Porous 3D Scaffolds Enhance MSC Vitality and Reduce Osteoclast Activity.

In the context of an aging population, unhealthy Western lifestyle, and the lack of an optimal surgical treatment, deep osteochondral defects pose a great challenge for the public health system. Biodegradable, biomimetic scaffolds seem to be a promising solution. In this study we investigated the biocompatibility of porous poly-((D,L)-lactide-ε-caprolactone)dimethacrylate (LCM) scaffolds in contrast to compact LCM scaffolds and blank cell culture plastic. Thus, morphology, cytotoxicity and metabolic activity of human mesenchymal stromal cells (MSC) seeded directly on the materials were analyzed after three and six days of culturing. Further, osteoclastogenesis and osteoclastic activity were assessed using reverse-transcriptase real-time PCR of osteoclast-specific genes, EIA and morphologic aspects after four, eight, and twelve days. LCM scaffolds did not display cytotoxic effects on MSC. After three days, metabolic activity of MSC was enhanced on 3D porous scaffolds (PS) compared to 2D compact scaffolds (CS). Osteoclast activity seemed to be reduced at PS compared to cell culture plastic at all time points, while no differences in osteoclastogenesis were detectable between the materials. These results indicate a good cytocompatibility of LCM scaffolds. Interestingly, porous 3D structure induced higher metabolic activity of MSC as well as reduced osteoclast activity.

Computed tomography for managing periprosthetic femoral fractures. A retrospective analysis.

BACKGROUND: Periprosthetic fractures (PPF) present a common cause for revision surgery after arthroplasty. The choice of performing either an osteosynthesis or revision arthroplasty depends on the orthopedic implant anchored and loosening. Standard diagnostics include x-ray imaging. CT is usually performed to confirm implant loosening in case of ambiguous diagnosis on standard x-ray imaging. This study aimed to examine the role of CT as a diagnostic modality and its implications for treatment planning and outcome. METHODS: Patients treated for PPF from January 2010 to February 2018 were included. X-ray and CT reports were analyzed to assess implant loosening. The planning for surgery and the final surgical treatment were evaluated. In addition, patient characteristics were analyzed and compared between patients with and without additional CT as a preoperative diagnostic procedure. RESULTS: Seventy-five patients were eligible for the study. X-ray imaging was performed in 90.7% of cases. CT was performed in 60% of the cases as part of the preoperative diagnostic. A clear statement on implant stability or loosening could not be made in 69.1% after X-ray imaging and in 84.4% following CT imaging. Revision arthroplasty for loosened femoral prosthesis components was necessary in 40% of cases. No difference could be determined comparing patients with X-ray imaging to those with X-ray and additional CT. In both groups, operative treatment did not deviate from the preoperative planning. DISCUSSION: In two thirds of the conventional radiographic findings, no reliable evaluation of implant loosening was possible in femoral PPFs. Intriguingly, additional CT did not improve the evaluation of implant loosening. Nonetheless, CT scans are often performed if loosening assessment is unclear on regular radiographs. This fact can explain the bias CT results in comparison to regular radiography. However, software-supported CT diagnosis could help to adequately answer the question of loosened implants in PPF in the near future. Since the diagnosis of fracture and their morphology assessment is currently adequately performed using X-rays, CT shall not be considered as the gold standard.

Radiocarpal fusion and midcarpal resection interposition arthroplasty: long-term results in severely destroyed rheumatoid wrists.

BACKGROUND: The aim of this retrospective study is to evaluate distal resection interposition arthroplasty of the wrist as a tool to restore mobility as well as to restore stability in severely destroyed wrist joints. METHODS: Thirty-four wrists in 28 rheumatoid arthritis patients were included. The mean follow-up time was 9 years after surgical treatment with clinical and radiological examination. The results were accessed based on a modification of Clayton ́s scoring system as well as a functional questionnaire. RESULTS: 71% patients were satisfied with pain, function and activities of daily life. Better results were reported by patients with a young age, early surgical intervention, a shorter duration of the disease, and lesser involvement of other joints. CONCLUSIONS: The results for radiocarpal arthrodesis were comparable to those of synovectomy or arthrodesis of the wrist. The results after total wrist joint arthroplasty varies probably as the result of different patient groups, implant types and evolution of prosthetic designs, and are not comparable with the present study.

Diaphyseal long bone nonunions - types, aetiology, economics, and treatment recommendations.

The intention of the current article is to review the epidemiology with related socioeconomic costs, pathophysiology, and treatment options for diaphyseal long bone delayed unions and nonunions. Diaphyseal nonunions in the tibia and in the femur are estimated to occur 4.6-8% after modern intramedullary nailing of closed fractures with an even much higher risk in open fractures. There is a high socioeconomic burden for long bone nonunions mainly driven by indirect costs, such as productivity losses due to long treatment duration. The classic classification of Weber and Cech of the 1970s is based on the underlying biological aspect of the nonunion differentiating between "vital" (hypertrophic) and "avital" (hypo-/atrophic) nonunions, and can still be considered to represent the basis for basic evaluation of nonunions. The "diamond concept" units biomechanical and biological aspects and provides the pre-requisites for successful bone healing in nonunions. For humeral diaphyseal shaft nonunions, excellent results for augmentation plating were reported. In atrophic humeral shaft nonunions, compression plating with stimulation of bone healing by bone grafting or BMPs seem to be the best option. For femoral and tibial diaphyseal shaft fractures, dynamization of the nail is an atraumatic, effective, and cheap surgical possibility to achieve bony consolidation, particularly in delayed nonunions before 24 weeks after initial surgery. In established hypertrophic nonunions in the tibia and femur, biomechanical stability should be addressed by augmentation plating or exchange nailing. Hypotrophic or atrophic nonunions require additional biological stimulation of bone healing for augmentation plating.

Ballistic Gels in Experimental Fracture Setting.

Biomechanical tests typically involve bending, compression, or shear stress, while fall tests are less common. The main challenge in performing fall tests is the non-reproducible directionality of bone when tested with soft tissue. Upon removal of the soft tissue, the explanted bone's resistance to impact diminishes. Therefore, ballistic gels can fix specimens in reproducible directions and simulate periosteal soft tissue. However, the use of ballistic gels in biomechanical studies is neither standardized nor widespread. This study aimed to optimize a ballistic gel consistency that mimics the upper thigh muscle in sheep. Our results suggest a standardized and flexible evaluation method by embedding samples in ballistic gel. Compression tests were conducted using cylindrical pieces of gluteal muscle from sheep. Various compositions of agarose and gelatin mixtures were tested to achieve a muscle-like consistency. The muscle-equivalent ballistic gel was found to consist of 29.5% gelatin and 0.35% agarose. Bones remained stable within the ballistic gel setup after freeze-thaw cycles between -20 °C and +20 °C. This method reduces the variability caused by muscle and improves storage quality, allowing for tests to be conducted under consistent conditionsBallistic gels of agarose and gelatin are suitable for bone fracture models. They have muscle-like strength, fix fractures simultaneously, are inexpensive to produce, and can be stored to allow repeated measurements of the same object with changing questions.

Treatment of hand and finger fractures with the Stryker Hand Plating System.

Objectives: 10% of all fractures occur in the fingers and metacarpal region. Early mobilization with preservation of grip function is the goal of any therapy for these injuries. Osteosyntheses with plates are used in complex fractures that do not allow any other treatment. The aim of this retrospective study was to evaluate the performance and safety of the Stryker Hand System. Patients and methods: Between 2010 and 2019, 190 patients underwent surgical treatment with plates for fractures of the fingers and metacarpal region. Of these, 140 operations could be analyzed according to the inclusion criteria based on clinical and radiological parameters. Results: Three-quarters of the patients were male. The mean age at the time of surgery was 39.3±16 years. Falling was the leading cause for hand fractures, and the most common were fractures of the shaft (>52%). More than 15% were complex hand injuries with more than one fractured finger. The majority of patients were healthy non-smokers without systemic diseases and relevant medical history. Conclusion: The Stryker Finger Plates are safe implants with good results that are consistent with those reported in the literature. The trend is also toward stable-angle implants for fracture treatment of the finger, in order to enable the earliest possible functional, safe mobilization. Level of Evidence: Level: IV; outcome-study, retrospective.

Microangiopathy in Inflammatory Diseases-Strategies in Surgery of the Lower Extremity.

BACKGROUND: Patients with an inflammatory disease frequently develop chronic angiopathy of the capillaries. Due to this pathology, there is an increased rate of complications in lower extremity surgical procedures. It is not uncommon for microangiopathic wound healing disorders to cause deep infections and fistulas, which lead to prolonged courses and hospitalizations. In addition, adhesions and ossifications of the contractile elements occur regularly. This sometimes results in serious limitations of the mobility of the patients. The study aims to present the results of a combination of vacuum and physical therapy. PATIENT AND METHODS: A retrospective study of six patients with systemic sclerosis undergoing joint-related procedures of the lower extremity between 2015 and 2020 was performed. In addition to characterization of the patients and therapy, special attention was paid to cutaneous wound healing, affection of the fascia and displacement layers, and sclerosis of the muscle and tendon insertion. RESULTS: The characterized structures (skin, tendon, fascia) show pathological changes at the microangiopathic level, which are associated with delayed healing and less physical capacity. Early suture removal regularly results in secondary scar dehiscence. With a stage-adapted vacuum therapy with sanitation of the deep structures and later on a dermal vacuum system, healing with simultaneous mobilization of the patients could be achieved in our patient cohort. CONCLUSION: In the case of necessary interventions on the lower extremity, such as trauma surgery, additional decongestive measures in the sense of regular and sustained lymphatic therapy and adapted physiotherapy are indispensable.

On the quantification of local power densities in a new vibration bioreactor.

We investigate the power densities which are obtainable locally in a vibration bioreactor. These reactor systems are of great relevance for research about oncological or antibacterial therapies. Our focus lies on the local liquid pressure caused by resonance vibration in the fluid contained by the reactor's petri dish. We use for the excitation one piezoelectric patch which offer advantages concerning controllability and reproducibility, when compared to ultrasound. The experimental work is extended by finite element analyses of bioreactor details. The peaks of the vibration response for water, sodium chloride (0.1N Standard solution), and McCoy's 5A culture medium are in good alignment. Several natural frequencies can be observed. Local power density can reach multiple times the magnitude used in ultrasound studies. Based on the observed local power densities, we are planning future work for the exposure of cell cultures to mechanical vibration.

Ultrasound-accelerated thrombolysis in high-risk perioperative pulmonary embolism: two case reports and review of literature.

INTRODUCTION: Treatment of high-risk pulmonary embolism (PE) in perioperative patients remains challenging. Systemic thrombolysis is associated with a high risk of major bleedings and intracranial haemorrhage. High mortality rates are reported for open pulmonary embolectomy. Therefore, postoperative surgical patients may benefit substantially from catheter-directed ultrasound-accelerated thrombolysis (USAT). CASE PRESENTATION: We report two cases of high-risk perioperative PE. Both patients developed severe haemodynamic instability leading to cardiac arrest. After the implantation of a veno-arterial extracorporeal membrane oxygenation (ECMO), they were both successfully treated with USAT. Adequate improvement of right ventricular function was achieved; thus, ECMO could be successfully weaned after 3 and 4 days, respectively. Both patients showed favourable outcomes and could be discharged to rehabilitation. CONCLUSION: Current guidelines on treatment of PE offer no specific therapies for perioperative patients with high-risk PE. However, systemic thrombolysis is often excluded due to the perioperative setting and the risk of major bleeding. Catheter-directed thrombolysis was shown to utilise less thrombolytic agent while obtaining comparable thrombolytic effects. The risk for major bleeding (including intracranial haemorrhage) is also significantly lowered. Until further trials determining the value of adopted treatment strategies of high-risk PE in perioperative patients are available, USAT should be considered in similar cases.

Long-Term Results of the Modular Physiological Wrist Prosthesis (MPW®) in Patients with Inflammatory Diseases.

The wrist is among the predilection sites of over 90% of cases of rheumatoid arthritis (RA). In advanced cases, total wrist arthroplasty (TWA) is an alternative to arthrodesis. The aim of this study is to present the long-term results of the modular physiological wrist prosthesis (MPW®) and to match them in context with the results of a standard population survey. In a retrospective study with follow-up, patients with an MPW® endoprosthesis were evaluated concerning the clinical and radiological outcome, complications were reviewed (incidence and type), and conversion to wrist fusion was assessed. Patient function measurements included the Mayo wrist score, the patient-specific wrist test, and therefore the DASH score (arm, shoulder, and hand). Thirty-four MPW® wrist prostheses were implanted in 32 patients, including thirty primary implantations and four changes of the type of the endoprosthesis. Sixteen patients (18 prostheses) underwent clinical and radiological follow-up. The average follow-up time was 8.5 years (1 to 16). Poor results of the MPW prosthesis are caused by the issues of balancing with luxation and increased PE wear. Salvage procedures included revision of the TWA or fusion. In successful cases, the flexion and extension movement averaged 40 degrees. The grip force was around 2.5 kg. The common DASH score was 79 points, with limited and problematic joints of the upper extremity. The MPW wrist prosthesis offered good pain relief and functional movement in over 80% of cases. The issues of dislocation and increased PE wear prevent better long-term results, as do the joints affected. A follow-up study with fittings under a contemporary anti-rheumatic therapy with biologicals suggests increasing score results. Type of study/level of evidence: Case series, IV.

Mortality, Risk Factors and Risk Assessment after Periprosthetic Femoral Fractures-A Retrospective Cohort Study.

Periprosthetic femoral fracture (PFF) is a devastating complication. Here, the authors aimed to determine the influence of the timing of surgery as a risk factor for mortality and poor postoperative outcome in patients suffering from PFF. A retrospective descriptive analysis of patients treated for PFF between January 2010 and March 2018 was performed. In addition to patient and treatment characteristics, we assessed mortality rates and postoperative functional outcome by using the Harris Hip and WOMAC score. One-year mortality after PFF was 10.7%. Delayed surgery after 48 h did not negatively influence mortality after PFF. The postoperative hospital stay did not influence the mortality rate, nor did it correlate with medical scores of comorbidities, general health or functionalities. Cementation of stem correlated negatively with the WOMAC score. Deceased patients had a higher Charlson Comorbidity Index (CCI) score, while American society of Anaesthesiologists (ASA) scores did not show a significant difference. There were no differences between ORIF and revision arthroplasty. In conclusion, delayed surgery after 48 h does not negatively influence mortality after PFF. The CCI seems to be a suitable tool to assess patients' risk for increased mortality after PFF, while the usually used ASA score is not able to achieve a relevant risk assessment.

Correction: On the quantification of local power densities in a new vibration bioreactor.

[This corrects the article DOI: 10.1371/journal.pone.0245768.].

DXA reference values of the humanoid sheep model in preclinical studies.

BACKGROUND: Merino land sheep are a popular pre-clinical large animal model in research on systemic skeletal diseases such as osteoporosis. Interpretation of studies is difficult because many reference parameters are missing or not established. This study aims to determine the reference parameters of the skeletal system (peak bone mass = PBM, T-Score). A defined standard allows an easier comparison of the study data of the animal model with human studies (T-Score). MATERIALS AND METHODS: A total of 116 Dual Energy X-ray Absorptiometry DXA measurements were performed on 74 untreated sheep. The average age of the animals was 57 months. The BMD, BMC, and fat content of the sheep were determined by the relevant human region of interest (ROI). From this, the PBM and from this the T-score for each of the animals were calculated. RESULTS: Using 682 DXA measurements BMD and BMC were determined to provide an indication to PBM. For BMD a significant correlation to the age of the animals was observed (p = 0.043). A significant correlation was also seen for BMC (B) (p ≤ 0.001). In the age-dependent analysis, a widespread of values above the linear regression line was measured for both BMD and BMC between the 50th and 90th months of life. From an age of about 90 months, a wider spread of values below the linear regression line was found, although the average values continued to rise. DISCUSSION: The evaluation of the 116 DXA measurements allowed the determination of the PBM for merino land sheep. With the help of the PBM, a T-score was calculated for each animal. The statistical analysis shows significant differences in BMD values between the different animal groups in each of the four ROIs investigated. Individual control or sham groups per study are therefore not sufficient. To improve comparability, an independent reference group should be established. CONCLUSION: An independent reference group for PBM and a T-score was established from four to six-year-old animals. The bone density increases with the age of the animals. Around the fourth year of life, a first peak could be observed. Also, after the seventh year of life, a further peak with the beginning plateau phase was observed. When compiling a group of animals for an osteoporosis model, animals from the age of seven years should, therefore, be used.

Large Animal Model of Osteoporotic Defect Healing: An Alternative to Metaphyseal Defect Model.

Osteoporosis is a common metabolic disorder diagnosed by lower bone density and higher risk of fracture. Fragility fractures because of osteoporosis are associated with high mortality rate. Deep understanding of fracture healing in osteoporosis is important for successful treatment. Therefore, the FDA approved the use of small and large animal models for preclinical testing. This study investigated the clinical relevance of a fracture defect model in the iliac crest of the osteoporotic sheep model and its several advantages over other models. The osteoporosis was achieved using ovariectomy (OVX) in combination with diet deficiency (OVXD) and steroid administration (OVXDS). Fluorochrome was injected to examine the rate of bone remodelling and bone mineralization. The defect areas were collected and embedded in paraffin and polymethyl metha acrylate (PMMA) for histological staining. OVXDS showed significantly lower bone mineral density (BMD) and bone mineral content (BMC) at all time points. Furthermore, variations in healing patterns were noticed, while the control, OVX and OVXD showed complete healing after 8 months. Bone quality was affected mostly in the OVXDS group showing irregular trabecular network, lower cortical bone thickness and higher cartilaginous tissue at 8 months. The mineral deposition rate showed a declining pattern in the control, OVX, and OVXD from 5 months to 8 months. One the contrary, the OVXDS group showed an incremental pattern from 5 months to 8 months. The defect zone in osteoporotic animals showed impaired healing and the control showed complete healing after 8 months. This unique established model serves as a dual-purpose model and has several advantages: no intraoperative and postoperative complications, no need for fixation methods for biomaterial testing, and reduction in animal numbers, which comply with 3R principles by using the same animal at two different time points.

Resonance vibration interventions in the femur: Experimental-numerical modelling approaches.

MOTIVE: External vibration excitation might be key to many novel non-surgical interventions for pathologies in the musculoskeletal system and in other parts of the human organism. Lack of understanding about vibration patterns, their controllability, and reproducibility are three limitations of ongoing research. This study establishes a bovine vibration model and animal model replacements for future research. METHODS: We used biological samples (n=5) and one polyurethane sample of the bovine femur. Mechanical resonance was measured experimentally and analysed numerically by finite element method. MAIN RESULTS: The experiments obtained 5 distinct mode shapes for the biological sample set, with standard deviation < 7.5%. Finite element analysis of the biological samples can replicate experimental mode shape deflection. The use of polyurethane changes resonance character but results are also good approximations of the biological samples. CONCLUSIONS: A model of the bovine femur with consistent resonance behaviour is presented with alternatives (polyurethane and finite element analysis) that can serve in reducing the number of necessary biological samples. Future work will be to adapt results to human anatomy. Of clinical interest will be to influence bone pathologies such as post-surgical non-union, or bone functionality as part of haematopoiesis and endocrine secretion.

Evidence of Prolonged Monitoring of Trauma Patients Admitted via Trauma Resuscitation Unit without Primary Proof of Severe Injuries.

Introductio: Although management of severely injured patients in the Trauma Resuscitation Unit (TRU) follows evidence-based guidelines, algorithms for treatment of the slightly injured are limited. METHODS: All trauma patients in a period of eight months in a Level I trauma center were followed. Retrospective analysis was performed only in patients ≥18 years with primary TRU admission, Abbreviated Injury Scale (AIS) ≤ 1, Maximum Abbreviated Injury Scale (MAIS) ≤ 1 and Injury Severity Score (ISS) ≤3 after treatment completion and ≥24 h monitoring in the units. Cochran's Q-test was used for the statistical evaluation of AIS and ISS changes in units. RESULTS: One hundred and twelve patients were enrolled in the study. Twenty-one patients (18.75%) reported new complaints after treatment completion in the TRU. AIS rose from the Intermediate Care Unit (IMC) to Normal Care Unit (NCU) 6.2% and ISS 6.9%. MAIS did not increase >2, and no intervention was necessary for any patient. No correlation was found between computed tomography (CT) diagnostics in TRU and AIS change. CONCLUSIONS: The data suggest that AIS, MAIS and ISS did not increase significantly in patients without a severe injury during inpatient treatment, regardless of the type of CT diagnostics performed in the TRU, suggesting that monitoring of these patients may be unnecessary.

Treatment of proximal fifth metatarsal fractures with an ulna hook plate.

INTRODUCTION: Fractures of the base of the fifth metatarsal bone present one of the commonest fractures of the metatarsal bones. Conventionally intramedullary screws and tension band wiring have been used as internal fixation methods. Lately hook plates have also served as an alternative fixation method. We hereby report on our experience with the hook plate used in treating fractures of the proximal fifth metatarsal. METHODS: 21 patients treated with the hook plate for proximal fifth metatarsal fractures were assessed clinically and radiologically. RESULTS: Average time to union in primarily treated fractures (n=18) was 7.7 weeks (range 4.5-16 weeks). Average time to return of activities of daily living (ADLs) was 10.3 weeks (range 4.5-37 weeks). The average AOFAS midfoot score was 30.4 preoperatively and 95.2 postoperatively (p<0.01). CONCLUSION: The ulna hook plate presents a suitable and adequate method of osteosynthesis used to primarily treat proximal fifth metatarsal fractures requiring surgical intervention with satisfactory post-operative outcomes.

Peri-Prosthetic Joint Infection after Finger Joint Arthroplasty.

Background: Endoprosthetic treatment of finger joints is an established procedure. However, data on peri-prosthetic finger joint infections (PJI) are rare. The goal of this retrospective study was to assess infection rates and treatment outcomes after PJI of the finger joints. Methods: Between 1984 and 2014, 1,195 finger joints (978 metacarpal and 217 proximal interphalangeal [PIP] joints) in 518 patients were treated. A retrospective record analysis was conducted. Besides demographic data, infection rates, types of revision surgery, and treatment outcomes were evaluated. Treatment strategies changed during the treatment period. Routinely assessed patient-reported outcome measures, namely the QuickDASH score, visual analogue scale (VAS), an everyday function score (activities of daily living; ADL), and an adapted Clayton score, were compared. Results: In 36 finger joints of 30 patients, a post-operative peri-prosthetic infection could be identified (3%). Infections occurred on average 3.8 years after arthroplasty. For meta-carpal phalangeal (MCP) joints, the best clinical outcomes could be observed after a two-stage revision procedure (QuickDASH score 86). Arthrodesis performed in a one-stage procedure achieved favorable outcomes in PIP joints (QuickDASH score 89). Re-infection mandating revision surgery occurred in seven joints in five patients (7/36; 19.4%). In 25 patients with 29 finger joints, there was no re-infection and no need for revision. Conclusion: Peri-prosthetic infection of finger joint prostheses occurs in approximately 3% of all cases, which is a higher rate than in the more common hip and knee procedures. For MCP joint revision surgery, a two-stage procedure seems to be the best treatment choice. For PIP joint revision, a single-stage revision with arthrodesis in a functional position achieves a good outcome.

Osteocytes. / Osteozyten.

For a long time, osteocytes were regarded as passive bystanders of bone metabolism. Bone remodeling was considered to be an interplay between bone forming osteoblasts and bone degrading osteoclasts. However, the dogma of osteocytes as bystanders within the bone has changed fundamentally since the turn of the millenium. Rather than being silent bystanders, osteocytes are the master cells of bone metabolism. To illustrate the central role of osteocytes, we performed a selective literature research in PubMed and Google Scholar using the search terms "osteocyte", "fracture healing", "bone healing", "bone remodeling", "bone metabolism", "sclerostin", "RANKL/OPG", "Wnt signaling pathway" and "FGF23". We included German and English clinical and preclinical studies as well as literature reviews. Osteocytes develop out of osteoblasts and are the key player in bone metabolism. They build a network within bone and make up 90 - 95% of all bone cells. In contrast to osteoblasts and osteoclasts, osteocytes can reach the age of the organism itself. Their morphology - with its dendritic connection through nexus - forms the perfect basis of osteocyte function. Besides the role as mechanosensor in bone, osteocytes control osteoblasts via sclerostin and osteoclasts via the RANK/RANKL/OPG pathway. Bone mineralisation is controlled by directing local phosphate concentrations. The systemic phosphate levels are regulated in interaction with the kidneys by the hormone FGF23. Understanding the role of osteocytes promises better therapies in clinical practice. Sclerostin antibodies and denusomab, an OPG agonist, are already established for clinical application in osteoporosis therapy. Antibodies against FGF23 or its receptors are used in preclinical and clinical trials. Bortezomib, an antibody which improves vitality of osteocytes, is already used for multiple myeloma therapy. For orthopaedic surgery, understanding the role of osteocytes promises new therapeutic approaches in future. Improvement in osseous integration of metallic implants and medical treatment of disturbed fracture healing are future fields in which therapies may be established by manipulating osteocytes.

Strontium and bisphosphonate coated iron foam scaffolds for osteoporotic fracture defect healing.

The purpose of this work was to investigate new bone formation in macroporous iron foams coated with strontium (FeSr) or bisphosphonate (FeBiP) compared to plain iron foam (Fe) and empty defect in a critical size metaphyseal bone defect model in ovariectomized rats. 60 female rats were subjected to bilateral ovariectomy and multi-deficient diet for 3 months. A 4 mm wedge shaped metaphyseal osteotomy was created, fixed with a mini-plate and subsequently filled with Fe, FeSr, FeBiP or left empty. After 6 weeks, µCt analysis revealed a statistically significant increased bone formation at the implant interface in FeSr compared to FeBiP (p = 0.035) and Fe (p = 0.002), respectively. Increased mineralized tissue was also seen within the pores in FeSr (p = 0.023) compared to Fe. Histomorphometry revealed significantly increased bone formation at the implant interface in FeSr (p < 0.001) and FeBiP (p = 0.006) compared to plain Fe with increased osteoblast and decreased osteoclast activity in combination with increased BMP2 and decreased RANKL/OPG in immunohistochemistry. ToF-SIMS analysis showed overlapping Ca signals with Fe for both FeSr and FeBiP thereby indicating tissue in-growth into the scaffolds. In conclusion, iron foam with strontium or bisphosphonate coating are of further interest in metaphyseal fracture defects in osteopenic bone.