Overlapping Stromal Alterations in Myeloid and Lymphoid Neoplasms.

Myeloid and lymphoid neoplasms share the characteristics of potential bone marrow infiltration as a primary or secondary effect, which readily leads to hematopoietic insufficiency. The mechanisms by which clonal malignant cells inhibit normal hematopoietic stem and progenitor cells (HSPCs) in the bone marrow (BM) have not been unraveled so far. Given the pivotal role of mesenchymal stromal cells (MSCs) in the regulation of hematopoiesis in the BM niche it is assumed that MSCs also play a relevant role in the pathogenesis of hematological neoplasms. We aimed to identify overlapping mechanisms in MSCs derived from myeloid and lymphoid neoplasms contributing to disease progression and suppression of HSPCs to develop interventions that target these mechanisms. MSCs derived from healthy donors (n = 44) and patients diagnosed with myeloproliferative neoplasia (n = 11), myelodysplastic syndromes (n = 16), or acute myeloid leukemia (n = 25) and B-Non-Hodgkin lymphoma (n = 9) with BM infiltration and acute lymphoblastic leukemia (n = 9) were analyzed for their functionality and by RNA sequencing. A reduced growth and differentiation capacity of MSCs was found in all entities. RNA sequencing distinguished both groups but clearly showed overlapping differentially expressed genes, including major players in the BMP/TGF and WNT-signaling pathway which are crucial for growth, osteogenesis, and hematopoiesis. Functional alterations in healthy MSCs were inducible by exposure to supernatants from malignant cells, implicating the involvement of these factors in disease progression. Overall, we were able to identify overlapping factors that pose potential future therapeutic targets.

Stromal alterations in patients with monoclonal gammopathy of undetermined significance, smoldering myeloma, and multiple myeloma.

ABSTRACT: The hallmark of multiple myeloma (MM) is a clonal plasma cell infiltration in the bone marrow accompanied by myelosuppression and osteolysis. Premalignant stages such as monoclonal gammopathy of undetermined significance (MGUS) and asymptomatic stages such as smoldering myeloma (SMM) can progress to MM. Mesenchymal stromal cells (MSCs) are an integral component of the bone marrow microenvironment and play an important role in osteoblast differentiation and hematopoietic support. Although stromal alterations have been reported in MM contributing to hematopoietic insufficiency and osteolysis, it is not clear whether alterations in MSC already occur in MGUS or SMM. In this study, we analyzed MSCs from MGUS, SMM, and MM regarding their properties and functionality and performed messenger RNA sequencing to find underlying molecular signatures in different disease stages. A high number of senescent cells and a reduced osteogenic differentiation capacity and hematopoietic support were already present in MGUS MSC. As shown by RNA sequencing, there was a broad spectrum of differentially expressed genes including genes of the BMP/TGF-signaling pathway, detected already in MGUS and that clearly increases in patients with SMM and MM. Our data may help to block these signaling pathways in the future to hinder progression to MM.

[Exercise therapy and basic treatment for osteoporosis]. / Trainingstherapie und Basistherapie bei Osteoporose.

Physical training is an important component in the prophylaxis of osteoporosis and the prevention of fractures. Physical training not only has a direct effect on muscle strength and muscular performance, but also on the risk of falling and the fear of falling. Therefore, physical training is also an integral part of the basic treatment for osteoporosis. The recommendations for basic treatment are an adequate intake of nutrients, including protein in particular. The intake of calcium and vitamin D in sufficient quantities is also important and, in the case of specific drug therapy, also to avoid side effects and to ensure the therapeutic effect. This article summarizes the recommendations of the updated S3 guideline on the diagnosis and treatment of osteoporosis and explains the background for the recommendations included.

Does adding exercise or physical activity to pharmacological osteoporosis therapy in patients with increased fracture risk improve bone mineral density and lower fracture risk? A systematic review and meta-analysis.

This prospectively registered systematic review and meta-analysis examines whether exercise (EX) training has an additive effect to osteoanabolic and/or antiresorptive pharmacological therapy (PT) in people with osteoporosis on bone mineral density (BMD), bone turnover markers (BTMs), fracture healing, and fractures. Four databases (inception to 6 May 2022), 5 trial registries, and reference lists were searched. Included were randomized controlled trials comparing the effect of EX + PT vs. PT with regard to BMD, BTM, fracture healing, and fractures. Risk of bias was assessed using the Cochrane RoB2 and certainty of evidence by the GRADE approach. Random-effects meta-analysis with Hartung-Knapp-Sidik-Jonkman adjustment was used to estimate standardized mean differences and 95% confidence intervals. Out of 2593 records, five RCTs with 530 participants were included. Meta-analysis showed with very low certainty evidence and wide confidence intervals that EX + PT compared to PT had larger effect sizes for BMD at 12 months at the hip (SMD [95%CI]: 0.18 [- 1.71; 2.06], n = 3 studies), tibia (0.25 [- 4.85; 5.34], n = 2), lumbar spine (0.20 [- 1.15; 1.55], n = 4), and forearm (0.05 [- 0.35; 0.46], n = 3), but not femoral neck (- 0.03 [- 1.80; 1.75], n = 3). Furthermore, no improvement was revealed for BTM such as bone ALP (- 0.68 [- 5.88; 4.53], n = 3), PINP (- 0.74 [- 10.42; 8.93], n = 2), and CTX-I (- 0.69 [- 9.61; 8.23], n = 2), but with very wide confidence intervals. Three potentially relevant ongoing trials were identified via registries. No data were found for fracture healing or fracture outcomes. It remains unclear whether EX has an additive impact to PT in people with osteoporosis. High-quality, adequately powered, targetted RCTs are required. PROTOCOL REGISTRATION: PROSPERO CRD42022336132.

Disease burden of and expectations from surgery in patients prior to total knee arthroplasty: Results of the prospective FInGK study.

BACKGROUND: Disease burden in patients prior to total knee arthroplasty (TKA) varies widely between studies and countries. We aimed to characterize individuals undergoing TKA and examine their expectations from the surgery, focusing on variations in disease burden. METHODS: Consecutive patients undergoing primary TKA in a German university hospital were recruited. A questionnaire including information on disease burden, preoperative expectations from surgery, health care utilization, demography, and socioeconomics was collected one day prior to surgery and linked to data from medical records. Patients were categorized into disease burden quartiles using the Western Ontario and McMaster Universities Osteoarthritis Index' (WOMAC) total score. Subsequently, study population's characteristics and expectations from surgery were analyzed stratified by disease burden. RESULTS: A total of 196 patients were included (41 % male; mean age: 68.2 years). The median WOMAC was 52.0 (IQR: 41.0-58.0). Patients in Q1 were more often males (Q1: 63 % vs Q4: 29 %) and had a shorter duration of complaints with the impaired knee. They were also less restricted in social participation, reported less often signs of depression, and were less often treated with physiotherapy (Q1: 27 % vs Q4: 54 %). Furthermore, expectations from surgery were highest in patients with a low disease burden. CONCLUSION: We found large variations in disease burden with a considerable number of patients undergoing TKA whose functional capacity is still maintained and for which guideline-recommended conservative treatment options are not fully exhausted. Further research on this subgroup as well as establishing an international consensus on specific thresholds for TKA indication are needed.

The influence of obesity on functional outcomes and patient satisfaction 8 weeks after total knee arthroplasty: results of the prospective FInGK study.

OBJECTIVES: To investigate obese versus non-obese subjects´ knee joint function, stiffness, pain, expectations, and outcome satisfaction before and two months after total knee arthroplasty (TKA). METHODS: This study is a secondary analysis of data retrieved via a prospective single-centre cohort study investigating knee joint function and health care services utilization in patients undergoing TKA (FInGK Study). For the primary study, elective TKA patients were consecutively recruited between December 2019 and May 2021. Preoperative expectations, Western Ontario and McMasters Universities Osteoarthritis Index (WOMAC), surgery outcome satisfaction, and sociodemographic variables were assessed via self-reported questionnaires. In the current study, obese (Body Mass Index (BMI) ≥ 30 kg/m²) versus non-obese (BMI < 30 kg/m²) subjects' data were exploratively compared before and two months after TKA. Multivariable logistic regression assessed factors associated with TKA satisfaction two months postoperatively. Linear regression evaluated factors associated with higher WOMAC change two months postoperatively. RESULTS: A total of 241 subjects participated (response: 85.2%). Eighty-seven were non-obese (mean age: 70.7 years, 63.2% female) and 154 were obese (mean age: 67.1 years, 57.8% female). Obese subjects reported inferior pre- and postoperative pain and knee joint function compared to non-obese subjects. Yet, WOMAC scores of obese and non-obese subjects significantly improved from preoperative means of 52.6 and 46.8 to 32.3 and 24.4 after surgery, respectively. The only significant TKA satisfaction predictor was subjects' smoking status. Non-obesity and worse preoperative WOMAC scores were predictive of higher WOMAC change scores after two months. CONCLUSION: Both obese and non-obese subjects reported significant symptom improvements. However, as obese subjects' short-term outcomes were still inferior, more research on TKA rehabilitation measures adapted to the needs of this growing patient group is warranted to maximize their benefits from TKA.

[Drug treatment of osteonecrosis]. / Medikamentöse Therapie von Osteonekrosen.

The medicinal treatment of osteonecrosis is described as part of the conservative treatment for atraumatic femoral head necrosis of the hip in adults and for Ahlbäck's disease of the knee joint. For femoral head necrosis, iloprost is used in the early stages (ARCO I and II) as a treatment attempt to eliminate pain and the accompanying bone marrow edema. This also applies to the use of bisphosphonates, whereby preferably small defects (< 30%) are suitable for treatment. Bisphosphonates are successfully used in the knee joint to treat Ahlbäck's disease, although the results are sometimes contradictory. Other locations, such as the humeral head, talus, scaphoid, lunate, proximal tibia, and metatarsal head, are sometimes successfully treated with bisphosphonates. Although the results seem promising, the groups are far too small to derive treatment recommendations in this regard.

Use of Physiotherapy Prior to Total Knee Arthroplasty-Results of the Prospective FInGK Study.

BACKGROUND: Data regarding physiotherapy (PT) utilization prior to total knee arthroplasty (TKA) are insufficient. Therefore, this study aims to examine which percentage of patients receive PT within 12 months prior to TKA and which factors are associated with its use. METHODS: Consecutive patients (≥18 years) undergoing primary or revision TKA in a German university hospital were recruited. A questionnaire including information on PT utilization, demography, and socioeconomics was collected one day prior to surgery and linked to medical hospital records. Multivariable logistic regression was conducted to determine variables associated with the use of PT. RESULTS: A total of 241 out of 283 (85%) patients participated (60% female; mean age: 68.4 years). Overall, 41% received PT at least once during 12 months prior to TKA, women more frequently than men (48% vs. 29%). Although high disease burden was associated with increased utilization, about one in two in this condition did not receive PT. Multivariable logistic regression showed that age 75+ years, low education level, and moderate-to-severe depressive symptoms were associated with decreased PT utilization. CONCLUSIONS: We found low use of recommended PT management in patients prior to TKA. This potential underuse was even higher in some vulnerable subgroups, indicating inequalities. Prescribers as well as patients should integrate PT more consistently into osteoarthritis management.

Acute Compartment Syndrome of the Lower Leg Using Navigated Endoprosthesis of the Knee. / Akutes Kompartmentsyndrom des Unterschenkels nach navigierter Kniegelenksendoprothetik ­ ein Fallbericht.

Acute compartment syndrome of the lower leg following computer navigated primary total knee arthroplasty is rare but potentially devastating. This could be triggered by a setting of the bicortical tibial navigation pin. It is essential to take care during the operation, and to implement close post-operative control, especially if there are risk factors or nerve blocks.

Osteoporotic Fractures of the Thoracic and Lumbar Vertebrae: Diagnosis and Conservative Treatment.

BACKGROUND: The prevalence of osteoporotic vertebral body fractures in Europe is 18-26%. Although most of these injuries can be treated conservatively, the underlying concepts have not been defined clearly or uniformly. In this article, we present the current state of the evidence on the diagnosis and conservative treatment of osteoporotic fractures of the thoracic and lumbar vertebrae. METHODS: A systematic review of the literature up to May 2020 was carried out in the PubMed and Web of Science Core Collection databases. 549 articles were identified, of which 36 were suitable for inclusion in the review. Articles were sought in the areas of diagnosis, provision of physical aids, pharmacotherapy, physiotherapy, and treatments from the realm of alternative medicine. RESULTS: The primary diagnostic technique was conventional x-ray in two planes (with the patient standing, if possible), which had 51.3% sensitivity and 75% specificity. If a fracture was suspected, magnetic resonance imaging (MRI) of the entire spine and regional computed tomography (CT) were carried out. The overall state of the evidence on treatment is poor; the best available evidence is for exercise therapy and physiotherapy, which are supported by three level I and four level II studies. Improvements were seen mainly in mobility and a reduced fear of falling. The use of an active orthosis can be useful as well. No evidence was found on the use of drugs or alternative medicine exclusively in the conservative treatment of osteoporotic vertebral body fractures. CONCLUSION: It is reasonable to evaluate instability with imaging repeatedly, at regular intervals, over a period of six months. There is still a lack of reliable data on the optimal intensity and duration of physiotherapy, and on the use of orthoses.

Acute myeloid leukemia-induced functional inhibition of healthy CD34+ hematopoietic stem and progenitor cells.

Acute myeloid leukemia (AML) is characterized by an expansion of leukemic cells and a simultaneous reduction of normal hematopoietic precursors in the bone marrow (BM) resulting in hematopoietic insufficiency, but the underlying mechanisms are poorly understood in humans. Assuming that leukemic cells functionally inhibit healthy CD34+ hematopoietic stem and progenitor cells (HSPC) via humoral factors, we exposed healthy BM-derived CD34+ HSPC to cell-free supernatants derived from AML cell lines as well as from 24 newly diagnosed AML patients. Exposure to AML-derived supernatants significantly inhibited proliferation, cell cycling, colony formation, and differentiation of healthy CD34+ HSPC. RNA sequencing of healthy CD34+ HSPC after exposure to leukemic conditions revealed a specific signature of genes related to proliferation, cell-cycle regulation, and differentiation, thereby reflecting their functional inhibition on a molecular level. Experiments with paired patient samples showed that these inhibitory effects are markedly related to the immunomagnetically enriched CD34+ leukemic cell population. Using PCR, ELISA, and RNA sequencing, we detected overexpression of TGFß1 in leukemic cells on the transcriptional and protein level and, correspondingly, a molecular signature related to TGFß1 signaling in healthy CD34+ HSPC. This inhibitory effect of TGFß1 on healthy hematopoiesis was functionally corrobated and could be pharmacologically reverted by SD208, an inhibitor of TGFß receptor 1 signaling. Overall, these data indicate that leukemic cells induce functional inhibition of healthy CD34+ HSPC, at least in part, through TGFß1, suggesting that blockage of this pathway may improve hematopoiesis in AML.

Does vitamin D deficiency predict tumour malignancy in patients with bone tumours? Data from a multi-center cohort analysis.

Vitamin D deficiency is a global health concern that is estimated to afflict over one billion people globally. The major role of vitamin D is that of a regulator of calcium and phosphate metabolism, thus, being essential for proper bone mineralisation. Concomitantly, vitamin D is known to exert numerous extra-skeletal actions. For example, it has become evident that vitamin D has direct anti-proliferative, pro-differentiation and pro-apoptotic actions on cancer cells. Hence, vitamin D deficiency has been associated with increased cancer risk and worse prognosis in several malignancies. We have recently demonstrated that vitamin D deficiency promotes secondary cancer growth in bone. These findings were partly attributable to an increase in bone remodelling but also through direct effects of vitamin D on cancer cells. To date, very little is known about vitamin D status of patients with bone tumours in general. Thus, the objective of this study was to assess vitamin D status of patients with diverse bone tumours. Moreover, the aim was to elucidate whether or not there is an association between pre-diagnostic vitamin D status and tumour malignancy in patients with bone tumours. In a multi-center analysis, 25(OH)D, PTH and calcium levels of 225 patients that presented with various bone tumours between 2017 and 2018 were assessed. Collectively, 76% of all patients had insufficient vitamin D levels with a total mean 25(OH)D level of 21.43 ng/ml (53.58 nmol/L). In particular, 52% (117/225) of patients were identified as vitamin D deficient and further 24% of patients (55/225) were vitamin D insufficient. Notably, patients diagnosed with malignant bone tumours had significantly lower 25(OH)D levels than patients diagnosed with benign bone tumours [19.3 vs. 22.75 ng/ml (48.25 vs. 56.86 nmol/L); p = 0.04). In conclusion, we found a widespread and distressing rate of vitamin D deficiency and insufficiency in patients with bone tumours. However, especially for patients with bone tumours sufficient vitamin D levels seem to be of great importance. Thus, we believe that 25(OH)D status should routinely be monitored in these patients. Collectively, there should be an increased awareness for physicians to assess and if necessary correct vitamin D status of patients with bone tumours in general or of those at great risk of developing bone tumours.

Utilization of Outpatient Physical and Occupational Therapy in People With Spinal Cord Injury in Germany: Results of the German Spinal Cord Injury Survey.

OBJECTIVE: The aim of the study was to assess factors determining the utilization of physical and occupational therapy in people with spinal cord injury. DESIGN: Data from the German Spinal Cord Injury study conducted in 2017 were analyzed. The 12-mo prevalence of physical therapy and occupational therapy utilization was determined. To identify underlying determinants, multivariable logistic regression was used. RESULTS: Of 1479 participants (response = 26.4%), 72.9% were male, with a mean (SD) age of 55.3 (14.6) yrs and a mean (SD) time since injury of 14.0 (12.0) yrs; 51.2% were people with paraplegia and 66.3% had an incomplete spinal cord injury. In the past 12 mos, 78.1% received physical and 29.3% occupational therapy. Physical therapy and occupational therapy were significantly associated with time since spinal cord injury occurrence, participation in lifelong care programs, and electric wheelchair dependency. Spinal cord injury characteristics, level of impairment, and time since spinal cord injury had a greater impact on occupational therapy than on physical therapy utilization. CONCLUSIONS: The use of physical therapy and occupational therapy is much higher in Germans with spinal cord injury than in the general population and in people with similar neurological conditions. Further research should focus on the frequency of use and the types of interventions. Guidelines for lifelong care should include recommendations on physical therapy and occupational therapy.

Release of Antibiotics Out of a Moldable Collagen-ß-Tricalciumphosphate-Composite Compared to Two Calcium Phosphate Granules.

Bacterial bone infections after revision surgeries and diseases, like osteomyelitis, are still a challenge with regard to surgical treatments. Local bone infections were treated with antibiotics directly or by controlled drug-releasing scaffolds, like polymethylmethacrylate (PMMA) spheres, which have to be removed at a later stage, but there is a risk of a bacterial contamination during the removement. Therefore, biomaterials loaded with antibiotics for controlled release could be the method of choice: The biomaterials degrade during the drug release, therefore, there is no need for a second surgery to remove the drug eluting agent. Even non-resorbable bone materials are available (e.g., hydroxyapatite (HA)) or resorbable bone graft materials (e.g., beta-tricalcium phosphate (ß-TCP)) that will be replaced by newly formed bone. Composite materials with organic additives (e.g., collagen) supports the handling during surgery and enhances the drug loading capacity, as well as the drug releasing time. The purpose of this study was to investigate the loading capacity and the release rate of Vancomycin and Gentamicin on TCP and HA granules in the shape of a degradable scaffold compared to composite materials from TCP mixed with porcine collagen. Its antibacterial efficacy to a more elementary drug with eluting in aqueous solution was examined. The loading capacity of the biomaterials was measured and compared according to the Minimum Inhibition Concentration (MIC) and the Minimum Biofilm Eradication Concentration (MBEC) of a bacterial biofilm after 24 h aging. Antibiotic elution and concentration of gentamycin and vancomycin, as well as inhibition zones, were measured by using the Quantitative Microparticle Systems (QMS) immunoassays. The antibiotic concentration was determined by the automated Beckman Coulter (BC) chemistry device. For examination of the antibacterial activity, inhibition zone diameters were measured. Generally, the antibiotic release is more pronounced during the first couple of days than later. Both TCP granules and HA granules experienced a significantly decline of antibiotics release during the first three days. After the fourth day and beyond, the antibiotic release was below the detection threshold. The antibiotic release of the composite material TCP and porcine collagen declined less drastically and was still in the frame of the specification during the first nine days. There was no significant evidence of interaction effect between antibiotic and material, i.e., the fitted lines for Gentamycin and Vancomycin are almost parallel. During this first in vitro study, ß-TCP-Collagen composites shows a significantly higher loading capacity and a steadily release of the antibiotics Gentamycin and Vancomycin, compared to the also used TCP and HA Granules.

[Importance of osteoporosis-related fractures for patients]. / Bedeutung osteoporosebedingter Frakturen für den Patienten.

BACKGROUND: Osteoporosis is a common disease that affects both women and men. Due to a reduced bone mineral density and increasing age, the risk for atraumatic fractures increases. These fractures cause pain due to the fracture itself and also have far-reaching sequelae in nearly all areas of life of patients. OBJECTIVE: The aim of this article is to summarize the consequences of osteoporotic fractures from the patient's point of view and to highlight the consequences of osteoporosis for the patient. The necessity for timely diagnostics and treatment after a fracture event is explained. MATERIAL AND METHODS: For each term a literature search was performed using key topic-related terms and the results are presented as a narrative review. RESULTS: Various areas of importance for patients were identified. A direct assessment of the patient's point of view was not feasible using a literature search; however, studies with surveys of patients could be identified and therefore, the patient's point of view could be integrated. Areas of interest that could be identified in the literature were pain, psychological well-being, cognitive abilities, mortality and long-term need for nursing. CONCLUSION: The effects of osteoporosis and fractures are multifactorial and often severe for the patient. The measures for prevention of osteoporotic fractures should be consistently implemented in the daily clinical routine and the necessary diagnostics and treatment should be rapidly initiated.

[Establishment of fracture liaison services in Germany]. / Etablierung von Frakturnetzwerken in Deutschland.

BACKGROUND: Osteoporosis results in fragility fractures that are associated with a high morbidity and mortality as well as an increased risk for subsequent fragility fractures. Thus, the first fragility fracture should be the last. To achieve this goal patients need treatment of osteoporosis according to the prevailing clinical guidelines. OBJECTIVE: This article presents the current clinical care situation of patients with a manifest osteoporosis in Germany and the accompanying risks. As a possible solution the concept of a fracture liaison service (FLS) as a new intersectoral care concept is presented and options for the establishment of FLS in Germany are provided. MATERIAL AND METHODS: A literature search (PubMed) was conducted using key terms. The practical experiences of the authors in the context of establishing an FLS were also considered. RESULTS: Compared to other countries, in Germany only a minority of patients receive treatment for osteoporosis after fragility fractures. To improve the care situation an intersectoral FLS provides a coordinated referral of patients with fragility fractures from inpatient care in hospitals to specialists in private practice. This enables the strict identification and treatment of high-risk patients according to the prevailing clinical guidelines. In Germany, different options exist to structure an FLS under consideration of the local circumstances. CONCLUSION: In Germany, FLS should be established nationwide and according to uniform standards. This would significantly improve the quality of clinical care of patients with manifest osteoporosis.

[Influence of frequently prescribed drugs on bone healing]. / Beeinflussung der Knochenheilung durch häufig verordnete Medikamente.

BACKGROUND: Bone healing after fractures is influenced by many different factors. Besides patient-related factors, such as age, gender and other comorbidities, other drugs taken also have a relevant impact on bone healing. OBJECTIVE: The aim of the study was to give an overview of the effects of frequently used drugs on fracture healing, with the exception of specific osteoporosis drugs and hormones. MATERIAL AND METHODS: This overview is based on a medline search with the search string of each pharmacological agent. RESULTS: Frequently used pharmacological substances were identified, for example corticosteroids, antihypertensive drugs, diuretics, antidepressive drugs, antiepileptics, statins, antibiotics, nonsteroidal anti-inflammatory drugs, anticoagulants and others. Except for antihypertensive drugs, thiazide diuretics and statins, which have osteoprotective effects and stimulate bone healing, all other drugs have negative effects on fracture healing in preclinical and animal studies. Clinical data are scarce. CONCLUSION: Data for the effects of the abovementioned pharmacological substances could be found mostly in preclinical studies. The effects of these agents on bone healing in humans has currently not been studied or published. Therefore, the use of these drugs should be discussed carefully in cases with a compromised fracture healing.

Vitamin D Deficiency: The Missing Etiological Factor in the Development of Juvenile Osteochondrosis Dissecans?

BACKGROUND: Vitamin D deficiency can result in rickets and hypocalcemia during infant and childhood growth. There is an increasing interest in the role of vitamin D with regards to childhood bone health. Osteochondrosis dissecans (OD) is a common disease affecting different joints. To date, the exact etiology of OD still remains unclear. The aim of this study was to evaluate a possible association of vitamin D deficiency and juvenile OD. METHODS: A retrospective chart review of the years 2010 to 2015 of all orthopaedic patients with an initial diagnosis of juvenile OD admitted to undergo operative treatment of the OD was performed. Patient demographics, medical history, information on sports activity (if available) and serum vitamin D (25-OH-D) level on admission date were obtained. For statistical comparison, we measured baseline prevalence of vitamin D insufficiency in age-matched orthopaedic patients presenting at the department of pediatric orthopaedics. RESULTS: A total of 80 patients were included in this study. Overall, 97.5% (n=78) of tested patients in the OD group had serum vitamin D levels below the recommended threshold of 30 ng/mL (mean value of 10.1 ng/mL (±6.7 ng/mL)). Over 60% (n=49) were vitamin D deficient, 29 patients (37%) showed serum levels below 10 ng/mL corresponding to a severe vitamin D deficiency. Of note, only 2 patients (2.5%) reached serum vitamin D levels above the recommended threshold of 30 ng/mL. No statistical difference was found in respect to sports activity level before onset of the symptoms (P=0.09). Statistical analysis found a significant difference in vitamin D levels between patients with OD and patients without an OD (P=0.026). CONCLUSIONS: We found an unexpected high prevalence of vitamin D deficiency in juveniles diagnosed with OD presenting with significant lower mean 25-OH-D level compared with a control group. These results suggest that vitamin D deficiency is potentially associated with the development of OD. Thus, vitamin D deficiency might be an important cofactor in the multifactorial development of juvenile OD. For this reason, supplementation of vitamin D might not only be a potential additional therapy but also be a possible preventative factor in patients with juvenile OD. However, future prospective studies are needed to confirm this preliminary data. LEVEL OF EVIDENCE: Level III-this is a case-control study.

[Update of the German S3 guideline on atraumatic femoral head necrosis in adults]. / Update S3-Leitlinie Atraumatische Femurkopfnekrose des Erwachsenen.

The update of the German S3 guideline on atraumatic femoral head necrosis in adults aims to provide an overview of diagnosis and treatment. All clinical studies, systematic reviews, and meta-analyses published in German or English between 01.05.2013 and 30.04.2017 were included. Of 427 studies, 28 were suitable for analysis. Risk factors are corticosteroids, chemotherapy, kidney transplants, hemoglobinopathies, and alcoholism. Differential diagnoses are for example bone marrow edema, insufficiency fracture, and destructive arthropathy. Radiography should be performed upon clinical suspicion. In patients with normal radiography findings but persistent complaints, magnetic resonance imaging (ARCO classification) is the method of choice. Computed tomography (CT) can be used to confirm/exclude articular surface collapse. A subchondral sclerosis zone >30% in CT indicates a better prognosis. Left untreated, a subchondral fracture will develop within 2 years. The risk of disease development in the opposite side is high during the first 2 years, but unlikely thereafter. In conservative therapy, iloprost and alendronate can be used in a curative approach, the latter for small, primarily medial necrosis. Conservative therapy alone as well as other drug-based and physical approaches are not suitable for treatment. No particular joint-preserving surgery can currently be recommended. Core decompression should be performed in early stages with <30% necrosis. From ARCO stage IIIc or in stage IV, the indication for total hip arthroplasty should be checked. Results after total hip arthroplasty are comparable with those after coxarthrosis, although the revision rate is higher due to the relatively young age of patients. Statements on the effectiveness of cell-based therapies such as expanded stem cells or bone marrow aspirates cannot currently be made.