44 results on '"Hans-Georg Zmierczak"'
Search Results
2. Prevalence of vertebral fractures and non-fracture deformities in young healthy men
- Author
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Stephanie De Smet, Hans-Georg Zmierczak, and Stefan Goemaere
- Subjects
Diseases of the musculoskeletal system ,RC925-935 - Published
- 2021
- Full Text
- View/download PDF
3. Relatively higher bone formation markers during puberty are correlated with more bone mass accrual independent of longitudinal growth in boys
- Author
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Thiberiu Banica, Sara Vandewalle, Hans-Georg Zmierczak, Stefan Goemaere, Jean De Schepper, Jean-Marc Kaufman, and Bruno Lapauw
- Subjects
Diseases of the musculoskeletal system ,RC925-935 - Published
- 2020
- Full Text
- View/download PDF
4. A Novel Disorder of Osteoporosis, Osteonecrosis, and Metaphyseal Fracture
- Author
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Hans‐Georg Zmierczak, Guy Taylor, and Tim Cundy
- Subjects
BISPHOSPHONATES ,METAPHYSEAL FRACTURES ,OSTEONECROSIS ,OSTEOPOROSIS ,Orthopedic surgery ,RD701-811 ,Diseases of the musculoskeletal system ,RC925-935 - Abstract
ABSTRACT We describe two unrelated women who in their fifth decade developed a severe disorder characterized by large joint osteonecrosis and multiple minimal trauma fractures in both the axial and appendicular skeleton, including unusual metaphyseal fractures of the proximal tibia. Bone density testing showed borderline osteoporosis of the spine and osteopenia of the femur. Therapy with bisphosphonates and teriparatide failed to prevent further fractures. To our knowledge, this disorder has not been described previously. Investigations to date, including a genetic screen, have not revealed its cause. © 2020 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.
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- 2020
- Full Text
- View/download PDF
5. Modest Changes in Sex Hormones During Early and Middle Adulthood Affect Bone Mass and Size in Healthy Men: A Prospective Cohort Study
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Thiberiu Banica, Charlotte Verroken, Guy T'Sjoen, Stefan Goemaere, Hans‐Georg Zmierczak, Tom Fiers, Jean‐Marc Kaufman, and Bruno Lapauw
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Adult ,Male ,Endocrinology, Diabetes and Metabolism ,Middle Aged ,Young Adult ,Absorptiometry, Photon ,Bone Density ,Tandem Mass Spectrometry ,Humans ,Testosterone ,Orthopedics and Sports Medicine ,Prospective Studies ,Gonadal Steroid Hormones ,Chromatography, Liquid - Abstract
Bone metabolism in men is in part determined by sex steroid exposure. This is especially clear during puberty and senescence but it remains to be established whether declines in sex steroid levels during young and middle adulthood are associated with changes in bone mass and size. This study investigated changes in bone mineral content (BMC), areal bone mineral density (aBMD), volumetric BMD (vBMD), and bone size in relation to sex steroid levels in 999 young adult men (age 24-46 years) of whom 676 were re-evaluated after a mean period of 12 years. Sex hormone-binding globulin (SHBG) levels were measured using immunoassay, testosterone (T) and estradiol (E2) using liquid chromatography-tandem mass spectrometry (LC-MS/MS), and free fractions were calculated (cFT and cFE2, respectively). Areal bone parameters and BMC were measured at the hip and lumbar spine using dual-energy X-ray absorptiometry (DXA). Radial and tibial vBMD and bone size were determined using peripheral quantitative computed tomography (pQCT). Linear mixed models were used for statistical analyses. With aging, we observed decreases in almost all bone mass and density indices, whereas changes in bone geometry resulted in larger bones with thinner cortices. These changes in bone mass and size appeared related to sex steroid levels. Specifically, decreases in cFT (but not total T) levels were associated with larger decreases in lumbar spine BMC and especially with geometric changes in cortical bone at the tibia. Similarly, decreases in total E2 and cFE2 were associated with larger decreases in bone mass (all sites) and also with some geometric changes. Also increases in SHBG were independently associated with aging-related changes in bone mass and size in these men. In summary, even small changes in T, E2, and SHBG levels during young and middle adulthood in healthy men are associated with changes in bone mass and size. © 2022 American Society for Bone and Mineral Research (ASBMR).
- Published
- 2022
6. Modest changes in sex hormones during early and middle adulthood affect bone mass and size in healthy men. A prospective cohort study
- Author
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Thiberiu, Banica, primary, Charlotte, Verroken, additional, Guy, T'Sjoen, additional, Stefan, Goemaere, additional, Hans-Georg, Zmierczak, additional, Tom, Fiers, additional, Jean-Marc, Kaufman, additional, and Bruno, Lapauw, additional
- Published
- 2022
- Full Text
- View/download PDF
7. The relationship between circulating hormone levels, bone turnover markers and skeletal development in healthy boys differs according to maturation stage
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Thiberiu Banica, Sara Vandewalle, Hans-Georg Zmierczak, Stefan Goemaere, Stefanie De Buyser, Tom Fiers, Jean-Marc Kaufman, Jean De Schepper, Bruno Lapauw, Mental Health and Wellbeing research group, Clinical sciences, Biology of the Testis, and Pediatrics
- Subjects
Male ,puberty ,Histology ,Adolescent ,Estradiol ,Physiology ,Endocrinology, Diabetes and Metabolism ,skeletal growth ,wnt-signalling markers ,Bone Density ,Child, Preschool ,healthy boys ,Humans ,Testosterone ,sex steroids ,Bone Remodeling ,Insulin-Like Growth Factor I ,Child ,bone turnover markers - Abstract
INTRODUCTION: This study investigates peri-pubertal changes in bone turnover markers, Wnt-signalling markers, insulin-like growth factor-1 (IGF-1) and sex steroid levels, and how they reflect skeletal development in peri-pubertal boys. MATERIALS AND METHODS: Population-based study in 118 peri-pubertal boys from the NINIOS cohort (age range at baseline 5.1-17.3 years) with repeated measurements at baseline and after two years. Serum levels of the classical bone turnover markers (BTM) procollagen type 1 N-terminal propeptide and carboxy-terminal collagen crosslinks, as well as sex-hormone binding globulin, IGF-1, osteoprotegerin, sclerostin and dickkopf-1 were measured using immunoassays. Sex steroids (estradiol, testosterone, and androstenedione) were measured using mass spectrometry and free fractions calculated. Dual energy x-ray absorptiometry was used for bone measurements at the lumbar spine and whole body. Volumetric bone parameters and bone geometry at the proximal and distal radius were assessed by peripheral QCT. Pubertal development was categorized based on Tanner staging. RESULTS: During puberty, sex steroid and IGF-1-levels along with most parameters of bone mass and bone size increased every next Tanner stage. In contrast, classical bone turnover markers and sclerostin peaked around mid-puberty, with subsequent declines towards adult values in late puberty. Especially classical BTM and sex steroid levels showed consistent associations with areal and volumetric bone parameters and bone geometry. However, observed associations differed markedly according to pubertal stage and skeletal site. CONCLUSION: Serum levels of sex steroids, IGF-1 and bone metabolism markers reflect skeletal development in peri-pubertal boys. However, skeletal development during puberty is nonlinear, and the relations between skeletal indices and hormonal parameters are nonlinear as well, and dependent on the respective maturation stage and skeletal site.
- Published
- 2022
8. Author response for 'Modest changes in sex hormones during early and middle adulthood affect bone mass and size in healthy men. A prospective cohort study'
- Author
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null Thiberiu Banica, null Charlotte Verroken, null Guy T'Sjoen, null Stefan Goemaere, null Hans‐Georg Zmierczak, null Tom Fiers, null Jean‐Marc Kaufman, and null Bruno Lapauw
- Published
- 2022
9. European expert consensus on practical management of specific aspects of parathyroid disorders in adults and in pregnancy: recommendations of the ESE Educational Program of Parathyroid Disorders (PARAT 2021)
- Author
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Jens Bollerslev, Lars Rejnmark, Alexandra Zahn, Ansgar Heck, Natasha M Appelman-Dijkstra, Luis Cardoso, Fadil M Hannan, Filomena Cetani, Tanja Sikjaer, Anna Maria Formenti, Sigridur Björnsdottir, Camilla Schalin-Jäntti, Zhanna Belaya, Fraser Gibb, Bruno Lapauw, Karin Amrein, Corinna Wicke, Corinna Grasemann, Michael Krebs, Eeva Ryhänen, Özer Makay, Salvatore Minisola, Sébastien Gaujoux, Jean-Philippe Bertocchio, Zaki Hassan-Smith, Agnès Linglart, Elizabeth M Winter, Martina Kollmann, Hans-Georg Zmierczak, Elena Tsourdi, Stefan Pilz, Heide Siggelkow, Neil Gittoes, Claudio Marcocci, Peter Kamenický, Zillikens Carola, Frost Morten, Rolighed Lars, Sitges-Serra Antonio, Corbetta Sabrina, Decallonne Brigitte, Gherlan Iuliana, Gianotti Laura, Grigorie Daniel, Hindié Elif, Kiely Mairead, Lindner Kirsten, Makras Polyzois, Obermayer-Pietsch Barbara, R Perez-Lopez Fastino, Pretorius Mikkel, Saponaro Federica, Trummer Christian, Vamvakidis Kyriakos, Vashakmadze Natia, and P Yavropoulou Maria
- Subjects
Adult ,Hypoparathyroidism ,Endocrinology, Diabetes and Metabolism ,Parathyroid Diseases ,Review ,CALCITROPIC HORMONES ,CALCIUM-SENSING RECEPTOR ,Endocrinology ,Pregnancy ,QUALITY-OF-LIFE ,Medicine and Health Sciences ,Humans ,Lactation ,VITAMIN-D ,PRIMARY HYPERPARATHYROIDISM ,LONG-TERM TREATMENT ,Infant, Newborn ,General Medicine ,AMERICAN ASSOCIATION ,Hyperparathyroidism, Primary ,SECONDARY HYPERPARATHYROIDISM ,Parathyroid Hormone ,FAMILIAL HYPOCALCIURIC HYPERCALCEMIA ,Hypercalcemia ,Calcium ,Female ,BONE-MINERAL DENSITY - Abstract
This European expert consensus statement provides recommendations for the diagnosis and management of primary hyperparathyroidism (PHPT), chronic hypoparathyroidism in adults (HypoPT), and parathyroid disorders in relation to pregnancy and lactation. Specified areas of interest and unmet needs identified by experts at the second ESE Educational Program of Parathyroid Disorders in 2019 were discussed during two virtual workshops in 2021 and subsequently developed by working groups with interest in the specified areas. PHPT is a common endocrine disease. However, its differential diagnosis of familial hypocalciuric hypercalcemia (FHH), the definition and clinical course of normocalcemic PHPT, and the optimal management of its recurrence after surgery represents areas of uncertainty requiring clarifications. HypoPT is an orphan disease characterized by low calcium concentrations due to insufficient PTH secretion, most often secondary to neck surgery. Prevention and prediction of surgical injury to the parathyroid glands are essential to limit the disease-related burden. Long-term treatment modalities including the place for PTH replacement therapy and the optimal biochemical monitoring and imaging surveillance for complications to treatment in chronic HypoPT need to be refined. The physiological changes in calcium metabolism occurring during pregnancy and lactation modify the clinical presentation and management of parathyroid disorders in these periods of life. Modern interdisciplinary approaches to PHPT and HypoPT in pregnant and lactating women and their newborn children are proposed. The recommendations on clinical management presented here will serve as background for further educational material aimed at a broader clinical audience and were developed with the focus on endocrinologists in training.
- Published
- 2022
10. Prevalence of vertebral fractures and non-fracture deformities in young healthy men
- Author
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Stefan Goemaere, Hans-Georg Zmierczak, and Stephanie De Smet
- Subjects
RC925-935 ,business.industry ,Endocrinology, Diabetes and Metabolism ,Fracture (geology) ,Medicine ,Dentistry ,Orthopedics and Sports Medicine ,Diseases of the musculoskeletal system ,business - Published
- 2021
11. The potential role of androgens as early determinants of body composition and metabolic health.
- Author
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Banica, Thiberiu, primary, Verroken, Charlotte, additional, Hans-Georg, Zmierczak, additional, Goemaere, Stefan, additional, TSjoen, Guy, additional, Fiers, Tom, additional, Jean-Marc, Kaufman, additional, and Lapauw, Bruno, additional
- Published
- 2021
- Full Text
- View/download PDF
12. A Novel Disorder of Osteoporosis, Osteonecrosis, and Metaphyseal Fracture
- Author
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Tim Cundy, Hans-Georg Zmierczak, and Guy Taylor
- Subjects
musculoskeletal diseases ,Bone density ,Appendicular skeleton ,OSTEONECROSIS ,Endocrinology, Diabetes and Metabolism ,Osteoporosis ,Diseases of the musculoskeletal system ,OSTEOPOROSIS ,METAPHYSEAL FRACTURES ,BISPHOSPHONATES ,Medicine and Health Sciences ,medicine ,Teriparatide ,Orthopedics and Sports Medicine ,Femur ,Metaphyseal fracture ,Orthodontics ,Orthopedic surgery ,business.industry ,Original Articles ,medicine.disease ,musculoskeletal system ,Osteopenia ,medicine.anatomical_structure ,RC925-935 ,Large joint ,Original Article ,business ,RD701-811 ,medicine.drug - Abstract
We describe two unrelated women who in their fifth decade developed a severe disorder characterized by large joint osteonecrosis and multiple minimal trauma fractures in both the axial and appendicular skeleton, including unusual metaphyseal fractures of the proximal tibia. Bone density testing showed borderline osteoporosis of the spine and osteopenia of the femur. Therapy with bisphosphonates and teriparatide failed to prevent further fractures. To our knowledge, this disorder has not been described previously. Investigations to date, including a genetic screen, have not revealed its cause. © 2020 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.
- Published
- 2020
13. Proandrogenic and Antiandrogenic Progestins in Transgender Youth: Differential Effects on Body Composition and Bone Metabolism
- Author
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Stefan Goemaere, Lloyd J.W. Tack, Kaatje Toye, Jean-Marc Kaufman, Martine Cools, Guy T'Sjoen, Sara Vandewalle, Margarita Craen, Bruno Lapauw, and Hans-Georg Zmierczak
- Subjects
Male ,medicine.medical_specialty ,Adolescent ,Bone density ,medicine.drug_class ,Endocrinology, Diabetes and Metabolism ,Clinical Biochemistry ,030209 endocrinology & metabolism ,Context (language use) ,Transgender Persons ,Biochemistry ,Lynestrenol ,Bone remodeling ,03 medical and health sciences ,Grip strength ,chemistry.chemical_compound ,Absorptiometry, Photon ,0302 clinical medicine ,Endocrinology ,Bone Density ,Sex Hormone-Binding Globulin ,Internal medicine ,medicine ,Humans ,Testosterone ,Quantitative computed tomography ,Child ,Cyproterone Acetate ,Bone Development ,Lumbar Vertebrae ,030219 obstetrics & reproductive medicine ,Estradiol ,Hand Strength ,medicine.diagnostic_test ,business.industry ,Biochemistry (medical) ,Cyproterone acetate ,Luteinizing Hormone ,Treatment Outcome ,chemistry ,Body Composition ,Lean body mass ,Female ,Follicle Stimulating Hormone ,Progestins ,business ,Progestin ,Transsexualism - Abstract
Context: Progestins can be used to attenuate endogenous hormonal effects in late-pubertal transgender (trans) adolescents (Tanner stage B4/5 and G4/5). Currently, no data are available on the effects of progestins on the development of bone mass or body composition in trans youth. Objective: To study prospectively the evolution of body composition and bone mass in late-pubertal trans adolescents using the proandrogenic or antiandrogenic progestins lynestrenol (L) and cyproterone acetate (CA), respectively. Design and Outcome Measurements: Forty-four trans boys (Tanner B4/5) and 21 trans girls (Tanner G4/5) were treated with L or CA for 11.6 (4 to 40) and 10.6 (5 to 31) months, respectively. Anthropometry, grip strength, body composition, and bone mass, size, and density were determined by dual-energy X-ray absorptiometry and peripheral quantitative computed tomography before the start of progestin and before addition of cross-sex hormones. Results: Using L, lean mass [+3.2 kg (8.6%)] and grip strength [+3 kg (10.6%)] significantly increased, which coincided with a more masculine body shape in trans boys. Trans girls showed loss of lean mass [-2.2 kg (4.7%)], gain of fat mass [+1.5 kg (9.4%)], and decreased grip strength Z scores. CA limited normal bone expansion and impeded pubertal bone mass accrual, mostly at the lumbar spine [Z score: -0.765 to -1.145 (P = 0.002)]. L did not affect physiological bone development. Conclusion: Proandrogenic and antiandrogenic progestins induce body composition changes in line with the desired appearance within 1 year of treatment. Bone health, especially at the lumbar spine, is of concern in trans girls, as bone mass accrual is severely affected by androgen suppressive therapy.
- Published
- 2018
14. Bone Turnover in Young Adult Men: Cross-Sectional Determinants and Associations With Prospectively Assessed Bone Loss
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Stefan Goemaere, Bruno Lapauw, Charlotte Verroken, Jean-Marc Kaufman, and Hans-Georg Zmierczak
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0301 basic medicine ,Bone mineral ,Peak bone mass ,medicine.medical_specialty ,biology ,business.industry ,Endocrinology, Diabetes and Metabolism ,030209 endocrinology & metabolism ,Bone remodeling ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Endocrinology ,medicine.anatomical_structure ,N-terminal telopeptide ,Internal medicine ,Osteocalcin ,biology.protein ,medicine ,Lean body mass ,Orthopedics and Sports Medicine ,Young adult ,business ,Femoral neck - Abstract
Biochemical markers of bone turnover are higher in young adult men than in middle-aged men or young adult women. Nonetheless, little is known about the determinants and clinical significance hereof. The present study examined determinants of serum bone turnover markers in men around peak bone mass age, and explored whether bone turnover at this age predicts subsequent changes in bone mass. We used cross-sectional and longitudinal data from 973 and 428 healthy men, respectively, aged 25 to 45 years at baseline, including baseline procollagen type I amino-terminal propeptide (P1NP), osteocalcin, and C-terminal telopeptide of type I collagen (CTX) from fasting serum samples, baseline questionnaire-assessed physical activity levels, and baseline and follow-up dual-energy X-ray absorptiometry-derived areal bone mineral density (aBMD) and body composition. Mean follow-up time was 12.4 ± 0.4 years. At baseline, all bone turnover markers were inversely associated with total body fat mass (β ≤ -0.20, p
- Published
- 2017
15. Serum levels of Wnt-signalling parameters poorly reflect bone mass and metabolism in healthy boys and men
- Author
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Thiberiu, Banica, primary, Charlotte, Verroken, additional, Hans-Georg, Zmierczak, additional, Stefan, Goemaere, additional, Sara, Vandewalle, additional, Jean-Marc, Kaufman, additional, and Bruno, Lapauw, additional
- Published
- 2019
- Full Text
- View/download PDF
16. Cortical Bone Size Deficit in Adult Patients With Type 1 Diabetes Mellitus
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Charlotte Verroken, Samyah Shadid, Bruno Lapauw, Loïc Beddeleem, Jean-Marc Kaufman, Hans-Georg Zmierczak, Wout Pieters, and Stefan Goemaere
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Adult ,Male ,0301 basic medicine ,medicine.medical_specialty ,Bone density ,Endocrinology, Diabetes and Metabolism ,Clinical Biochemistry ,030209 endocrinology & metabolism ,Context (language use) ,Biochemistry ,Bone remodeling ,03 medical and health sciences ,Absorptiometry, Photon ,0302 clinical medicine ,Endocrinology ,Bone Density ,Internal medicine ,Cortical Bone ,medicine ,Humans ,Quantitative computed tomography ,Glycemic ,Femoral neck ,Glycated Hemoglobin ,Bone mineral ,medicine.diagnostic_test ,Femur Neck ,business.industry ,Biochemistry (medical) ,Organ Size ,Middle Aged ,Bone Diseases, Metabolic ,Radius ,Cross-Sectional Studies ,Diabetes Mellitus, Type 1 ,030104 developmental biology ,medicine.anatomical_structure ,Case-Control Studies ,Cancellous Bone ,Osteoporosis ,Female ,Cortical bone ,Tomography, X-Ray Computed ,business - Abstract
Context The increased fracture risk associated with type 1 diabetes mellitus (T1DM) remains unexplained by traditional risk factors such as low areal bone mineral density (aBMD). Nonetheless, few data exist on other determinants of bone strength in T1DM, including volumetric bone mineral density (vBMD) and bone geometry. Objective We compared areal and volumetric bone parameters and cortical bone geometry in adult T1DM patients and sex- and age-matched controls. Design Cross-sectional study including 64 adult T1DM patients (38 men; mean age, 41.1 ± 8.1 years) and 63 sex- and age-matched controls. Main outcome measures Areal bone parameters using dual-energy X-ray absorptiometry; volumetric bone parameters and cortical bone geometry using peripheral quantitative computed tomography. Results T1DM was associated with lower aBMD at the total body, femoral neck, and total hip; lower trabecular vBMD at the distal radius; and higher cortical but lower total vBMD at the radial shaft. In addition, subjects with T1DM had a similar periosteal but larger endosteal circumference, smaller cortical thickness, and lower cortical over total bone area ratio. Differences in bone parameters could not be explained by differences in bone turnover markers or body composition, but cortical area was inversely associated with glycemic variability and long-term glycemic control. Conclusions Besides decreased aBMD and trabecular vBMD, adult T1DM patients present with a cortical bone size deficit, which may contribute to their increased fracture risk. This deficit is mainly situated at the endosteal envelope, suggesting imbalanced remodeling rather than compromised modeling processes as the underlying mechanism.
- Published
- 2017
17. Insulin Resistance Is Associated With Smaller Cortical Bone Size in Nondiabetic Men at the Age of Peak Bone Mass
- Author
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Stefan Goemaere, Hans-Georg Zmierczak, Bruno Lapauw, Jean-Marc Kaufman, and Charlotte Verroken
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Blood Glucose ,Leptin ,Male ,0301 basic medicine ,Bone density ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Clinical Biochemistry ,Biochemistry ,Absorptiometry, Photon ,0302 clinical medicine ,Endocrinology ,Bone Density ,Tandem Mass Spectrometry ,Sex Hormone-Binding Globulin ,Insulin ,Testosterone ,Insulin-Like Growth Factor I ,Vitamin D ,Quantitative computed tomography ,Bone mineral ,Estradiol ,medicine.diagnostic_test ,Organ Size ,Middle Aged ,Radius ,medicine.anatomical_structure ,Parathyroid Hormone ,Body Composition ,Adiponectin ,Procollagen ,Adult ,Peak bone mass ,medicine.medical_specialty ,Osteocalcin ,030209 endocrinology & metabolism ,Collagen Type I ,03 medical and health sciences ,Insulin resistance ,Internal medicine ,Cortical Bone ,medicine ,Humans ,Muscle Strength ,Muscle, Skeletal ,Serum Albumin ,Tibia ,business.industry ,Biochemistry (medical) ,Type 2 Diabetes Mellitus ,medicine.disease ,Peptide Fragments ,030104 developmental biology ,Cortical bone ,Insulin Resistance ,Peptides ,Tomography, X-Ray Computed ,business ,Chromatography, Liquid - Abstract
In type 2 diabetes mellitus, fracture risk is increased despite preserved areal bone mineral density. Although this apparent paradox may in part be explained by insulin resistance affecting bone structure and/or material properties, few studies have investigated the association between insulin resistance and bone geometry.We aimed to explore this association in a cohort of nondiabetic men at the age of peak bone mass.Nine hundred ninety-six nondiabetic men aged 25 to 45 years were recruited in a cross-sectional, population-based sibling pair study at a university research center.Insulin resistance was evaluated using the homeostasis model assessment of insulin resistance (HOMA-IR), with insulin and glucose measured from fasting serum samples. Bone geometry was assessed using peripheral quantitative computed tomography at the distal radius and the radial and tibial shafts.In age-, height-, and weight-adjusted analyses, HOMA-IR was inversely associated with trabecular area at the distal radius and with cortical area, periosteal and endosteal circumference, and polar strength strain index at the radial and tibial shafts (β ≤ -0.13, P0.001). These associations remained essentially unchanged after additional adjustment for dual-energy X-ray absorptiometry-derived body composition, bone turnover markers, muscle size or function measurements, or adiponectin, leptin, insulin-like growth factor 1, or sex steroid levels.In this cohort of nondiabetic men at the age of peak bone mass, insulin resistance is inversely associated with trabecular and cortical bone size. These associations persist after adjustment for body composition, muscle size or function, or sex steroid levels, suggesting an independent effect of insulin resistance on bone geometry.
- Published
- 2016
18. Relatively higher bone formation markers during puberty are correlated with more bone mass accrual independent of longitudinal growth in boys
- Author
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Sara Vandewalle, Jean De Schepper, Jean-Marc Kaufman, Hans-Georg Zmierczak, Bruno Lapauw, Stefan Goemaere, and Thiberiu Banica
- Subjects
medicine.medical_specialty ,lcsh:Diseases of the musculoskeletal system ,Accrual ,business.industry ,Endocrinology, Diabetes and Metabolism ,Longitudinal growth ,Endocrinology ,Internal medicine ,medicine ,Orthopedics and Sports Medicine ,Bone formation ,lcsh:RC925-935 ,business ,Bone mass - Published
- 2020
19. Association of Jumping Mechanography-Derived Indices of Muscle Function with Tibial Cortical Bone Geometry
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Charlotte Verroken, Hans-Georg Zmierczak, Jean-Marc Kaufman, Stefan Goemaere, and Bruno Lapauw
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Male ,0301 basic medicine ,Endocrinology, Diabetes and Metabolism ,Geometry ,Bone strength ,medicine.disease_cause ,Quadriceps Muscle ,0302 clinical medicine ,Endocrinology ,Jumping ,Jumping mechanography ,YOUNG-ADULTS ,STRENGTH ,Medicine and Health Sciences ,Orthopedics and Sports Medicine ,Quantitative computed tomography ,education.field_of_study ,Pqct ,medicine.diagnostic_test ,HEALTHY MALE SIBLINGS ,Anatomy ,Middle Aged ,Circumference ,Biomechanical Phenomena ,medicine.anatomical_structure ,POSTMENOPAUSAL WOMEN ,Peak force ,Adult ,BODY-COMPOSITION ,Population ,030209 endocrinology & metabolism ,MASS ,Mechanical loading ,03 medical and health sciences ,LOWER LEG ,Cortical Bone ,medicine ,Humans ,Tibia ,education ,Exercise ,Bone geometry ,business.industry ,MECHANICAL SIGNALS ,Siblings ,QUANTITATIVE COMPUTED-TOMOGRAPHY ,PHYSICAL-ACTIVITY ,Cross-Sectional Studies ,030104 developmental biology ,Lean body mass ,Cortical bone ,business - Abstract
Jumping mechanography has been developed to estimate maximum voluntary muscle forces. This study assessed associations of jumping mechanography-derived force and power measurements with tibial cortical bone geometry, compared to other estimates of muscle mass, size, and function. Healthy men (n = 181; 25-45 years) were recruited in a cross-sectional, population-based sibling-pair study. Muscle parameters include isokinetic peak torque of the quadriceps, DXA-derived leg lean mass, mechanography-derived peak jump force and power, and pQCT-derived mid-tibial (66 %) muscle cross-sectional area (CSA). Mid-tibial cortical bone parameters were assessed by pQCT. In age, height, and weight-adjusted analyses, jump force and power correlated positively with cortical bone area, cortical thickness, and polar strength-strain index (SSIp) (β = 0.23-0.34, p ≤ 0.001 for force; β = 0.25-0.30, p ≤ 0.007 for power) and inversely with endosteal circumference adjusted for periosteal circumference (ECPC) (β = -0.16, p
- Published
- 2015
20. Bone Turnover in Young Adult Men: Cross-Sectional Determinants and Associations With Prospectively Assessed Bone Loss
- Author
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Charlotte, Verroken, Hans-Georg, Zmierczak, Stefan, Goemaere, Jean-Marc, Kaufman, and Bruno, Lapauw
- Subjects
Adult ,Male ,Middle Aged ,Young Adult ,Cross-Sectional Studies ,Bone Density ,Body Composition ,Humans ,Bone Remodeling ,Prospective Studies ,Bone Resorption ,Exercise ,Biomarkers ,Follow-Up Studies - Abstract
Biochemical markers of bone turnover are higher in young adult men than in middle-aged men or young adult women. Nonetheless, little is known about the determinants and clinical significance hereof. The present study examined determinants of serum bone turnover markers in men around peak bone mass age, and explored whether bone turnover at this age predicts subsequent changes in bone mass. We used cross-sectional and longitudinal data from 973 and 428 healthy men, respectively, aged 25 to 45 years at baseline, including baseline procollagen type I amino-terminal propeptide (P1NP), osteocalcin, and C-terminal telopeptide of type I collagen (CTX) from fasting serum samples, baseline questionnaire-assessed physical activity levels, and baseline and follow-up dual-energy X-ray absorptiometry-derived areal bone mineral density (aBMD) and body composition. Mean follow-up time was 12.4 ± 0.4 years. At baseline, all bone turnover markers were inversely associated with total body fat mass (β ≤ -0.20, p 0.001), and positively with physical activity during sports activities (β ≥ 0.09, p ≤ 0.003), and, albeit not independently from fat mass, total body lean mass (β ≥ 0.20, p ≤ 0.003). Mean annual aBMD changes in the longitudinal cohort were -0.19% ± 0.24% at the total body, -0.14% ± 0.42% at the spine, -0.49% ± 0.47% at the femoral neck, and -0.25% ± 0.37% at the total hip (all p 0.001). Higher bone turnover markers at baseline were associated with larger decreases in aBMD at all measurement sites (β ≤ -0.08, p ≤ 0.081 for P1NP; β ≤ -0.16, p ≤ 0.002 for osteocalcin; and β ≤ -0.21, p 0.001 for CTX). In conclusion, our findings show that sports activities and body composition, primarily fat mass, are the main identified determinants of bone turnover in men around peak bone mass age. Further, bone turnover at this age is an important determinant of subsequent changes in bone mass, with higher levels of bone turnover markers being associated with greater decreases in aBMD. © 2017 American Society for Bone and Mineral Research.
- Published
- 2017
21. Maternal age at childbirth is associated with offspring insulin sensitivity: a cross-sectional study in adult male siblings
- Author
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Charlotte Verroken, Hans-Georg Zmierczak, Stefan Goemaere, Bruno Lapauw, and Jean-Marc Kaufman
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Adult ,Male ,medicine.medical_specialty ,Adolescent ,Offspring ,Endocrinology, Diabetes and Metabolism ,Birth weight ,medicine.medical_treatment ,Population ,030209 endocrinology & metabolism ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Endocrinology ,Insulin resistance ,Pregnancy ,Internal medicine ,medicine ,Childbirth ,Humans ,education ,education.field_of_study ,030219 obstetrics & reproductive medicine ,Adiponectin ,business.industry ,Insulin ,Gestational age ,Middle Aged ,medicine.disease ,Cross-Sectional Studies ,Female ,Birth Order ,Insulin Resistance ,business ,Maternal Age - Abstract
SummaryObjective Maternal age at childbirth is increasing worldwide, but studies investigating the consequences of this trend on offspring metabolic health are scarce. We investigated the associations of maternal age at childbirth with metabolic outcomes in adult male siblings. Methods We used data from 586 men aged 25–45 participating in a cross-sectional, population-based sibling-pair study, including maternal age at childbirth and offspring birthweight, adult weight, height, dual-energy X-ray absorptiometry (DXA)-derived body composition, blood pressure, and total cholesterol, glucose and insulin levels from fasting serum samples. Insulin sensitivity was evaluated using the homeostasis model assessment of insulin resistance (HOMA-IR). Results Maternal age at childbirth was 27·1 ± 4·7 years and was inversely associated with glucose levels (β = −0·10, P = 0·022) and HOMA-IR (β = −0·06, P = 0·065) in age- and body composition-adjusted analyses. Moreover, sons of younger (aged
- Published
- 2016
22. Cortical bone size deficit in adult patients with type 1 diabetes mellitus
- Author
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Wout Pieters, Jean Kaufman, Charlotte Verroken, Stefan Goemaere, Hans-Georg Zmierczak, Loïc Beddeleem, and Bruno Lapauw
- Subjects
medicine.medical_specialty ,Type 1 diabetes ,medicine.anatomical_structure ,Endocrinology ,Adult patients ,business.industry ,Internal medicine ,medicine ,Cortical bone ,medicine.disease ,business - Published
- 2016
23. Advancing maternal age at childbirth is associated with less favourable trabecular bone mineral density and tibial cortical bone geometry in young adult male offspring
- Author
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Hans-Georg Zmierczak, Charlotte Verroken, Jean Kaufman, Bruno Lapauw, and Stefan Goemaere
- Subjects
Trabecular bone ,medicine.anatomical_structure ,Mineral density ,business.industry ,Offspring ,Young adult male ,Medicine ,Childbirth ,Cortical bone ,General Medicine ,Anatomy ,business - Published
- 2016
24. Indications for a genetic association of a VCP polymorphism with the pathogenesis of sporadic Paget's disease of bone, but not for TNFSF11 (RANKL) and IL-6 polymorphisms
- Author
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Filip Vanhoenacker, Stefan Goemaere, Hans-Georg Zmierczak, René Westhovens, Greet Beyens, Piet Geusens, Leon Verbruggen, Steven Boonen, Wim Van Hul, Jan Van Offel, Jean-Pierre Devogelaer, Fenna de Freitas, Pui Yan Jenny Chung, Internal Medicine Specializations, Interne Geneeskunde, and RS: CAPHRI School for Public Health and Primary Care
- Subjects
Male ,Candidate gene ,Endocrinology, Diabetes and Metabolism ,Valosin-containing protein ,Population ,Cell Cycle Proteins ,Single-nucleotide polymorphism ,Bioinformatics ,Polymorphism, Single Nucleotide ,Biochemistry ,Association ,Endocrinology ,Gene Frequency ,Valosin Containing Protein ,Genetics ,medicine ,Humans ,SNP ,Genetic Predisposition to Disease ,education ,Molecular Biology ,Alleles ,Genetic association ,Adenosine Triphosphatases ,education.field_of_study ,biology ,Interleukin-6 ,RANK Ligand ,Haplotype ,RANKL ,Middle Aged ,Osteitis Deformans ,medicine.disease ,TNFSF11 ,IL6 ,Paget's disease of bone ,Haplotypes ,biology.protein ,Female ,Human medicine ,Kappa-B ligand ,VCP - Abstract
Paget's disease of bone (PDB) is, after osteoporosis, the second most common metabolic bone disorder in the elderly Caucasian population. Mutations in the sequestosome 1 gene (SQSTM1) are responsible for the etiology of PDB in a subset of patients, but the disease pathogenesis in the remaining PDB patients is still unknown. Therefore association studies investigating the relationship between genetic polymorphisms and sporadic PDB have been performed in order to find the susceptibility polymorphisms. In this paper, we sought to determine whether polymorphisms in 3 functional candidate genes play a role in the development of sporadic PDB: TNFSF11 (receptor activator of nuclear factor κB ligand, RANKL), VCP (valosin-containing protein) and IL-6 (interleukin 6). Analyzing 9 tag SNPs and 2 multi-marker tests (MMTs) in TNFSF11, 3 tag SNPs and 1 MMT in VCP and 8 tag SNPs in IL-6 in a population of 196 Belgian patients with sporadic PDB and 212 Belgian control individuals revealed that one VCP SNP (rs565070) turned out to be associated with PDB in this Belgian study population (p = 5.5 × 10− 3). None of the tag SNPs or MMTs selected for TNFSF11 or IL-6 was associated with PDB. Still, replication of our findings in the VCP gene in other populations is important to confirm our results. However, when combining data of VCP with those from other susceptible gene regions from previous association studies (i.e. TNFRSF11A, CSF1, OPTN and TM7SF4), independent effect of each gene region was found and the cumulative population attributable risk is 72.7%.
- Published
- 2011
25. Thyroid hormone status within the physiological range affects bone mass and density in healthy men at the age of peak bone mass
- Author
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Stefan Goemaere, Hans-Georg Zmierczak, Youri Taes, Tom Fiers, Jean-Marc Kaufman, Bruno Lapauw, and Greet Roef
- Subjects
Male ,HYPERTHYROIDISM ,Aging ,Bone density ,Endocrinology, Diabetes and Metabolism ,Absorptiometry, Photon ,Endocrinology ,Bone Density ,Sex Hormone-Binding Globulin ,Medicine and Health Sciences ,THYROXINE ,Medicine ,Quantitative computed tomography ,Gonadal Steroid Hormones ,RISK ,Bone mineral ,Anthropometry ,medicine.diagnostic_test ,Smoking ,Thyroid ,General Medicine ,Middle Aged ,medicine.anatomical_structure ,POSTMENOPAUSAL WOMEN ,Body Composition ,Adult ,musculoskeletal diseases ,Peak bone mass ,Thyroid Hormones ,medicine.medical_specialty ,Bone and Bones ,SERUM TSH ,Internal medicine ,Humans ,Life Style ,MALE SIBLINGS ,Bone Development ,business.industry ,POLYMORPHISM ,Cross-Sectional Studies ,HYPOTHYROIDISM ,STIMULATING HORMONE ,Bone maturation ,MINERAL DENSITY ,Cortical bone ,Tomography, X-Ray Computed ,business ,Biomarkers ,Hormone - Abstract
ContextThe hormonal factors involved in the regulation of peak bone mass (PBM) in men have not been fully investigated. Apart from gonadal steroids and somatotropic hormones, thyroid hormones are known to affect bone maturation and homeostasis and are additional candidate determinants of adult bone mass.ObjectiveWe aimed to investigate between-subject physiological variation in free and total thyroid hormone concentrations, TSH, and thyroid binding globulin (TBG) in relation to parameters of bone mass, geometry, and mineral density in healthy men at the age of PBM.Design and settingWe recruited 677 healthy male siblings aged 25–45 years in a cross-sectional, population-based study. Areal and volumetric bone parameters were determined using dual-energy x-ray absorptiometry (DXA) and peripheral quantitative computed tomography (pQCT). Total and free thyroid hormones, TBG, and TSH were determined using immunoassays.ResultsFree and total thyroid hormone concentrations were inversely associated with bone mineral density (BMD) and bone mineral content (BMC) at the hip and total body (free triiodothyronine (FT3), total T3 (TT3), and total T4 (TT4)) and at the spine (FT3). TBG was negatively associated with BMC and areal BMD at all sites. At the radius, cortical bone area was inversely associated with TT3, TT4, and TBG, and trabecular bone density was inversely associated with free thyroxine, TT4, and TBG. We observed inverse associations between cortical bone area at the mid-tibia and FT3, TT3, TT4, and TBG. No associations between TSH and DXA or pQCT measurements were found.ConclusionIn healthy men at the age of PBM, between-subject variation in thyroid hormone concentrations affects bone density, with higher levels of FT3, TT3, TT4, and TBG being associated with less favorable bone density and content.
- Published
- 2011
26. Sex Hormone-Binding Globulin as an Independent Determinant of Cortical Bone Status in Men at the Age of Peak Bone Mass
- Author
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Jean-Marc Kaufman, Bruno Lapauw, Youri Taes, Hans-Georg Zmierczak, Griet Vanbillemont, Veerle Bogaert, and Stefan Goemaere
- Subjects
Adult ,Leptin ,Male ,Peak bone mass ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Clinical Biochemistry ,Population ,Context (language use) ,Biochemistry ,Bone and Bones ,Cohort Studies ,Absorptiometry, Photon ,Endocrinology ,Sex hormone-binding globulin ,Sex Hormone-Binding Globulin ,Internal medicine ,medicine ,Humans ,Insulin ,Tibia ,Insulin-Like Growth Factor I ,Quantitative computed tomography ,Gonadal Steroid Hormones ,education ,education.field_of_study ,Bone Development ,Anthropometry ,medicine.diagnostic_test ,biology ,business.industry ,Biochemistry (medical) ,Organ Size ,Middle Aged ,Cross-Sectional Studies ,medicine.anatomical_structure ,Body Composition ,Linear Models ,biology.protein ,Cortical bone ,Tomography, X-Ray Computed ,business ,Gonadotropins ,hormones, hormone substitutes, and hormone antagonists ,Hormone - Abstract
Context: Sex steroids are important determinants of the skeletal development, growth, and maintenance after achievement of peak bone mass. A large fraction of these hormones are bound by SHBG, and previous studies have shown that SHBG could be a determinant of bone characteristics.Objective: We investigated associations of serum SHBG levels with cortical and trabecular bone characteristics in young healthy men.Design and Settings: A total of 677 healthy male siblings aged 25–45 yr were recruited in a cross-sectional, population-based study.Main Outcomes: Areal bone parameters were assessed using dual-energy x-ray absorptiometry. Cortical bone parameters at the tibia and radius and trabecular vBMD at the radius were assessed using peripheral quantitative computed tomography. Serum testosterone, estradiol, and SHBG levels were measured using immunoassays.Results: Regression models including age, height, and weight showed that SHBG levels were positively associated with bone area at the hip and the whole body, but not with areal bone mineral density (BMD). Higher SHBG levels were associated with a larger cortical bone area and periosteal and endosteal circumferences at both the tibia and the radius, whereas trabecular volumetric BMD at the radius was negatively associated with SHBG levels. Associations persisted after adjustment for (free) sex steroid levels. No associations were found with cortical volumetric BMD or cortical thickness.Conclusion: In this population of healthy adult men at the age of peak bone mass, SHBG levels were positively associated with cortical bone size, independently from sex-steroid levels. This suggests a possible independent role of SHBG in the determination of adult bone size.
- Published
- 2010
27. ASBMR 31st Annual Meeting SA0001-SA0464
- Author
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Stefan Goemaere, Youri Taes, Jean Kaufman, Bruno Lapauw, and Hans-Georg Zmierczak
- Subjects
Idiopathic osteoporosis ,Trabecular bone ,Pathology ,medicine.medical_specialty ,medicine.anatomical_structure ,business.industry ,Endocrinology, Diabetes and Metabolism ,Medicine ,Orthopedics and Sports Medicine ,Cortical bone ,business - Published
- 2009
28. The decline of serum testosterone levels in community-dwelling men over 70 years of age: descriptive data and predictors of longitudinal changes
- Author
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Youri Taes, Ahmed Mahmoud, Stijn Vansteelandt, Dirk De Bacquer, Stefan Goemaere, Jean Kaufman, I Van Pottelbergh, Hans-Georg Zmierczak, and Bruno Lapauw
- Subjects
Male ,Aging ,medicine.medical_specialty ,Globulin ,medicine.drug_class ,Endocrinology, Diabetes and Metabolism ,Estrogen receptor ,Biology ,Aromatase ,Endocrinology ,Sex hormone-binding globulin ,Predictive Value of Tests ,Residence Characteristics ,Sex Hormone-Binding Globulin ,Internal medicine ,medicine ,Humans ,Insulin ,Testosterone ,Longitudinal Studies ,Insulin-Like Growth Factor I ,Life Style ,Aged ,Aged, 80 and over ,Polymorphism, Genetic ,Estradiol ,Estrogen Receptor alpha ,Testosterone (patch) ,General Medicine ,Luteinizing Hormone ,Anthropometry ,Androgen ,Predictive value of tests ,Body Composition ,biology.protein ,Follicle Stimulating Hormone ,Men's Health ,Hormone - Abstract
ObjectiveThis study was designed to assess longitudinal changes in serum testosterone levels, explore relationships with aging, genetic-, health-, and lifestyle-related factors, and investigate predictors of changes in healthy elderly men.DesignPopulation-based, longitudinal, 4-year observational study in 221 community-dwelling men aged 71–86 years at baseline.MethodsHormone levels assessed by immunoassay, anthropometry, questionnaires on general health, and genetic polymorphisms. Predictors of changes in testosterone levels explored using linear mixed-effects modeling for longitudinal analyses.ResultsTotal testosterone (TT), free testosterone, and bioavailable testosterone (BioT) levels decreased with aging, decreases in BioT being most marked. No changes in sex hormone-binding globulin (SHBG) or estradiol (E2), while LH and FSH levels increased during follow-up. Subjects who gained weight displayed a greater decline in TT levels, mainly due to decreasing SHBG levels. However, baseline body composition was not predictive of subsequent changes in testosterone levels. Baseline E2 (P=0.023 to 0.004), LH (P=0.046 to 0.005), and FSH (PP=0.041–0.035). Carriers of a ‘TA’ haplotype of the estrogen receptor α gene (ERα) PvuII and XbaI polymorphisms displayed a slower decline of TT and BioT (P=0.041–0.007).ConclusionsIn elderly men with already low serum testosterone levels, a further decline was observed, independent of baseline age. The identification of FSH levels as a predictor of this decline appears to reflect the testicular mechanisms of aging-related changes in testosterone production, whereas associations with E2 and ERα polymorphisms are suggestive of estrogen-related processes, possibly related to changes in the neuroendocrine regulation of testosterone production.
- Published
- 2008
29. Comprehensive treatment of dactylitis in psoriatic arthritis
- Author
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Shawn, Rose, Sergio, Toloza, Wilson, Bautista-Molano, Philip S, Helliwell, and Hans-Georg, Zmierczak
- Subjects
Male ,medicine.medical_specialty ,Immunology ,Risk Assessment ,Severity of Illness Index ,Dactylitis ,Psoriatic arthritis ,Biological Factors ,Rheumatology ,Psoriasis ,Finger Joint ,Ustekinumab ,medicine ,Immunology and Allergy ,Humans ,In patient ,Evidence-Based Medicine ,business.industry ,Anti-Inflammatory Agents, Non-Steroidal ,Arthritis, Psoriatic ,medicine.disease ,Prognosis ,Dermatology ,Infliximab ,Systematic review ,Treatment Outcome ,Antirheumatic Agents ,Practice Guidelines as Topic ,Drug Therapy, Combination ,Female ,Antirheumatic drugs ,business ,medicine.drug - Abstract
Dactylitis, a hallmark clinical feature of psoriatic arthritis (PsA) and other spondyloarthropathies, may also be a severity marker for PsA and psoriasis. Traditionally, clinicians have used nonsteroidal antiinflammatory drugs and local corticosteroid injections to treat dactylitis, although conventional disease-modifying antirheumatic drugs are also used. We performed a systematic literature review to determine the most efficacious current treatment options for dactylitis in PsA. Effect sizes were greatest for the biologic agents ustekinumab, certolizumab, and infliximab, suggesting that therapy with one of these agents should be initiated in patients with dactylitis. However, the limited data highlight the need for randomized, placebo-controlled trials, with dactylitis as a primary outcome, to determine a valid, reliable, and responsive clinical outcome measure for PsA patients with dactylitis.
- Published
- 2014
30. Osteoporosis in the aging population: the male perspective
- Author
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Hans-Georg Zmierczak, Jean Kaufman, and Stefan Goemaere
- Subjects
Bone mineral ,Bone geometry ,Fracture risk ,Gerontology ,Gynecology ,Population ageing ,medicine.medical_specialty ,Senile osteoporosis ,business.industry ,Public health ,Osteoporosis ,medicine.disease ,medicine ,Geriatrics and Gerontology ,Risk factor ,business - Abstract
The importance of senile osteoporosis in men as a public health problem has long been underestimated. Elderly men are at substantial risk for fracture, and morbidity after osteoporotic fractures appears to be more serious and mortality more common in men than in women. Risk factors for osteoporotic fractures in men appear to be qualitatively similar to those in women, but there are quantitative differences. Low bone mineral density (BMD) is an important risk factor for fracture in men; however, further clarification of the relationship between BMD, bone geometry and fracture risk is needed before formulating definitive proposals on operational densitometric criteria for diagnosis of osteoporosis in men and the identification of men at high risk for fracture. Understanding of the mechanisms underlying senile bone loss and the pathogenesis of senile osteoporosis in men remains fragmentary with, in particular, the need for further clarification regarding the precise impact of hormonal status in elderly men o...
- Published
- 2001
31. Serum sclerostin levels in men with idiopathic osteoporosis
- Author
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Julien Collette, Sara Vandewalle, Jean-Marc Kaufman, Stefan Goemaere, Youri Taes, Bruno Lapauw, and Hans-Georg Zmierczak
- Subjects
Male ,when adjusting for age ,Endocrinology, Diabetes and Metabolism ,+0%2E11%29%2E+Testosterone%22">neither were sclerostin levels associated with BMC at the radius or lumbar spine (all P > 0.11). Testosterone ,Pathogenesis ,chemistry.chemical_compound ,Endocrinology ,Absorptiometry, Photon ,Medicine and Health Sciences ,Quantitative computed tomography ,Child ,Testosterone ,Bone mineral ,Aged, 80 and over ,medicine.diagnostic_test ,Osteoblast ,General Medicine ,Middle Aged ,medicine.anatomical_structure ,Bone Morphogenetic Proteins ,P < 0.001). In both groups ,+0%2E14%29%2E+In+multivariate+analyses%22">no associations with anthropometrics were observed (P > 0.14). In multivariate analyses ,was inversely related to sclerostin levels in the probands. No difference in sclerostin levels was found in their sons when compared with their controls ,Adult ,Genetic Markers ,as well as with trabecular and cortical volumetric bone mineral density (vBMD) at the tibia in the probands. No clear associations were observed in the control group ,medicine.medical_specialty ,Adolescent ,In 116 men with idiopathic osteoporosis (<= 65 years old) [Methods] ,and volumetric and geometric bone parameters were measured using peripheral quantitative computed tomography. Serum analytes were measured using immunoassays and estradiol (E-2) levels using liquid chromatography-tandem mass spectrometry ,areal bone parameters were measured using dual-energy X-ray absorptiometry ,Men with idiopathic low bone mass had lower levels of sclerostin than the controls (0.54 +/- 0.17 vs 0.66 +/- 0.23 ng/ml [Results] ,Young Adult ,sclerostin levels were strongly associated with age ,but not E-2 ,Internal medicine ,medicine ,Humans ,Lower rather than higher serum sclerostin levels in the probands with idiopathic low bone mass suggest that aberrant sclerostin secretion is not involved in the pathogenesis of low bone mass in these subjects. [Conclusion] ,Tibia ,40 of their sons and healthy controls ,Adaptor Proteins, Signal Transducing ,Aged ,Sclerostin inhibits osteoblast differentiation and bone formation. If aberrant sclerostin action is involved in less efficient bone acquisition in men with idiopathic low bone mass [Objective] ,business.industry ,this might be reflected in higher serum sclerostin levels ,Anthropometry ,sclerostin levels displayed a positive association with whole-body bone mineral content (BMC) and areal BMD (aBMD) ,chemistry ,Sclerostin ,Osteoporosis ,business ,Biomarkers - Abstract
ObjectiveSclerostin inhibits osteoblast differentiation and bone formation. If aberrant sclerostin action is involved in less efficient bone acquisition in men with idiopathic low bone mass, this might be reflected in higher serum sclerostin levels.MethodsIn 116 men with idiopathic osteoporosis (≤65 years old), 40 of their sons and healthy controls, areal bone parameters were measured using dual-energy X-ray absorptiometry, and volumetric and geometric bone parameters were measured using peripheral quantitative computed tomography. Serum analytes were measured using immunoassays and estradiol (E2) levels using liquid chromatography–tandem mass spectrometry.ResultsMen with idiopathic low bone mass had lower levels of sclerostin than the controls (0.54±0.17 vs 0.66±0.23 ng/ml;PP>0.14). In multivariate analyses, sclerostin levels displayed a positive association with whole-body bone mineral content (BMC) and areal BMD (aBMD), as well as with trabecular and cortical volumetric bone mineral density (vBMD) at the tibia in the probands. No clear associations were observed in the control group, neither were sclerostin levels associated with BMC at the radius or lumbar spine (allP>0.11). Testosterone, but not E2, was inversely related to sclerostin levels in the probands. No difference in sclerostin levels was found in their sons when compared with their controls.ConclusionLower rather than higher serum sclerostin levels in the probands with idiopathic low bone mass suggest that aberrant sclerostin secretion is not involved in the pathogenesis of low bone mass in these subjects.
- Published
- 2013
32. Body composition and metabolic parameters are associated with variation in thyroid hormone levels among euthyroid young men
- Author
-
Stefan Goemaere, Greet Roef, Kaatje Toye, Hans-Georg Zmierczak, Jean-Marc Kaufman, Bruno Lapauw, and Youri Taes
- Subjects
Adult ,Leptin ,Male ,medicine.medical_specialty ,Thyroid Hormones ,Endocrinology, Diabetes and Metabolism ,Population ,Thyrotropin ,Thyroglobulin ,Body Mass Index ,Thyroxine-Binding Proteins ,Endocrinology ,Insulin resistance ,Internal medicine ,Sex Hormone-Binding Globulin ,medicine ,Humans ,Euthyroid ,Testosterone ,Insulin-Like Growth Factor I ,education ,education.field_of_study ,Triiodothyronine ,Estradiol ,business.industry ,Thyroid disease ,Thyroid ,Membrane Proteins ,Confounding Factors, Epidemiologic ,General Medicine ,Middle Aged ,medicine.disease ,Thyroxine ,medicine.anatomical_structure ,Cross-Sectional Studies ,Insulin-Like Growth Factor Binding Protein 3 ,Adipose Tissue ,Lean body mass ,Body Composition ,Insulin Resistance ,business ,Carrier Proteins ,Biomarkers ,Hormone - Abstract
Objective Thyroid disorders affect metabolism and body composition. Existing literature has been conflicting on whether this is also the case for thyroid hormone levels within the euthyroid range. Therefore, we have investigated the relationship between thyroid hormone concentrations and body composition together with metabolic parameters in a population of healthy euthyroid men. Methods Healthy male siblings (n=941, 25–45 years, median BMI 24.6) were recruited in a cross-sectional, population-based study; a history or treatment of thyroid disease and thyroid autoimmunity were exclusion criteria. Body composition and muscle cross-sectional area were assessed by dual-energy X-ray absorptiometry and peripheral quantitative computed tomography. Total (triiodothyronine (T3; TT3) thyroxine and (T4; TT4)) and free thyroid hormones (FT3 and FT4), TSH, and reverse T3 (rT3) and thyroid-binding globulin (TBG) were determined using immunoassays. Results BMI was positively associated with (F)T3 (P3 and with (F)T4 and TBG (P≤0.0006). Positive associations were further observed between leptin and (F)T3, TT4, and TBG (P≤0.0002). Inverse associations between lean mass and muscle cross-sectional area and (F)T3, (F)T4, and TBG were observed (P≤0.0003). Higher levels of (F)T3 and TBG were associated with lower insulin sensitivity, assessed by homeostatic model assessment of insulin resistance (IR; P≤0.0001). No associations between TSH and body composition or metabolic parameters were seen. Conclusion We show that a less favorable body composition (with higher fat and lower muscle mass and accompanying higher leptin concentrations) and IR are associated with higher thyroid hormone levels in healthy young men with well characterized euthyroidism.
- Published
- 2012
33. Genetic variation in the TNFRSF11A gene encoding RANK is associated with susceptibility to Paget's disease of bone
- Author
-
Stuart H. Ralston, Anna Daroszewska, Philip Riches, Steven Boonen, Hans-Georg Zmierczak, Liesbeth Van Wesenbeeck, Jan Van Offel, Jean-Pierre Devogelaer, Erik Fransen, Fenna de Freitas, Marcel Karperien, Pui Yan Jenny Chung, Piet Geusens, Wim Van Hul, Stefan Goemaere, Filip Vanhoenacker, Karen Jennes, Socrates E. Papapoulos, René Westhovens, Greet Beyens, Leon Verbruggen, Internal Medicine Specializations, Interne Geneeskunde, and RS: CAPHRI School for Public Health and Primary Care
- Subjects
Adult ,Male ,Quality Control ,Genetic variants ,Endocrinology, Diabetes and Metabolism ,Single-nucleotide polymorphism ,Disease ,Biology ,Genetic analysis ,Polymorphism, Single Nucleotide ,Belgium ,Meta-Analysis as Topic ,Genes, Reporter ,Genetic variation ,medicine ,SNP ,TNFRSF11A RANK PAGET'S DISEASE OF BONE GENETIC VARIANTS SEX-DEPENDENT EFFECT familial expansile osteolysis chromosome 18q sqstm1 mutations measles-virus postmenopausal women sequestosome-1 gene functional-analysis tandem duplication domain mutations british descent ,Humans ,Orthopedics and Sports Medicine ,Genetic Predisposition to Disease ,Luciferases ,Aged ,Genetics ,Aged, 80 and over ,Receptor Activator of Nuclear Factor-kappa B ,Haplotype ,NF-kappa B ,TNFRSF11A ,Genetic Variation ,Reproducibility of Results ,Osteopetrosis ,Exons ,Sequence Analysis, DNA ,Middle Aged ,medicine.disease ,Osteitis Deformans ,Rank ,Introns ,sex-dependent effect ,Paget's disease of bone ,Genetics, Population ,Haplotypes ,METIS-273457 ,Female ,Human medicine - Abstract
RANK (receptor activator of nuclear factor-κB), encoded by TNFRSF11A, is a key protein in osteoclastogenesis. TNFRSF11A mutations cause Paget's disease of bone (PDB)–like diseases (ie, familial expansile osteolysis, expansile skeletal hyperphosphatasia, and early-onset PDB) and an osteoclast-poor form of osteopetrosis. However, no TNFRSF11A mutations have been found in classic PDB, neither in familial nor in isolated cases. To investigate the possible relationship between TNFRSF11A polymorphisms and sporadic PDB, we conducted an association study including 32 single-nucleotide polymorphisms (SNPs) in 196 Belgian sporadic PDB patients and 212 control individuals. Thirteen SNPs and 3 multimarker tests (MMTs) turned out to have a p value of between .036 and 3.17 × 10−4, with the major effect coming from females. Moreover, 6 SNPs and 1 MMT withstood the Bonferroni correction (p
- Published
- 2010
34. The majority of the genetic risk for Pagets disease of bone is explained by genetic variants close to the **CSF1**, **OPTN**, **TM7SF4**, and **TNFRSF11A** genes
- Author
-
Greet Beyens, Leon Verbruggen, Stefan Goemaere, Erik Fransen, Filip Vanhoenacker, Pui Yan Jenny Chung, Rene Westhovens, Wim Van Hul, Piet Geusens, Steven Boonen, Socrates E. Papapoulos, Marcel Karperien, Hans-Georg Zmierczak, Jan Van Offel, Jean-Pierre Devogelaer, Interne Geneeskunde, RS: CAPHRI School for Public Health and Primary Care, Internal Medicine Specializations, and Faculty of Science and Technology
- Subjects
Adult ,Male ,Familial aggregation ,Candidate gene ,IR-58571 ,SQSTM1 mutations ,Cell Cycle Proteins ,Genome-wide association study ,Single-nucleotide polymorphism ,Biology ,Polymorphism, Single Nucleotide ,Transcription Factor TFIIIA ,Genetics ,medicine ,Humans ,Genetic Predisposition to Disease ,Gene ,Genetics (clinical) ,Adaptor Proteins, Signal Transducing ,Aged ,Genetic association ,METIS-273440 ,Aged, 80 and over ,Receptor Activator of Nuclear Factor-kappa B ,Chromosome 18Q ,Macrophage Colony-Stimulating Factor ,Osteoclast formation ,nf-kappa-b ubiquitin-associated domain sqstm1 mutations uba domain familial aggregation chromosome 18q osteoclast formation sequestosome-1 gene functional-analysis british descent ,Haplotype ,Membrane Proteins ,Membrane Transport Proteins ,Ubiquitin-associated domain ,Middle Aged ,NF-Kappa-B ,Osteitis Deformans ,medicine.disease ,Paget's disease of bone ,Haplotypes ,UBA domain ,Chromosomal region ,Female ,Human medicine ,Genome-Wide Association Study - Abstract
Paget's disease of bone (PDB) is one of the most frequent metabolic bone disorders (1-5%), next to osteoporosis, affecting individuals above age 55. Sequestosome1 mutations explain a part of the PDB patients, but still the disease pathogenesis in the remaining PDB patients is largely unknown. Therefore, association studies investigating the relationship between genetic polymorphisms and sporadic PDB have been performed to find the genetic risk variants. Previously such studies indicated a role of the OPG and RANK gene. The latter was recently confirmed in a genome-wide association study (GWAS) which also indicated the involvement of chromosomal regions harbouring the CSF1 and OPTN gene. In this study, we sought to replicate these findings in a Belgian and a Dutch population. Similar significant results were obtained for the single nucleotide polymorphisms and the haplotypes. The most significant results are found in the CSF1 gene region, followed by the OPTN and TNFRSF11A gene region (p values ranging from 1.3 × 10(-4) to 3.8 × 10(-8), OR = 1.523-1.858). We next obtained significant association with a polymorphism from the chromosomal region around the TM7SF4 gene (p = 2.7 × 10(-3), OR = 1.427), encoding DC-STAMP which did not reach genome-wide significance in the GWAS, but based on its function in osteoclasts it can be considered a strong candidate gene. After meta-analysis with the GWAS data, p values ranged between 2.6 × 10(-4) and 8.8 × 10(-32). The calculated cumulative population attributable risk of these four loci turned out to be about 67% in our two populations, indicating that most of the genetic risk for PDB is coming from genetic variants close to these four genes.
- Published
- 2010
35. Anthropometric and skeletal phenotype in men with idiopathic osteoporosis and their sons is consistent with deficient estrogen action during maturation
- Author
-
Kaatje Toye, Stefan Goemaere, Bruno Lapauw, Jean-Marc Kaufman, Hans-Georg Zmierczak, and Youri Taes
- Subjects
Adult ,Male ,medicine.medical_specialty ,Aging ,Appendicular skeleton ,medicine.drug_class ,Endocrinology, Diabetes and Metabolism ,Clinical Biochemistry ,Osteoporosis ,Context (language use) ,Biochemistry ,Bone and Bones ,Functional Laterality ,Bone remodeling ,Body Mass Index ,Endocrinology ,Sex hormone-binding globulin ,Internal medicine ,Sex Hormone-Binding Globulin ,Medicine ,Humans ,Testosterone ,Femur ,Quantitative computed tomography ,Femoral neck ,biology ,medicine.diagnostic_test ,Anthropometry ,Estradiol ,Tibia ,business.industry ,Hypogonadism ,Biochemistry (medical) ,Estrogens ,Middle Aged ,medicine.disease ,Spine ,Radius ,medicine.anatomical_structure ,Cross-Sectional Studies ,Estrogen ,biology.protein ,Body Composition ,business - Abstract
Pathophysiology of deficient bone mass acquisition in male idiopathic osteoporosis (IO) remains poorly understood.Our objective was to investigate volumetric and geometric parameters of the appendicular skeleton, biochemical markers, and anthropometrics in men with IO.Our cross-sectional study included 107 men diagnosed with idiopathic low bone mass, 23 of their adult sons, and 130 age-matched controls.Body composition and areal bone parameters (dual-energy x-ray absorptiometry) and volumetric and geometric parameters of radius and tibia (peripheral quantitative computed tomography) were assessed. Serum levels of testosterone, estradiol (E(2)), and SHBG, and bone turnover markers were measured using immunoassays. Free hormone fractions were calculated.Men with idiopathic low bone mass had lower weight (-9.6%), truncal height (-3.3%), and upper/lower body segment ratio (-2.7%; all P0.001) and presented at the radius and tibia lower trabecular (-19.0 and -23.6%, respectively; both P0.001) and cortical volumetric bone mineral density (vBMD) (-2.4 and -1.7%; both P0.001) and smaller cortical areas (-9.7 and -13.6%; both P0.001) and thicknesses (-13.5 and -14.5%, both P0.001) due to larger endosteal circumferences (+11.8 and +7.4%, both P0.001) than controls. Furthermore, (free) E(2) was lower and SHBG higher (both P0.01). Their sons had lower trabecular vBMD (-10.3%, P = 0.036) and a thinner cortex (-8.3%, P = 0.024) at the radius.Bone mass deficits in men with idiopathic low bone mass involve trabecular and cortical bone, resulting from lower vBMD and smaller cortical bone cross-sectional areas and thicknesses. A similar bone phenotype is present in at least part of their sons. The lower E(2), together with characteristics as lower upper/lower body segment ratio, larger endosteal circumferences and lower vBMD, may indicate an estrogen-related factor in the pathogenesis of male IO.
- Published
- 2009
36. Serum estradiol is associated with volumetric BMD and modulates the impact of physical activity on bone size at the age of peak bone mass: a study in healthy male siblings
- Author
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Griet Vanbillemont, Veerle Bogaert, Jean-Marc Kaufman, Hans-Georg Zmierczak, Stefan Goemaere, Youri Taes, Bruno Lapauw, and Dirk De Bacquer
- Subjects
Peak bone mass ,Adult ,Male ,medicine.medical_specialty ,medicine.drug_class ,Endocrinology, Diabetes and Metabolism ,Population ,Physical exercise ,Biceps ,Bone and Bones ,Absorptiometry, Photon ,Bone Density ,Internal medicine ,medicine ,Humans ,Orthopedics and Sports Medicine ,Tibia ,Quantitative computed tomography ,education ,Exercise ,education.field_of_study ,medicine.diagnostic_test ,Estradiol ,business.industry ,Bone age ,Organ Size ,Middle Aged ,Endocrinology ,Estrogen ,business - Abstract
This study investigates determinants of peak bone mass (PBM) in healthy men, focusing on effects and interactions of parameters reflecting mechanical loading and sex steroids. Healthy male siblings (n = 677; 25-45 yr) were recruited in a cross-sectional, population-based study. Physical activity score was assessed by a self-reported questionnaire. Cross-sectional muscle area (CSMA) and bone parameters of radius (4% and 66% site) and tibia (66% site) were assessed using pQCT. Peak torque of biceps and quadriceps muscles was assessed by isokinetic dynamometry. Serum testosterone (T) and estradiol (E(2)) levels were measured using immunoassays; free hormone fractions were calculated. Relations between indices of bone strength, CSMA, muscle strength, and sex steroids were studied using linear mixed-effects modeling. Physical activity, CSMA, and muscle strength were positively associated with indices of bone strength, except for volumetric BMD (vBMD). After controlling for age, weight, and height, free E(2) levels were positively associated with trabecular and cortical vBMD, negatively associated with endosteal circumference at the radius, and positively associated with cortical vBMD at the tibia. In addition, positive interactions between physical activity and serum E(2) concentrations were observed for bone size at the tibia. No associations between free T levels and pQCT bone parameters were found. In this population of healthy men at the age of PBM, parameters reflecting mechanical loading are confirmed as important determinants of bone size. E(2), but not T, levels are positively associated with vBMD and modulate the impact of physical activity on bone size at the tibia.
- Published
- 2008
37. Founder effect in different European countries for the recurrent P392L **SQSTM1** mutation in Paget's disease of bone
- Author
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Pui Yan Jenny Chung, Liesbeth Van Wesenbeeck, Karen Jennes, Greet Beyens, Rene Westhovens, Wim Van Hul, Marcel Karperien, Jan Van Offel, Marelise E. M. W. Eekhoff, Hans-Georg Zmierczak, Erwin Offeciers, Jean-Pierre Devogelaer, Steven Boonen, Socrates E. Papapoulos, Núria Guañabens, Piet Geusens, Internal medicine, and Faculty of Science and Technology
- Subjects
Endocrinology, Diabetes and Metabolism ,DNA Mutational Analysis ,Single-nucleotide polymorphism ,Biology ,Polymorphism, Single Nucleotide ,White People ,Endocrinology ,Sequestosome-1 Protein ,medicine ,Humans ,Orthopedics and Sports Medicine ,Mutation frequency ,Adaptor Proteins, Signal Transducing ,Genetics ,Genetic heterogeneity ,Haplotype ,IR-83265 ,METIS-253646 ,Osteitis Deformans ,medicine.disease ,Founder Effect ,Europe ,Paget's disease of bone ,Haplotypes ,Mutation ,Mutation (genetic algorithm) ,Mutation testing ,Human medicine ,Founder effect - Abstract
Paget's Disease of Bone (PDB) is one of the most frequent metabolic bone diseases, affecting 1-5% of Western populations older than 55 years. Mutations in the sequestosome1 (SQSTM1) gene cause PDB in about one-third of familial PDB cases and in 2.4-9.3% of nonfamilial PDB cases, with the 1215C→T (P392L) mutation being the most frequent one. We investigated whether a founder effect of the P392L SQSTM1 mutation was present in Belgian (n = 233), Dutch (n = 82), and Spanish (n = 64) patients without a PDB family history. First, direct sequencing analysis of exon 8 in these three populations showed that the P392L mutation occurred in 17 Belgian patients (7.3%), three Dutch patients without a family history (3.7%), and two Dutch patients with a family history. In the Spanish population, 15.6% of patients (n = 10) had the P392L mutation, including one homozygous mutant. This is by far the highest mutation frequency of all populations investigated so far. Next, we examined the genetic background of 33 mutated chromosomes by analyzing haplotypes. We genotyped four single-nucleotide polymorphisms (SNPs) in exon 6 and the 3′-untranslated region of SQSTM1 (rs4935C/T, rs4797G/A, rs10277T/C, and rs1065154G/T) and used software programs WHAP and PHASE to reconstruct haplotypes. Finally, allele-specific primers allowed us to assign the mutation to one of the two haplotypes from each individual. Sequencing results revealed that all 33 P392L mutations were on the CGTG (H2) haplotype. The chance to obtain this result due to 33 independent mutation events is 3.97 × 10-14, providing strong evidence for a founder effect of the P392L SQSTM1 mutation in Belgian, Dutch, and Spanish patients with PDB.
- Published
- 2008
38. Part of the interindividual variation in serum testosterone levels in healthy men reflects differences in androgen sensitivity and feedback set point: contribution of the androgen receptor polyglutamine tract polymorphism
- Author
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Veerle Bogaert, Patricia Crabbe, Jean Kaufman, Dirk De Bacquer, Stefan Goemaere, and Hans-Georg Zmierczak
- Subjects
Adult ,Male ,medicine.medical_specialty ,medicine.drug_class ,Endocrinology, Diabetes and Metabolism ,Clinical Biochemistry ,Population ,Context (language use) ,Biology ,Biochemistry ,Endocrinology ,Polymorphism (computer science) ,Internal medicine ,medicine ,Medicine and Health Sciences ,Humans ,Testosterone ,education ,Feedback, Physiological ,Observer Variation ,education.field_of_study ,Polymorphism, Genetic ,Biochemistry (medical) ,Polyglutamine tract ,Middle Aged ,Androgen ,Androgen receptor ,Cross-Sectional Studies ,Receptors, Androgen ,Androgens ,Peptides ,Pharmacogenetics - Abstract
There is a large interindividual variation in serum (free) testosterone (FT) levels in men, underlain in part by genetic components.The objective of the study was to explore the hypothesis that this variability results in part from differences in androgen sensitivity and feedback loop set point and assess the role of the androgen receptor (AR) polyglutamine tract polymorphism encoded by a CAG repeat of variable length in exon 1 of the AR gene.We performed a cross-sectional analysis in two independent populations of healthy men, consisting of 2322 men aged 35-59 yr (Belstress study) and 358 men aged 25-45 yr (Siblos study), respectively.Serum hormonal levels and the AR gene CAG repeat length were determined.In the Belstress population, serum testosterone and calculated FT showed a positive linear association with LH (P0.001). In the 200 men with lowest FT, CAG repeat number was lower than in the 200 men with highest FT (P = 0.004). As studied in a larger subset of the population consisting of 857 men covering the whole FT range, FT increased progressively with CAG repeat length (P = 0.003). These findings of a positive relation of FT with both LH and CAG repeat length were confirmed in the Siblos study population (both Por = 0.001). Difference in FT between extreme quartiles of CAG repeat was 10 and 14% in the Belstress and Siblos study, respectively. In both study populations, CAG repeat length was also positively associated with serum total testosterone (Por = 0.004).The data support the view that between-subject variability in serum FT in healthy men is underlain in part by differences in androgen sensitivity and feedback set point, with a contributory role of AR polymorphism. These findings have potential implications for the interpretation of epidemiological studies, diagnosis of hypogonadism, and pharmacogenetics of androgen treatment in men.
- Published
- 2007
39. Identification of sex-specific associations between polymorphisms of the osteoprotegerin gene, TNFRSF11B, and Paget's disease of bone
- Author
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Wim Van Hul, Filip Vanhoenacker, René Westhovens, Erik Fransen, Fenna de Freitas, Anna Daroszewska, Hans-Georg Zmierczak, Greet Beyens, Jan Van Offel, Leon Verbruggen, Jean-Pierre Devogelaer, Stuart H. Ralston, and Internal Medicine Specializations
- Subjects
Male ,Ubiquitin binding ,Endocrinology, Diabetes and Metabolism ,Population ,Single-nucleotide polymorphism ,Biology ,association study ,Polymorphism, Single Nucleotide ,Belgium ,Meta-Analysis as Topic ,medicine ,TNFRSF11B ,Humans ,Orthopedics and Sports Medicine ,Genetic Predisposition to Disease ,International HapMap Project ,education ,Genotyping ,Aged ,HapMap SNP selection ,Genetics ,Aged, 80 and over ,education.field_of_study ,Sex Characteristics ,Haplotype ,Exons ,Middle Aged ,medicine.disease ,Osteitis Deformans ,United Kingdom ,Paget's disease of bone ,Haplotypes ,osteoprotegerin ,Population study ,Female ,Biomarkers - Abstract
We studied the role of TNFRSF11B polymorphisms on the risk to develop Paget's disease of bone in a Belgian study population. We observed no association in men, but a highly significant association was found in women, and this was confirmed in a population from the United Kingdom. Introduction: Juvenile Paget's disease has been shown to be caused by mutations in TNFRSF11B encoding osteoprotegerin. Although mutations in this gene have never been found in patients with typical Paget's disease of bone (PDB), there are indications that polymorphisms in TNFRSF11B might contribute to the risk of developing PDB. Materials and Methods: We recruited a population of 131 Belgian patients with sporadic PDB and 171 Belgian controls. By means of the HapMap, we selected 17 SNPs that, in combination with four multimarker tests, contain most information on common genetic variation in TNFRSF11B. To replicate the findings observed in the Belgian study population, genotyping data of SNPs generated in a UK population were reanalyzed. Results: In our Belgian study population, associations were found for two SNPs (rs11573871, rs1485286) and for one multimarker test involving rs1032129. When subsequently analyzing men and women separately, these associations turned out to be driven by women (56 cases, 78 controls). In addition, three other tagSNPs turned out to be associated in women only. These were rs2073617 (C950T), rs6415470, and rs11573869. Reanalysis of genotyping data from a UK study population indicated that the associations found for C950T and C1181G were also exclusively driven by women (146 cases, 216 controls). Meta-analysis provided evidence for risk increasing effects of the T allele of C950T and the G allele of C1181G in the female population (p = 0.002 and 0.003, respectively). The haplotypes formed by the SNPs associated in the Belgian population were also distributed differentially between female cases and controls. Conclusions: We showed for the first time that SNPs influencing the risk to develop PDB could be sex-specific. Further research is necessary to identify the causative variants in TNFRSF11B and to elucidate the molecular pathogenic mechanism.
- Published
- 2007
40. Problems with the definition of axial and peripheral disease patterns in psoriatic arthritis
- Author
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William J, Taylor, Hans-Georg, Zmierczak, and Philip S, Helliwell
- Subjects
Diagnosis, Differential ,Arthritis, Psoriatic ,Humans ,Joints ,Spondylitis, Ankylosing - Published
- 2005
41. Perturbed sex steroid status in men with idiopathic osteoporosis and their sons
- Author
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Stefan Goemaere, Jean Kaufman, I Van Pottelbergh, and Hans-Georg Zmierczak
- Subjects
Peak bone mass ,Adult ,Male ,congenital, hereditary, and neonatal diseases and abnormalities ,medicine.medical_specialty ,Bone density ,Genotype ,Endocrinology, Diabetes and Metabolism ,Clinical Biochemistry ,Osteoporosis ,Biochemistry ,Nuclear Family ,Endocrinology ,Sex hormone-binding globulin ,Aromatase ,Polymorphism (computer science) ,Bone Density ,Internal medicine ,Sex Hormone-Binding Globulin ,medicine ,Humans ,Testosterone ,Femoral neck ,Bone mineral ,biology ,Estradiol ,Chemistry ,Biochemistry (medical) ,Middle Aged ,medicine.disease ,medicine.anatomical_structure ,biology.protein ,Regression Analysis ,Body mass index - Abstract
We reported previously that a gender-specific defect of acquisition of lumbar bone mass plays an important role in the pathogenesis of male idiopathic osteoporosis (IO) and that there is a strong heritability of this maturational defect, which is particularly manifest in sons of men with IO. A hypothetical role of an altered sex steroid status and/or of a (TTTA)(n)- repeat polymorphism of the aromatase (CYP19) gene in male IO remains to be established. We evaluated bone mineral density (BMD) at the lumbar spine and femoral neck in 64 male IO probands (selected on the basis of a z-score of -2 or less), 21 of their sons, 41 of their brothers, and 126 healthy, age-matched controls. Serum testosterone (T), estradiol (E(2)), and SHBG levels were measured by immunoassays. Free T (FT) and free E(2) (FE(2)) levels were calculated from total T, E(2), SHBG, and albumin concentrations using a previously validated equation. Probands, sons, and brothers had lower body weight than age-matched controls, with mean differences of 5.0, 4.6, and 4.0 kg, respectively. In probands, sons, and brothers, SHBG levels were higher compared with controls. Significantly lower FE(2) levels were observed in probands and sons compared with their respective controls (P < 0.05 and P < 0.01, respectively). The brothers had nonsignificantly lower FE(2) levels compared with their controls. In the total group of sons with significantly lower FE(2) levels, tertile analysis according to lumbar spine BMD showed that only in the subgroup of sons belonging to the lowest tertile both FE(2) and FT were decreased compared with their controls. The differences in FE(2) levels in IO probands and their sons remained significant after adjustment for body mass index (BMI), even though in multivariate analyses BMI was a major determinant of BMD. The frequency distribution of the CYP19 gene (TTTA)(n)- repeat length (determined by fragment analysis, GeneScan) was not different between men with IO and their controls. In conclusion, the finding of a relative FE(2) deficit in both men with IO as well as their affected sons, even after adjustment for BMI, suggests that estrogen-related perturbances may be involved in the pathogenesis of the deficient acquisition of peak bone mass in male IO.
- Published
- 2004
42. Candida glabrata arthritis: case report and review of the literature of Candida arthritis
- Author
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G. Verbruggen, Herman Mielants, Eric Veys, Hans-Georg Zmierczak, and Stefan Goemaere
- Subjects
Adult ,Male ,medicine.medical_specialty ,medicine.drug_class ,Itraconazole ,Arthritis ,Injections, Intra-Articular ,Rheumatology ,Internal medicine ,Amphotericin B ,Synovial Fluid ,Medicine ,Humans ,Candida ,First episode ,Arthritis, Infectious ,Candida glabrata ,biology ,business.industry ,Candidiasis ,General Medicine ,biology.organism_classification ,medicine.disease ,Surgery ,Radiography ,Corticosteroid ,business ,Fluconazole ,Ankle Joint ,medicine.drug - Abstract
We report a case of arthritis due to Candida (Torulopsis) glabrata in two different joints at different times in the same patient. The first episode of arthritis was situated in the right ankle and lasted more than 1 year before the patient agreed to the proposed treatment. Therapy with intravenous amphotericin B and oral fluconazole failed. A cure was achieved with weekly intra-articular administration of amphotericin B, which was continued for more than 20 weeks and combined with oral itraconazole. Several weeks later the patient developed Candida glabrata arthritis of the left knee while still taking itraconazole. Immediately, intravenous amphotericin B therapy was started and was successful. Because there were no previous invasive point manipulations or trauma, the infections were considered to be haematogenously disseminated. Chronic corticosteroid and repeated antibiotic therapy for infectious exacerbations of chronic obstructive pulmonary disease and alcohol abuse are the presumed risk factors in this otherwise immunocompetent patient.
- Published
- 1999
43. Thyroid hormone status within the euthyroid range is associated with bone mass and density in healthy young men at the age of peak bone mass
- Author
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Jean Kaufman, Greet Roef, Hans-Georg Zmierczak, Bruno Lapauw, Stefan Goemaere, Youri Taes, and Tom Fiers
- Subjects
Peak bone mass ,medicine.medical_specialty ,Histology ,Physiology ,Range (biology) ,business.industry ,Endocrinology, Diabetes and Metabolism ,Thyroid ,Endocrinology ,medicine.anatomical_structure ,Internal medicine ,medicine ,Euthyroid ,business ,Bone mass ,Hormone - Published
- 2011
44. Cortical bone geometry in relation to prevalent fractures in young healthy men at age of peak bone mass
- Author
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Griet Vanbillemont, Bruno Lapauw, Greet Roef, Stefan Goemaere, Jean Kaufman, Hans-Georg Zmierczak, and Youri Taes
- Subjects
Orthodontics ,Peak bone mass ,Histology ,medicine.anatomical_structure ,Physiology ,business.industry ,Endocrinology, Diabetes and Metabolism ,Medicine ,Dentistry ,Cortical bone ,business - Published
- 2010
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