Publications by authors named "Christian Muschitz"

46 Publications

[Osteoporosis in pneumological diseases : Joint guideline of the Austrian Society for Bone and Mineral Research (ÖGKM) and the Austrian Society for Pneumology (ÖGP)].

Wien Klin Wochenschr 2021 Jun 16;133(Suppl 4):155-173. Epub 2021 Jun 16.

Department of Pathophysiology and Allergy Research, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Wien, Österreich.

Chronic inflammation induces proinflammatory cytokine cascades. In addition to systemic inflammation, hypoxemia, hypercapnia, a catabolic metabolism, gonadal or thyroid dysfunction, musculoskeletal dysfunction and inactivity as well as vitamin D deficiency contribute to an increased risk of fragility fractures. Iatrogenic causes of osteoporosis are long-term use of inhaled or systemic glucocorticoids (GC). Inhalative GC application in asthma is often indicated in childhood and adolescence, but interstitial lung diseases such as chronic organizing pneumonia, COPD, sarcoid or rheumatic diseases with lung involvement are also treated with inhalative or oral GC. In patients with cystic fibrosis, malabsorption in the context of pancreatic insufficiency, hypogonadism and chronic inflammation with increased bone resorption lead to a decrease in bone structure. After lung transplantation, immunosuppression with GC is a risk factor.The underlying pneumological diseases lead to a change in the trabecular and cortical bone microarchitecture and to a reduction in osteological formation and resorption markers. Hypercapnia, acidosis and vitamin D deficiency can accelerate this process and thus increase the individual risk of osteoporotic fragility fractures.A bone mineral density measurement with a T‑Score < -2.5 is a threshold value for the diagnosis of osteoporosis; in contrast the vast majority of all osteoporotic fractures occur with a T‑Score > -2.5. A history of low-trauma fracture indicates osteological therapy.All antiresorptive or anabolic drugs approved in Austria for the treatment of osteoporosis are also indicated for pneumological patients with an increased fragility fracture risk of bone fractures in accordance with the national reimbursement criteria.
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http://dx.doi.org/10.1007/s00508-021-01896-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8206904PMC
June 2021

Attenuation of COVID-19-induced cytokine storm in a young male patient with severe respiratory and neurological symptoms.

Wien Klin Wochenschr 2021 Sep 27;133(17-18):973-978. Epub 2021 Apr 27.

Medical Department II-the VINFORCE Study Group, Academic Teaching Hospital of the Medical University of Vienna, St. Vincent Hospital Vienna, Stumpergasse 13, 1060, Vienna, Austria.

Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), the etiological agent of coronavirus disease 2019 (COVID-19), produces protean manifestations and causes indiscriminate havoc in multiple organ systems. This rapid and vast production of proinflammatory cytokines contributes to a condition termed cytokine storm. A 35-year-old, otherwise healthy, employed, male patient was tested positive for COVID-19. He was admitted to the hospital on disease day 10 due to retarded verbal reactions and progressive delirium. On account of these conditions and the need for noninvasive/invasive ventilation, a combination treatment with baricitinib and remdesivir in conjunction with standard of care was initiated. The cytokine storm was rapidly blocked, leading to a vast pulmonary recovery with retarded recovery of the central nervous system. We conclude that the rapid blockade of the COVID-19-induced cytokine storm should be considered of avail as a principle of careful decision-making for effective recovery.
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http://dx.doi.org/10.1007/s00508-021-01867-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8076667PMC
September 2021

Analysis of bone architecture using fractal-based TX-Analyzer™ in adult patients with osteogenesis imperfecta.

Bone 2021 06 13;147:115915. Epub 2021 Mar 13.

Ludwig Boltzmann Institute of Osteology at Hanusch Hospital of OEGK and AUVA Trauma Center Vienna-Meidling, Vienna, Austria; Hanusch Hospital Vienna, I Medical Department, Vienna, Austria; Sigmund Freud University Vienna, Medical Faculty of Bone Diseases, Vienna, Austria. Electronic address:

Background: Osteogenesis imperfecta (OI) is a rare genetic disorder characterized by impaired bone quality and quantity. Established imaging techniques have limited reliability in OI. The TX-Analyzer™ is a new, fractal-based software allowing a non-invasive assessment of bone structure based on conventional radiographs. We explored whether the TX-Analyzer™ can discriminate OI patients and healthy controls. Furthermore, we investigated the correlation between TX-Analyzer™ parameters and (i) bone mineral density (BMD) by Dual Energy X-ray Absorptiometry (DXA), (ii) trabecular bone score (TBS), and (iii) bone microstructure by high-resolution peripheral quantitative computed tomography (HR-pQCT).

Material And Methods: Data of 29 adult OI patients were retrospectively analyzed. Standard radiographs of the thoracic and lumbar spine were evaluated using the TX-Analyzer™. Bone Structure Value (BSV), Bone Variance Value (BVV), and Bone Entropy Value (BEV) were measured at the vertebral bodies T7 to L5. Data were compared to a healthy, age- and gender-matched control group (n = 58). BMD by DXA, TBS, and trabecular bone microstructure by means of HR-pQCT were correlated to TX-Analyzer™ parameters in OI patients. The accuracy of the TX-Analyzer™ parameters in detecting OI was assessed with area under curve (AUC) analysis of receiver operating characteristic (ROC).

Results: BEV of the thoracic and the lumbar spine were significantly lower in OI patients compared to controls (both p < 0.001). BEV of the thoracic spine was significantly correlated to TBS (ρ = 0.427, p = 0.042) as well as trabecular number (Tb.N) at the radius (ρ = 0.603, p = 0.029) and inhomogeneity of the trabecular network (Tb.1/N.SD) at the radius (ρ = -0.610, p = 0.027), when assessed by HR-pQCT. No correlations were found between BEV and BMD by DXA. BEV of the thoracic and the lumbar spine had an AUC of 0.81 (95% confidence interval [CI] 0.67-0.94, p < 0.001) and 0.73 (95% CI 0.56-0.89, p = 0.008), respectively. BSV and BVV did not differ between OI patients and controls.

Conclusion: The software TX-Analyzer™ is able to discriminate patients with OI from healthy controls. ROC curves of BEV values suggest a suitable clinical applicability. Low to no correlations with conventional methods suggest, that the TX-Analyzer™ may indicate a new and independent examination tool in OI.
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http://dx.doi.org/10.1016/j.bone.2021.115915DOI Listing
June 2021

Zoledronic Acid Substantially Improves Bone Microarchitecture and Biomechanical Properties After Rotator Cuff Repair in a Rodent Chronic Defect Model.

Am J Sports Med 2020 07 16;48(9):2151-2160. Epub 2020 Jun 16.

AUVA Trauma Center Vienna-Meidling, Department for Trauma Surgery, Vienna, Austria.

Background: Bone mineral density at the humeral head is reduced in patients with chronic rotator cuff tears. Bone loss in the humeral head is associated with repair failure after rotator cuff reconstruction. Bisphosphonates (eg, zoledronic acid) increase bone mineral density.

Hypothesis: Zoledronic acid improves bone mineral density of the humeral head and biomechanical properties of the enthesis after reconstruction of chronic rotator cuff tears in rats.

Study Design: Controlled laboratory study.

Methods: A total of 32 male Sprague-Dawley rats underwent unilateral (left) supraspinatus tenotomy with delayed transosseous rotator cuff reconstruction after 3 weeks. All rats were sacrificed 8 weeks after rotator cuff repair. Animals were randomly assigned to 1 of 2 groups. At 1 day after rotator cuff reconstruction, the intervention group was treated with a single subcutaneous dose of zoledronic acid at 100 µg/kg bodyweight, and the control group received 1 mL of subcutaneous saline solution. In 12 animals of each group, micro-computed tomography scans of both shoulders were performed as well as biomechanical testing of the supraspinatus enthesis of both sides. In 4 animals of each group, histological analyses were conducted.

Results: In the intervention group, bone volume fraction (bone volume/total volume [BV/TV]) of the operated side was higher at the lateral humeral head ( = .005) and the medial humeral head ( = .010) compared with the control group. Trabecular number on the operated side was higher at the lateral humeral head ( = .004) and the medial humeral head ( = .001) in the intervention group. Maximum load to failure rates on the operated side were higher in the intervention group ( < .001). Cortical thickness positively correlated with higher maximum load to failure rates in the intervention group ( = 0.69; = .026). Histological assessment revealed increased bone formation in the intervention group.

Conclusion: Single-dose therapy of zoledronic acid provided an improvement of bone microarchitecture at the humeral head as well as an increase of maximum load to failure rates after transosseous reconstruction of chronic rotator cuff lesions in rats.

Clinical Relevance: Zoledronic acid improves bone microarchitecture as well as biomechanical properties after reconstruction of chronic rotator cuff tears in rodents. These results need to be verified in clinical investigations.
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http://dx.doi.org/10.1177/0363546520926471DOI Listing
July 2020

Osteoporosis and other musculoskeletal disorders-treatment is challenging!

Wien Med Wochenschr 2020 04;170(5-6):103

Medical Department II, St. Vincent Hospital, Stumpergasse 13, 1060, Vienna, Austria.

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http://dx.doi.org/10.1007/s10354-020-00745-2DOI Listing
April 2020

Correction to: Serum levels of sclerostin reflect altered bone microarchitecture in patients with hepatic cirrhosis.

Wien Klin Wochenschr 2020 04;132(7-8):216

Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria.

Correction to: Wien Klin Wochenschr 2019 https://doi.org/10.1007/s00508-019-01595-8 The original version of this article unfortunately contained a mistake. The last sentence should read: Patients with ALD had significantly lower sclerostin levels, compared to controls. The authors apologize for the ….
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http://dx.doi.org/10.1007/s00508-020-01613-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7645530PMC
April 2020

Serum levels of sclerostin reflect altered bone microarchitecture in patients with hepatic cirrhosis.

Wien Klin Wochenschr 2020 Jan 7;132(1-2):19-26. Epub 2020 Jan 7.

Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria.

Background: Patients with hepatic cirrhosis are at increased risk of bone loss. Recent work on areal bone mineral density has reported contradictory findings. As the assessment of bone microarchitecture is complex, a search was made for correlations with new serum markers of bone turnover. Current data on serum sclerostin levels in patients with increased fracture risk are divergent and to date only one study has examined patients with hepatic cirrhosis. Therefore, the aim of this study was to evaluate serum sclerostin levels and to test for correlations with microarchitecture.

Methods: This study was performed in 32 patients with recently diagnosed hepatic cirrhosis and 32 controls. The parameters of bone microarchitecture were assessed by high-resolution peripheral quantitative computed tomography. Sclerostin was detected via a new ELISA that detects the active receptor interaction site at loop 2 of the sclerostin core region.

Results: Sclerostin levels were slightly, but not significantly lower in the patient group, compared to controls. In contrast, patients with alcoholic liver cirrhosis had significantly lower levels than the controls. A significant correlation with areal bone mineral density (BMD) and trabecular microarchitecture was observed in the patient group. However, there was hardly any correlation between sclerostin and bone microarchitecture in the controls.

Conclusion: In hepatic cirrhosis, sclerostin is related to altered bone microarchitecture and lower areal BMD. In alcoholic liver disease, low sclerostin concentrations were seen.
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http://dx.doi.org/10.1007/s00508-019-01595-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6978289PMC
January 2020

Bone Stress Injuries Are Associated With Differences in Bone Microarchitecture in Male Professional Soldiers.

J Orthop Res 2019 12 26;37(12):2516-2523. Epub 2019 Aug 26.

Medical Department II-VINFORCE Study Group, St. Vincent Hospital, Academic Teaching Hospital of the Medical University of Vienna, Stumpergasse 13, Vienna, A-1060, Austria.

Bone stress injuries are commonly due to repetitive loading, as often described in competitive athletes or military recruits. The underlying pathophysiology of bone stress injuries is multifactorial. The present cross-sectional study investigated (i) cortical and trabecular bone microstructure as well as volumetric bone mineral density in subjects with bone stress injuries at the tibial diaphysis, measured at the distal tibia and the distal radius by means of high-resolution peripheral quantitative computed tomography (CT), (ii) areal bone mineral density using dual-energy X-ray absorptiometry as well as calcaneal dual X-ray absorptiometry and laser, and (iii) the influence on bone turnover markers of formation and resorption at the early phase after injury. A total of 26 Caucasian male professional soldiers with post-training bone stress injury at the tibial diaphysis were included (case group). A total of 50 male, Caucasian professional soldiers from the same military institution served as controls (control group). High-resolution peripheral quantitative CT revealed a higher total area at the radius within the case group. Cortical bone mineral density was reduced at the radius and tibia within the case group. The trabecular number and trabecular thickness were reduced at the tibia in the case group. The trabecular network was more inhomogeneous at the radius and tibia within the case group. Calcaneal dual X-ray absorptiometry and laser was significantly reduced in the case group. This study quantified differences in bone microstructure among otherwise healthy individuals. Differences in bone microarchitecture may impair the biomechanical properties by increasing the susceptibility to sustain bone stress injuries. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2516-2523, 2019.
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http://dx.doi.org/10.1002/jor.24442DOI Listing
December 2019

Substantial Biomechanical Improvement by Extracorporeal Shockwave Therapy After Surgical Repair of Rodent Chronic Rotator Cuff Tears.

Am J Sports Med 2019 07 17;47(9):2158-2166. Epub 2019 Jun 17.

Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, Vienna, Austria.

Background: Characteristics of chronic rotator cuff tears include continuous loss of tendon structure as well as tendon elasticity, followed by a high failure rate after surgical reconstruction. Several studies have already shown the beneficial effect of extracorporeal shockwave therapy (ESWT) on tissue regeneration in tendon pathologies.

Hypothesis: ESWT improves biomechanical tendon properties as well as functional shoulder outcomes in chronic rotator cuff reconstruction in rodents.

Study Design: Controlled laboratory study.

Methods: After tendon detachment and 3 weeks of degeneration, a subsequent transosseous reattachment of the supraspinatus tendon was performed in 48 adult male Sprague-Dawley rats (n = 16 per group). Rodents were randomly assigned to 3 study groups: no ESWT/control group, intraoperative ESWT (IntraESWT), and intra- and postoperative ESWT (IntraPostESWT). Shoulder joint function, as determined by gait analysis, was assessed repeatedly during the observation period. Eight weeks after tendon reconstruction, the rats were euthanized, and biomechanical and gene expression analyses were performed.

Results: Macroscopically, all repairs were intact at the time of euthanasia, with no ruptures detectable. Biomechanical analyses showed significantly improved load-to-failure testing results in both ESWT groups in comparison with the control group (control, 0.629; IntraESWT, 1.102; IntraPostESWT, 0.924; IntraESWT vs control, ≤ .001; IntraPostESWT vs control, ≤ .05). Furthermore, functional gait analyses showed a significant enhancement in intensity measurements for the IntraPostESWT group in comparison with the control group (≤ .05). Gene expression analysis revealed no significant differences among the 3 groups.

Conclusion: Clearly improved biomechanical results were shown in the single-application and repetitive ESWT groups. Furthermore, functional evaluation showed significantly improved intensity measurements for the repetitive ESWT group.

Clinical Relevance: This study underpins a new additional treatment possibility to prevent healing failure. Improved biomechanical stability and functionality may enable faster remobilization as well as an accelerated return to work and sports activities. Furthermore, as shockwave therapy is a noninvasive, easy-to-perform, cost-effective treatment tool with no undesired side effects, this study is of high clinical relevance in orthopaedic surgery. Based on these study results, a clinical study has already been initiated to clinically confirm the improved functionality by ESWT.
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http://dx.doi.org/10.1177/0363546519854760DOI Listing
July 2019

[Diagnosis and management of patients with diabetes and co-existing osteoporosis (Update 2019) : Common guideline of the Autrian Society for Bone and Mineral Research and the Austrian Diabetes Society].

Wien Klin Wochenschr 2019 May;131(Suppl 1):174-185

Externe Lehre, Medizinische Universität Wien, Wien, Österreich.

Fragility fractures are increasingly recognized as a complication of both type 1 and type 2 diabetes, with fracture risk that increases with disease duration and poor glycemic control. The identification and management of fracture risk in these patients remains challenging. This manuscript explores the clinical characteristics of bone fragility in adults with diabetes and highlights recent studies that have evaluated areal bone mineral density (BMD), bone microstructure and material properties, biochemical markers, and fracture prediction algorithms (FRAX) in these patients. It further reviews the impact of diabetes drugs on bone tissue as well as the efficacy of osteoporosis treatments in this population. An algorithm for the identification and management of diabetic patients at increased fracture risk is proposed.
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http://dx.doi.org/10.1007/s00508-019-1462-0DOI Listing
May 2019

Fracture patterns in patients with multiple fractures: the probability of multiple fractures and the most frequently associated regions.

Eur J Trauma Emerg Surg 2020 Oct 12;46(5):1151-1158. Epub 2019 Feb 12.

St. Vincent Hospital-Metabolic Bone Diseases Unit, The VINFORCE Study Group, Vienna, Austria.

Introduction: Multiple fractures are of high clinical relevance, as a significant increase in mortality rate has been described. The purpose of this study was to evaluate differences in age and gender distribution in multiple fractures dependent on severity of trauma. Furthermore, affected anatomic regions and frequently associated fracture regions were investigated.

Methods: Patients who had sustained multiple fractures between 2000 and 2012 were included in this study. At hospital admission, patients were divided according to trauma severity (high- vs low-traumatic), gender, and age for demographic analysis. Fractures were grouped in anatomical regions, and multiple fracture event probabilities as well as frequently associated regions were calculated.

Results: In total, 25,043 patients at an age range of 0-100 years (5.8% of all fracture patients; 14,769 male and 10,274 female patients) who sustained 57,862 multiple fractures were included. The lumbar/thoracic spine, cervical spine, femoral shaft, skull, and pelvis showed a probability of more than 40% of the presence of further fractures in each high-traumatic fracture event. In high-traumatic fracture events, male patients were more affected (p < 0.001). Considering low-traumatic fractures, female patients had a significantly higher proportion (p < 0.001) of multiple fractures among all fractures than male patients.

Conclusions: As a novelty, gender as well as age distributions in multiple fracture patients and a probability statement with the most affected anatomic regions, the risk of presence of further fractures for every region, and the frequently associated fracture regions including the percentage of occurrence are provided. These aspects yield new opportunities for clinical work and may reduce the high rate of overlooked fractures stated in the literature.
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http://dx.doi.org/10.1007/s00068-019-01087-4DOI Listing
October 2020

Bone matrix hypermineralization associated with low bone turnover in a case of Nasu-Hakola disease.

Bone 2019 06 11;123:48-55. Epub 2018 Oct 11.

Ludwig Boltzmann Institute of Osteology at Hanusch Hospital of WGKK and AUVA Trauma Centre Meidling, 1st Med. Dept. Hanusch Hospital, Vienna, Austria; Orthopedic Hospital of Speising, Pediatric Department, Vienna, Austria.

Analysis of tissue from a 34-years-old male patient from Austrian origin with a history of multiple fractures associated with painful episodes over the carpal, tarsal and at the end of the long bones respectively is presented. Radiographic images and axial 3DCT scans showed widespread defects in trabecular bone architecture and ill-defined cortices over these skeletal sites in the form of discrete cystic-like lesions. Family history indicated two sisters (one half and one full biological sisters) also with a history of fractures. Whole exome sequencing revealed two heterozygous missense mutations in TYROBP (MIM 604142; NM_003332.3) gene encoding for a cell-surface adaptor protein, which is part of a signaling complex triggering activation of immune responses. It is expressed in cells of the ectoderm cell linage such as NK and dendritic cells, macrophages, monocytes, myeloid cells, microglia cells and osteoclasts. The phenotype and genotype of the patient were consistent with the diagnosis of Nasu-Hakola disease (NHD) (OMIM 221770). Investigations at the bone material level of a transiliac bone biopsy sample from the patient using polarized light microscopy and backscatter electron imaging revealed disordered lamellar collagen fibril arrangement and extensively increased matrix mineralization. These findings are the first bone material data in a patient with NHD and point toward an osteoclast defect involvement in this genetic condition.
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http://dx.doi.org/10.1016/j.bone.2018.10.008DOI Listing
June 2019

Cortical bone loss is an early feature of nonradiographic axial spondyloarthritis.

Arthritis Res Ther 2018 08 30;20(1):202. Epub 2018 Aug 30.

Department of Internal Medicine 3, Friedrich Alexander University Erlangen-Nurnberg and Universitätsklinikum Erlangen, Ulmenweg 18, 91054, Erlangen, Germany.

Background: In the present study, we investigated bone geometry, microstructure, and volumetric bone mineral density (vBMD) in a cohort of patients with nonradiographic axial spondyloarthritis (nr-axSpA) in order to define the early bone changes occurring in axial spondyloarthritis (axSpA) and to define potential factors for deterioration of bone microstructure.

Methods: Patients with axSpA (n = 107) and healthy control subjects (n = 50) of similar age and sex were assessed for geometric, volumetric, and microstructural parameters of bone using high-resolution peripheral quantitative computed tomography (HR-pQCT) at the radius. Additionally, demographic and disease-specific characteristics of patients with axSpA were recorded.

Results: Patients with nr-axSpA and control subjects were comparable in age, sex, and body mass index. Geometric and microstructural analysis by HR-pQCT revealed a significantly reduced cortical area (p = 0.022) and cortical thickness (p = 0.006) in patients with nr-axSpA compared with control subjects. Total and cortical vBMD were significantly reduced in patients with nr-axSpA (p = 0.042 and p = 0.007, respectively), whereas there was no difference in trabecular vBMD. Patients with a short disease duration (< 2 years; n = 46) also showed significant reduction of cortical thickness and cortical area compared with control subjects. Patients with disease duration > 2 years (n = 55) additionally developed a decrease of cortical and total vBMD. Multiple regression models identified male sex to be associated with lower cortical vBMD and female sex to be associated with lower trabecular vBMD.

Conclusions: Bone microstructure in patients with nr-axSpA is characterized primarily by deterioration of cortical bone. Cortical bone loss starts early and is evident within the first 2 years of the disease.
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http://dx.doi.org/10.1186/s13075-018-1620-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6117894PMC
August 2018

Bone-related Circulating MicroRNAs miR-29b-3p, miR-550a-3p, and miR-324-3p and their Association to Bone Microstructure and Histomorphometry.

Sci Rep 2018 03 20;8(1):4867. Epub 2018 Mar 20.

Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, Vienna, Austria.

The assessment of bone quality and the prediction of fracture risk in idiopathic osteoporosis (IOP) are complex prospects as bone mineral density (BMD) and bone turnover markers (BTM) do not indicate fracture-risk. MicroRNAs (miRNAs) are promising new biomarkers for bone diseases, but the current understanding of the biological information contained in the variability of miRNAs is limited. Here, we investigated the association between serum-levels of 19 miRNA biomarkers of idiopathic osteoporosis to bone microstructure and bone histomorphometry based upon bone biopsies and µCT (9.3 μm) scans from 36 patients. Four miRNAs were found to be correlated to bone microarchitecture and seven miRNAs to dynamic histomorphometry (p < 0.05). Three miRNAs, namely, miR-29b-3p, miR-324-3p, and miR-550a-3p showed significant correlations to histomorphometric parameters of bone formation as well as microstructure parameters. miR-29b-3p and miR-324-p were found to be reduced in patients undergoing anti-resorptive therapy. This is the first study to report that serum levels of bone-related miRNAs might be surrogates of dynamic histomorphometry and potentially reveal changes in bone microstructure. Although these findings enhance the potential value of circulating miRNAs as bone biomarkers, further experimental studies are required to qualify the clinical utility of miRNAs to reflect dynamic changes in bone formation and microstructure.
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http://dx.doi.org/10.1038/s41598-018-22844-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5861059PMC
March 2018

Long-Term Effects of Severe Burn Injury on Bone Turnover and Microarchitecture.

J Bone Miner Res 2017 Dec 9;32(12):2381-2393. Epub 2017 Nov 9.

St. Vincent Hospital, Medical Department II-VINFORCE, Academic Teaching Hospital of the Medical University of Vienna, Vienna, Austria.

Severe burn injury triggers massive alterations in stress hormone levels with a dose-dependent hypermetabolic status including increased bone resorption. This study evaluated bone microarchitecture measured by noninvasive high-resolution peripheral quantitative computed tomography (HR-pQCT). Changes of serum bone turnover markers (BTM) as well as regulators of bone signaling pathways involved in skeletal health were assessed. Standardized effect sizes as a quantitative measure regarding the impact of serum changes and the prediction of these changes on bone microarchitecture were investigated. In total, 32 male patients with a severe burn injury (median total body surface area [TBSA], 40.5%; median age 40.5 years) and 28 matched male controls (median age 38.3 years) over a period of 24 months were included. In patients who had sustained a thermal injury, trabecular and cortical bone microstructure showed a continuous decline, whereas cortical porosity (Ct.Po) and pore volume increased. Initially, elevated levels of BTM and C-reactive protein (CRP) continuously decreased over time but remained elevated. In contrast, levels of soluble receptor activator of NF-κB ligand (sRANKL) increased over time. Osteocalcin, bone-specific alkaline phosphatase (BALP), intact N-terminal type 1 procollagen propeptide (P1NP), and cross-linked C-telopeptide (CTX) acutely reflected the increase of Ct.Po at the radius (R  = 0.41), followed by the reduction of trabecular thickness at the tibia (R  = 0.28). In adult male patients, early and sustained changes of markers of bone resorption, formation and regulators of bone signaling pathways, prolonged inflammatory cytokine activities in conjunction with muscle catabolism, and vitamin D insufficiency were observed. These alterations are directly linked to a prolonged deterioration of bone microstructure. The probably increased risk of fragility fractures should be of clinical concern and subject to future interventional studies with bone-protective agents. © 2017 American Society for Bone and Mineral Research.
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http://dx.doi.org/10.1002/jbmr.3211DOI Listing
December 2017

Circulating microRNA Signatures in Patients With Idiopathic and Postmenopausal Osteoporosis and Fragility Fractures.

J Clin Endocrinol Metab 2016 11 23;101(11):4125-4134. Epub 2016 Aug 23.

St. Vincent Hospital-Medical Department II (R.K., C.M., R.D., F.P., X.F., H.Res.), The VINFORCE Study Group, Academic Teaching Hospital of Medical University of Vienna, 1090 Vienna, Austria; TAmiRNA, GmbH (E.G., S.S, M.H..), 1190 Vienna, Austria; Department of Statistics and Operations Research (A.B.), University of Vienna, 1090 Vienna, Austria; Ludwig Boltzmann Institute for Experimental and Clinical Traumatology (R.K., P.H., H.Red.), 1200 Vienna, Austria; Karl Donath Laboratory for Hard Tissue and Biomaterial Research, Department of Oral Surgery (P.H.), Medical University of Vienna, 1090 Vienna, Austria; Department of Internal Medicine, Division of Endocrinology and Diabetes (A.F.-P.), Medical University of Graz, 8010 Graz, Austria; Christian Doppler Laboratory on Biotechnology of Skin Aging, Department of Biotechnology (J.G.), University of Natural Resources and Life Sciences Vienna, 1180 Viena, Austria; Austrian Cluster for Tissue Regeneration (H.Red., J.G.), Department of Traumatology, Medical University of Vienna, 1090 Vienna, Austria; and Medical Faculty of Bone Diseases (H.Red.), Sigmund Freud University-Vienna, 1020 Vienna, Austria.

Context: Established bone turnover markers do not reflect fracture risk in idiopathic male and premenopausal osteoporosis and the role of microRNAs (miRNAs) in these patients is currently unclear. miRNAs are a class of small non-coding RNAs that regulate gene expression and bone tissue homeostasis. They are considered a new class of endocrine regulators with promising potential as biomarkers.

Objective: Evaluation of circulating miRNA signatures in male and female subjects with idiopathic and postmenopausal osteoporotic low-traumatic fractures.

Design, Setting, And Patients: This was a case-control study of cross-sectional design of 36 patients with prevalent low-traumatic fractures and 39 control subjects Main Outcome Measures: One hundred eighty-seven miRNAs were quantified in serum by qPCR, compared between groups and correlated with established bone turnover markers.

Results: Significant differences in serum levels of circulating miRNAs were identified in all three subgroups (46 in premenopausal, 52 in postmenopausal, 55 in male). A set of 19 miRNAs was consistently regulated in all three subgroups. Eight miRNAs [miR-152-3p, miR-30e-5p, miR-140-5p, miR-324-3p, miR-19b-3p, miR-335-5p, miR-19a-3p, miR-550a-3p] were excellent discriminators of patients with low-traumatic fractures, regardless of age and sex, with area under the curve values > 0.9. The 11 remaining miRNAs showed area under the curve values between 0.81 and 0.89. Correlation analysis identified significant correlations between miR-29b-3p and P1NP, and miR-365-5p and iPTH, TRAP5b, P1NP and Osteocalcin, as well as BMD and miR-19b-3p, miR-324-3p, miR-532-5p, and miR-93-5p.

Conclusions: Specific serum miRNA profiles are strongly related to bone pathologies. Therefore miRNAs might be directly linked to bone tissue homeostasis. In particular, miR-29b-3p has previously been reported as regulator of osteogenic differentiation and could serve as a novel marker of bone turnover in osteoporotic patients as a member of a miRNA signature.
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http://dx.doi.org/10.1210/jc.2016-2365DOI Listing
November 2016

Diagnosis and treatment of Paget's disease of bone : A clinical practice guideline.

Wien Med Wochenschr 2017 Feb 6;167(1-2):18-24. Epub 2016 Sep 6.

Metabolic Bone Diseases Unit, St. Vincent Hospital, Stumpergasse 13, 1060, Vienna, Austria.

Paget's disease of bone (osteitis deformans) is a benign focal disorder of accelerated skeletal remodeling. Either a single bone (monostotic) or multiple bones (polyostotic) can be affected. In patients with suspected Paget's disease plain radiographs of the suspicious regions of the skeleton are recommended. The initial biochemical evaluation of a patient should be done using serum total ALP (alkaline phosphatase) or with the use of a more specific marker of bone formation: PINP (intact N-terminal type 1 procollagen propeptide) or CTX (cross-linked C‑telopeptide). Treatment with a bisphosphonate is recommended for most patients with active Paget's disease who are at risk for further skeletal and extraskeletal complications. A single dose of 5 mg i.v. zoledronate as the treatment of choice in patients without contraindications is suggested. Oral bisphosphonates are less potent when compared to zoledronate. Treatment with an antiresorptive agent induces a more rapid decrease in resorption markers compared to formation marker. Measurement of total ALP or other baseline disease activity markers (e. g. CTX) at 6 to 12 weeks, when bone turnover will have shown a substantial decline, is an acceptable and cost-effective option. Maximum suppression of high bone turnover may require measurement at 6 months after administration. In patients with increased bone turnover, biochemical follow-up is recommended to be used as a more objective indicator of relapse rather than symptoms. The prolonged response after zoledronate treatment should be assessed every 1-2 years after normal bone turnover. With less potent drugs, every 6 to 12 months is appropriate.
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http://dx.doi.org/10.1007/s10354-016-0502-xDOI Listing
February 2017

Bone microarchitecture deteriorations and a fragility fracture in a patient with beta and alpha heterozygous thalassemia: a case report.

Wien Klin Wochenschr 2017 Mar 30;129(5-6):212-216. Epub 2016 Jun 30.

Medical Department II, St. Vincent Hospital Vienna, Academic Teaching Hospital of the Medical University Vienna, Stumpergasse 13, 1060, Vienna, Austria.

To date there are few studies that have investigated bone mineral density (BMD) and markers of bone metabolism in patients with thalassemia minor form. None of the previous trials presented bone structure analysis in the patient populations. We present the case of a 24-year-old Turkish woman with heterozygous beta and alpha thalassemia who sustained a low-trauma fracture of the inferior pubic ramus. Despite normal markers of bone metabolism, the dual X‑ray absorptiometry (DXA) showed decreased areal bone mineral density. Furthermore, severely reduced bone structure parameters and reduced volumetric bone mineral density was assessed by high-resolution peripheral quantitative computed tomography (HR-pQCT). Due to these diagnostic findings at time of peak bone mass, an osteoanabolic therapy with teriparatide for 24 months was initiated. The findings concerning BMD and bone structure in this patient can be seen as caused by the beta and alpha thalassemia.
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http://dx.doi.org/10.1007/s00508-016-1032-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5346126PMC
March 2017

High-resolution Quantitative Computed Tomography Demonstrates Structural Defects in Cortical and Trabecular Bone in IBD Patients.

J Crohns Colitis 2016 May 27;10(5):532-40. Epub 2016 Jan 27.

Department of Internal Medicine 3,

Background And Aims: To investigate the macro- and microstructural changes of bone in patients with inflammatory bowel disease [IBD] and to define the factors associated with bone loss in IBD.

Methods: A total of 148 subjects, 59 with Crohn's disease [CD], 39 with ulcerative colitis [UC], and 50 healthy controls were assessed for the geometric, volumetric and microstructural properties of bone using high-resolution peripheral quantitative computed tomography. In addition, demographic and disease-specific characteristics of IBD patients were recorded.

Results: IBD patients and controls were comparable in age, sex, and body mass index. Total [p = 0.001], cortical [p < 0.001], and trabecular volumetric bone mineral density [BMD] [p = 0.03] were significantly reduced in IBD patients compared with healthy controls. Geometric and microstructural analysis revealed significantly lower cortical area [p = 0.001] and cortical thickness [p < 0.001] without differences in cortical porosity, pore volume, or pore diameter. CD showed a more severe bone phenotype than UC: cortical bone loss was observed in both diseases, but CD additionally showed profound trabecular bone loss with reduced trabecular BMD [p = 0.008], bone volume [p = 0.008], and trabecular thickness [p = 0.009]. Multivariate regression models identified the diagnosis of CD, female sex, lower body mass index, and the lack of remission as factors independently associated with bone loss in IBD.

Conclusion: IBD patients develop significant cortical bone loss, impairing bone strength. Trabecular bone loss is limited to CD patients, who exhibit a more severe bone phenotype compared with UC patients.
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http://dx.doi.org/10.1093/ecco-jcc/jjw012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4957457PMC
May 2016

Early and Sustained Changes in Bone Metabolism After Severe Burn Injury.

J Clin Endocrinol Metab 2016 04 20;101(4):1506-15. Epub 2016 Jan 20.

Division of Plastic and Reconstructive Surgery (G.K.M., A.F., S.N., I.T., T.R.), Department of Surgery, and Department of Pathophysiology and Allergy Research (P.P.), Center for Pathophysiology, Infectiology and Immunology, The Medical University of Vienna, and Department of Statistics and Operations Research (A.B.), The University of Vienna, 1090 Vienna, Austria; Department of Plastic, Reconstructive and Aesthetic Surgery (E.S.), The Medical University Innsbruck, 6020 Innsbruck, Austria; St. Vincent Hospital (R.K., H.M., J.H., H.R., C.M.), Medical Department II, Academic Teaching Hospital of The Medical University of Vienna, and Karl Landsteiner Institute for Gastroenterology and Rheumatology (H.R.), 1060 Vienna, Austria.

Context: Severe burn injury causes a massive stress response, consecutively heightened serum levels of acute phase proteins, cortisol, and catecholamines with accompanying disturbance in calcium metabolism.

Objective: Evaluation of early and prolonged changes of serum bone turnover markers (BTMs) and regulators of bone metabolism.

Design: Longitudinal observational design.

Setting: University clinic.

Patients: A total of 32 male patients with a median age of 40.5 years and a median burned total body surface area of 40% (83% patients with full thickness burn injury).

Interventions: None.

Main Outcome Measures: Comparison of changes of BTM/regulators of bone metabolism in the early (d 2–7) and prolonged (d 7–56) phases after trauma.

Results: All investigated BTM/regulators significantly changed. During the early phase, pronounced increases were observed for serum type 1 collagen cross-linked C-telopeptide, intact N-terminal propeptide of type I procollagen, sclerostin, Dickkopf-1, bone-specific alkaline phosphatase, fibroblast growth factor 23, and intact parathyroid hormone levels, whereas 25-hydroxyvitamin D, albumin, serum, and ionized calcium levels decreased. Changes of osteoprotegerin, osteocalcin, and phosphate were less pronounced but remained significant. In the prolonged phase, changes of intact N-terminal propeptide of type I procollagen were most pronounced, followed by elevated sclerostin, osteocalcin, bone-specific alkaline phosphatase, and lesser changes for albumin levels. Calcium and ionized calcium levels tardily increased and remained within the limit of normal. In contrast, levels of intact parathyroid hormone, fibroblast growth factor 23, C-reactive protein, and to a lesser extent serum type 1 collagen cross-linked C-telopeptide and phosphate levels declined significantly during this phase of investigation.

Conclusions: Ongoing changes of BTM and regulators of bone metabolism suggest alterations in bone metabolism with a likely adverse influence on bone quality and structure in male patients with severe burn injuries.
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http://dx.doi.org/10.1210/jc.2015-3575DOI Listing
April 2016

The Impact of Vitamin D, Calcium, Protein Supplementation, and Physical Exercise on Bone Metabolism After Bariatric Surgery: The BABS Study.

J Bone Miner Res 2016 Mar 30;31(3):672-82. Epub 2015 Sep 30.

Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, the Medical University of Vienna, Vienna, Austria.

Laparoscopic Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) are common and effective methods to treat severe obesity, but these procedures can adversely influence bone metabolism and areal bone mineral density (aBMD). This was a prospective 24-month single-center interventional two-arm study in 220 women and similarly aged men (median age 40.7 years) with a body mass index (BMI) >38 kg/m(2) after RYGB and SG procedures. Patients were randomized into: 1) an intervention group receiving: 28,000 IU cholecalciferol/wk for 8 weeks before bariatric surgery, 16,000 IU/wk and 1000 mg calciummonocitrate/d after surgery, daily BMI-adjusted protein supplementation and physical exercise (Nordic walking, strength perseverance, and equipment training); 2) a non-intervention group: no preoperative loading, nutritional supplementation, or obligatory physical exercise. At study endpoint, when comparing the intervention group to the non-intervention group, the relative percentage changes of serum levels of sclerostin (12.1% versus 63.8%), cross-linked C-telopeptide (CTX, 82.6% versus 158.3%), 25-OH vitamin D (13.4% versus 18.2%), phosphate (23.7% versus 32%, p < 0.001 for all), procollagen type 1 amino-terminal propeptide (P1NP, 12% versus 41.2%), intact parathyroid hormone (iPTH, -17.3% versus -7.6%), and Dickkopf-1 (-3.9% versus -8.9%, p < 0.05 for all) differed. The decline in lumbar spine, total hip and total body aBMD, changes in BMI, lean body mass (LBM), as well as changes in trabecular bone score (TBS) values (p < 0.005 for all) were less, but significantly, pronounced in the intervention group. We conclude that vitamin D loading and ongoing vitamin D, calcium, and BMI-adjusted protein supplementation in combination with physical exercise decelerates the loss of aBMD and LBM after bariatric surgery. Moreover, the well-known increases of bone turnover markers are less pronounced.
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http://dx.doi.org/10.1002/jbmr.2707DOI Listing
March 2016

Osteogenesis imperfecta type III and hypogonadotropic hypogonadism result in severe bone loss: a case report.

Wien Med Wochenschr 2015 Jul 21;165(13-14):285-9. Epub 2015 Jul 21.

Medical Department II, St. Vincent Hospital Vienna, Academic Teaching Hospital of the Medical University Vienna, Stumpergasse 13, 1060, Vienna, Austria.

We present the case of a 33-year-old male patient with multiple fractures and typical radiographical and clinical characteristics of osteogenesis imperfecta (OI) type III. Furthermore, the patient has suffered from hypogonadotropic hypogonadism since childhood. On the basis of antiresorptive therapy, no further fractures occurred within several years. Recently, recurrent nontraumatic fractures without bone healing were observed. Decreased bone mineral density was assessed by dual X-ray absorptiometry (DXA). High-resolution peripheral quantitative computed tomography (HR-pQCT) showed impaired trabecular bone structure. Due to recurrent fragility fractures and severe deterioration of bone structure, an osteoanabolic treatment with teriparatide was initiated to potentially stimulate fracture healing and to increase bone formation.
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http://dx.doi.org/10.1007/s10354-015-0367-4DOI Listing
July 2015

Vitamin D levels and comorbidities in ambulatory and hospitalized patients in Austria.

Wien Klin Wochenschr 2015 Sep 17;127(17-18):675-84. Epub 2015 Jul 17.

Labcon-Medical Laboratories Ltd., St. Vincent Group, Vienna, Austria.

Vitamin D in its hormonal active form, 1,25-dihydroxyvitamin D (calcitriol), has a major impact on bone turnover by regulating calcium and phosphate homoeostasis. By binding the active vitamin D hormone to the vitamin D receptor (VDR), it acts as a nuclear transcription factor (Bouillon et al., Endocr Rev 29(6):726-776, 2008). The discovery that almost all tissues and cells in the body express the VDR and that several tissues possess the enzymatic capability to convert 25-hydroxyvitamin D (25(OH)-D3; cholecalciferol) to the active form, suggests that vitamin D fulfills various extra-osseous functions (Bouillon et al., Endocr Rev 29(6):726-776, 2008; Holick, N Engl J Med 357(3):266-281, 2007). For example, VDR ensures adequate intestinal calcium absorption by regulating the synthesis of several calcium transport proteins in the duodenum (Bouillon et al., Endocr Rev 29(6):726-776, 2008). Additionally, vitamin D is important for proper muscle function, and some studies suggest it may contribute to prevent type 1 diabetes mellitus, certain autoimmune diseases, hypertension, and several types of cancer (Holick, N Engl J Med 357(3):266-281, 2007).
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http://dx.doi.org/10.1007/s00508-015-0824-5DOI Listing
September 2015

Atypical Femoral Fractures-Ongoing and History of Bone-Specific Therapy, Concomitant Diseases, Medications, and Survival.

J Clin Densitom 2016 Jul-Sep;19(3):359-67. Epub 2015 Jun 23.

Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology, and Immunology, Medical University of Vienna, Vienna, Austria.

Although atypical femoral fractures (AFFs) are generally rare events; several studies have indicated a potential link between AFF and long-term bone-specific therapies (BSTs). The aim of this study was to analyze the frequency of AFF and potential associations with prior or ongoing BST. A total of 8851 Caucasian female and male patients with de novo hip fractures treated in the largest Austrian level 1 trauma center from 2000 to 2013 were selected. Of the total, 194 patients with a de novo low-traumatic subtrochanteric or shaft fractures were identified: 35 atypical and 159 typical fractures. Of these patients, concomitant diseases, medication, previous fractures, and survival data were retrieved and analyzed. Female patients in both groups were significantly older. The median survival was significantly shorter in patients with AFF (9 vs 18 months; p < 0.0001). Cardiovascular disease, sarcopenia, chronic kidney disease, type 2 diabetes, smoking (past or current history), and prevalent fragility fractures were more frequent in AFF patients, as well as the concomitant use of phenprocoumon, furosemide, and sulfonylurea. Although the number of patients with current BST was less in (14.5%) both groups, more patients in the AFF group were previously treated with BST (71% vs 49%; p = 0.016), and they received these therapies for a longer time period. A combination of severe comorbidities, long-term pharmaceutical therapies, and a history of previous or ongoing BST was associated with an increased individual risk for AFF.
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http://dx.doi.org/10.1016/j.jocd.2015.05.070DOI Listing
February 2018

TBS reflects trabecular microarchitecture in premenopausal women and men with idiopathic osteoporosis and low-traumatic fractures.

Bone 2015 Oct 16;79:259-66. Epub 2015 Jun 16.

St. Vincent Hospital, Medical Department II, Academic Teaching Hospital of the Medical University of Vienna, Austria.

Transiliac bone biopsies, while widely considered to be the standard for the analysis of bone microstructure, are typically restricted to specialized centers. The benefit of Trabecular Bone Score (TBS) in addition to areal bone mineral density (aBMD) for fracture risk assessment has been documented in cross-sectional and prospective studies. The aim of this study was to test if TBS may be useful as a surrogate to histomorphometric trabecular parameters of transiliac bone biopsies. Transiliac bone biopsies from 80 female patients (median age 39.9 years-interquartile range, IQR 34.7; 44.3) and 43 male patients (median age 42.7 years-IQR 38.9; 49.0) with idiopathic osteoporosis and low traumatic fractures were included. Micro-computed tomography values of bone volume fraction (BV/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N), trabecular separation (Tb.Sp), structural model index (SMI) as well as serum bone turnover markers (BTMs) sclerostin, intact N-terminal type 1 procollagen propeptide (P1NP) and cross-linked C-telopeptide (CTX) were investigated. TBS values were higher in females (1.282 vs 1.169, p< 0.0001) with no differences in spine aBMD, whereas sclerostin levels (45.5 vs 33.4 pmol/L) and aBMD values at the total hip (0.989 vs 0.971 g/cm(2), p<0.001 for all) were higher in males. Multiple regression models including: gender, aBMD and BTMs revealed TBS as an independent, discriminative variable with adjusted multiple R(2) values of 69.1% for SMI, 79.5% for Tb.N, 68.4% for Tb.Sp, and 83.3% for BV/TV. In univariate regression models, BTMs showed statistically significant results, whereas in the multiple models only P1NP and CTX were significant for Tb.N. TBS is a practical, non-invasive, surrogate technique for the assessment of cancellous bone microarchitecture and should be implemented as an additional tool for the determination of trabecular bone properties.
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http://dx.doi.org/10.1016/j.bone.2015.06.007DOI Listing
October 2015

Ibandronate increases sclerostin levels and bone strength in male patients with idiopathic osteoporosis.

Calcif Tissue Int 2015 Jun 25;96(6):477-89. Epub 2015 Apr 25.

Medical Department II, St. Vincent Hospital, Academic Teaching Hospital of the Medical University of Vienna, Stumpergasse 13, 1060, Vienna, Austria,

The pathomechanism of male idiopathic osteoporosis (MIO) differs from postmenopausal osteoporosis with regard to alterations in osteoblast activity. We evaluated intravenous ibandronate (IBN) in 25 MIO patients with fragility fractures in a prospective, monocentric, single-arm, and open-label study for 24 months. The impact and changes of sclerostin (Scl), Dickkopf-1 (DKK-1), CTX, and PINP were examined. Additionally, volumetric cortical, trabecular and areal bone mineral density (BMD), trabecular bone score (TBS), and finite element analyses (FEA) were evaluated. Compared to baseline, median Scl levels were increased after 1 month (Δ 121%, p < 0.0001) and remained elevated for 12 months. DKK-1 decreased (p < 0.001) to a lesser extent until month 9 with values comparable to baseline at study endpoint. Early changes (baseline-month 1) of Scl negatively correlated with early changes of DKK-1 (-0.72), CTX (-0.82), and PINP (-0.55; p < 0.005 for all). The overall changes over the 24 months study period of Scl negatively correlated with decreased CTX (-0.32) and DKK-1 levels (-0.57, p < 0.0001 for both); CTX and PINP changes positively correlated at each time point (p < 0.001). Volumetric hip BMD increased by 12 and 18%, respectively (p < 0.0001 for both). Cross-sectional moment of inertia and section modulus for total hip significantly improved (p < 0.05 for all). Areal BMD at total hip, spine, and TBS increased. FEA displayed an increase in bone strength both in the hip (17%) and vertebrae (13%, all p < 0.0001) at anatomical sites susceptible for fragility fracture. IBN increases Scl and improves cortical and trabecular bone strength with early and ongoing vigorous suppression of bone resorption.
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http://dx.doi.org/10.1007/s00223-015-0003-8DOI Listing
June 2015

Quantitative and Qualitative Changes of Bone in Psoriasis and Psoriatic Arthritis Patients.

J Bone Miner Res 2015 Oct 10;30(10):1775-83. Epub 2015 May 10.

Department of Internal Medicine 3 and Institute of Clinical Immunology, University of Erlangen-Nuremberg, Erlangen, Germany.

Psoriatic arthritis (PsA) is a chronic inflammatory disease characterized by periarticular bone loss and new bone formation. Current data regarding systemic bone loss and bone mineral density (BMD) in PsA are conflicting. The aim of this study was to evaluate bone microstructure and volumetric BMD (vBMD) in patients with PsA and psoriasis. We performed HR-pQCT scans at the ultradistal and periarticular radius in 50 PsA patients, 30 psoriasis patients, and 70 healthy, age- and sex-related controls assessing trabecular bone volume (BV/TV), trabecular number (Tb.N), inhomogeneity of the trabecular network, cortical thickness (Ct.Th), and cortical porosity (Ct.Po), as well as vBMD. Trabecular BMD (Tb.BMD, p = 0.021, 12.0%), BV/TV (p = 0.020, -11.9%), and Tb.N (p = 0.035, 7.1%) were significantly decreased at the ultradistal radius and the periarticular radius in PsA patients compared to controls. In contrast, bone architecture of the ultradistal radius and periarticular radius was similar in patients with psoriasis and healthy controls. Duration of skin disease was associated with low BV/TV and Tb.N in patients with PsA. These data suggest that trabecular BMD and bone microstructure are decreased in PsA patients. The observation that duration of skin disease determines bone loss in PsA supports the concept of subclinical musculoskeletal disease in psoriasis patients.
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http://dx.doi.org/10.1002/jbmr.2521DOI Listing
October 2015

Anti-TNFs in axial spondyloarthritis.

Wien Med Wochenschr 2015 Jan 9;165(1-2):10-3. Epub 2015 Jan 9.

St. Vincent Hospital-Medical Department II, Academic Teaching Hospital, The VINFORCE Study Group, Medical University of Vienna, Stumpergasse 13, 1060, Vienna, Austria,

Since there is no evidence regarding the efficacy of conventional synthetic disease modifying anti-rheumatic drugs in the improvement of axial spondyloarthritis (SpA), anti-tumor necrosis factors (anti-TNFs) are recommended if nonsteroidal anti-inflammatory drugs fail, or in case of high disease activity. Anti-TNFs show encouraging data regarding pain reduction, improved mobility and quality of life in both ankylosing spondylitis and non-radiographic axial spondyloarthritis. However, withdrawal of anti-TNF therapy leads to relapse of disease activity in SpA. Moreover, osteoproliferation does not seem to be influenced by anti-TNFs.
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http://dx.doi.org/10.1007/s10354-014-0338-1DOI Listing
January 2015

Sclerostin levels and changes in bone metabolism after bariatric surgery.

J Clin Endocrinol Metab 2015 Mar 9;100(3):891-901. Epub 2014 Dec 9.

St Vincent Hospital, Medical Department II (C.M., R.K., C.M., A.R.N., H.R.), Academic Teaching Hospital of Medical University of Vienna, Stumpergasse 13, Vienna, Austria; Division of Plastic and Reconstructive Surgery, Department of Surgery (G.K.M.), Medical University of Vienna, Vienna, Austria; Department of Pathophysiology and Allergy Research (P.P.), Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna. Vienna, Austria.

Context: The role of sclerostin as a key regulator of bone formation remains unknown after Roux-en-Y gastric bypass (RYGB) or laparoscopic sleeve gastrectomy (SG).

Objectives: The study objectives were evaluation of sclerostin and Dickkopf-1 (DKK-1) serum levels after surgery and correlations with bone turnover markers (P1NP, CTX), parathyroid hormone (iPTH) and areal bone mineral density (BMD), changes at total body, lumbar spine and total hip.

Design And Setting: This was a prospective observational single-center two-arm study in premenopausal women with acute adipositas over 24 months.

Participants: Participants were 52 premenopausal women (40 ± 8 years, BMI 43.4) after RYGB and 38 premenopausal women (41 ± 7 years, BMI 45.7) after SG.

Main Outcome Measures: Prior to surgery and 1, 3, 6, 9, 12, 18, and 24 months after surgery sclerostin, DKK-1, CTX, P1NP levels and BMD were measured.

Results: Sclerostin, CTX and (to a lesser extent) P1NP increased after surgery and remained elevated during the entire study period (P < 0.001). DKK-1 declined during months 3-9 (P < 0.005) and then remained unchanged, serum phosphate continuously increased (P < 0.001), iPTH remained within the upper normal limit. Sclerostin increases were significantly positively correlated with CTX and P1NP increases and negatively correlated with BMD loss. BMD independently declined regardless of RYGB and SG. Elevations of sclerostin, CTX, P1NP, and phosphate, but not DKK-1 and iPTH, were significant discriminating factors for BMD loss (AUC 0.920).

Conclusion: Rapid and sustained increases of sclerostin, CTX, and to a lesser extent, P1NP cause an increase in bone metabolism and result in BMD loss at all skeletal sites.
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http://dx.doi.org/10.1210/jc.2014-3367DOI Listing
March 2015

Biological agents in psoriatic arthritis.

Wien Med Wochenschr 2015 Jan 10;165(1-2):36-9. Epub 2014 Sep 10.

Medical Department II, St. Vincent Hospital,Academic Teaching Hospital of Medical University of Vienna, The VINFORCE Study Group, Stumpergasse 13, 1060, Vienna, Austria,

Anti-tumor necrosis factors (TNFs) are effective drugs for the treatment of psoriatic arthritis (PsA) regarding reduction of pain and inflammation, enthesitis, dactylitis, as well as psoriatic skin and nail disease. Moreover, radiographic progression in PsA is decelerated. The efficacy of anti-TNFs seems to be independent of synthetic disease-modifying anti-rheumatic drugs, suggesting only a minor role of combination therapy in PsA. Anti-TNFs are generally well tolerated in patients with PsA. Adverse events are similar to those reported in patients with rheumatoid arthritis. Ustekinumab, a recently approved IL-12/IL-23-antibody is another promising biological agent in the treatment of PsA.
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http://dx.doi.org/10.1007/s10354-014-0300-2DOI Listing
January 2015
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