Publikationen

Long-term Effects of Severe Burn Injury on Bone Turnover and Microarchitecture. J Bone Miner Res. 2017

Muschitz GK, Schwabegger E, Kocijan R, Baierl A, , Fochtmann A, Nickl S, , Haschka J, Resch H, Rath T, Pietschmann P, Muschitz C. Long-term Effects of Severe Burn Injury on Bone Turnover and Microarchitecture.

J Bone Miner Res. 2017

6,284

Impact Factor

Overlapping and Continued Alendronate or Raloxifene Administration in Patients on Teriparatide:
Effects on Areal and Volumetric Bone Mineral Density The CONFORS Study.

Muschitz C, Kocijan R, Fahrleitner-Pammer A, Pavo I, Haschka J, Schima W, Kapiotis S, Resch H.

J Bone Miner Res. 2014 Mar 11. doi: 10.1002/jbmr.2216. [Epub ahead of print]

Context

Nine month teriparatide (TPTD) monotherapy followed by co-administration of raloxifene (RAL) or alendronate (ALN) for another nine months resulted in incremental bone mineral density (BMD) increase. The aim of this study was to investigate the effects of continued antiresorptive treatments for 12 months in the extension phase. Postmenopausal women (n = 125) with severe osteoporosis on ongoing TPTD treatment for 9 months were randomized into three open-label groups for another 9 months: ALN (70 mg/week, n = 41), RAL (60 mg/d, n = 37) in addition to TPTD or no additional medication (n = 47) except Ca and vitamin D. After discontinuation of TPTD the respective antiresorptives were continued for a further 12 months, while patients in the TPTD monotherapy group received Ca and vitamin D. Amino-terminal propeptide of type I procollagen (P1NP) and cross-linked C-telopeptide (CTX), areal and volumetric BMD at the lumbar spine (LS) and hip were assessed. ALN resulted in continued BMD increase in LS (4.3 ± 1.5%; mean ± SD), femoral neck (4.2 ± 1.6%) and total hip (4 ± 1.6%; p < 0.001 for all), while RAL was only effective at the LS (2.4 ± 1.7%, p < 0.001) but no changes at the femoral neck (0.4 ± 1.4%) and small decrease in total hip (-0.8 ± 1.5%, p < 0.005) were observed. Cortical bone increased in the ALN group only (femoral neck 6.7  ±  2.7%vs. - 1.3 ± 2.5%; total hip 6.8 ± 2.6% vs. -2.3 ± 2.5% for ALN vs. RAL, p < 0.001 for both comparisons). Analyzing the entire 30 months of therapy, the ALN group revealed the largest BMD increase in all regions. Our results suggest that the addition of ALN to ongoing TPTD and continuing ALN after TPTD was stopped may be beneficial for patients in terms of areal and volumetric BMD increase. Further research is warranted to determine the optimal timing of the initiation of the combination treatment, the respective antiresorptive medication and the potential benefit of this BMD increase regarding fracture prevention. © 2014 American Society for Bone and Mineral Research. [/av_toggle] [/av_toggle_container] [/av_four_fifth] [av_one_fifth min_height='' vertical_alignment='' space='' custom_margin='' margin='0px' padding='0px' border='' border_color='' radius='0px' background_color='' src='' background_position='top left' background_repeat='no-repeat' animation='' mobile_breaking='' mobile_display=''] [av_animated_numbers number='6,128' icon_select='no' icon='ue800' font='entypo-fontello' font_size='' font_size_description='' link='' linktarget='no' color='' custom_color='#444444' admin_preview_bg=''] Impact Factor [/av_animated_numbers] [/av_one_fifth] [av_hr class='custom' height='50' shadow='no-shadow' position='center' custom_border='av-border-fat' custom_width='50px' custom_border_color='#f2f2f2' custom_margin_top='50px' custom_margin_bottom='80px' icon_select='no' custom_icon_color='#f2f2f2' icon='ue89a' font='entypo-fontello' admin_preview_bg=''] [av_four_fifth first min_height='' vertical_alignment='' space='' custom_margin='' margin='0px' padding='0px' border='' border_color='' radius='0px' background_color='' src='' background_position='top left' background_repeat='no-repeat' animation='' mobile_breaking='' mobile_display=''] [av_textblock size='' font_color='' color='' av-medium-font-size='' av-small-font-size='' av-mini-font-size='' admin_preview_bg='']
Serum sclerostin levels are decreased in adult patients with different types of osteogenesis imperfecta.

Kocijan R, Muschitz C, Fahrleitner-Pammer A, Amrein K, Pietschmann P, Haschka J, Dinu S, Kapiotis S, Resch H.

J Clin Endocrinol Metab. 2014 Feb;99(2):E311-9. doi: 10.1210/jc.2013-2244. Epub 2013 Nov 7
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Abstract

Context: There are no specific biochemical bone markers available for osteogenesis imperfecta (OI), and the role of sclerostin as a key regulator of bone formation in OI is unknown.

Objectives: We aimed to evaluate the role of sclerostin and its association with bone turnover markers as well as body composition parameters in adult patients with different types of OI.

Design, Setting, and Participants: This was a case-control study in 27 adult patients and 50 healthy age- and gender-matched controls.

Main Outcome Measures: Serum sclerostin levels and bone turnover markers including serum osteocalcin, amino terminal propeptide of type I procollagen, and CrossLaps as well as body composition parameters were determined in mild OI stage I (OI-I) and moderate-severe OI stages III-IV (OI-III-IV), according to Sillence classification. Data were compared with healthy controls.

Results: Sclerostin levels were significantly lower in OI-I (19.9 ± 10.9 pmol/L; P < .001) and OI-III-IV (13.3 ± 10.0 pmol/L; P < .001) compared with healthy adults (45.3 ± 14.9 pmol/L), even after adjustment for age, sex, bone mineral content, and body mass index. CrossLaps and PTH were significantly lower in OI-I (0.197 ± 0.15 ng/L; P = .007 and 33.7 ± 19.1 pg/L; P = .033, respectively) and OI-III-IV (0.221 ± 0.18 ng/L; P = .039, and 27.9 ± 14.7 pg/L; P = .001, respectively) than in healthy controls (0.322 ± 0.15 ng/L and 45.0 ± 16.6 pg/L). Amino-terminal propeptide of type I procollagen was below the reference range for OI-I and OI-III-IV. Patients with OI were shorter and lighter and had a decreased bone mineral content (P < .001) but similar fat distribution and lean body mass, compared with controls. Serum sclerostin levels were not related to any bone marker except osteocalcin, the number of prevalent fractures, or body composition readings. Conclusion: Decreased sclerostin levels in OI might reflect a down-regulation or negative feedback mechanism to prevent further bone loss. [/av_toggle] [/av_toggle_container] [/av_four_fifth] [av_one_fifth min_height='' vertical_alignment='' space='' custom_margin='' margin='0px' padding='0px' border='' border_color='' radius='0px' background_color='' src='' background_position='top left' background_repeat='no-repeat' animation='' mobile_breaking='' mobile_display=''] [av_animated_numbers number='6,430' icon_select='no' icon='ue800' font='entypo-fontello' font_size='' font_size_description='' link='' linktarget='no' color='' custom_color='#444444' admin_preview_bg=''] Impact Factor [/av_animated_numbers] [av_hr class='invisible' height='20' shadow='no-shadow' position='center' custom_border='av-border-thin' custom_width='50px' custom_border_color='' custom_margin_top='30px' custom_margin_bottom='30px' icon_select='yes' custom_icon_color='' icon='ue808' font='entypo-fontello' admin_preview_bg=''] [av_button label='PDF' link='manually,http://muschitz.info/christian/wp-content/uploads/2017/11/Kocijan_JCEM.pdf' link_target='_blank' size='small' position='center' icon_select='yes' icon='ue84c' font='entypo-fontello' color='theme-color' custom_bg='#444444' custom_font='#ffffff' admin_preview_bg=''] [/av_one_fifth] [av_hr class='custom' height='50' shadow='no-shadow' position='center' custom_border='av-border-fat' custom_width='50px' custom_border_color='#f2f2f2' custom_margin_top='50px' custom_margin_bottom='80px' icon_select='no' custom_icon_color='#f2f2f2' icon='ue89a' font='entypo-fontello' admin_preview_bg=''] [av_four_fifth first min_height='' vertical_alignment='' space='' custom_margin='' margin='0px' padding='0px' border='' border_color='' radius='0px' background_color='' src='' background_position='top left' background_repeat='no-repeat' animation='' mobile_breaking='' mobile_display=''] [av_textblock size='' font_color='' color='' av-medium-font-size='' av-small-font-size='' av-mini-font-size='' admin_preview_bg='']

Ibandronate treatment of 24 months normalizes bone matrix mineralization and reduces cortical porosity in male osteoporosis: a paired biospsy study.

Misof BM, Patsch JM, Roschger P, Muschitz C, Gamsjäger S, Paschalis EP, Prokop E, Klaushofer K, Pietschmann P, Resch H

Journal of Bone and Mineral Research: the official journal of the American Society for Bone and Mineral Research 01/2014
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6,04

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Intravenous treatment with ibandronate normalizes bone matrix mineralization and reduces cortical porosity after two years in male osteoporosis: A paired biopsy study.

Barbara M Misof, Janina M Patsch, Paul Roschger, Christian Muschitz, Sonja Gamsjaeger, Eleftherios P Paschalis, Eva Prokop, Klaus Klaushofer, Peter Pietschmann, Heinrich Resch

Journal of Bone and Mineral Research: the official journal of the American Society for Bone and Mineral Research 07/2013;

Abstract

There are no specific biochemical bone markers available for osteogenesis imperfecta (OI), and the role of sclerostin as a key regulator of bone formation in OI is unknown.

Objectives: We aimed to evaluate the role of sclerostin and its association with bone turnover markers as well as body composition parameters in adult patients with different types of OI.

Design, Setting, and Participants: This was a case-control study in 27 adult patients and 50 healthy age- and gender-matched controls. Main Outcome Measures: Serum sclerostin levels and bone turnover markers including serum osteocalcin, amino terminal propeptide of type I procollagen, and CrossLaps as well as body composition parameters were determined in mild OI stage I (OI-I) and moderate-severe OI stages III-IV (OI-III-IV), according to Sillence classification. Data were compared with healthy controls.

Results: Sclerostin levels were significantly lower in OI-I (19.9 ± 10.9 pmol/L; P < .001) and OI-III-IV (13.3 ± 10.0 pmol/L; P < .001) compared with healthy adults (45.3 ± 14.9 pmol/L), even after adjustment for age, sex, bone mineral content, and body mass index. CrossLaps and PTH were significantly lower in OI-I (0.197 ± 0.15 ng/L; P = .007 and 33.7 ± 19.1 pg/L; P = .033, respectively) and OI-III-IV (0.221 ± 0.18 ng/L; P = .039, and 27.9 ± 14.7 pg/L; P = .001, respectively) than in healthy controls (0.322 ± 0.15 ng/L and 45.0 ± 16.6 pg/L). Amino-terminal propeptide of type I procollagen was below the reference range for OI-I and OI-III-IV. Patients with OI were shorter and lighter and had a decreased bone mineral content (P < .001) but similar fat distribution and lean body mass, compared with controls. Serum sclerostin levels were not related to any bone marker except osteocalcin, the number of prevalent fractures, or body composition readings. Conclusion: Decreased sclerostin levels in OI might reflect a down-regulation or negative feedback mechanism to prevent further bone loss. [/av_toggle] [/av_toggle_container] [/av_four_fifth][av_one_fifth min_height='' vertical_alignment='' space='' custom_margin='' margin='0px' padding='0px' border='' border_color='' radius='0px' background_color='' src='' background_position='top left' background_repeat='no-repeat' animation='' mobile_breaking='' mobile_display=''] [av_animated_numbers number='6,04' icon_select='no' icon='ue800' font='entypo-fontello' font_size='' font_size_description='' link='' linktarget='no' color='' custom_color='#444444' admin_preview_bg=''] Impact Factor [/av_animated_numbers] [/av_one_fifth] [av_hr class='custom' height='50' shadow='no-shadow' position='center' custom_border='av-border-fat' custom_width='50px' custom_border_color='#f2f2f2' custom_margin_top='50px' custom_margin_bottom='80px' icon_select='no' custom_icon_color='#f2f2f2' icon='ue89a' font='entypo-fontello' admin_preview_bg=''] [av_four_fifth first min_height='' vertical_alignment='' space='' custom_margin='' margin='0px' padding='0px' border='' border_color='' radius='0px' background_color='' src='' background_position='top left' background_repeat='no-repeat' animation='' mobile_breaking='' mobile_display=''] [av_textblock size='' font_color='' color='' av-medium-font-size='' av-small-font-size='' av-mini-font-size='' admin_preview_bg='']

The discriminatory capacity of BMD measurements by DXA and dual X-ray and laser (DXL) at the calcaneus including clinical risk factors for detecting patients with vertebral fractures.

C Muschitz, H P Dimai, R Kocijan, A Kaider, A Zendeli, F Kühne, A Trubrich, S Lung, R Waneck, H Resch

Osteoporosis International 01/2013;
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Abstract


Osteoporotic fracture risk depends on bone mineral density (BMD) and clinical risk factors (CRF). Five hundred and eighty-eight untreated female and male outpatient subjects were evaluated, 160 with vertebral fractures. BMD was measured both by using calcaneal dual X-ray and laser (DXL) and dual-energy X-ray absorptiometry (DXA), and CRF were evaluated. Detection frequencies for different BMD methods with or without CRF are presented.

INTRODUCTION: Osteoporotic fracture risk depends on bone mineral density and clinical risk factors. DXA of the spine/hip is considered a gold standard for BMD assessment, but due to degenerative conditions, particularly among the older population, assessment of BMD at the lumbar spine has been shown to be of limited significance. Portable calcaneal dual X-ray technology and laser can be an easily obtainable alternative.

METHODS: Vertebral fractures were evaluated in a baseline analysis of 588 females and males (median age 64.4, range 17.6-93.1 years), comparing BMD measurements by using DXL and DXA and CRF with/without BMD. One hundred and sixty subjects had radiological verified vertebral fractures. Area under receiver-operating characteristic curves (AUROCC) and univariate and multiple logistic regressions were calculated.

RESULTS: AUROCC for detection of vertebral fractures was comparable for DXL at calcaneus and DXA at femoral neck (DXL 0.665 and DXA 0.670). Odds ratio for prevalent vertebral fracture was generally weak for DXA femoral neck (0.613) and DXL (0.521). Univariate logistic regression among CRF without BMD revealed age, prevalent fragility fracture, and body mass index significantly associated with prevalent vertebral fracture (AUROCC = 0.805). Combining BMD and CRF, a prognostic improvement in case of DXA at femoral neck (AUROCC 0.869, p = 0.02), DXL at calcaneus (AUROCC 0.869, p = 0.059), and DXA at total hip (AUROCC 0.861, p = 0.06) was observed. CONCLUSIONS: DXL was similarly sensitive compared with DXA for identification of subjects with vertebral fragility fractures, and combination of CRF with BMD by DXL or DXA further increased the discriminatory capacity for detection of patients susceptible to vertebral fracture.

4,58

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Changes of circulating sclerostin levels after different kinds of physical exercise with high impact on musculoskeletal system in healthy young females.

J. Haschka, R. Kocijan, C. Muschitz, J.M. Patsch, C. Bittighofer, A. Trubrich, W. Woloszczuk, S. Dinu, S. Kapiotis, H. Resch

Bone 12/2012; 51(6):S19 – S20.

4,02

Impact Factor

Enhanced Callus Formation After Six Weeks of Parathyroid Hormone Treatment in a Man with Multiple Pelvic Fractures and Osteogenesis Imperfecta Type IV

Roland Kocijan, Judith Haschka, Christian Muschitz, Angela Trubrich, Janina Patsch, Heinrich Resch

The Journal of Bone and Joint Surgery 11/2012; 2(4).

3,27

Impact Factor

Impact of denosumab on the peripheral skeleton of postmenopausal women with osteoporosis: bone density, mass, and strength of the radius, and wrist fracture.

James A Simon, Christopher Recknor, Alfred H Moffett, Jonathan D Adachi, Edward Franek, E Michael Lewiecki, Michael R McClung, Carlos A Mautalen, Sergio Ragi-Eis, Geoffrey C Nicholson, Christian Muschitz, Ranuccio Nuti, Ove Törring, Andrea Wang, Cesar Libanati

Menopause (New York, N.Y.) 09/2012;

Abstract

OBJECTIVE: The aim of this study was to report the effects of denosumab on radius cortical and trabecular bone density, mass, and strength, and wrist fracture incidence in the FREEDOM (Fracture REduction Evaluation of Denosumab in Osteoporosis every 6 Months) study.

METHODS: In the FREEDOM study, postmenopausal women with osteoporosis (N = 7,808) received placebo or 60 mg of denosumab every 6 months for 36 months. Radius bone mineral density (BMD), bone mineral content, and strength (polar moment of inertia) were evaluated in two prespecified substudies using dual-energy x-ray absorptiometry (placebo, n = 209; denosumab, n = 232) or quantitative CT (placebo, n = 48; denosumab, n = 62). Prespecified analysis assessed wrist fracture incidence in all FREEDOM participants (placebo, N = 3,906; denosumab, N = 3,902), and post hoc subgroup analyses evaluated those with higher fracture risk (baseline femoral neck T-score ≤-2.5; placebo, N = 1,406; denosumab, N = 1,384).

RESULTS: Denosumab significantly increased areal BMD (assessed by dual-energy x-ray absorptiometry) and volumetric BMD, bone mineral content, and polar moment of inertia (assessed by quantitative CT), compared with placebo, in radius cortical and trabecular bone at all time points evaluated (all P < 0.05). Wrist fracture incidence was 2.9% for placebo and 2.5% for denosumab (relative risk reduction, 16%; P = 0.21) on month 36. Participants with a femoral neck T-score of -2.5 or lower were at increased risk for wrist fracture, and denosumab significantly reduced wrist fracture incidence compared with placebo (placebo, 4.0%; denosumab, 2.4%; relative risk reduction, 40%; absolute risk reduction, 1.6%; P = 0.03). CONCLUSIONS: Denosumab significantly improves radius bone density, mass, and strength compared with placebo. In higher-risk women, denosumab significantly reduces wrist fracture risk. [/av_toggle] [/av_toggle_container] [/av_four_fifth] [av_one_fifth min_height='' vertical_alignment='' space='' custom_margin='' margin='0px' padding='0px' border='' border_color='' radius='0px' background_color='' src='' background_position='top left' background_repeat='no-repeat' animation='' mobile_breaking='' mobile_display=''] [av_animated_numbers number='3,08' icon_select='no' icon='ue800' font='entypo-fontello' font_size='' font_size_description='' link='' linktarget='no' color='' custom_color='#444444' admin_preview_bg=''] Impact Factor [/av_animated_numbers] [av_hr class='invisible' height='20' shadow='no-shadow' position='center' custom_border='av-border-thin' custom_width='50px' custom_border_color='' custom_margin_top='30px' custom_margin_bottom='30px' icon_select='yes' custom_icon_color='' icon='ue808' font='entypo-fontello' admin_preview_bg=''] [av_button label='PDF' link='manually,http://muschitz.info/christian/wp-content/uploads/2017/11/2012_Menopause_Dmab_radius_wrist_fx.pdf' link_target='_blank' size='small' position='center' icon_select='yes' icon='ue84c' font='entypo-fontello' color='theme-color' custom_bg='#444444' custom_font='#ffffff' admin_preview_bg=''] [/av_one_fifth] [av_hr class='custom' height='50' shadow='no-shadow' position='center' custom_border='av-border-fat' custom_width='50px' custom_border_color='#f2f2f2' custom_margin_top='50px' custom_margin_bottom='80px' icon_select='no' custom_icon_color='#f2f2f2' icon='ue89a' font='entypo-fontello' admin_preview_bg=''] [av_four_fifth first min_height='' vertical_alignment='' space='' custom_margin='' margin='0px' padding='0px' border='' border_color='' radius='0px' background_color='' src='' background_position='top left' background_repeat='no-repeat' animation='' mobile_breaking='' mobile_display=''] [av_textblock size='' font_color='' color='' av-medium-font-size='' av-small-font-size='' av-mini-font-size='' admin_preview_bg='']

Femoral geometric parameters and BMD measurements by DXA in adult patients with different types of osteogenesis imperfecta.

Roland Kocijan, Christian Muschitz, Nadja Fratzl-Zelman, Judith Haschka, Hans-Peter Dimai, Angela Trubrich, Christina Bittighofer, Heinrich Resch

Skeletal Radiology 09/2012;
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Abstract

OBJECTIVES: Osteogenesis imperfecta (OI) is an inherited disorder characterized by increased bone fragility with recurrent fractures that leads to skeletal deformities in severe cases. Consequently, in most OI patients, the hip is the only reliable measuring site for estimating future fracture risk. The aim of the study was to assess the applicability of hip structure analysis (HSA) by DXA in adult patients with osteogenesis imperfecta.
MATERIALS AND METHODS: We evaluated bone mineral density (BMD) and hip structure analysis (HSA) by DXA, including cross-sectional area (CSA), cross-sectional moment of inertia (CSMI) and femoral strength index (FSI) in 30 adult patients with different types of OI and 30 age-matched healthy controls (CO). The OI total group (OI-tot) was divided into two subgroups: the mild OI I group (OI-I) and the more severe OI III and IV group (OI-III-IV).
RESULTS: The mean neck BMD of OI-I and OI-III-IV were significantly lower compared to CO (-15.9 %, p < 0.005 and - 37.5 %, p < 0.001 respectively). Similar results were observed at trochanter and total hip. CSA and the CSMI value were significantly lower for OI-I (-23.2 %, p < 0.001) and OI-III-IV (-45.9 %, p <0.001) in comparison to CO. In addition, significant differences were found between the mild OI-I and the severe OI-III-IV group (- 29.6 %, p < 0.05). FSI was significantly decreased in the OI-III-IV (25.7 %, p < 0.05) in comparison to the CO. Furthermore, significant correlations between BMD and HSA and between HSA and height and weight were found in osteogenesis imperfecta and controls.
CONCLUSION: BMD measurement in osteogenesis imperfecta patients is very critical. The combination of BMD and geometric structural measurements at the hip in osteogenesis imperfecta patients may represent an additional helpful means in estimating bone strength and fracture risk.

1,54

Impact Factor

Antiresorptives overlapping ongoing teriparatide treatment result in additional increases in bone mineral density.

Christian Muschitz, Roland Kocijan, Astrid Fahrleitner-Pammer, Solveig Lung, Heinrich Resch

Journal of Bone and Mineral Research: the official journal of the American Society for Bone and Mineral Research 07/2012;

Abstract

During teriparatide (TPTD) treatment, high levels of bone formation are accompanied by an increase in bone resorption. The aim of this work was to test if coadministration of raloxifene (RAL) or alendronate (ALN) following 9 months of ongoing TPTD therapy would reopen the anabolic window, thereby exerting additional benefit on bone mineral density (BMD). Postmenopausal women (n = 125) with severe osteoporosis on TPTD treatment for 9 months were randomized into three open-label groups for a further 9 months: ALN (70 mg/week) in addition to TPTD; RAL (60 mg/d) in addition to TPTD; or no medication in addition to TPTD. Amino-terminal propeptide of type I procollagen (P1NP) and cross-linked C-telopeptide (CTX), and areal and volumetric BMD at the lumbar spine and hip were assessed. During the combination period, P1NP concentrations did not change on TPTD monotherapy (693% ± 371%, p<0.0001) and decreased in the ALN (360% ± 153%, p<0.0001) and RAL (482% ± 243%, p<0.0001) combination groups; whereas CTX did not change on TPTD monotherapy (283% ± 215%, p<0.0001), decreased to the starting level in the ALN combination group (17% ± 72%, p=0.39), and remained elevated in the RAL combination group (179% +- 341%, p<0.0001). The increase in lumbar spine BMD was 5% ± 6.3% in the ALN and 6% +- 5.2% in the RAL combination groups compared with 2.8% ± 9.3% in the TPTD monotherapy group (p=0.085 and p=0.033, respectively). The increase of trabecular lumbar spine BMD for both the ALN and RAL combination groups was superior to TPTD monotherapy. Total hip BMD changes were 4% ± 5.3% for the ALN combination group and 1.4% ± 5.1% for the TPTD monotherapy (p=0.032), and 1.4% ± 3.4% (p=0.02) for the RAL combination group. With the exception of no differences in the trabecular compartment of femoral neck, volumetric BMD changes in the ALN combination group for all other comparisons were significantly superior to the two other groups. Our data suggest that ALN when added to TPTD 9 months after initiation of TPTD monotherapy results in a more robust increase in BMD, probably due to a reopening of the anabolic window. The clinical relevance of the BMD increase is unknown.
6,04

Impact Factor

Update on denosumab in postmenopausal osteoporosis-recent clinical data.

Christian Muschitz, Astrid Fahrleitner-Pammer, Johannes Huber, Elisabeth Preisinger, Stefan Kudlacek, Heinrich Resch

Wiener Medizinische Wochenschrift 06/2012; 162(17-18):374-379.

Abstract

Denosumab, a fully human monoclonal antibody against the key osteoclastogenic factor RANK ligand, is currently approved for the treatment of postmenopausal osteoporosis. Denosumab differs from bisphosphonates in many aspects, for example, its ability to act in the extracellular compartment and its likelihood to be distributed throughout the skeleton. In contrast, bisphosphonates have to be internalized by osteoclasts and are mainly located across bone surfaces. This could explain why patients with osteoporosis, who are already treated with bisphosphonates, might experience further benefit when switching to denosumab. Head-to-head studies revealed that transition to denosumab resulted in a greater increase of bone mineral density (BMD) and a greater reduction of bone turnover than did continued alendronate. Additional analyses of the phase 3 FREEDOM trial demonstrated that fracture reduction was particularly high in cortical bone, such as the wrist. In addition, denosumab treatment for a 5- and 8-year period showed sustained reduction in fracture risk, increase in BMD and continued to be well tolerated. The 7-year extension study of FREEDOM and a phase 3 trial evaluating denosumab for the treatment of male osteoporosis are still ongoing and will provide supportive data in the near future.
The 5-year follow-up of a cortical stress fracture resulting in a spontaneous atypical subtrochanteric femoral fracture in a female patient with severe osteoporosis and bisphosphonate therapy over 15 years.

Judith Haschka, Friederike Kühne, Christian Muschitz, Thomas Pirker, Roland Kocijan, Christina Bittighofer, Angela Trubrich, Heinrich Resch

Wiener Klinische Wochenschrift 08/2011; 123(21-22):684-7.

Abstract

Atypical fractures under long term treatment with bisphosphonates (BP) have been reported, although no causal connection has been known. As an explanation the suppression of bone turnover with poor bone metabolism and consequently deterioration of bone microarchitecture has been suggested. In our case we describe retrospectively the course of radiological and clinical changes in a 75 years old female patient who has been treated with oral BP due to postmenopausal osteoporosis over 15 years. After 10 years of treatment she developed a cortical stress fracture in the subtrochanteric region of the femoral shaft, which finally caused a spontaneous atypical subtrochanteric fracture 5 years later.
0,81

Impact Factor

Severe osteoporosis with multiple vertebral fractures after gender reassignment therapy – is it male or female osteoporosis?

Eva-Maria Fischer, Janina Patsch, Christian Muschitz, Stephan Becker, Heinrich Resch

Gynecological Endocrinology 05/2011; 27(5):341-4.

Abstract

We report about a 49-years-old patient with severe osteoporosis and multiple vertebral fractures after male-to-female reassignment therapy. The patient had 12 years of hormone replacement therapy (HRT) with very low serum levels of estradiol and testosterone at the time the fractures occurred. The reasons are currently not known. Most likely the patient seems to be non-compliant with the HRT intake. Bone mineral density (BMD) measurements showed highly decreased T-Scores between -3.5 and -4.5. All routine laboratory parameters, especially the markers of bone turnover, were within the normal range. μ-CT 3D-structural analysis of the bone biopsy showed a highly reduced trabecular connectivity (Conn.Dens.). Bone mineral density distribution (BMDD), measured by quantitative backscattered electron imaging (qBEI), showed a BMDD within normal range, except heterogeneity index (Ca(WIDTH)) and fraction of highly mineralised bone (Ca(HIGH)), which were increased. We conclude that our patient has a cross-sex hormonal therapy induced total imbalance of bone homeostasis, because of the long lasting under monitored hormone therapy which led to severe interferences in physiological maturities. Male-to-female transsexuals without an adequate estrogen treatment are at increased risk of developing osteoporosis.
1,58

Impact Factor

Trabecular bone microstructure and local gene expression in iliac crest biopsies of men with idiopathic osteoporosis.

Janina M Patsch, Thomas Kohler, Andrea Berzlanovich, Christian Muschitz, Christian Bieglmayr, Paul Roschger, Heinrich Resch, Peter Pietschmann

Journal of Bone and Mineral Research: the official journal of the American Society for Bone and Mineral Research 02/2011; 26(7):1584-92.

Abstract

Male idiopathic osteoporosis (MIO) is a metabolic bone disease that is characterized by low bone mass, microstructural alterations, and increased fracture risk in otherwise healthy men. Although the detailed pathophysiology of MIO has yet to be clarified, evidence increasingly suggests an osteoblastic defect as the underlying cause. In this study we tested the hypothesis that the expression profile of certain osteoblastic or osteoblast-related genes (ie, WNT10B, RUNX2, Osterix, Osteocalcin, SOST, RANKL, and OPG) is different in iliac crest biopsies of MIO patients when compared with healthy controls. Furthermore, we investigated the relation of local gene expression characteristics with histomorphometric, microstructural, and clinical features. Following written informed consent and diligent clinical patient characterization, iliac crest biopsies were performed in nine men. While RNA extraction, reverse-transcription, and real-time polymerase chain reactions (PCRs) were performed on one biopsy, a second biopsy of each patient was submitted for histomorphometry and micro-computed tomography (ηCT). Age-matched bone samples from forensic autopsies served as controls. MIO patients displayed significantly reduced WNT10B, RUNX2, RANKL, and SOST expression. Performing ηCT for the first time in MIO biopsies, we found significant decreases in trabecular number and connectivity density. Trabecular separation was increased significantly, but trabecular thickness was similar in both groups. Histomorphometry revealed decreased BV/TV and osteoid volume and fewer osteoclasts in MIO. By providing evidence for reduced local WNT10B, RUNX2, and RANKL gene expression and histomorphometric low turnover, our data support the osteoblast dysfunction model discussed for MIO. Further, MIO seems to lead to a different microstructural pathology than age-related bone loss.
6,04

Impact Factor

Fragility fractures in men with idiopathic osteoporosis are associated with undermineralization of the bone matrix without evidence of increased bone turnover.

Nadja Fratzl-Zelman, Paul Roschger, Barbara M Misof, Kamilla Nawrot-Wawrzyniak, Sarah Pötter-Lang, Christian Muschitz, Heinrich Resch, Klaus Klaushofer, Elisabeth Zwettler

Calcified Tissue International 02/2011; 88(5):378-87.

Abstract

The pathogenesis of primary osteoporosis in younger individuals is still elusive. An important determinant of the biomechanical competence of bone is its material quality. In this retrospective study we evaluated bone material quality based on quantitative backscattered electron imaging to assess bone mineralization density distribution (BMDD) in bone biopsies of 25 male patients (aged 18-61 years) who sustained fragility fractures but were otherwise healthy. BMDD of cancellous bone was compared with previously established adult reference data. Complementary information was obtained by bone histomorphometry. The histomorphometric results showed a paucity of osteoblasts and osteoclasts on the bone surface in the majority of patients. BMDD revealed a significant shift to lower mineralization densities for cancellous bone values: CaMean (weighted mean Ca content, -5.9%), CaPeak (mode of the BMDD, -5.6%), and CaHigh (portion of fully mineralized bone, -76.8%) were decreased compared to normative reference; CaWidth (heterogeneity in mineralization, +18.5%) and CaLow (portion of low mineralized bone, +68.8; all P < 0.001) were significantly increased. The shift toward lower mineral content in the bone matrix in combination with reduced indices of bone formation and bone resorption suggests an inherent mineralization defect leading to undermineralized bone matrix, which might contribute to the susceptibility to fragility fractures of the patients. The alteration in bone material might be related to osteoblastic dysfunction and seems fundamentally different from that in high bone turnover osteoporosis with a negative bone balance.
2,38

Impact Factor

Fracture risk prediction using clinical risk factors in comparison to BMD measurements of the calcaneus and other skeletal areas in Austrian males and females

C. Bittighofer, C. Muschitz, A. Trubrich, F. Kühne, J. Haschka, R. Kocijan, A. Kaider, H. Resch

Bone 01/2011; 48.

4,02

Impact Factor

The effect of PTH(1-84) or strontium ranelate on bone formation markers in postmenopausal women with primary osteoporosis: results of a randomized, open-label clinical trial.

J M Quesada-Gómez, C Muschitz, J Gómez-Reino, H Greisen, H S Andersen, H P Dimai

Osteoporosis International 10/2010; 22(9):2529-37.

Abstract

We explored the effects of PTH(1-84) compared with strontium ranelate on bone remodeling as measured by bone remodeling markers in postmenopausal women with osteoporosis. Biochemical markers of bone formation were significantly increased after treatment with PTH(1-84) but not strontium ranelate, indicating a different mechanism of action between these agents. PTH(1-84) and strontium ranelate (SR) are both known to reduce fracture risk in osteoporosis. Measuring changes in biochemical markers of bone turnover induced by these agents can help in characterizing the action of PTH(1-84) and SR on bone remodeling. A 24-week, randomized, open-label, parallel group, phase IV trial was conducted in 81 postmenopausal women with primary osteoporosis (≥50 years of age, lumbar spine, or total hip T-score ≤-2.5 SD) to assess the effect of SR as compared to PTH(1-84) on bone formation markers P1NP and BSAP. The bone resorption marker CTX was also measured. Subjects were randomly assigned to receive daily either 100 ηg PTH(1-84) (n = 41) (subcutaneous injection) or oral 2 g SR (n = 40) for 24 weeks with daily supplements of 800 IU vitamin D(3) and 1,000 mg calcium. Patient-reported outcomes were collected to investigate the effect of treatment on quality of life (QoL). Percentage changes from baseline in P1NP and BSAP were significantly increased for PTH(1-84) by week 24 compared with SR (p < 0.0001). Significant changes from baseline in P1NP and BSAP were noted for PTH(1-84) from week 4 onwards; no significant changes were noted for SR. A trend towards a positive impact on QoL was seen with PTH(1-84) treatment. Safety profiles concur with previous analyses. PTH(1-84) had a more rapid and higher effect on bone formation markers compared to SR, indicating that SR has a different mode of action on bone remodeling than the bone building agent PTH(1-84) in postmenopausal women with osteoporosis.
4,58

Impact Factor

Decreased RUNX2, RANKL and sost gene expression in transiliac bone biopsies of men with untreated idiopathic osteoporosis

J. M. Patsch, C. Muschitz, T. Wägerbauer, A. Berzlanovich, K. Wahl, H. Resch, P. Pietschmann

Bone 01/2010; 47.

4,02

Impact Factor

Prevalence of vertebral fracture in elderly men and women with osteopenia.

Christian Muschitz, Janina Patsch, Elisabeth Buchinger, Elise Edlmayr, Günther Nirnberger, Vasilis Evdokimidis, Reinhart Waneck, Peter Pietschmann, Heinrich Resch

Wiener klinische Wochenschrift 08/2009; 121(15-16):528-36

Abstract

The objective of our cross-sectional, not population-based, observational study was to determine the prevalence of patients with osteopenia in relation to bone mineral density (BMD) and vertebral fractures and to identify risk factors for vertebral fractures above the osteoporotic BMD T-score threshold of -2.5. A total of 698 consecutive hospitalized and ambulatory white patients with T-scores between -1.0 and -2.5 were investigated in an academic medical center in Austria between January 2005 and June 2006. Measurements of BMD (T-score at spine and hip) by DXA, spinal X-ray, laboratory data of bone metabolism and vitamin D, and sex-specific data were assessed. A multivariate general linear model was used to calculate vertebral and non-vertebral fractures, age, BMI and lowest T-score at measured anatomic sites. Overall, 218 patients (31.2%) with a mean age of 72.2 years and mean BMI of 26.0 presented with vertebral fractures; in comparison, patients with non-vertebral fractures had a mean age of 62.6 years and BMI 24.6, and patients without fractures had a mean age of 61.3 years and BMI 24.0 (P < 0.001). Serum markers of bone resorption and formation had no influence on fracture occurrence but 73% of the patients had vitamin D deficiency (25.2 +/- 9.8 ng/ml). The lowest T-score in all fracture patients was found at the femoral neck. At this site 64.3% patients with vertebral fractures had a T-score within the range -1.0 to -2.0 (95% CI 57.3-70.8). The prevalence of vertebral fractures increased stepwise (P < 0.05) and at T-scores between -1.5 and -2.0 the increase was linear. We conclude that a significant proportion of non-osteoporotic elderly men and women with mean age 72 years, BMI 26.0 and a threshold T-score above -2.0 are susceptible to osteoporotic vertebral fractures. These patients are not adequately detected by BMD measurements based on WHO thresholds. Early assessment, prior to their first fracture, is important for identifying individuals with clinical risk factors.
0,81

Impact Factor

73 Hip Geometry and Bone Density in Japanese Women in Relation to Fragility Fracture

M. Ito, T. Nakata, C. Muschitz

Journal of Clinical Densitometry – J CLIN DENSITOM. 01/2009; 12(1):121-122.

Die Prävalenz von vertebralen Frakturen bei älteren Frauen und Männern mit Osteopenie

Christian Muschitz, Janina Patsch, Elisabeth Buchinger, Elise Edlmayr, Günther Nirnberger, Vasilis Evdokimidis, Reinhart Waneck, Peter Pietschmann, Heinrich Resch

Wiener Klinische Wochenschrift – WIEN KLIN WOCHENSCHR. 01/2009; 121:528-536.

Maligner Ascites – Möglichkeiten der Symptomkontrolle

Astrid Bodisch, Christian Muschitz, Meinolf Karthaus

Wiener Medizinische Wochenschrift 11/2008; 158(23):687-694..

Abstract

Maligner, therapierefraktärer Ascites ist ein belastendes Problem für viele Palliativpatienten in den letzten Lebensmonaten ihrer Krebserkrankung. Mittels Paracentese ist schnell eine Symptomerleichterung erzielbar, wenngleich dies bei den meisten Patienten keine dauerhafte Symptomkontrolle erbringt. Allerdings ist auch die Evidenz für den Einsatz von Diuretika und Shuntverfahren in dieser Situation schwach. Anhand eines Fallbeispieles werden verschiedenen Therapiemöglichkeiten bei malignem Ascites beschrieben und ihre Anwendung in der letzten Lebensphase diskutiert. Die Geschichte einer jungen Frau mit Ovarialkarzinom wird vorgestellt. Behandlungsempfehlungen und Erfahrungen werden dargestellt und diskutiert.
Ascites remains a challenge in many patients with advanced cancers in palliative care. Although paracentesis, diuretics and shunting are the commonly used procedures, the evidence is weak. A fast but temporary effect is achieved on symptom relief by paracentesis. Some inherent risks have to be taken into account. On the basis of a case report, different attempts to control malignant ascites are discussed. The report of a young woman with relapsing ovarian cancer and recurrent ascites is presented including the management of symptomatic malignant ascites.
Intracellular and surface RANKL are differentially regulated in patients with ankylosing spondylitis.

Daniela Stupphann, Martina Rauner, Dagmar Krenbek, Janina Patsch, Thomas Pirker, Christian Muschitz, Heinrich Resch, Peter Pietschmann

Rheumatology International 08/2008; 28(10):987-93.

Abstract

Ankylosing spondylitis (AS) is characterized by ankylosis of axial joints but osteoporosis is also a well-reported feature. T cells have been implicated as a source of receptor activator of NFkappaB ligand (RANKL) in inflammatory bone diseases. Hence, we assessed whether T cells in patients with AS act as a source of RANKL too. Therefore, we investigated the expression of RANKL on T cells from 21 patients with AS by flow cytometry. Bone mineral density (BMD) was evaluated by quantitative computer tomography (QCT) and dual X-ray absorptiometry (DXA) and correlated with serum levels of osteoprotegerin (OPG) and RANKL. BMD was decreased in 45% of all patients when measured with DXA (48% with QCT) and correlated negatively with OPG. Expression of intracellular RANKL was increased on CD4+ (84 vs. 70%) and CD8+ (85.2 vs. 65.3%, P < 0.05) T cells in patients with AS, whereas expression of membrane-bound RANKL was significantly lower (CD4+: 2.2 vs. 8.5% and CD8+: 0.7 vs. 3.2%, P < 0.01). Our results indicate that surface and intracellular RANKL production is differentially regulated on T cells of patients with AS.
1,88

Impact Factor

Methods of symptom control in malignant ascites

Astrid Bodisch, Christian Muschitz, Meinolf Karthaus

Wiener Medizinische Wochenschrift 02/2008; 158(23-24):687-94.

Abstract

Ascites remains a challenge in many patients with advanced cancers in palliative care. Although paracentesis, diuretics and shunting are the commonly used procedures, the evidence is weak. A fast but temporary effect is achieved on symptom relief by paracentesis. Some inherent risks have to be taken into account. On the basis of a case report, different attempts to control malignant ascites are discussed. The report of a young woman with relapsing ovarian cancer and recurrent ascites is presented including the management of symptomatic malignant ascites.

T04-O-04 Severe osteoporosis with multiple vertebral fractures after gender reassignment therapy – is it male or female osteoporosis?

J. Patsch, T. H. Woegerbauer, C. H. Muschitz, P. Pietschmann, H. Resch

Sexologies 01/2008; 17.

High-dose bisphosphonate therapy in an urgent case of spontaneous multiple vertebral fractures in a 55 year old woman.

Christian Muschitz, Paul Roschger, Janina Patsch, Isabella Pollhammer, Bruno Koller, Klaus Klaushofer, Heinrich Resch

Wiener Medizinische Wochenschrift 02/2007; 157(15-16):388-91. 

Abstract

An early postmenopausal Caucasian woman aged 55 sustained multiple vertebral fractures after a minor trauma. After exclusion of any kind of secondary osteoporosis, we administered due to clinical severity combined oral and cyclic intravenous bisphosphonate therapy (oral risedronate 35 mg/week, i.v. pamidronate 30 mg quarterly) with adequate calcium and vitamin D supplementation for 28 months. We performed a transiliac bone biopsy at baseline and at month 28. The paired samples were investigated by histomorphometry, by microCT-analysis for 3d structure and by qBEI representing bone mineral density distribution. Mineralisation of the bone matrix was not influenced by supplementation of calcium and vitamin D. Parameters of bone architecture and BMD improved; and a reduction of pain and increased mobility was observed. No further osteoporotic fractures occurred during the time of investigation.

Hochdosierte Bisphosphonat-Therapie bei einer 55 jährigen Patientin mit multiplen Wirbelkörperfrakturen

Christian Muschitz, Paul Roschger, Janina Patsch, Isabella Pollhammer, Bruno Koller, Klaus Klaushofer, Heinrich Resch

Wiener Medizinische Wochenschrift. 01/2007; 157:388-391.

Of mice and men: pathophysiology of male osteoporosis

Janina Patsch, Christian Muschitz, Heinrich Resch, Peter Pietschmann

The Journal of Men’s Health & Gender. 01/2007; 4(1):87-93. 

Abstract

In both old and young men osteoporosis is a severe but frequently neglected condition. This review deals with the multifactorial pathogenesis of impaired bone strength in men. Male bones are not only influenced by androgens, but, somewhat surprisingly – according to the current state of knowledge – female sex hormones may be the major players in calcified tissue remodelling. As a matter of principle, gender shapes bone geometry on a life-long basis. In men, age-dependant bone loss is outweighed by increased periosteal apposition. Contrary to women, the male gender-specific resorption pattern is mainly based on trabecular thinning. Therefore the connectivity remains rather intact, which again positively influences the biomechanical tissue properties and the resistance to fractures. Since affected patients often present with a family history of fractures or low bone density, the genetics of male osteoporosis is one of the main fields of interest in current bone research. Several gene polymorphisms involving the α1 chain of type 1 collagen (COLIA-1), aromatase, vitamin D receptor (VDR), low-density lipoprotein receptor-related protein 5 (LPR5) and the lactase phlorizin hydrolase (LCT) have recently been described. But apart from such exciting research novelties, the classical every-day violaters of both male and female bone health (vitamin D deficiency, low calcium intake and inadequate life-style) must still be taken into account.

Die Effekte von Tamoxifen auf die Knochendichte und das Frakturrisiko

C. Muschitz, A. Resch, H. Resch

Osteologie. 01/2007; 16(01):30-39.

Increased expression of receptor activator of NFκB ligand (RANKL) in stimulated T cells
from patient with ankylosing spondylitis

Daniela Stupphann, Martina Rauner, Dagmar Krenbek, Janina Patsch, Thomas Pirker, Christian Muschitz, Heinrich Resch, Peter Pietschmann, M Sc

Department of Pathophysiology, Center of Physiology and Pathophysiology, Medical University of Vienna, Vienna, Austria; Medical Department II, St. Vincent Hospital, Vienna, Austria; Medical University of Vienna Institute of Pathophysiology Währingergürtel, 18-20 1090, Vienna, Austria

The effect of PTH(1–84) or strontium ranelate on bone formation markers in postmenopausal women with primary osteoporosis: res

Vergleich der Profile von Serum-Knochenstoffwechselmarkern bei zwei osteoanabolen Substanzen

Journal: Osteoporosis International

Sekundäre Osteoporose bei Antiepileptika

Bericht über Frakturhäufigkeit und Ursachen einer sekundären Osteoporose bei Epilepsie und antiepileptischer Therapie

Osteoporose 2010

Überblick über Diagnostik & Therapie in Österreich inkl DFP-Punkte

Severe Osteoporosis with multiple vertebral fractures after gender reassignment therapy – is it male or female osteoporosis

Case Report über einen Patienten/Patientin nach Geschlechtsumwandlung mit einer fortgeschrittenen Osteoporose mit multiplen Wirbelkörpereinbrüchen

Effekte einer knochenanabolen Therapie mit Teriparatid bei juveniler sekundärer männlicher Osteoporose

Artikel im Universum Innere Medizin mit einem Fallbeispiel über einen jungen Mann mit einer Wirbelkörperfraktur und schlechter Knochendichte sowie einem effektiven Therapieansatz

Determinanten der Knochenqualität

Artikel mit Fragen für DFP Zertifizierung der Österreichischen Ärztekammer (Seite 6-10)

DXA and QCT geometric structural measurements of proximal femoral strength

Vergleich einer 2D Methode (DXA) und einer 3D Messmethode der Knochendichte am Femur

High-dose bisphoshonate therapy in an urgent case of spontaneous multiple vertebral fractures in a 55 year old woman

Eine frühe postmenopausale 55-järige weiße Frau erlitt nach einem leichten Trauma multiple Wirbelkörperfrakturen.

Die Effekte von Tamoxifen auf die Knochendichte und das Frakturrisiko

Schlüsselwörter: Mammakarzinom – Fraktur – Osteoporose – Knochendichte – Aromatasehemmer

Of mice and men: Pathophysiology of male osteoporosis

Keywords: Osteoporosis in men; Pathophysiology; Gender

Increased expression of receptor activator of NF-kB ligand (RANKL) in stimulated T cells from patient with ankylosing spondyliti

Keywords: ankylosing spondylitis, T cells, receptor activator of nuclear factor, kappaB (NF-kB) ligand, osteoprotegerin, interleukin 17, bone mineral density

Vertebrale Frakturen bei Frauen und Männern mit osteopenischer Knochendichte

Das klinische Ziel dieser Observationsstudie ist die Ermittlung der Prävalenz von vertebralen Frakturen bei Patienten mit osteopenischer Knochenmineraldichte (BMD) sowie die Identifikation von Risikofaktoren über dem osteoporotischen WHO Schwellenwert des T-Scores von -2,5.

Raloxifen – eine (oft unterschätzte) Substanz mit breitem Wirkspektrum.

Zusammenfassung der verschiedenen Wirkungen des SERMs Raloxifen

Hinweis

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