Perspectives on Fracture Liaison Service in Austria: clinical and economic considerations.

Osteoporosis is a widespread disease and affects over 500,000 people in Austria. Fragility fractures are associated with it and represent not only an individual problem for the patients, but also an enormous burden for the healthcare system. While trauma surgery care is well provided in Vienna, there is an enormous treatment gap in secondary prevention after osteoporotic fracture. Systematic approaches such as the Fracture Liaison Service (FLS) aim to identify patients with osteoporosis after fracture, to clarify diagnostically, to initiate specific therapy, and to check therapy adherence. The aim of this article is to describe the practical implementation and operational flow of an already established FLS in Vienna. This includes the identification of potential FLS inpatients, the diagnostic workup, and recommendations for an IT solution for baseline assessment and follow-up of FLS patients. We summarize the concept, benefits, and limitations of FLS and provide prospective as well as clinical and economic considerations for a city-wide FLS, managed from a central location. Future concepts of FLS should include artificial intelligence for vertebral fracture detection and simple IT tools for the implementation of FLS in the outpatient sector.

Use of Complementary and Alternative Medicine in Patients with Rare Bone Diseases and Osteoporosis.

(1) Background: The use of complementary and alternative medicine (CAM) has seen a notable increase in popularity. However, there is an absence of data regarding the prevalence of CAM use in patients with rare bone diseases (RBDs). (2) Methods: This monocentric, cross-sectional study was carried out in a reference hospital for RBDs. RBD patients included individuals with osteogenesis imperfecta, hypophosphatasia and X-linked hypophosphatemia, and their data were compared with those of patients with osteoporosis (OPO) and of healthy controls (CON). This study utilized the German version (I-CAM-G) of the I-CAM questionnaire. (3) Results: This study comprised 50 RBD patients [mean age (SD) of 48.8 (±15.9), 26% male], 51 OPO patients [66.6 (±10.0), 9.8% male] and 52 controls [50.8 (±16.3), 26.9% male]. Treatments by naturopaths/healers were more prevalent in the RBD group (11.4%) compared with OPO (0%) and CON (5.8%) (p = 0.06). More than half of the OPO (60.8%) and CON (63.5%) patients and 46% of the RBD patients reported vitamin/mineral intake within the past 12 months (p = 0.16). Individuals with tertiary education had a significantly higher odds ratio of 2.64 (95% CI: 1.04-6.70, p = 0.04) for visiting any CAM provider. Further, OPO patients were significantly less likely to use self-help techniques compared with the CON group (OR = 0.42, 95% CI: 0.19-0.95; p = 0.04). (4) Conclusions: Herbal medicine, vitamin and mineral supplements, and self-help techniques were the most common forms of CAM reported by patients with RBDs. However, the use of CAM was generally low.

Health-related quality of life and fatigue in adult rare bone disease patients: A cross-sectional study from Austria.

OBJECTIVES: To assess physical and mental health domains of health related quality of life (HRQoL) as well as fatigue in rare bone disease (RBD) patients and to compare to patients with osteoporosis (OPO) and healthy controls (CTRL) without known bone diseases and to study associations of Fatique Severity Scale (FSS) with eight domains of HRQoL. METHODS: Monocentric, cross-sectional study carried out between 2020 and 2022 in a hospital affiliated with the Vienna Bone and Growth Center (European Reference Network Center for Rare Bone Disease) in Vienna, Austria. The study comprised three types of RBD: Osteogenesis imperfecta, Hypophosphatasia and X-linked Hypophosphatemia. Fatigue was assessed by FSS. The higher score indicates more fatigue severity. HRQoL was assessed by Short-Form Health Survey (SF-36 v2). Physical component (PCS) and mental component summary scores (MCS) were calculated and normalised to a general population. A higher score indicates better HRQoL. Age-adjusted ANCOVA was used to assess differences in PCS and MCS between groups. Spearman correlation was used for associations of FSS with eight domains of HRQoL. RESULTS: Study comprised 50 RBD patients [Mean age (SD) 48.8 (±15.9), 26 % male], 51 OPO patients [66.6 (±10.0), 9.8 % male] and 52 controls [50.8 (±16.3), 26.9 % male]. RBD patients had significantly higher mean age-adjusted FSS (3.5, 95 % CI 3.1-4.0) than controls (2.6, 95 % CI 2.2-3.0, p = 0.008), but not in comparison to osteoporotic patients 2.6 (95 % CI 2.2-3.0, p = 0.69). Diminished age-adjusted PCS of HRQoL was observed in RBD patients with a mean score of 37.1 (95 % CI 33.4-40.8), whereas their MCS of 50.1 (95 % CI 46.6-53.7) was comparable to controls (52.9, 95 % CI 49.8-56.0) and osteoporotic patients (50.2, 95 % CI 45.4-54.9). FSS score was negatively correlated with physical and mental component in RBD (ρ = -0.37, p < 0.05 and ρ = -0.54, p < 0.01, respectively) and OPO patients (ρ = -0.37, p < 0.05 and ρ = -0.35, p < 0.01, respectively). CONCLUSIONS: The HRQoL in adult patients with rare bone diseases is lower than compared to osteoporotic and control group in this Austrian population. Fatigue has significant negative impact on HRQoL and it is important to address it when meeting with RBD patients in clinical practice.

The challenge of hypophosphatasia diagnosis in adults: results from the HPP International Working Group Literature Surveillance.

Hypophosphatasia (HPP) is an inborn error of metabolism caused by reduced or absent activity of the tissue non-specific alkaline phosphatase (TNSALP) enzyme, resulting from pathogenic variants in the ALPL gene. Clinical presentation of HPP is highly variable, including lethal and severe forms in neonates and infants, a benign perinatal form, mild forms manifesting in adulthood, and odonto-HPP. Diagnosis of HPP remains a challenge in adults, as signs and symptoms may be mild and non-specific. Disease presentation varies widely; there are no universal signs or symptoms, and the disease often remains underdiagnosed or misdiagnosed, particularly by clinicians who are not familiar with this rare disorder. The absence of diagnosis or a delayed diagnosis may prevent optimal management for patients with this condition. Formal guidelines for the diagnosis of adults with HPP do not exist, complicating efforts for consistent diagnosis. To address this issue, the HPP International Working Group selected 119 papers that explicitly address the diagnosis of HPP in adults through a Medline, Medline In-Process, and Embase search for the terms "hypophosphatasia" and "HPP," and evaluated the pooled prevalence of 17 diagnostic characteristics, initially selected by a group of HPP clinical experts, in eligible studies and in patients included in these studies. Six diagnostic findings showed a pooled prevalence value over 50% and were considered for inclusion as major diagnostic criteria. Based on these results and according to discussion and consideration among members of the Working Group, we finally defined four major diagnostic criteria and five minor diagnostic criteria for HPP in adults. Authors suggested the integrated use of the identified major and minor diagnostic criteria, which either includes two major criteria, or one major criterion and two minor criteria, for the diagnosis of HPP in adults.

Hypophosphatasia diagnosis: current state of the art and proposed diagnostic criteria for children and adults.

BACKGROUND: This manuscript provides a summary of the current evidence to support the criteria for diagnosing a child or adult with hypophosphatasia (HPP). The diagnosis of HPP is made on the basis of integrating clinical features, laboratory profile, radiographic features of the condition, and DNA analysis identifying the presence of a pathogenic variant of the tissue nonspecific alkaline phosphatase gene (ALPL). Often, the diagnosis of HPP is significantly delayed in both adults and children, and updated diagnostic criteria are required to keep pace with our evolving understanding regarding the relationship between ALPL genotype and associated HPP clinical features. METHODS: An International Working Group (IWG) on HPP was formed, comprised of a multidisciplinary team of experts from Europe and North America with expertise in the diagnosis and management of patients with HPP. Methodologists (Romina Brignardello-Petersen and Gordon Guyatt) and their team supported the IWG and conducted systematic reviews following the GRADE methodology, and this provided the basis for the recommendations. RESULTS: The IWG completed systematic reviews of the literature, including case reports and expert opinion papers describing the phenotype of patients with HPP. The published data are largely retrospective and include a relatively small number of patients with this rare condition. It is anticipated that further knowledge will lead to improvement in the quality of genotype-phenotype reporting in this condition. CONCLUSION: Following consensus meetings, agreement was reached regarding the major and minor criteria that can assist in establishing a clinical diagnosis of HPP in adults and children.

Proposed diagnostic criteria for the diagnosis of hypophosphatasia in children and adolescents: results from the HPP International Working Group.

Hypophosphatasia (HPP) is a rare inborn error of metabolism that presents variably in both age of onset and severity. HPP is caused by pathogenic variants in the ALPL gene, resulting in low activity of tissue nonspecific alkaline phosphatase (TNSALP). Patients with HPP tend have a similar pattern of elevation of natural substrates that can be used to aid in diagnosis. No formal diagnostic guidelines currently exist for the diagnosis of this condition in children, adolescents, or adults. The International HPP Working Group is a comprised of a multidisciplinary team of experts from Europe and North America who have expertise in the diagnosis and management of patients with HPP. This group reviewed 93 papers through a Medline, Medline In-Process, and Embase search for the terms "HPP" and "hypophosphatasia" between 2005 and 2020 and that explicitly address either the diagnosis of HPP in children, clinical manifestations of HPP in children, or both. Two reviewers independently evaluated each full-text publication for eligibility and studies were included if they were narrative reviews or case series/reports that concerned diagnosis of pediatric HPP or included clinical aspects of patients diagnosed with HPP. This review focused on 15 initial clinical manifestations that were selected by a group of clinical experts.The highest agreement in included literature was for pathogenic or likely pathogenic ALPL variant, elevation of natural substrates, and early loss of primary teeth. The highest prevalence was similar, including these same three parameters and including decreased bone mineral density. Additional parameters had less agreement and were less prevalent. These were organized into three major and six minor criteria, with diagnosis of HPP being made when two major or one major and two minor criteria are present.

Combined press-fit and extracortical fixation in patellar tendon anterior cruciate ligament reconstruction results in reliable graft fixation and early bone block incorporation.

BACKGROUND: Anterior cruciate ligament (ACL) reconstruction with bone-patellar-tendon-bone (BPTB) autograft has the potential biological advantage of direct bone-to-bone healing over soft tissue grafts. The primary aim of this study was to investigate possible graft slippage and therefore fixation strength in a modified BPTB autograft technique with suspensory fixation on both sides for primary ACL reconstruction until bony integration takes place. METHODS: Twenty-one patients undergoing primary ACL reconstruction with a modified BPTB autograft (bone-on-bone (BOB) technique) between August 2017 and August 2019 were included in this prospective study. A computed tomography (CT) scan of the affected knee was performed directly postoperatively, as well as 3 months postoperatively. Examiner-blinded parameters for graft slippage, early tunnel widening, bony incorporation, as well as remodeling of the autologous refilled patellar harvest site were investigated. RESULTS: A series of 21 patients treated with a BPTB autograft with this technique underwent two CT investigations. Comparison of CT scans showed no bone block displacement and therefore no graft slippage in the patient cohort. Only one patient showed signs of early tunnel enlargement. Radiological bone block incorporation took place showing bony bridging of the graft to the tunnel wall in 90% of all patients. Furthermore, 90% showed less than 1 mm bone resorption of the refilled harvest site at the patella. CONCLUSIONS: Our findings suggest graft fixation stability and reliability of anatomic BPTB ACL reconstruction with a combined press-fit and suspensory fixation technique by absence of graft slippage within the first 3 months postoperatively.

The ankle in XLH: Reduced motion, power and quality of life.

Background: X-linked hypophosphatemia (OMIM 307800) is a rare bone disease caused by a phosphate-wasting condition with lifelong clinical consequences. Those affected suffer from bone pain, complex skeletal deformities, impaired mobility and a reduced quality of life. Early osteoarthritis and reduced range of motion of the lower limbs are known pathologies in XLH patients. However, XLH-specific data on the affected compartments such as the ankle joint through the evaluation of radiographic and gait analysis data is still lacking. Patients and methods: In this cross-sectional study, patients with genetically verified XLH, age ≥ 16 - 50 years and a complete record of gait analysis and or radiographic analysis data were included. Clinical examination, radiological and gait analysis data were compared to norms using the dataset of our gait laboratory registry. Radiographic analysis included tibial deformity analysis and assessment of osteoarthritis and enthesopathies. Western Ontario and McMaster Universities Arthritis Index (WOMAC), SF36v2, American Orthopedic Foot and Ankle Society score (AOFAS) and the Foot and Ankle Outcome Score (FAOS) were used. Twentythree participants with 46 limbs were eligible for the study. Results: A total of 23 patients (n=46 feet) met the inclusion criteria. Patients with XLH had significantly reduced gait quality, ankle power and plantar flexion (p < 0.001) compared to a historic gait laboratory control group. Ankle valgus deformity was detected in 22 % and ankle varus deformity in 30 % of the patients. The subtalar joint (59.1%) as well as the anterior tibiotalar joint (31.1%) were the main localizations of moderate to severe joint space narrowing. Ankle power was decreased in moderate and severe subtalar joint space narrowing (p < 0.05) compared to normal subtalar joint space narrowing. No lateral or medial ligament instability of the ankle joint was found in clinical examination. Tibial procurvatum deformity led to lower ankle power (p < 0.05). Conclusions: This study showed structural and functional changes of the ankle in patients with XLH. Subtalar ankle osteoarthritis, patient reported outcome scores and clinical ankle restriction resulted in lower gait quality and ankle power.

Identification of circulating microRNA patterns in patients in psoriasis and psoriatic arthritis.

OBJECTIVE: miRNAs are small non-coding RNAs that control gene expression. Specific intra- and extracellular miRNA signatures have been identified in various diseases. Whether certain miRNA signatures are associated with psoriasis (PsO) and PsA is currently unknown. We aimed to search for circulating miRNA signatures associated with PsO and PsA patients. METHODS: Expression of miRNAs was analysed by reverse transcription quantitative real-time PCR (RT-qPCR) in the serum of PsA, PsO patients and healthy controls. Demographic and disease-specific characteristics and imaging data from hand MRI were recorded. In the discovery phase, 192 miRNA assays were analysed in 48 samples (PsA, PsO, controls: each N = 16). For validation, 17 selected miRNAs were measured in the total population. RESULTS: A total of 141 patients and controls were analysed (51 PsA, 40 PsO, 50 controls). In the discovery phase 51 miRNAs in PsO and 64 miRNAs in PsA were down- or upregulated compared with controls, with 33 miRNAs being changed in both (adj. P < 0.05). The 17 top candidates from discovery were assessed in the validation phase, 9 of them discriminated PsA and PsO from controls [area under the curve (AUC) ≥0.70, all P < 0.05]. Four miRNAs (miR-19b-3p, miR-21-5p, miR-92a-3p and let-7b-5p) were significantly differently regulated between PsO and PsA. A combination of these miRNAs increased the AUC to 0.92 in multivariate regression model to discriminate PsO and PsA. CONCLUSION: miRNA signatures in PsA and PsO patients differ from controls. Nine miRNAs were differentially regulated in PsA and PsO patients, five of them previously reported to be involved in bone and cartilage metabolism, indicating an intimate association of psoriatic inflammation and bone/cartilage changes.

Dissociation of clinical, laboratory, and bone biopsy findings in adult X-linked hypophosphatemia: a case report.

X­linked hypophosphatemia (XLH) is a phosphate wasting disorder. Typical serum constellations include low serum phosphate as well as high alkaline phosphatase (ALP) and fibroblast growth factor 23 (FGF-23 ) levels. Adult XLH patients usually suffer from (pseudo)fractures, enthesopathies, impaired mobility, and osteoarthritis. We report the case of a middle-aged woman with clinically mild disease, relatively balanced laboratory values, but bone non-healing of the femur post-surgery. Transiliac bone biopsy revealed pronounced osteomalacia and severe deterioration of bone microstructure. Due to the lack of XLH-typical symptoms, the patient was not substituted with calcitriol and phosphate in adulthood. Thus, laboratory findings and radiological examinations do not necessarily reflect bone metabolism in XLH. Bone biopsies should be considered in unclear cases or prior to surgery in adults with XLH.

Circulating miRNAs Respond to Denosumab Treatment After 2 Years in Postmenopausal Women With Osteoporosis-the MiDeTe study.

CONTEXT: MicroRNAs (miRNAs)-short, single-stranded, noncoding RNAs-regulate several biological processes, including bone metabolism. OBJECTIVE: We investigated circulating miRNAs as promising biomarkers for treatment monitoring in women with postmenopausal osteoporosis on denosumab (DMAB) therapy. METHODS: In this prospective, observational, single-center study, 21 postmenopausal women treated with DMAB were included for a longitudinal follow-up of 2 years. Next-generation sequencing (NGS) was performed to screen for serological miRNAs at baseline, month 6, and month 24. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was used to confirm NGS findings in the entire cohort. Bone turnover markers (BTM) P1NP and CTX, and bone mineral density (BMD) by dual x-ray absorptiometry were assessed and correlated to miRNAs. RESULTS: BMD at the hip (5.5%, P = 0.0006) and lumbar spine significantly increased (11.4%, P = 0.017), and CTX (64.1%, P < 0.0001) and P1NP (69.3%, P < 0.0001) significantly decreased during treatment. NGS analysis revealed significant changes in miRNAs after 2 years of DMAB treatment but not after 6 months. Seven miRNAs were confirmed by RT-qPCR to be significantly changed during a 2-year course of DMAB treatment compared to baseline. Four of these were mainly transcribed in blood cells, including monocytes. Correlation analysis identified significant correlation between change in miRNA and change in BTMs as well as BMD. Based on effect size and correlation strength, miR-454-3p, miR-26b-5p, and miR-584-5p were defined as top biomarker candidates, with the strongest association to the sustained effect of denosumab on bone in osteoporotic patients. CONCLUSION: Two years of DMAB treatment resulted in upregulation of 7 miRNAs, 4 of which are mainly transcribed in monocytes, indicating a potential impact of DMAB on circulating osteoclast precursor cells. These changes were associated to BMD gain and BTM suppression and could therefore be useful for monitoring DMAB treatment response.

Chondrosarcoma of the spine-a case report.

CASE: A 73-year-old male patient presented with a 3-month history of back pain. In bone scintigraphy and the FDG PET-CT scan (fluorodeoxyglucose positron-emission computed tomography), highly suspect uptake levels were found in TH12-L1. Accordingly, an osteodestructive process was found on MRI (magnetic resonance imaging). Following a successfully performed biopsy of TH12, histologic analysis of the bone material revealed a chondrosarcoma (G1; T4N2M0). Complete resection of the tumor was successfully performed, since chondrosarcoma are resistant to radiation and chemotherapy. CONCLUSION: As chondrosarcoma is a rare bone neoplasm, it must be considered in the differential diagnosis of lower back pain to initiate adequate treatment.

Identifying adult hypophosphatasia in the rheumatology unit.

BACKGROUND: The most frequent manifestation in adult hypophosphatasia (HPP) is musculoskeletal pain. The unspecific nature of its clinical presentation may prevent correct diagnosis. The aim of the study was to assess the prevalence of ALPL mutations in adult patients treated in rheumatological outpatient facilities with evident musculoskeletal symptoms typical for HPP. METHODS: Over a period of 10 years 9,522 patients were screened in the rheumatology outpatient clinic of the Hanusch hospital Vienna. Serum ALP levels ≤ 40 U/L were found in 524 patients. After screening for secondary causes, 73 patients were invited for clinical evaluation. Genetic testing was performed in 23 patients with suspected HPP. Logistic regression models with Firth penalisation were used to estimate the unadjusted and BMI-adjusted association of each clinical factor with HPP. RESULTS: Mutations in the ALPL gene were observed in 57% of genetically screened patients. Arthralgia, fractures, and pain were the leading symptoms in individuals with ALPL mutation. Chondrocalcinosis (OR 29.12; 95% CI 2.02-1593.52) and dental disease (OR 8.33; 95% CI 0.93-143.40) were associated with ALPL mutation, independent of BMI. Onset of symptoms in patients with ALPL mutation was at 35.1 (14.3) years, with a mean duration from symptoms to diagnosis of 14.4 (8.1) years. Bone mineral density (BMD) and trabecular bone score (TBS) as well as bone turnover markers were not indicative for HPP or ALPL mutation. CONCLUSION: HPP can mimic rheumatologic diseases. Thus, HPP should be considered as a possible diagnosis in adult patients presenting with musculoskeletal pain of unknown origin in rheumatology outpatient clinics. In patients with persistently low ALP serum levels and unclear musculoskeletal pain, HPP as the underlying cause has to be considered.

Metabolic Bone Diseases-A Topic of Great Diversity.

The progress in research has improved the understanding of the epidemiology and pathogenesis of osteoporosis and bone disorders in general [...].

Muscle-Specific Micro-Ribonucleic Acids miR-1-3p, miR-133a-3p, and miR-133b Reflect Muscle Regeneration After Single-Dose Zoledronic Acid Following Rotator Cuff Repair in a Rodent Chronic Defect Model.

BACKGROUND: Zoledronic acid improves bone microarchitecture and biomechanical properties after chronic rotator cuff repair (RCR) in rats. Besides the positive effects of zoledronic acid on bone mineral density and bone microarchitecture, bisphosphonates have positive effects on skeletal muscle function. PURPOSES/HYPOTHESIS: The purposes of this study were to (1) longitudinally evaluate circulating bone- and muscle-specific serum micro-ribonucleic acids (miRNAs) and (2) investigate supraspinatus muscle tissue after tenotomy and delayed RCR in a rat model. It was hypothesized that zoledronic acid would improve muscle regeneration after chronic RCR in rats. STUDY DESIGN: Controlled laboratory study. METHODS: A total of 34 male Sprague-Dawley rats underwent unilateral (left) supraspinatus tenotomy (time point 1) with delayed transosseous RCR after 3 weeks (time point 2). All rats were sacrificed 8 weeks after RCR (time point 3). Animals were randomly assigned to 2 groups. One day after RCR, the control group was given 1 mL of subcutaneous saline solution, and the intervention group was treated with a subcutaneous single-dose of 100 µg/kg body weight of zoledronic acid. All 34 study animals underwent miRNA analysis at all 3 time points. In 4 animals of each group, histological analyses as well as gene expression analyses were conducted. RESULTS: Circulating miRNAs showed significantly different expressions between both study groups. In the control group, a significant downregulation was observed for muscle-specific miR-1-3p (P = .004), miR-133a-3p (P < .001), and miR-133b (P < .001). Histological analyses showed significantly higher rates of regenerating myofibers on the operated side (left) of both study groups compared with the nonoperated side (right; P = .002). On the nonoperated side, significantly higher rates of regenerating myofibers were observed in the intervention group compared with the control group (P = .031). The myofiber cross-sectional area revealed significantly smaller myofibers on both sides within the intervention group compared with both sides of the control group (P < .001). Within the intervention group, significantly higher expression levels of muscle development/regeneration marker genes embryonal Myosin heavy chain (P = .017) and neonatal Myosin heavy chain (P = .016) were observed on the nonoperated side compared with the operated side. CONCLUSION: An adjuvant single-dose of zoledronic acid after RCR in a chronic defect model in rats led to significant differences in bone- and muscle-specific miRNA levels. Therefore, miR-1-3p, miR-133a-3p, and miR-133b might be used as biomarkers for muscle regeneration after RCR. CLINICAL RELEVANCE: Adjuvant treatment with zoledronic acid may improve muscle regeneration after chronic RCR in humans, thus counteracting fatty muscle infiltration and atrophy.

Dispensing anti-osteoporotic drugs changed during the COVID-19 pandemic.

OBJECTIVES: Caring for osteoporosis patients has proven challenging during the COVID-19 pandemic due to repeated lockdowns in Austria. The distinct possibility of insufficient treatment regimens is therefore a matter of pressing concern. The aim of the study was to assess alterations in dispensing anti-osteoporotic drugs during the COVID-19 pandemic. PATIENTS/METHODS: This study was a nationwide retrospective register-based observational study which included all patients in Austria aged ≥50 who received at least one prescription for anti-osteoporotic medication between January 2016 and November 2020. Pseudonymised individual-level patients' data were obtained from social insurance authorities. Anti-osteoporotic agents were divided into: (i) oral bisphosphonates, (ii) intravenous bisphosphonates, (iii) selective estrogen receptor modulators (SERMs), (iv) teriparatide (TPTD) and (v) denosumab (DMAB). We used interrupted time series analysis with autoregressive integrated moving average models (ARIMA) to predict drug dispensing. RESULTS: There were 2,884,374 dispensations of anti-osteoporotic drugs to 224,598 patients between 2016 and 2020. The mean monthly prescriptions for oral bisphosphonates (-14.5 %) and SERMs (-12.9 %) decreased during the COVID-19 pandemic when compared to the non-COVID-19 period. Dispensing for intravenous bisphosphonates (1.7 %) and teriparatide (9.5 %) increased. Prescriptions for DMAB decreased during the first lock-down, however increased by 29.1 % for the total observation time. The Arima models showed that in March 2020 (beginning of the 1st COVID-19 lockdown), there was a decrease of 778 dispensings, with a further increase of 14 dispensings every month for denosumab; a decrease by 178 dispensings, with a further increase of 23 dispensings every month for zolendronic acid; a decrease by 2950 dispensings, but with a further increase of 236 dispensings every other month for ibandronate and a decrease by 1443 dispensing with a further decrease of 29 dispensings for alendronate than predicted, had the lockdown not occurred. CONCLUSIONS: The total number of prescriptions dispensed to patients treated with anti-osteoporotic medications declined rapidly during first COVID-19 lockdown. The observed decrease of DMAB during the first lockdown rebounded in the following months. Considering the massive treatment gap for osteoporosis, and the related fracture risk, clinicians should continue treatment, even during a pandemic.

Pelvic Fractures-An Underestimated Problem? Incidence and Mortality Risk after Pelvic Fracture in Austria, 2010-2018.

(1) Background: Pelvic fractures (PFs) are related to osteoporosis, and represent a serious individual and socioeconomic burden. (2) Methods: We examined age- and sex-standardised incidence rates (SIRs) of PF, along with rates of all-cause overall and one-year mortality among patients with PF. We compared the mortality rates between PF patients and a matched fracture-free cohort. Patients ≥50 years old in Austria hospitalised with PF in 2010−2018, along with their dates of death, were recorded. (3) Results: We identified 54,975 patients with PF, of whom 70.9% were women. Between 2010 and 2018 the SIR of PF increased in men by 10.0%­from 125.3 (95% Confidence Interval 118.9−132.0) to 137.8 (95% CI 131.8−144.0) per 100,000­and in women by 2.7%­from 218.7 (95% CI 212.0−225.6) to 224.7 (95% CI 218.3−231.3) per 100,000. The one-year post-PF mortality rate was higher in men than in women (13.0% and 11.1%, respectively; p < 0.001). Pelvic fracture patients aged ≥65 had an elevated mortality risk (Hazard Ratio 1.75, 95% CI 1.71−1.79, p < 0.001) compared to controls. (4) Conclusions: There is a clear increase in the incidence of PF in the elderly population, with a greater increase in men over time. Pelvic fracture itself contributes to increased mortality in individuals aged 65 and above.

Bone Involvement in Patients with Spondyloarthropathies.

Spondyloarthropathies (SpA) are common systemic inflammatory rheumatic diseases, in which, as in other rheumatic diseases, levels of markers of bone resorption are elevated, leading to bone loss and elevated risk of vertebral fractures. However, the diseases are also associated with new bone formation in the spine, the so-called syndesmophytes. We tried to unravel the pathogenesis of formation and growth of syndesmophytes and evaluated new diagnostic and treatment options. After a successful meeting of the Working Group on Rheumatic Diseases at the ECTS 2020, we (WL and CR) were excited about the quality of the speakers (CM, JH, AG, and GL) and their complimentary lectures. Given the relative lack of reviews on spondyloarthropathies and bone, we decided to work together on a comprehensive review that might be interesting for basic scientists and clinically relevant for clinicians. Radiographic progression in axSpA is linked to several risk factors, like male sex, smoking, HLA-B-27, increased levels of CRP, presence of syndesmophytes, and marked inflammation on MRI. The potential role of mechanical stress in the context of physically demanding jobs has been also suggested to promote structural damages. Different treatment options from NSAIDs to biologic agents like TNF inhibitors (TNFi) or IL-17inhibitors (IL-17i) result in a reduction of inflammation and symptoms. However, all these different treatment options failed to show clear and reproducible results on inhibition on syndesmophyte formation. The majority of data are available on TNFi, and some studies suggested an effect in subgroups of patients with ankylosing spondylitis. Less information is available on NSAIDs and IL-17i. Since IL-17i have been introduced quite recently, more studies are expected. IL-17 inhibitors (Il-17i) potently reduce signs and symptoms, but serum level of IL-17 is not elevated, therefore, IL-17 probably has mainly a local effect. The failure of anti-IL-23 in axSpA suggests that IL-17A production could be independent from IL-23. It may be upregulated by TNFα, resulting in lower expression of DKK1 and RANKL and an increase in osteogenesis. In active AS markers of bone resorption are increased, while bone formation markers can be increased or decreased. Bone Turnover markers and additional markers related to Wnt such as DKK1, sclerostin, and RANKL are valuable for elucidating bone metabolism on a group level and they are not (yet) able to predict individual patient outcomes. The gold standard for detection of structural lesions in clinical practice is the use of conventional radiographics. However, the resolution is low compared to the change over time and the interval for detecting changes are 2 years or more. Modern techniques offer substantial advantages such as the early detection of bone marrow edema with MRI, the fivefold increased detection rate of new or growing syndesmophytes with low-dose CT, and the decrease in 18F-fluoride uptake during treatment with TNFα-inhibitors (TNFi) in a pilot study in 12 AS patients. Detection of bone involvement by new techniques, such as low-dose CT, MRI and 18-Fluoride PET-scans, and bone turnover markers, in combination with focusing on high-risk groups such as patients with early disease, elevated CRP, syndesmophytes at baseline, male patients and patients with HLA-B27 + are promising options for the near future. However, for optimal prevention of formation of syndesmophytes we need more detailed insight in the pathogenesis of bone formation in axSpA and probably more targeted therapies.

Improved biomechanics in experimental chronic rotator cuff repair after shockwaves is not reflected by bone microarchitecture.

PURPOSE: The aim of this study was to investigate the effect of extracorporeal shockwave therapy (ESWT) on bone microstructure as well as the bone-tendon-interface and the musculo-tendinous transition zone to explain the previously shown improved biomechanics in a degenerative rotator cuff tear animal model. This study hypothesized that biomechanical improvements related to ESWT are a result of improved bone microstructure and muscle tendon properties. METHODS: In this controlled laboratory study unilateral supraspinatus (SSP) tendon detachment was performed in 48 male Sprague-Dawley rats. After a degeneration period of three weeks, SSP tendon was reconstructed transosseously. Rats were randomly assigned into three groups (n = 16 per group): control (noSW); intraoperative shockwave treatment (IntraSW); intra- and postoperative shockwave treatment (IntraPostSW). Eight weeks after SSP repair, all rats were sacrificed and underwent bone microstructure analysis as well as histological and immunohistochemical analyses. RESULTS: With exception of cortical porosity at the tendon area, bone microstructure analyses revealed no significant differences between the three study groups regarding cortical and trabecular bone parameters. Cortical Porosity at the Tendon Area was lowest in the IntraPostSW (p≤0.05) group. Histological analyses showed well-regenerated muscle and tendon structures in all groups. Immunohistochemistry detected augmented angiogenesis at the musculo-tendinous transition zone in both shockwave groups indicated by CD31 positive stained blood vessels. CONCLUSION: In conclusion, bone microarchitecture changes are not responsible for previously described improved biomechanical results after shockwave treatment in rotator cuff repair in rodents. Immunohistochemical analysis showed neovascularization at the musculo-tendinous transition zone within ESWT-treated animals. Further studies focusing on neovascularization at the musculo-tendinous transition zone are necessary to explain the enhanced biomechanical and functional properties observed previously. CLINICAL RELEVANCE: In patients treated with a double-row SSP tendon repair, an improvement in healing through ESWT, especially in this area, could prevent a failure of the medial row, which is considered a constantly observed tear pattern.