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X‑linked 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., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, ein Teil von Springer Nature.)

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., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, ein Teil von Springer Nature.)

Injection therapy is a frequently used method for the treatment of subacute and chronic low back pain (LBP) despite scant evidence for its effectiveness. To date there are relatively few studies comparing this method with other treatments. Moreover, there are many possible side effects associated with injection therapies, some of which are potentially life threatening. We present the case of a 59-year-old woman admitted to the emergency department with confluent abscess formations of autochthonous back muscles and staphylococcal sepsis caused by injection therapy performed by a general practitioner for LBP. The findings of this case report emphasize a careful selection of patients for this type of treatment and a multidisciplinary approach to treatment of LBP., (© 2020. Springer-Verlag GmbH Austria, ein Teil von Springer Nature.)

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., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

In recent years, new treatment options for both common and rare bone diseases have become available. The sclerostin antibody romosozumab is the most recently approved drug for the therapy of postmenopausal osteoporosis. Its anabolic capacity makes it a promising treatment option for severe osteoporosis. Other sclerostin antibodies for the treatment of rare bone diseases such as osteogenesis imperfecta are currently being investigated. For rare bone diseases such as X‑linked hypophosphatemia (XLH) and hypophosphatasia (HPP), specific therapies are now also available, showing promising data in children and adults with a severe disease course. However, long-term data are needed to assess a sustained benefit for patients.

X‑linked hypophosphatemic rickets (XLH, OMIM #307800) is a rare genetic metabolic disorder caused by dysregulation of fibroblast-like growth factor 23 (FGF23) leading to profound reduction in renal phosphate reabsorption. Impaired growth, severe rickets and complex skeletal deformities are direct consequences of hypophosphatemia representing major symptoms of XLH during childhood. In adults, secondary complications including early development of osteoarthritis substantially impair quality of life and cause significant clinical burden. With the global approval of the monoclonal FGF23 antibody burosumab, a targeted treatment with promising results in phase III studies is available for children with XLH. Nevertheless, complete phenotypic rescue is rarely achieved and remaining multisystemic symptoms demand multidisciplinary specialist care. Coordination of patient management within the major medical disciplines is a mainstay to optimize treatment and reduce disease burden. This review aims to depict different perspectives in XLH patient care in the setting of a multidisciplinary centre of expertise for rare bone diseases.

We examined differences in patients' survival after hip fracture (HF) and risk for subsequent HF among patients treated with oral and intravenous bisphosphonates (oBPs, iBPs), denosumab (DMAB), and patients without therapy. We used data from all patients in Austria aged ≥ 50 who sustained a HF between 2012 and 2017 and were followed for a subsequent HF and all-cause mortality until 2017. Antiosteoporotic treatment-naïve patients, who were incident users of BPs and DMAB, were eligible for propensity score matching 1:1 to obtain comparable user groups. We applied competing risk approach and calculated cumulative incidence functions and subdistribution-hazards for refracture. Cox regression models were applied for mortality risk. A total of 54,145 hip-fractured patients were observed (1919 oBPs; 1870 iBPs; 555 DMAB users; and 42,795 untreated patients were included in the matched sets) and followed up for a median (interquartile range) of 22.6 months (26.2). Patients treated with antiresorptive medications had significantly longer survival time than patients without treatment. Receiving treatment significantly decreased a hazard of dying only for women by 17% for iBPs (HR 0.83, 95% CI 0.71-0.98, p = 0.023). For DMAB and oBPs, the results were not statistically significant. Higher risk of a subsequent HF was observed in women on DMAB (SHR 1.77, 95% CI 1.08-2.91) and on iBP (SHR 1.81, 95% CI 1.35-2.41), and in men on oBPs (SHR 2.89, 95% CI 1.58-5.30). Patients who were treated with antiresorptive medications after HF had longer survival than patients without treatment, highlighting the importance of initiation of antiresorptive treatment after HF.

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.

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.

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.

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.

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.

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