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ZusammenfassungEtwa 50 % der Frauen und 20 % der Mann ab 50 Jahren erleiden eine osteoporosebedingte Fraktur. Knochenbrüche im Alter sind die Ursache für ein erhöhtes Risiko für weitere Frakturen, eine erhöhte Sterblichkeit, zusätzliche Erkrankungen und Einschränkung der körperlichen Funktionen und dadurch reduzierte Lebensqualität und Verlust der Unabhängigkeit im täglichen Leben. Das übergeordnete Ziel der Diagnostik und Behandlung von Osteoporosepatienten besteht darin, Frakturen zu verhindern.

Zusammenfassung Einleitung: Die bisher in Deutschland durchgefuhrten Studien bezuglich der Versorgungssituation von Patienten mit osteoporotischer Fraktur beruhen zumeist auf Krankenkassendaten. Es werden daher nur diagnostizierte Erkrankungen erfasst. Ziel der Studie war es, die Dunkelziffer an nicht Osteoporose diagnostizierten Patienten zu erfassen, und die Einleitung von Diagnostik und Therapie nach Fragilitatsfrakturen im Allgemeinen und unter dem Einfluss von Risikofaktoren zu analysieren. Material und Methode: In einer retrospektiven Beobachtungsstudie an orthopadischen und unfallchirurgischen Abteilungen im Rhein-Main-Gebiet wurde eine Analyse der versorgten Frakturen durchgefuhrt. Eingeschlossen wurden Patienten im Alter von > 50 Jahren mit einer ICD verschlusselten Fraktur als Aufnahmediagnose. Die in der Krankenakte enthaltenden Daten wurden nach pravalenten Frakturen, nach fur den Knochen-Stoffwechsel und fur die Knochen-Stabilitat relevanten Grunderkrankungen, einer vorbekannten Osteoporose, durchgefuhrter Diagnostik zur Sicherung oder Widerlegung der Diagnose einer Osteoporose, der Diagnosestellung einer Osteoporose und ggf. erfolgter Therapieeinleitung und - empfehlung nach einem vorliegenden Erhebungsbogen systematisch ausgewertet. Ergebnisse: Insgesamt wurden 2142 Patienten alter als 50 Jahre mit einer Fraktur ausgewertet. 1544 (72,1 %) waren weiblich und 598 (27,9 %) mannlich. Davon wurde bei 1460 (68,2 %) der Patienten die Fraktur als osteoporotisch eingestuft. 80,3 % der Patienten mit osteoporotischer Fraktur waren alter als 70 Jahre. Die Huftfraktur (55,2 %) war die haufigste Frakturlokalisation, gefolgt von der Wirbelkorperfraktur (14 %). Eine pravalente Fraktur gaben 14 % in der Anamnese an. Insgesamt nur bei 29,9 % der Patienten wurde eine Osteoporose als Ursache der Fraktur diagnostiziert. Bei 67,2 % der osteoporotischen Wirbelkorperfrakturen wurde die Osteoporose erkannt, jedoch nur bei 16,3 % der osteoporotischen Huftfrakturen. Zum Zeitpunkt der Entlassung wurden 6,6 % der Patienten mit einem antiosteoporotischen Medikament therapiert und bei 5,1 % wurde diesbezuglich eine Empfehlung im Entlassungsbrief ausgesprochen. Die Ergebnisse dieser Studie zeigen, dass bei 70 % der Patienten die Diagnosestellung einer Osteoporose versaumt und dass 88,3 % der Patienten ohne eine spezifische antiosteoporotische Therapie oder einer Therapieempfehlung aus dem Krankenhaus entlassen wurden. Zusammenfassung: Somit zeigt sich eine deutliche Versorgungslucke zwischen evidenzbasierter Medizin und alltaglicher Praxis. Frakturen bei alteren Menschen fuhren selten zur einer Diagnostik oder Therapie bezuglich Osteoporose. Angesichts der hohen Pravalenz der Osteoporose und der Zunahme der Inzidenz osteoporotischer Frakturen sind Konzepte zur besseren Versorgung gerade dieser Hochrisikopatienten notwendig. Die international zunehmende Etablierung von Fracture Liaison Services (FLS) zeigt in Untersuchungen, dass ein solches Konzept effektiv ist, um ein optimales Osteoporose-Management nach einer Fragilitatsfraktur zu erreichen und sekundare Frakturen zu verhindern. Summary Introduction: Investigations conducted in Germany regarding the care situation of patients with osteoporotic fractures are mostly based on health insurance data. Therefore, only diagnosed diseases are recorded. The aim of the study was to record the unreported number of non-osteoporotic patients and to analyze the initiation of diagnosis and treatment after fragility fractures in general and under the influence of risk factors. Material and method: In a retrospective observational study in orthopedic and trauma surgery departments in the Rhine-Main area an analysis of the treated fractures was conducted. Included were patients aged > 50 years with an ICD encoded fracture as admission diagnosis. The collected information in the medical records were systematically evaluated according to an available questionnaire for prevalent fractures, for underlying bone diseases, for metabolism and bone stability compromising underlying diseases, a known osteoporosis, performed diagnostics to back up or rule out the diagnosis of osteoporosis, initiated therapy and - recommendations. Results: A total of 2142 patients older than 50 years with a fracture were evaluated. 1544 (72.1 %) were female and 598 (27.9 %) were male. Of these, 1460 (68.2 %) of the patients considered the fracture to be osteoporotic. 80.3 % of patients with osteoporotic fracture were older than 70 years. The hip fracture (55.2 %) was the most common fracture localization, followed by the vertebral fracture (14 %). A prevalent fracture was reported in 14 % in the medical history. Overall, only 29.9 % of patients were diagnosed with osteoporosis as the cause of the fracture. Osteoporosis was detected in 67.2 % of osteoporotic vertebral fractures, but only in 16.3 % of osteoporotic hip fractures. At the time of discharge, 6.6 % of patients were treated with an anti-osteoporotic medication and 5.1 % were given recommendation in the discharge letter. The results of this study indicate that 70 % of patients failed to diagnose osteoporosis and that 88.3 % of patients were discharged from the hospital without specific anti-osteoporotic therapy or therapy recommendation. Summary: Thus, there is a clear gap between evidence-based medicine and everyday practice in osteoporosis. Fractures in the elderly rarely lead to a diagnosis or therapy for osteoporosis. Given the high prevalence of osteoporosis and the increase in the incidence of osteoporotic fractures, concepts are needed to better care for these high-risk patients. The increasing international establishment of Fracture Liaison Services (FLS) show in studies that such a concept is effective to achieve optimal osteoporosis management after a fragility fracture and to prevent secondary fractures.

SummaryVitamin D deficiency is a global health problem of enormous and increasing dimensions. In the past decades, numerous studies have centered on the role of vitamin D in the pathogenesis and course of many diseases including several types of cancer. Indeed, vitamin D has been widely acknowledged to be involved in the regulation of cell proliferation, differentiation and apoptosis in numerous cancer cells. While the full range of molecular mechanisms involveld in cancer cell growth and progression remains to be elucidated, recent research has deepened our understanding of the processes that may be affected by vitamin D or vitamin D deficiency.In this review, we consider the properties of bone that enable cancer cells to grow and thrive within the skeleton, and the role of vitamin D and the vitamin D receptor in the process of primary and secondary cancer growth in bone.

ZusammenfassungDer Einfluss von Vitamin D im Rahmen der Pathogenese von muskuloskeletalen Erkrankungen ist aktuell ein Thema von hohem wissenschaftlichem Interesse. Nahezu alle Altersschichten der Bevölkerung sind von einer Vitamin-D-Unterversorgung gefährdet. Vitamin D ist ein essenzieller Faktor für die Knochengesundheit und Muskelfunktion, beides Kernelemente der Orthopädie. Zahlreiche Studien zeigten einen möglichen Zusammenhang zwischen dem Serum Vitamin-D-Spiegel und orthopädisch/traumatologischen Krankheitsbildern. In diesen Beobachtungsstudien wurden diverse negative Auswirkungen eines Vitamin-D-Mangels auf das Ergebnis nach Endoprothesenoperationen und den Verlauf orthopädisch/traumatologischer Krankheitsbilder beschrieben. Die vorliegende Arbeit soll einen Überblick über dieses stetig wachsende Themengebiet bieten.

Background The present study aimed to evaluate the functional, radiological and histological outcome of a customized focal implant for the treatment of focal full-thickness cartilage defects in sheep. Methods The study used magnetic resonance imaging data as the basis for construction of the titanium implant using a three-dimensional printing technique. This was then placed on the medial condyle of the knee joint in eight sheep and left in place in vivo over a period of six months. Following euthanasia, the local biological response was analyzed using micro-computed tomography, light microscopy and histological evaluation (International Cartilage Repair Society (ICRS) score). The variables were analyzed using a generalized linear mixed model. Odds ratios were given with 95% confidence intervals. Results The osseointegration rate was 62.1% (SD 3.9%). All implants were prone to the neighboring cartilage bed (4.4–1096.1 μm). Using the IRCS score, the elements ‘surface’, ‘matrix’, ‘cell distribution’ and ‘cell population’ all showed pathological changes on the operated side, although these did not correlate with implant elevation. On average, a difference of 0.7 mm (± 2 mm) was found between the digitally planned implant and the real implant. Conclusions As a result of imprecise segmentation and difficult preparation conditions at the prosthesis bed, as well as changes at the surface of the implant over the operational lifetime of the prosthesis, it must be stated that the approach implemented here of using a customized implant for the treatment of focal full-thickness cartilage defects at the knee did not meet our expectations.

Die Prognose von Patienten mit Knochenmetastasen ist individuell abhangig vom zugrunde liegenden Primarius. In den letzten Jahren ist die Lebenserwartung von Patienten durch die Fortschritte in der systemischen Therapie (Chemotherapie, Immuntherapie, antihormonelle Therapie) und der radioonkologischen Interventionen deutlich verbessert worden. Dieses Kapitel stellt die Anwendung der gangigen Osteologika bei ossarer Metastasierung, die Radionuklidtherapie und chirurgisch-orthopadische Moglichkeiten vor sowie die ethischen Aspekte, die beim Scoring von Patienten mit Knochenmetastasen zu berucksichtigen sind.

Hypovitaminosis D has been identified as a common risk factor for fragility fractures and poor fracture healing. Epidemiological data on vitamin D deficiency have been gathered in various populations, but the association between vertebral fragility fractures and hypovitaminosis D, especially in males, remains unclear. The purpose of this study was to evaluate serum levels of 25-hydroxyvitamin D (25-OH D) in patients presenting with vertebral fragility fractures and to determine whether patients with a vertebral fracture were at greater risk of hypovitaminosis D than a control population. Furthermore, we studied the seasonal variations in the serum vitamin D levels of tested patients in order to clarify the relationship between other known risk factors for osteoporosis and vitamin D levels. We measured the serum 25-OH D levels of 246 patients admitted with vertebral fractures (105 men, 141 female, mean age 69 years, sd 8.5), and in 392 orthopaedic patients with back pain and no fractures (219 men, 173 female, mean age 63 years, sd 11) to evaluate the prevalence of vitamin D insufficiency. Statistical analysis found a significant difference in vitamin D levels between patients with vertebral fragility fracture and the control group (p = 0.036). In addition, there was a significant main effect of the tested variables: obesity (p < 0.001), nicotine abuse (p = 0.002) and diabetes mellitus (p < 0.001). No statistical difference was found between vitamin D levels and gender (p = 0.34). Vitamin D insufficiency was shown to be a risk factor for vertebral fragility fractures in both men and women. Cite this article: Bone Joint J 2015;97-B:89–93.

Vitamin D is a key player in calcium homeostasis and bone health. Beyond these well-known effects, new data suggest that vitamin D deficiency potentiates a variety of chronic disease states, including diabetes, cancer, and depression. Extremely low vitamin D levels have been associated with osteomalacia and impaired muscle function, both core elements in the field of orthopedic surgery. Good muscle function and healthy bones are essential for fast rehabilitation and positive outcome after orthopedic surgery as well, especially for elderly patients seeking good physical function. Physical function is important for the preservation of independence in daily life and for the prevention of falls, which are associated with fractures and high mortality. This review focuses on the role of vitamin D deficiency in elderly orthopedic patients.

Aseptic loosening is a serious complication after total joint arthroplasty. Plain radiography, along with clinical signs of prosthesis loosening, is the technique of first choice to evaluate loosening of joint replacements. Nevertheless, radiographical signs of osteolysis may not be apparent until progressed stages of loosening. Thus the search for alternative diagnostic methods is of great importance. The purpose of the present study was to evaluate the potential diagnostic significance of TRAP 5b, Osteocalcin, CrossLaps and Bone ALP for aseptic loosening of total joint replacements.Thirty-seven patients (25 women, 12 men, mean age 65 years, age range 54-76 years) treated with revision surgery due to clinically and radiologically confirmed late aseptic prosthesis loosening were examined prospectively. Serum levels of TRAP 5b, Osteocalcin, CrossLaps and Bone ALP were compared with a matched control group (n = 39).We found a significant decrease in TRAP 5B level in patients with aseptic loosening. Bone ALP and Osteocalcin as markers of osteoblast activity, and CrossLaps as another resorption marker did not allow any prediction of bone remodeling in this late phase of loosening.In the "late" phase of aseptic joint replacement loosening, no increase of TRAP 5b and therefore no increase of osteoclast number and activity was measurable. Thus, in this situation an anti-osteolytic therapy with a bisphosphonate or denosumab would not gain any further benefit.

SummaryIt is important to understand compliance and persistence with medication use in the clinical practice of osteoporosis treatment. The purpose of this work is to describe the “intravenous ibandronate versus oral alendronate” (VIVA) study, a non-interventional trial to assess the compliance and persistence of osteopenic postmenopausal women with treatment via weekly oral alendronate or intravenous ibandronate (Bonviva®) every three months.4477 patients receiving ibandronate 3 mg i. v. quarterly and 1491 patients receiving alendronate 70 mg orally weekly were included in the study. Matched pairs of 901 subjects in each group were also generated. Matching was performed on the basis of age, body mass index, fracture history at study inclusion, prior treatment with bisphosphonates and the number of concomitant disorders. Secondary outcome measures of osteoporosis related fractures, mobility restriction and pain, analgesia, quality of life questionnaires as well as attitudes to medications were assessed. The primary outcome parameters of compliance and persistence will be tracked in these subjects.At baseline, the entire collectives differed significantly on body weight (less in ibandronate group), duration since osteo - porosis diagnosis (longer in ibandronate), and incidence of prior osteoporotic fracture (higher in ibandronate group). The matched-pairs differed only on mobility restriction and quality of life (both worse in ibandronate group).The results from the VIVA study trial will provide scientific rationale for clinical recommendations in the pharmacological treatment of postmenopausal osteoporosis.

Vitamin D plays an essential role in bone health and muscle function. Some studies have shown a widespread rate of vitamin D deficiency in the general population, but few have reported on the vitamin D status of orthopaedic patients.We investigated (1) the extent of hypovitaminosis D in orthopaedic patients, (2) seasonal variations in vitamin D levels, and (3) possible risk factors for insufficient vitamin D levels.Vitamin D levels in 1119 patients consecutively admitted to an orthopaedic surgery department in 2011 were measured. To investigate the correlation between climate factors and vitamin D levels, the sunshine hours for each month in 2011 were collected by Deutscher Wetterdienst (the German weather service) in the region where most tested patients lived. The prevalence of normal (30 ng/mL), insufficient (20-30 ng/mL), and deficient (20 ng/mL) 25-hydroxyvitamin D levels was determined. Univariate and multivariate analyses were used to assess risk factors for insufficient vitamin D levels.Overall, 84% of patients had insufficient levels of vitamin D and 60% were vitamin D deficient. Only 15% were in the target range of 30 to 60 ng/mL. The prevalence of low vitamin D levels was greater during winter and months with fewer sunshine hours. Vitamin D levels did not vary according to age, sex, and disease. Individuals with obesity, hypertension, and osteoporosis were more likely to have low vitamin D levels compared with their healthy counterparts.There is an alarmingly high rate of hypovitaminosis D and vitamin D deficiency among orthopaedic patients in this region of Germany, whose latitude (50° N) is approximately the same as those of Vancouver (49°, 15' N) and Paris (48°, 51' N). Given the well-known effects on bone metabolism and muscle health, low vitamin D levels may negatively affect patients. Screening and treating hypovitaminosis D appears to be important in this patient population.

Summary Background: Systemic mastocytosis is a rare disease characterised by accumulation of mast cells in at least one extracutaneous organ, including bone marrow. It is increasingly recognized as a possible cause of secondary osteoporosis. We conducted a literature review on the role of mast cells in osteoporosis including data/peer reviewed articles/ journals from 1957 to 2012. Our aim was to evaluate the current state of research and to offer an overview of current therapeutic options/measures/treatments. Methods: A retrospective review of peer r eviewed/published literature was performed using MEDLINE databases from 1957 to 2012. The keywords “osteoporosis” and “mast cells/mastocytosis” revealed 201 articles, limi ted to English and German articles. The following criteria were included: studies on, or case studies of either mastocytosis induced osteoporosis, or the role of mast cells in osteoporosis or the relation of bone remodeling and mastocytosis. Results/Conclusion: Mast cells seem to play an important role in bone turnover. Their byproducts are responsible for increased bone resorption. However, the skeletal involvement is mainly situated in trabecular bone, which determines vertebral collapse. This review increases the awareness that patients with systemic mastocytosis would benefit from diagnostic workup with regard to bone health, as this rather rare cause of secondary osteoporosis can lead to significantly high rates of mortality.

Introduction Oral thromboprophylaxis with dabigatran etexilate should be initiated as a half dose 1 to 4 h after major orthopaedic surgery. However, a delay in dosing could occur for clinical or logistical reasons. A post hoc analysis was carried out to determine if patients with delayed dosing received adequate anticoagulation. Patients and methods The RE-MODEL™ and RE-NOVATE® trials compared 220 mg and 150 mg dabigatran etexilate with 40 mg enoxaparin. Pooled data for major venous thromboembolism (VTE) and VTE-related mortality (efficacy outcome) and major bleeding events (MBE), MBE/clinically relevant bleeding events, and all bleeding events (safety outcomes) were analysed. Results in patients with dosing delayed more than 4 h postsurgery were compared with those of patients without a delay. Results Onset of treatment was delayed in 724 (13.3%) of 5425 patients. Efficacy of 220 mg dabigatran etexilate was similar in patients without delayed dosing, patients with a delay and patients with a delay until the day after surgery. Rates of efficacy outcome were higher in patients on 150 mg dabigatran etexilate, but more than 80% of these patients were undertreated based on age or renal clearance status. Some differences in bleeding events were seen among patient groups by treatment arm. Conclusion Dabigatran etexilate thromboprophylaxis should be initiated 1 to 4 h postsurgery. Results from our post-hoc analysis indicate that no loss of efficacy appears to occur if initiation of dabigatran etexilate 220 mg needs to be delayed.

Background Radiofrequency ablation is a minimal invasive therapy in the treatment of bone metastases. In this study we present a new ablation system enabling an ablation in multiple directions and with an adaptable size and shape. Material and methods VX-2 tumor was used for the induction of experimental bone metastases in the femur of six New Zealand white rabbits. X-ray imaging as well as CT and MRI scans before and after treatment was carried out. After detecting bone tumor, radiofrequency ablation was performed. The ablation instrument contained a 10 g bipolar, articulated extendable electrode and a proprietary generator with an impedance controlled algorithm. All bones and the soft tissue were examined histologically. Results All animals developed local bone tumor. Mean duration until first osteolytic lesions on CT-scans was 48±14 days. The mean lesion area was 26 mm2. No systemic tumor spread was seen. 6 radiofrequency procedures were carried out with a mean application time of 6 min±2:30 and an average temperature in the region of effect of 55 °C±4. MRI imaging demonstrated an ablation zone of 23±6 mm around the electrode. Histopathology showed an extensive heat necrosis with no remaining tumor cells in the ablation area. Conclusion Radiofrequency ablation is a quickly developing treatment option on the field of minimal invasive bone tumor therapy. The electrode enables an ablation adapted to size and shape of the metastases. Further clinical studies are necessary to test and enhance this radiofrequency system.

SummaryPatients undergoing total hip or knee arthroplasty should receive anticoagulant therapy because of the high risk of venous thromboembolism. However, many are already taking non-steroidal anti-inflammatory drugs (NSAIDs) or acetylsalicylic acid (ASA) that can have antihaemostatic effects. We assessed the bleeding risk in patients treated with thromboprophylactic dabigatran etexilate, with and without concomitant NSAID or ASA. A post-hoc analysis was undertaken of the pooled data from trials comparing dabigatran etexilate (220 mg and 150 mg once daily) and enoxaparin. Major bleeding event (MBE) rates were determined and odds ratios (ORs) generated for patients who received study treatment plus NSAID (half-life ≤12 hours) or ASA (≤160 mg/day) versus study treatment alone. Relative risks were calculated for comparisons between treatments. Overall, 4,405/8,135 patients (54.1%) received concomitant NSAID and 386/8,135 (4.7%) received ASA.ORs for the comparison with/without concomitant NSAID were 1.05 (95% confidence interval [CI] 0.55–2.01) for 220 mg dabigatran etexilate; 1.19 (0.55–2.55) for 150 mg; and 1.32 (0.67–2.57) for enoxaparin. ORs for the comparison with/without ASA were 1.14 (0.26–5.03); 1.64 (0.36–7.49); and 2.57 (0.83–7.94), respectively. For both NSAIDs and ASA there was no significant difference in bleeding between patients with and without concomitant therapy in any treatment arm. Patients concomitantly taking NSAIDs or ASA have a similar risk of MBE to those taking dabigatran etexilate alone. No significant differences in MBE were detected between dabigatran etexilate and enoxaparin within comedication subgroups, suggesting that no increased major bleeding risk exists when dabigatran etexilate is administered with NSAID or ASA.Investigation performed at multiple centres participating in the RE-MODEL™, RE-NOVATE®, and RE-MOBILIZE® trials.

Background Three randomized, double-blind trials compared dabigatran, an oral direct thrombin inhibitor, with enoxaparin for the primary prevention of venous thromboembolism (VTE) in patients undergoing elective total hip and knee arthroplasty. Objectives and Methods We conducted a pre-specified pooled analysis of these trials. 8,210 patients were randomized, of whom 8,135 were treated (evaluable for safety) with dabigatran 220 mg or 150 mg once-daily, or subcutaneous enoxaparin (40 mg once-daily or 30 mg twice-daily). Efficacy analyses were based on the modified intention-to-treat population of 6,200 patients with an evaluable outcome. The common risk difference (RD) of treatment effect between each dabigatran dose and enoxaparin was estimated using fixed-effects models, and statistical heterogeneity was estimated using the I 2 statistic. Results The composite outcome of major VTE (proximal deep vein thrombosis and/or pulmonary embolism) and VTE-related mortality occurred in 3.3% of the enoxaparin group versus 3.0% of the dabigatran 220 mg group (RD vs. enoxaparin -0.2%, 95% CI -1.3% to 0.9%, I 2 = 37%) and 3.8% of the 150 mg group (RD vs. enoxaparin 0.5%, -0.6% to 1.6%, I 2 = 0%). Major bleeding occurred in 1.4% of the enoxaparin group versus 1.4% of the dabigatran 220 mg group (RD vs. enoxaparin -0.2%, -0.8% to 0.5%, I 2 = 40%) and 1.1% of the 150 mg group (RD vs. enoxaparin -0.4%, -1.0% to 0.2%, I 2 = 0%). Conclusions Oral dabigatran was as effective as subcutaneous enoxaparin in reducing the risk of major VTE and VTE-related mortality after hip or knee arthroplasty and has a similar bleeding profile.

Pain relief is an important treatment goal for breast cancer patients with metastatic bone disease and treatment should be associated with a low rate of side effects. This interim analysis of a prospective non-interventional study documents the efficacy and safety of the amino-bisphosphonate ibandronate in the treatment of metastatic bone disease under real-life conditions.For up to 24 weeks 913 breast cancer patients received IV infusions of 6 mg ibandronate every 3-4 weeks or 50 mg of oral ibandronate once daily. Efficacy variables included pain severity, analgesic use, and skeletal-related events; the major safety parameter was renal function, assessed by serum creatinine levels. Subgroup analyses were performed according to pretreatment with bisphosphonates (none, ibandronate, or other bisphosphonates).At baseline, patients with ibandronate pretreatment tended to have lower mean pain scores and lower serum creatinine levels than those pre-treated with other bisphosphonates. Over the observation period, analgesic use did not increase. Among the 712 patients reporting pain at baseline, 70% achieved an improvement in pain severity during treatment with ibandronate, and there was no evidence to suggest relevant differences in mean pain reductions with IV or oral administration of ibandronate or according to prior bisphosphonate treatment. Skeletal-related events were rare (7%). Changes in serum creatinine levels during ibandronate treatment were small and both formulations of ibandronate were rated as well tolerated by physicians and patients.Data from this non-interventional study confirm the analgesic efficacy and safety profile of IV and oral ibandronate under real-life conditions.

ZusammenfassungPrimäre Knochentumoren der Wirbelsäule stellen eine Seltenheit dar. Aus diesem Grund ist es wichtig, dass der Wirbelsäulenchirurg frühzeitig die klinischen Zeichen deutet und darüber hinaus die richtigen Untersuchungen sowohl in der Klinik als auch in der Bildgebung einleitet, so dass eine adäquate Therapie frühzeitig beginnen kann. Die unspezifischen Rückenschmerzen der Patienten erklären die lange Zeit zwischen Initialsymptomen und definitiver Erstdiagnose. Neben der konventionellen Röntgenaufnahme spielen CT und MRT eine wichtige Rolle in der diagnostischen Bildgebung der Knochentumoren. Schlussendlich wird die Verdachtsdiagnose durch eine Biopsie erhärtet. Die „häufigsten seltenen” gutartigen Vertreter der primären Knochentumoren an der Wirbelsäule sind das Osteoidosteom, das Osteoblastom, das Osteo-chondrom, das Hämangiom, die aneurysmatische Knochenzyste und das eosinophile Granulom. Je nach Rezidivfreudigkeit und Aggressivität des Tumors sollte entsprechend eine intraläsionale Kürettage oder eine marginale Enbloc-Resektion angestrebt werden. Da letztere antomisch nicht immer möglich ist sollten Strahlen-und Chemotherapie assistiv berücksichtigt werden. Hauptvertreter der bösartigen Tumoren sind das multiple Myelom, das Plasmozytom, das Ewing-Sarkom, das Osteosarkom, das Chordom und das Chondrosarkom. Eine marginale oder weite En-bloc-Resektion sollte angestrebt werden, wobei die Einführung der neoadjuvanten Chemotherapie neue Möglichkeiten eröffnet hat.

ZusammenfassungHibernome sind seltene benigne, von braunem Fettgewebe differenzierte Tumoren. Sie treten hauptsächlich in der dritten bis fünften Lebensdekade bei vermutlich leichter Bevorzugung des männlichen Geschlechts auf. Die am häufigsten betroffene anatomische Lokalisation ist der Oberschenkel gefolgt von Schulter, Rücken und Hals. Die in der Regel asymptomatischen Tumoren werden oft als Zufallsbefund entdeckt und gewinnen oft erst durch ihre kontinuierliche Größenzunahme klinische Bedeutung. Histologisch unterscheidet man vier morphologische Formen: die typische Variante mit Subtypen, die myxoide, die lipomähnliche und die spindelzellige Variante. Die kernspintomografische Diagnostik zeigt charakteristische aber nicht spezifische Merkmale, so dass die abschließende Diagnosesicherung durch eine histologische Begutachtung zu stellen ist. Vereinzelt sind lokale Rezidive nach intraläsionaler Resektion beschrieben. Für den Fall einer sicheren marginalen Resektion bestehen diese Bedenken nicht, so dieses Vorgehen bei gegebener operativer Indikation zu empfehlen ist. Bislang existieren in der Literatur keine Hinweise auf eine eingetretene Metastasierung durch ein Hibernom.

Aim As an increasing number of patients suffer from osteoporosis-related disorders worldwide, the medical as well as the socioeconomic impact of this problem is significant. Although evidence-based guidelines for diagnosis and treatment are available, their application in daily practice is insufficient. The aim of our initiative was to develop a strategy for supporting this transfer. Methods An expert group of the German Society of Orthopaedics and Traumatology (DGOU) has analysed the current scientific as well as health-care data bases regarding diagnosis and treatment of osteoporosis. Then a set of recommendations has been developed in order to improve this situation. Results The identified support strategy will focus on better identification of patients with osteoporosis and frailty, enhanced interdisciplinary approaches and increased activity to disseminate available guidelines. Additionally, more research activities are necessary in order to highlight the socioeconomic burden of the disease and to continuously improve surgical treatment strategies in the future. Conclusion To ensure a successful application of the recommendations, continuous support of involved health professionals as well as political institutions, national health insurance systems, scientific societies and patient organisations is necessary.

ZusammenfassungPrimär maligne Tumoren des Skelettsystems stellen im Kindes- und Jugendalter eine Seltenheit dar. Gerade deswegen ist es wichtig, die Diagnose frühzeitig zu stellen, um eine adäquate Therapie einzuleiten. Die häufigsten Vertreter sind das Osteosarkom, seltener das Ewing-Sarkom und das Adamantinom. Das Chondrosarkom ist im Jugendalter auch unter den Tumoren eine Rarität.Die Einführung der neoadjuvanten Chemotherapie hat in der Behandlung des Osteosarkoms und des Ewing-Sarkoms zu einer deutli-chen Verbesserung der Überlebenswahrscheinlichkeit geführt. Zudem kann durch neue Therapieprotokolle oftmals eine Extremitäten-erhaltende Operation durchgeführt werden.Im Rahmen der Tumoroperation ist oftmals eine Resektion angrenzender Gelenke und großer Muskelgruppen erforderlich, sodass post-operativ mit einem funktionellen Defizit gerechnet werden muss. Zur Versorgung der Defekte dienen spezielle Tumorprothesen mit Gelenkersatz. Eine Defektüberbrückung kann allerdings auch über vaskularisierte autologe Transplantate wie etwa ein Fibulatransplantat erfolgen. Eine weitere Möglichkeit mit einer anschließenden, funktionell guten exoprothetischen Versorgungsmöglichkeit bietet die Rotationsplastik.Dieser Artikel soll eine Übersicht über die genannten Tumoren sowie deren Diagnostik und Therapie geben.

Summary Background Recent HIV therapies have improved life expectancy in HIV positive patients. For the purpose of the following retrospective investigation, we analyzed the results of total joint replacement in HIV positive patients. This study exemplifies orthopaedic treatment options and perioperative problems in HIV positive patients. Our population included a high proportion of hemophilic patients. Design and methods Between 1988 and 2000, we performed 55 endoprosthetic procedures (20 total hip replacements (THR), 33 total knee replacements (TKR), two shoulder replacements) in 41 patients suffering form HIV. Thirty patients are afflicted with hemophilia, seven patients were intravenous drug addicts. The mean follow-up was 81 months (2–14) years. Patients were seen annually; either the Harris Hip Score or the Knee Society Rating System was applied. Results The following septic complications were observed: a mycotic abscess of both hips 5/10 months after bilateral THR, two early infections following coxitis in patients with intravenous drug abuse, and one further case of septic loosening after 15 months in one patient after THR. Furthermore, one aseptic loosening of a THR after 14 months in a hemophilic patient was seen. After TKR, two early infections in patients with intravenous drug addiction were seen. The total complication rate was 12.7%. A coherency between the infection rate and the CD4+ count was not seen. Discussion An analysis of the results shows that the complications occurred in patients living under difficult social circumstances. Whereas total joint replacement in hemophilic patients with or without HIV seems to be a fairly safe procedure concerning the postoperative infection rate, intravenous drug abuse increases the risk. Functional outcome does not differ from an HIV negative population both in the TKR and THR groups.

After total hip replacement, increased bone metabolism is seen. A local periprosthetic osteopenia can be measured by dual-energy X-ray absorptiometry (DXA), but it is still unkown whether biochemical markers can be used to monitor the local remodeling at an earlier stage.In this prospective study we compared the biochemical markers tartrate-resistant acid phosphatase 5b (TRAP 5b), bone ALP, osteocalcin and CrossLaps with periprosthetic DXA in 17 consecutive patients after uncemented total hip replacement.We found a highly significant early increase in TRAP 5b after 2 weeks and 6 weeks, which was followed by a densitometrically detectable decrease in bone mineral density after 26 weeks, especially in periprosthetic section Gruen zone 7. Bone ALP and osteocalcin levels as markers of osteoblast activity, and also Cross-Laps as a further marker of osteoclast activity, did not appear to allow any significant prediction of local bone remodeling.Our findings show that TRAP 5b is a sensitive parameter for monitoring of osteoclast activity after cementless total hip replacement, and may predict local osteopenia.

Breast and prostate cancer are amongst the most prevalent malignancies globally and up to 40% of patients will develop metastatic disease, particularly to the skeleton. Multiple myeloma is the most common cancer to affect bone with up to 90% of patients developing bone lesions. Although several studies demonstrated that endocrine changes such as vitamin D deficiency promote secondary cancer growth in bone, relatively few have reported its prevalence. For this reason, the purpose of the present study was to evaluate the prevalence of hypovitaminosis D in patients with bone metastases and multiple myeloma.Serum 25-OH-D levels of patients with metastatic bone disease were measured on admission. Statistical analyses was performed to evaluate for possible confounders of hypo-vitaminosis D.We found a widespread and alarming rate of vitamin D deficiency in patients with metastatic bone disease and multiple myeloma. Of note, patients with bone metastases due to breast cancer, prostate cancer and multiple myeloma rarely reached sufficient serum 25-OH-D levels.It is of utmost clinical importance to assess vitamin D levels in cancer patients, especially in those with, or at high risk of developing metastatic bone disease.

Background The purpose of this observational study was to evaluate serum levels of 25-OH-D in patients scheduled to undergo elective hip or knee arthroplasty. We hypothesised that 25-OH-D level is an independent risk factor for length of stay in orthopaedic patients after elective hip or knee arthoplasty. Materials and methods 25-OH-D levels were measured in 1083 patients admitted to an orthopaedic surgery department to undergo elective hip or knee arthroplasty. Comparisons were performed using Chi square or Student’s t test, followed by univariate and multiple linear regression analysis examining the correlation between the length of stay in the orthopaedic department and 25-OH-D level while adjusting for possible confounders. Results Overall, 86 % of patients had insufficient serum levels of 25-OH-D, and over 60 % were vitamin D deficient. The mean length of stay was 13.2 ± 8.3 days. In patients with hypovitaminosis D, the length of stay was significantly longer compared to patients with normal serum 25-OH-D levels (15.6 ± 7.2 compared to 11.3 ± 7.9 days, P = 0.014). In univariate analyses, serum 25-OH-D level was inversely related to the length of stay in our orthopaedic department compared to patients with normal vitamin D levels (r = −0.16; P = 0.008). In multivariate analyses, the length of stay remained significantly associated with low 25-OH-D levels (P = 0.002), indicating that low vitamin D levels increase the length of stay. Conclusions We found a high frequency of hypovitaminosis D among orthopaedic patients scheduled to undergo elective arthroplastic surgery. Low vitamin D levels showed a significant inverse association to the length of stay in our orthopaedic department. Patients with vitamin D levels in the target range were hospitalised 4.3 days less than patients with hypovitaminosis D. Level 3 of evidence according to “The Oxford 2011 levels of evidence”.

Background/Aim: Severe bone pain is experienced by 60–80% of patients with metastatic bone disease, and has a profound impact on quality of life. Therefore, effective pain relief is an important goal in managing metastatic bone disease. Orthopedic surgeons are often challenged with patients presenting with newly diagnosed bone metastases and severe and disabling bone pain. It is important to provide fast and sufficient analgesia. Clinical trials have demonstrated that bisphosphonates reduce effectively and sustained bone pain by approved standard dosage over time. Open label prospective trials have shown that short time high dose i.v. Ibandronate is effective in rapid pain relief in different primary tumors. Patients and methods: In 33 patients with metastatic bone pain from newly diagnosed skeletal metastases we utilized the loading-dose concept for intravenous ibandronate (6 mg infused over 1 h on 3 consecutive days). Results: In 33 patients loading-dose ibandronate therapy significantly reduced bone pain within the first 5–7 days (VAS day 0: 6–8 vs. day 7: 3–4). Only 3 patients showed no response concerning a distinct pain reduction within the first days of therapy. There was no increase in pain medication. Conclusion: This clinical observational study in selected patients with severe metastatic bone pain undergoing an intensive high dosed ibandronate-therapy for a short period demonstrated that loading-dose ibandronate (6 mg i.v., 3 consecutive days) resulted in a reduction of pain within days.

Increasing evidence suggests that ibandronate, a single-nitrogen, non-cyclic bisphosphonate, provides relief of metastatic bone pain (MBP). In phase III trials, both intravenous and oral formulations of ibandronate significantly reduced MBP below baseline for up to 2 years, with concurrent improvements in patient functioning and quality of life compared with placebo. Phase II studies in patients with severe or opioid-resistant MBP suggest that loading-dose ibandronate (intravenous ibandronate 6 mg administered daily for 3 consecutive days) can provide rapid and substantial pain relief within a few days. These findings have been confirmed in clinical pilot studies. Ibandronate is the only intravenous bisphosphonate with a renal safety profile that allows loading-dose treatment. The efficacy of ibandronate in MBP should be considered when choosing a bisphosphonate treatment for metastatic bone disease.

After introduction of ceramics in total hip replacement, there have been several studies on wear and fracture of the femoral head component. Though reports on fractures are few, we saw four fractures within 2 months. In all patients, a cementless hip prosthesis by four different surgeons was implanted between 3/2001 and 2/2004. In three patients, a ceramic-on-polyethylene pair and in one, a ceramic-on-ceramic pair was used. Only one patient suffered an adequate trauma. The mean survival of the ceramic head was 27 months (11-42). In two patients with polyethylene inlays, the inlay showed signs of wear out due to the fractured head. All four revision surgeries had a good outcome with satisfying results and no complications. Though we observe the postoperative development after implantation of ceramic components closely, we still believe that ceramics in total hip replacement in young and active patients are indicated with good long term results.

In the last 30 years bisphosphonates have been used in the treatment of different bone diseases. Bisphosphonates in their oral pharmaceutical form are an established and approved medication in osteoporosis treatment for years. Latest research developed more potent bisphosphonates in different application forms: oral and parenteral. Therefore, their prospects for medical treatment could be enlarged to the fields of oncology, hematology, and osteology. Bisphosphonates are innovative in case of adjuvant therapy as well as in adequate pain therapy. In the medical treatment of osteoporosis and metabolic osteopathies bisphosphonates could be rightly denoted as groundbreaking.

Arthropathy of the hip is moderate in frequency in haemophiliac patients, but is less common than ankle, knee or elbow arthropathy. We report about our experience with total hip replacement in patients with severe bleeding disorders over a period of 30 years. Between July 1972 and 2002, 15 hips in 13 patients were replaced. The main bleeding disorders were Haemophilia A in ten patients and severe v. Willebrand disease in three patients. The mean follow-up was 132 months (range 12–363). We can demonstrate good long-term results, with only one aseptic loosening after 14 years and one septic loosening after 14 months in an HIV-positive patient. The Harris Hip Score increased from 48 points (32–66) preoperatively to 89 (76–100) postoperatively. In conclusion, total hip replacement performed in a specialised haemophiliac centre is a safe procedure, and results in pain relief and improvement of the quality of life in patients with severe bleeding disorders.

Osteoporosis is known to impair the process of implant osseointegration. Bisphosphonates are drugs that inhibit osteoclast-mediated bone resorption and normalize the high rate of bone turnover that characterizes this disease. Consequently, there is a rationale for using bisphosphonates to enhance the early stabilization of implants in subjects with low bone mass. In this study, 84 rats received titanium-only or hydroxyapatite (HA)-coated titanium femoral implants, 3 months after being ovariectomized (OVX) or sham operated. They were then treated for 4 weeks. The OVX rats were randomly assigned to daily subcutaneous injections of either saline or the bisphosphonate ibandronate (at a dose of 1 microg/kg or 25 microg/kg), while the sham-operated animals received saline throughout. The 1 microg/kg or 25 microg/kg ibandronate doses are considered translatable to doses used to treat osteoporosis and metastatic bone disease (MBD), respectively, in rats, and roughly reflect those used in humans. At the end of the treatment period, bone mineral density (BMD) at the lumbar spine increased in both of the ibandronate-treated groups when compared with the OVX control animals and to a level similar to that of the sham-operated control group. Osseointegration, determined by histomorphometric analysis and expressed as percentage of osseointegration implant surface (OIS), did not differ between groups for the titanium-only implants. For the HA-coated implants, however, OIS was 113.5% and 185% higher in the groups receiving 1 microg/kg or 25 microg/kg ibandronate, respectively, relative to the OVX controls. In turn, the OIS of the HA-coated implants was 56.5% lower in the OVX control group than in the sham control group. These findings clearly demonstrate that OVX-induced osteopenia impairs the osseointegration of HA-coated titanium implants and that ibandronate, administered at doses analogous to those used to clinically treat osteoporosis and MBD, counters this harmful effect. Ibandronate may, therefore, have a role in improving the osseointegration of implants in patients with osteoporosis and MBD.

Cementless total joint replacement in osteopenic bone is suspected to deteriorate long-term survival of implants because results in dental implantology research indicate that bone ingrowth of dental implants in osteoporotic bone is impaired. The present investigation was designed to determine whether osteopenic bone stock, experimentally created in ovariectomized rats, influences the active bone-implant integration process. 40 Sprague-Dawley rats were randomly assigned to two treatment groups; one group underwent ovariectomy, the other sham ovariectomy. Successful development of osteopenia was assessed by bone mineral density measurement of the lumbar vertebra L5 before implant surgery and before sacrifice. An uncoated and a hydroxyapatite-coated titanium implant were surgically inserted into the medullary canal of each femur. After 28 days specimens were prepared for histomorphometry to determine the osseointegrated implant surface. The results showed a successful development of experimentally induced osteopenia in ovariectomized rats. For hydroxyapatite-coated implants the histomorphometry revealed a mean osseointegrated implant surface of 54.5% in the sham group versus 23.7% in the ovariectomy group. There was no significant difference for uncoated titanium implants. The present study in rats clearly demonstrates that osteopenic bone loss induced by ovariectomy impairs bone-implant ingrowth of hydroxyapatite-coated implants in the metaphysis of the femur. This is a potential risk for deterioration of long-term outcome of cementless metal implants in osteopenic bone. In consequence, the quality of bone stock has to be taken into account while making a decision for cemented or cementless joint replacements.

Vitamin D is increasingly being recognized as an important mediator of immune function and may have a preventive role in the pathogenesis of periprosthetic joint infection. To the best of our knowledge, no other study has examined possible associations between periprosthetic joint infection and vitamin D deficiency. We investigated the rate of vitamin D deficiency in patients treated for periprosthetic joint infection and whether vitamin D deficiency is independent of other risk factors for vitamin D deficiency in patients with periprosthetic joint infection.Serum 25-hydroxyvitamin D (25OHD) levels of every patient scheduled to receive a total prosthesis either of the hip, knee, or shoulder in the orthopaedic department of the Johannes-Guttenberg-University Hospital in Mainz, Germany (109 patients), were measured after admission. Furthermore, serum 25OHD levels were measured for every patient presenting with periprosthetic joint infection (n = 50) or aseptic loosening of the prosthesis (n = 31) scheduled to undergo revision surgery. The prevalence of normal (30 ng/ml), insufficient (20-30 ng/ml), and deficient (20 ng/ml) 25OHD levels was determined.All tested patient subgroups showed low vitamin D levels. Statistical analysis found no significant difference in vitamin D levels comparing patients with prosthesis and patients with aseptic prosthesis loosening (p = 0.58). Significant differences in 25OHD levels were found comparing patients with periprosthetic joint infection and patients scheduled for primary arthroplasty (p0.001). In addition, we found a significant difference (p0,001) in 25OHD levels of patients with periprosthetic joint infection compared with patients with aseptic prosthesis loosening.We found a high frequency of vitamin D deficiency in patients being treated by primary arthroplasty and those with aseptic joint prosthetic loosening and periprosthetic joint infection. Vitamin D deficiency was severe in patients with periprosthetic joint infection.

Objective. To investigate the application of micro-computed tomography (µCT) for the assessment of density differences and deterioration of three-dimensional architecture of trabecular bone in an experimental rat model for tumor- induced osteolytic defects. Design and materials. Walker carcinosarcoma 256 malignant breast cancer cells (W256) were surgically implanted into the medullary canal of the left femur of 15 4-month-old rats. Twenty-eight days after surgery all animals were killed and both femora from each rat were harvested. A total of 30 specimens (left and right femur) were scanned in a desk-top µCT imaging system (µCT 20, Scanco Medical) to assess densitometric and architectural parameters. For each specimen a total of 200 micro-tomographic slices with a resolution of 30 µm in the distal metaphysis was taken. Bone mineral content (BMC) was analyzed for both cortical and trabecular bone (ctBMC), and for trabecular bone only (tBMC). Architectural indices (BV/TV, Tb.N, Tb.Th, Tb.Sp) according to standard definitions used in histomorphometry were calculated for trabecular bone. Results. The quantitative analysis of density parameters revealed significantly (P

Pathologic fractures from a reduction in bone mass and strength are a debilitating complication affecting the quality of life of individuals with metastatic lesions. There are a number of existing animal models for studying the effects of bone metastases experimentally, but these models are unsuitable for measuring structural changes in metastatic bone. Our goal was to present an in vivo model for directly investigating the densitometric and structural consequences of tumor-induced osteolysis in long bones. One femur from female Sprague Dawley rats was implanted with Walker Carcinosarcoma 256 malignant breast cancer cells or with a Sham implant. After 28 days, the animals were killed, and both femora of each animal evaluated using histomorphometry, densitometry, and mechanical testing. Compared to Sham-operated controls, we found an 11% decrease in bone mineral content, a 9% decrease in bone mineral density using dual energy X-ray absorptiometry, and a 16% decrease in bone density using peripheral quantitative computed tomography in the group with tumor cell implants. In addition, failure torque was decreased by 35% compared to the contralateral controls and by 41% compared to the Sham-operated controls. Torsional stiffness in the tumor cell-implanted femora was decreased by 35% compared to contralateral controls and by 39% compared to Sham-operated controls. Bone density was only weakly to moderately associated with bone strength in our model. By creating reproducible localized tumor-induced osteolytic lesions in a long bone, this model provides the most direct evaluation of the structural consequences of bone metastases. In the future, this model may provide a method for determining the effects of new therapeutic approaches on the preservation of bone mass and bone strength in the presence of metastatic bone disease.

This retrospective study reveals medium-term postoperative results in anterior cruciate ligament reconstruction with a bone-tendon-bone autograft of the middle third of the patellar ligament, 5 to 8 years after surgery. A total of 44 patients with a mean age of 34.7 years was followed up for an average of 72.5 months. Objective stability of the knee was evaluated by means of Lachman, pivot shift, anterior drawer and KT-1000 arthrometer measurements. 95.5% of the knees were stable, with a side-to-side difference : 2 mm in the KT-1000 measurement. Reconstruction of the anterior cruciate ligament using a bone-tendon-bone autograft of the patellar ligament leads to good medium-term results with minimal progression of osteoarthritis. Restoration of ligamentous stability of the knee is important in preventing or retarding the progression of osteoarthritis following anterior cruciate ligament injury.

Summary Background After hip replacement surgery, prophylaxis following discharge from hospital is recommended to reduce the risk of venous thromboembolism. Our aim was to assess the oral, direct thrombin inhibitor dabigatran etexilate for such prophylaxis. Methods In this double-blind study, we randomised 3494 patients undergoing total hip replacement to treatment for 28–35 days with dabigatran etexilate 220 mg (n=1157) or 150 mg (1174) once daily, starting with a half-dose 1–4 h after surgery, or subcutaneous enoxaparin 40 mg once daily (1162), starting the evening before surgery. The primary efficacy outcome was the composite of total venous thromboembolism (venographic or symptomatic) and death from all causes during treatment. On the basis of the absolute difference in rates of venous thromboembolism with enoxaparin versus placebo, the non-inferiority margin for the difference in rates of thromboembolism was defined as 7·7%. Efficacy analyses were done by modified intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00168818. Findings Median treatment duration was 33 days. 880 patients in the dabigatran etexilate 220 mg group, 874 in the dabigatran etexilate 150 mg group, and 897 in the enoxaparin group were available for the primary efficacy outcome analysis; the main reasons for exclusion in all three groups were the lack of adequate venographic data. The primary efficacy outcome occurred in 60 (6·7%) of 897 individuals in the enoxaparin group versus 53 (6·0%) of 880 patients in the dabigatran etexilate 220 mg group (absolute difference −0·7%, 95% CI −2·9 to 1·6%) and 75 (8·6%) of 874 people in the 150 mg group (1·9%, −0·6 to 4·4%). Both doses were thus non-inferior to enoxaparin. There was no significant difference in major bleeding rates with either dose of dabigatran etexilate compared with enoxaparin (p=0·44 for 220 mg, p=0·60 for 150 mg). The frequency of increases in liver enzyme concentrations and of acute coronary events during the study did not differ significantly between the groups. Interpretation Oral dabigatran etexilate was as effective as enoxaparin in reducing the risk of venous thromboembolism after total hip replacement surgery, with a similar safety profile.

Bone marrow contains a population of rare progenitor cells capable of differentiating into bone, cartilage, tendon, and other connective tissues. These cells, referred to as mesenchymal stem cells, can be purified and culture-expanded from animals and humans and have been shown to regenerate functional tissue when delivered to the site of musculoskeletal defects in experimental animals. To test the ability of purified human mesenchymal stem cells to heal a clinically significant bone defect, mesenchymal stem cells isolated from normal human bone marrow were culture-expanded, loaded onto a ceramic carrier, and implanted into critical-sized segmental defects in the femurs of adult athymic rats. For comparison, cell-free ceramics were implanted in the contralateral limb. The animals were euthanized at 4, 8, or 12 weeks, and healing bone defects were compared by high-resolution radiography, immunohistochemistry, quantitative histomorphometry, and biomechanical testing. In mesenchymal stem cell-loaded samples, radiographic and histologic evidence of new bone was apparent by 8 weeks and histomorphometry demonstrated increasing bone formation through 12 weeks. Biomechanical evaluation confirmed that femurs implanted with mesenchymal stem cell-loaded ceramics were significantly stronger than those that received cell-free ceramics. These studies demonstrate that human mesenchymal stem cells can regenerate bone in a clinically significant osseous defect and may therefore provide an alternative to autogenous bone grafts.

Vitamin D is essential to bone health and is a major regulator of calcium homeostasis. Many recent reports demonstrated worldwide high rates of vitamin D deficiency, but few studies have been published on the vitamin D status of orthopaedic patients. The present study aimed to investigate the extent of hypovitaminosis D of orthopaedic patients and possible variations in vitamin D status according to the body region which was scheduled to undergo surgery. We measured the vitamin D level of 1119 patients consecutively admitted to an orthopaedic surgery department of a university hospital in Germany in 2011. The prevalence of normal (or =30 ng/ml), insufficient (20-30 ng/ml) and deficient (or =20 ng/ml) 25-OH-D levels was determined. Serum Vitamin D levels and rates of insufficiency and deficiency were compared between the different cohorts using two-tailed tests. The level of significance was set at por =0.05. The serum 25-OH-D levels for all participants were normally distributed, with a mean of 2057 ng/ml. Overall, we noted an alarmingly high rate of vitamin D insufficiency or deficiency among orthopaedic patients. No significant difference was found related with the various body regions scheduled to undergo surgery. Given the well-known effects of vitamin D on bone metabolism and muscle health, vitamin D insufficiency may negatively affect patients.

Erratum to: International Orthopaedics (SICOT) DOI 10.1007/s00264-011-1393-5 The Article Title of the original publication of this paper contained an error. The correct Article Title should have been “Thromboprophylaxis in patients older than 75 years or with moderate renal impairment undergoing knee or hip replacement surgery”.