESULTS: The mean aBMD decreased by 0.32%/year at FN and 0.22%/year at TH and increased by 0.32%/year at LS. Higher baseline levels of β C-terminal cross-linked telopeptide (β-CTX) and N-terminal propeptide of type I procollagen (PINP) were significantly associated with higher loss of hip aBMD in the whole cohort and men aged 60-79 years. These associations remained significant after adjustment for age, centre and body mass index (BMI). Men aged 60-79 years with β-CTX in the upper quintile were more likely of being in the upper quintile of annual percentage (%) aBMD loss at FN (OR=4.27; 95% CI=2.09-8.73) and TH (OR=3.73; 95% CI=1.84-7.57). The positive predictive value (PPV) was 46% at both hip sites. CONCLUSION: Older men with high bone turnover have a higher risk of accelerated hip bone loss, but the PPV is low. BTMs are therefore unlikely to be of clinical utility in predicting accelerated hip bone loss in individual subjects.

17 Article Bone: Which model to predict fracture risk? 2014

Bouillon, Roger / Vanderschueren, Dirk. ·Clinical and Experimental Endocrinology, KU Leuven, Herestraat 49 ON1 Box 902, 3000 Leuven, Belgium. ·Nat Rev Endocrinol · Pubmed #24514261.

ABSTRACT: -- No abstract --

18 Article Genetic determinants of heel bone properties: genome-wide association meta-analysis and replication in the GEFOS/GENOMOS consortium. 2014

Moayyeri, Alireza / Hsu, Yi-Hsiang / Karasik, David / Estrada, Karol / Xiao, Su-Mei / Nielson, Carrie / Srikanth, Priya / Giroux, Sylvie / Wilson, Scott G / Zheng, Hou-Feng / Smith, Albert V / Pye, Stephen R / Leo, Paul J / Teumer, Alexander / Hwang, Joo-Yeon / Ohlsson, Claes / McGuigan, Fiona / Minster, Ryan L / Hayward, Caroline / Olmos, José M / Lyytikäinen, Leo-Pekka / Lewis, Joshua R / Swart, Karin M A / Masi, Laura / Oldmeadow, Chris / Holliday, Elizabeth G / Cheng, Sulin / van Schoor, Natasja M / Harvey, Nicholas C / Kruk, Marcin / del Greco M, Fabiola / Igl, Wilmar / Trummer, Olivia / Grigoriou, Efi / Luben, Robert / Liu, Ching-Ti / Zhou, Yanhua / Oei, Ling / Medina-Gomez, Carolina / Zmuda, Joseph / Tranah, Greg / Brown, Suzanne J / Williams, Frances M / Soranzo, Nicole / Jakobsdottir, Johanna / Siggeirsdottir, Kristin / Holliday, Kate L / Hannemann, Anke / Go, Min Jin / Garcia, Melissa / Polasek, Ozren / Laaksonen, Marika / Zhu, Kun / Enneman, Anke W / McEvoy, Mark / Peel, Roseanne / Sham, Pak Chung / Jaworski, Maciej / Johansson, Åsa / Hicks, Andrew A / Pludowski, Pawel / Scott, Rodney / Dhonukshe-Rutten, Rosalie A M / van der Velde, Nathalie / Kähönen, Mika / Viikari, Jorma S / Sievänen, Harri / Raitakari, Olli T / González-Macías, Jesús / Hernández, Jose L / Mellström, Dan / Ljunggren, Osten / Cho, Yoon Shin / Völker, Uwe / Nauck, Matthias / Homuth, Georg / Völzke, Henry / Haring, Robin / Brown, Matthew A / McCloskey, Eugene / Nicholson, Geoffrey C / Eastell, Richard / Eisman, John A / Jones, Graeme / Reid, Ian R / Dennison, Elaine M / Wark, John / Boonen, Steven / Vanderschueren, Dirk / Wu, Frederick C W / Aspelund, Thor / Richards, J Brent / Bauer, Doug / Hofman, Albert / Khaw, Kay-Tee / Dedoussis, George / Obermayer-Pietsch, Barbara / Gyllensten, Ulf / Pramstaller, Peter P / Lorenc, Roman S / Cooper, Cyrus / Kung, Annie Wai Chee / Lips, Paul / Alen, Markku / Attia, John / Brandi, Maria Luisa / de Groot, Lisette C P G M / Lehtimäki, Terho / Riancho, José A / Campbell, Harry / Liu, Yongmei / Harris, Tamara B / Akesson, Kristina / Karlsson, Magnus / Lee, Jong-Young / Wallaschofski, Henri / Duncan, Emma L / O'Neill, Terence W / Gudnason, Vilmundur / Spector, Timothy D / Rousseau, François / Orwoll, Eric / Cummings, Steven R / Wareham, Nick J / Rivadeneira, Fernando / Uitterlinden, Andre G / Prince, Richard L / Kiel, Douglas P / Reeve, Jonathan / Kaptoge, Stephen K. ·Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK. ·Hum Mol Genet · Pubmed #24430505.

ABSTRACT: Quantitative ultrasound of the heel captures heel bone properties that independently predict fracture risk and, with bone mineral density (BMD) assessed by X-ray (DXA), may be convenient alternatives for evaluating osteoporosis and fracture risk. We performed a meta-analysis of genome-wide association (GWA) studies to assess the genetic determinants of heel broadband ultrasound attenuation (BUA; n = 14 260), velocity of sound (VOS; n = 15 514) and BMD (n = 4566) in 13 discovery cohorts. Independent replication involved seven cohorts with GWA data (in silico n = 11 452) and new genotyping in 15 cohorts (de novo n = 24 902). In combined random effects, meta-analysis of the discovery and replication cohorts, nine single nucleotide polymorphisms (SNPs) had genome-wide significant (P < 5 × 10(-8)) associations with heel bone properties. Alongside SNPs within or near previously identified osteoporosis susceptibility genes including ESR1 (6q25.1: rs4869739, rs3020331, rs2982552), SPTBN1 (2p16.2: rs11898505), RSPO3 (6q22.33: rs7741021), WNT16 (7q31.31: rs2908007), DKK1 (10q21.1: rs7902708) and GPATCH1 (19q13.11: rs10416265), we identified a new locus on chromosome 11q14.2 (rs597319 close to TMEM135, a gene recently linked to osteoblastogenesis and longevity) significantly associated with both BUA and VOS (P < 8.23 × 10(-14)). In meta-analyses involving 25 cohorts with up to 14 985 fracture cases, six of 10 SNPs associated with heel bone properties at P < 5 × 10(-6) also had the expected direction of association with any fracture (P < 0.05), including three SNPs with P < 0.005: 6q22.33 (rs7741021), 7q31.31 (rs2908007) and 10q21.1 (rs7902708). In conclusion, this GWA study reveals the effect of several genes common to central DXA-derived BMD and heel ultrasound/DXA measures and points to a new genetic locus with potential implications for better understanding of osteoporosis pathophysiology.

19 Article Sarcopenia and its relationship with bone mineral density in middle-aged and elderly European men. 2013

Verschueren, S / Gielen, E / O'Neill, T W / Pye, S R / Adams, J E / Ward, K A / Wu, F C / Szulc, P / Laurent, M / Claessens, F / Vanderschueren, D / Boonen, S. ·Research Group for Musculoskeletal Rehabilitation, Department of Rehabilitation Sciences, KU Leuven, Leuven, Belgium. ·Osteoporos Int · Pubmed #22776861.

ABSTRACT: INTRODUCTION: In men, the relationship between reduced muscle mass (sarcopenia) and BMD(a) is unclear. This study aimed to determine this relationship in middle-aged and elderly community-dwelling men. METHODS: Men aged 40-79 years from the Manchester (UK) and Leuven (Belgium) cohorts of the European Male Ageing Study were invited to attend for assessment including dual-energy X-ray absorptiometry, from which appendicular lean mass (aLM), fat mass (FM) and whole-body, spine and hip BMD(a) were determined. Relative appendicular skeletal muscle mass (RASM) was calculated as aLM/height². Muscle strength was assessed in subjects from Leuven. Sarcopenia was defined by RASM at <7.26 kg/m² and by the recent definition of the European Working Group on Sarcopenia in Older People (RASM at <7.26 kg/m(2) plus low muscle function). Linear regression was used to determine the associations between aLM, FM, muscle strength and BMD(a) and logistic regression to determine the association between sarcopenia and osteoporosis. RESULTS: Six hundred seventy-nine men with a mean age of 59.6 (SD = 10.7), contributed data to the analysis; 11.9 % were sarcopenic by the conventional definition. After adjustment for age and centre, aLM, RASM and FM were positively associated with BMD(a). Men with RASM at <7.26 kg/m² had significantly lower BMD(a) compared with those with RASM at ≥7.26 kg/m(2). In a multivariable model, aLM was most consistently associated with BMD(a). Men with sarcopenia were more likely to have osteoporosis compared with those with normal RASM (odds ratio = 3.0; 95 % CI = 1.6-5.8). CONCLUSIONS: Sarcopenia is associated with low BMD(a) and osteoporosis in middle-aged and elderly men. Further studies are necessary to assess whether maintaining muscle mass contributes to prevent osteoporosis.

20 Article Fracture risk and zoledronic acid therapy in men with osteoporosis. 2012

Boonen, Steven / Reginster, Jean-Yves / Kaufman, Jean-Marc / Lippuner, Kurt / Zanchetta, Jose / Langdahl, Bente / Rizzoli, Rene / Lipschitz, Stanley / Dimai, Hans Peter / Witvrouw, Richard / Eriksen, Erik / Brixen, Kim / Russo, Luis / Claessens, Frank / Papanastasiou, Philemon / Antunez, Oscar / Su, Guoqin / Bucci-Rechtweg, Christina / Hruska, Josef / Incera, Elodie / Vanderschueren, Dirk / Orwoll, Eric. ·Katholieke Universiteit Leuven, Leuven, Belgium. en.boonen@uz.kuleuven.ac.be ·N Engl J Med · Pubmed #23113482.

ABSTRACT: BACKGROUND: Fractures in men are a major health issue, and data on the antifracture efficacy of therapies for osteoporosis in men are limited. We studied the effect of zoledronic acid on fracture risk among men with osteoporosis. METHODS: In this multicenter, double-blind, placebo-controlled trial, we randomly assigned 1199 men with primary or hypogonadism-associated osteoporosis who were 50 to 85 years of age to receive an intravenous infusion of zoledronic acid (5 mg) or placebo at baseline and at 12 months. Participants received daily calcium and vitamin D supplementation. The primary end point was the proportion of participants with one or more new morphometric vertebral fractures over a period of 24 months. RESULTS: The rate of any new morphometric vertebral fracture was 1.6% in the zoledronic acid group and 4.9% in the placebo group over the 24-month period, representing a 67% risk reduction with zoledronic acid (relative risk, 0.33; 95% confidence interval, 0.16 to 0.70; P=0.002). As compared with men who received placebo, men who received zoledronic acid had fewer moderate-to-severe vertebral fractures (P=0.03) and less height loss (P=0.002). Fewer participants who received zoledronic acid had clinical vertebral or nonvertebral fractures, although this difference did not reach significance because of the small number of fractures. Bone mineral density was higher and bone-turnover markers were lower in the men who received zoledronic acid (P<0.05 for both comparisons). Results were similar in men with low serum levels of total testosterone. The zoledronic acid and placebo groups did not differ significantly with respect to the incidence of death (2.6% and 2.9%, respectively) or serious adverse events (25.3% and 25.2%). CONCLUSIONS: Zoledronic acid treatment was associated with a significantly reduced risk of vertebral fracture among men with osteoporosis. (Funded by Novartis Pharma; ClinicalTrials.gov number, NCT00439647.).

21 Article Time to onset of antifracture efficacy and year-by-year persistence of effect of zoledronic acid in women with osteoporosis. 2012

Boonen, Steven / Eastell, Richard / Su, Guoqin / Mesenbrink, Peter / Cosman, Felicia / Cauley, Jane A / Reid, Ian R / Claessens, Frank / Vanderschueren, Dirk / Lyles, Kenneth W / Black, Dennis M. ·University of Leuven, Leuven, Belgium. steven.boonen@uz.kuleuven.ac.be ·J Bone Miner Res · Pubmed #22431413.

ABSTRACT: Oral bisphosphonates reduce fracture risk in osteoporotic patients but are often associated with poor compliance, which may impair their antifracture effects. This post hoc analysis assessed the time to onset and persistence of the antifracture effect of zoledronic acid, a once-yearly bisphosphonate infusion, in women with osteoporosis. Data from 9355 women who were randomized in two placebo-controlled pivotal trials were included. Endpoints included reduction in the rate of any clinical fracture at 6, 12, 18, 24, and 36 months in the zoledronic acid group compared with placebo, and the year-by-year incidence of all clinical fractures over 3 years. Cox proportional hazards regression was used to determine the timing of onset of antifracture efficacy. A generalized estimating equation model was used to assess fracture reduction for the 3 consecutive years of treatment, thereby evaluating persistence of effect. Safety results from women in the two studies were collated. Zoledronic acid reduced the risk of all clinical fractures at 12 months (hazard ratio [HR] = 0.75, 95% confidence interval [CI] 0.61-0.92, p = 0.0050) with significant reductions maintained at all subsequent time points. Year-by-year analysis showed that zoledronic acid reduced the risk for all clinical fractures compared with the placebo group in each of the 3 years (year 1: odds ratio [OR] = 0.74, 95% CI 0.60-0.91, p = 0.0044; year 2: OR = 0.53, 95% CI 0.42-0.66, p < 0.0001; year 3: OR = 0.61, 95% CI 0.48-0.77, p < 0.0001). This antifracture effect was persistent over 3 years, with the reductions in years 2 and 3 slightly larger than in year 1 (p = 0.097). This analysis shows that zoledronic acid offered significant protection from clinical fractures as early as 12 months. When administered annually, its beneficial effects persisted for at least 3 years.

22 Article Once-yearly zoledronic acid in older men compared with women with recent hip fracture. 2011

Boonen, Steven / Orwoll, Eric / Magaziner, Jay / Colón-Emeric, Cathleen S / Adachi, Jonathan D / Bucci-Rechtweg, Christina / Haentjens, Patrick / Kaufman, Jean-Marc / Rizzoli, Rene / Vanderschueren, Dirk / Claessens, Frank / Sermon, An / Witvrouw, Richard / Milisen, Koen / Su, Guoqin / Lyles, Kenneth W / Anonymous5170710. ·Center for Musculoskeletal Research, Leuven University, Leuven, Belgium. boonen@uz.kuleuven.ac.be ·J Am Geriatr Soc · Pubmed #22091563.

ABSTRACT: OBJECTIVES: To assess the efficacy of once-yearly zoledronic acid (ZOL) 5 mg in increasing bone mineral density (BMD) in men with a recent hip fracture participating in the Health Outcomes and Reduced Incidence with Zoledronic Acid Once- Yearly Recurrent Fracture Trial and to compare the efficacy with that in women from the same study. DESIGN: Randomized, placebo-controlled, double-blind trial. SETTING: International multicenter. PARTICIPANTS: Five hundred and eight men and 1,619 women within 90 days of surgical repair of low-trauma hip fracture in the same study (for comparison). INTERVENTION: Once-yearly intravenous (IV) ZOL 5 mg (n = 248) or placebo (n = 260), loading dose of vitamin D, daily calcium, and vitamin D supplements. MEASUREMENT: Changes in BMD. RESULTS: Percentage change from baseline in total hip BMD at Months 12 and 24 was significantly higher with ZOL than with placebo (between-group difference, 2.0%, P = .003, and 3.8%, P = .002, respectively). Percentage change from baseline in femoral neck BMD at Month 24 was significantly higher with ZOL than with placebo (3.8%, P = .003). The BMD benefit was comparable with that observed in women in this study. New clinical fractures occurred in 36 (7.1%) participants (ZOL, n = 16; placebo, n = 20; P = .64). The ZOL safety profile was comparable with that of placebo, with no significant differences in cardiovascular or long-term renal function and a trend toward lower mortality in ZOL-treated men. CONCLUSION: Once-yearly IV ZOL 5 mg increases bone mass at the hip and femoral neck in men within 90 days of repair of a low-trauma hip fracture. Increases were of a similar magnitude to those observed in women in the same study.

23 Article 7α-methyl-19-nortestosterone vs. testosterone implants for hypogonadal osteoporosis: a preclinical study in the aged male orchidectomized rat model. 2011

Sinnesael, M / Callewaert, F / Morreels, M / Kumar, N / Sitruk-Ware, R / Van Proeyen, K / Hespel, P / Boonen, S / Claessens, F / Vanderschueren, D. ·Department of Experimental Medicine, Center for Musculoskeletal Research, Katholieke Universiteit Leuven, Leuven, Belgium. ·Int J Androl · Pubmed #21790658.

ABSTRACT: Overt male hypogonadism induces not only osteoporosis but also unfavourable changes in body composition, which can be prevented by testosterone (T) replacement. In this preclinical study, the potential of synthetic androgen 7α-methyl-19-nortestosterone (MENT) as alternative treatment for male hypogonadism was evaluated in comparison with T. Eleven-month-old male rats were orchidectomized (orch) and left untreated for 2-months. Subsequently, the effects of 4-month MENT (12 μg/day) and T (72 μg/day) treatment on bone, muscle and fat were analysed using microcomputed tomography, dual-energy X-ray absorptiometry, dynamic bone histomorphometry and muscle fibre typing. At the onset of treatment, orch rats were clearly hypogonadal. This was evidenced by significant reductions of androgen-sensitive organ weight, lean mass, cortical thickness and trabecular bone volume compared with sham-operated aged-matched controls (sham). MENT and T restored weight of androgen-sensitive organs to a similar extent, with a superior anabolic action of MENT on levator ani muscle. Both androgens not only fully rescued hypogonadal loss of lean mass but also restored muscle fibre type composition and trabecular bone volume. Cortical bone loss was similarly prevented by MENT and T, but without full recovery to sham. Both androgens stimulated periosteal bone formation, but with a stronger effect of T. By contrast, MENT more strongly suppressed endocortical bone formation and bone turnover rate and reduced fat mass and serum leptin to a greater extent than T. MENT and T are both effective replacement therapies to stimulate bone and muscle in hypogonadal rats, with stronger lipolytic action of MENT.

24 Article Influence of lifestyle factors on quantitative heel ultrasound measurements in middle-aged and elderly men. 2010

Pye, Stephen R / Devakumar, Vinodh / Boonen, Steven / Borghs, Herman / Vanderschueren, Dirk / Adams, Judith E / Ward, Kate A / Bartfai, Gyorgy / Casanueva, Felipe F / Finn, Joseph D / Forti, Gianni / Giwercman, Aleksander / Han, Thang S / Huhtaniemi, Ilpo T / Kula, Krzysztof / Lean, Michael E J / Pendleton, Neil / Punab, Margus / Silman, Alan J / Wu, Frederick C W / O'Neill, Terence W / Anonymous3020652. ·ARC Epidemiology Unit, Manchester Academic Health Science Centre, The University of Manchester, Oxford Road, Manchester M13 9PT, UK. ·Calcif Tissue Int · Pubmed #20205346.

ABSTRACT: We examined the distribution of quantitative heel ultrasound (QUS) parameters in population samples of European men and looked at the influence of lifestyle factors on the occurrence of these parameters. Men aged between 40 and 79 years were recruited from eight European centers and invited to attend for an interviewer-assisted questionnaire, assessment of physical performance, and quantitative ultrasound (QUS) of the calcaneus (Hologic; Sahara). The relationships between QUS parameters and lifestyle variables were assessed using linear regression with adjustments for age, center, and weight. Three thousand two hundred fifty-eight men, mean age 60.0 years, were included in the analysis. A higher PASE score (upper vs. lower tertile) was associated with a higher BUA (beta coefficient = 2.44 dB/ Mhz), SOS (beta = 6.83 m/s), and QUI (beta = 3.87). Compared to those who were inactive, those who walked or cycled more than an hour per day had a higher BUA (beta = 3.71 dB/Mhz), SOS (beta = 6.97 m/s), and QUI (beta = 4.50). A longer time to walk 50 ft was linked with a lower BUA (beta = -0.62 dB/ Mhz), SOS (beta = -1.06 m/s), and QUI (beta = -0.69). Smoking was associated with a reduction in BUA, SOS, and QUI. There was a U-shaped association with frequency of alcohol consumption. Modification of lifestyle, including increasing physical activity and stopping smoking, may help optimize bone strength and reduce the risk of fracture in middle-aged and elderly European men.

25 Article Sex steroids during bone growth: a comparative study between mouse models for hypogonadal and senile osteoporosis. 2009

Ophoff, J / Venken, K / Callewaert, F / Boonen, S / Bouillon, R / Vanderschueren, D. ·Bone Research Unit, Laboratory for Experimental Medicine and Endocrinology, Department of Experimental Medicine, Katholieke Universiteit Leuven, Herestraat 49, 3000, Leuven, Belgium. Jill.Ophoff@med.kuleuven.be ·Osteoporos Int · Pubmed #19238307.

ABSTRACT: SUMMARY: In this study, the role of disturbed bone mineral acquisition during puberty in the pathogenesis of osteoporosis was studied. To this end, a mouse model for senile and hypogonadal osteoporosis was used. Longitudinal follow-up showed that bone fragility in both models results from deficient bone build-up during early puberty. INTRODUCTION: Male osteoporosis may result from impaired bone growth. This study characterizes the mechanisms of deficient peak bone mass acquisition in models for senile (SAMP6) and hypogonadal (orchidectomized SAMR1) osteoporosis. METHODS: Bone mineral acquisition was investigated longitudinally in SAMP6 and orchidectomized SAMR1 mice (eight to ten animals per group) using peripheral quantitative computed tomography and histomorphometry. Additionally, the effects of long-term 5alpha-dihydrotestosterone (DHT) and 17beta-estradiol (E2) replacement were studied. Statistical analysis was performed using ANOVA and Student's t test. RESULTS: SAMP6 mice showed an early (4 weeks) medullary expansion of the cortex due to impaired endocortical bone formation (-43%). Despite compensatory periosteal bone formation (+47%), cortical thickness was severely reduced in 20-week-old SAMP6 versus SAMR1. Orchidectomy reduced periosteal apposition between 4 and 8 weeks of age and resulted in high bone turnover and less trabecular bone gain in SAMP6 and SAMR1. DHT and E2 stimulated periosteal expansion and trabecular bone in orchidectomized SAMP6 and SAMR1. E2 stimulated endocortical apposition in SAMP6. Moreover, sex steroid action occurred between 4 and 8 weeks of age. CONCLUSION: Bone fragility in both models resulted from deficient bone build-up during early puberty. DHT and E2 improved bone mass acquisition in orchidectomized animals, suggesting a role for AR and ER in male skeletal development.