Interleukin-6 as a critical inflammatory marker for early diagnosis of surgical site infection after spine surgery.

PURPOSE: Early diagnosis of surgical site infections (SSIs) could prevent surgical revision. Inflammatory markers (IMs), such as procalcitonin (PCT), interleukin-6 (IL-6), and tumor necrosis factor α (TNF-α), seem more accurate in diagnosing SSI than C-reactive protein (CRP) and white blood cell (WBC) count. The aim was to compare the predictive values of CRP, WBC count, PCT, IL-6, and TNF-α in SSI detection. METHODS: A total of 130 patients undergoing dorsal spondylodesis from 2019 to 2024 were enrolled in a prospective diagnostic study at a maximum care spine center. IMs were measured preoperatively and on the postoperative days (PODs) 1, 2, 3, 5, and 7. Patients with high suspicion of SSI underwent revision surgery. SSI was diagnosed when the microbiological evidence was positive. Patients were divided a posteriori into the non-infection and infection groups. RESULTS: IMs of 118 patients (66.9 ± 13.0 years, 61.0% females) were measured. Fifteen of the 118 patients (12.7%) developed an SSI. The groups differed with respect to existing hypertension, number of instrumented segments, region of surgery, CRPPOD1,7, PCTPOD7, and IL-6POD3,5,7. Binary logistic regression for SSI detection including these parameters showed an area under the curve (AUC) of 0.88 (95% CI 0.79-0.98; P < 0.001). The main effect for SSI detection was maintained by IL-6POD7 (odds ratio = 1.13; 95% CI 1.05-1.23; P = 0.001), which itself showed an AUC of 0.86 (95% CI 0.75-0.97). CONCLUSION: Compared to CRP, WBC count, PCT, and TNF-α, IL-6 seems to be the critical IM for the early detection of an SSI. TRIAL REGISTRATION: drks.de: DRKS00033773, date of registration: 29.02.2024, retrospectively registered; Postoperative Markers of Inflammation in Spine Surgery (POMIS) Trial.

Can Early Post-Operative Scoring of Non-Traumatic Amputees Decrease Rates of Revision Surgery?

Background and Objectives: Medical registries evolved from a basic epidemiological data set to further applications allowing deriving decision making. Revision rates after non-traumatic amputation are high and dramatically impact the following rehabilitation of the amputee. Risk scores for revision surgery after non-traumatic lower limb amputation are still missing. The main objective was to create an amputation registry allowing us to determine risk factors for revision surgery after non-traumatic lower-limb amputation and to develop a score for an early detection and decision-making tool for the therapeutic course of patients at risk for non-traumatic lower limb amputation and/or revision surgery. Materials and Methods: Retrospective data analysis was of patients with major amputations lower limbs in a four-year interval at a University Hospital of maximum care. Medical records of 164 patients analysed demographics, comorbidities, and amputation-related factors. Descriptive statistics analysed demographics, prevalence of amputation level and comorbidities of non-traumatic lower limb amputees with and without revision surgery. Correlation analysis identified parameters determining revision surgery. Results: In 4 years, 199 major amputations were performed; 88% were amputated for non-traumatic reasons. A total of 27% of the non-traumatic cohort needed revision surgery. Peripheral vascular disease (PVD) (72%), atherosclerosis (69%), diabetes (42%), arterial hypertension (38%), overweight (BMI > 25), initial gangrene (47%), sepsis (19%), age > 68.2 years and nicotine abuse (17%) were set as relevant within this study and given a non-traumatic amputation score. Correlation analysis revealed delayed wound healing (confidence interval: 64.1% (47.18%; 78.8%)), a hospital length of stay before amputation of longer than 32 days (confidence interval: 32.3 (23.2; 41.3)), and a BKA amputation level (confidence interval: 74.4% (58%; 87%)) as risk factors for revision surgery after non-traumatic amputation. A combined score including all parameters was drafted to identify non-traumatic amputees at risk for revision surgery. Conclusions: Our results describe novel scoring systems for risk assessment for non-traumatic amputations and for revision surgery at non-traumatic amputations. It may be used after further prospective evaluation as an early-warning system for amputated limbs at risk of revision.

Effects of ligandrol as a selective androgen receptor modulator in a rat model for osteoporosis.

INTRODUCTION: The selective androgen receptor modulator ligandrol (LGD-4033 or VK5211) has been shown to improve muscle tissue. In the present study, the effect of ligandrol on bone tissue was investigated in ovariectomized rat model. MATERIALS AND METHODS: Three-month-old Sprague Dawley rats were either ovariectomized (OVX, n = 60) or left intact (NON-OVX, n = 15). After 9 weeks, OVX rats were divided into four groups: untreated OVX (n = 15) group and three OVX groups (each of 15 rats) treated with ligandrol orally at doses of 0.03, 0.3, or 3 mg/kg body weight. After five weeks, lumbar vertebral bodies (L), tibiae, and femora were examined using micro-computed tomographical, biomechanical, ashing, and gene expression analyses. RESULTS: In the 3-mg ligandrol group, bone structural properties were improved (trabecular number: 38 ± 8 vs. 35 ± 7 (femur), 26 ± 7 vs. 22 ± 6 (L), 12 ± 5 vs. 6 ± 3 (tibia) and serum phosphorus levels (1.81 ± 0.17 vs.1.41 ± 0.17 mmol/l), uterus (0.43 ± 0.04 vs. 0.11 ± 0.02 g), and heart (1.13 ± 0.11 vs. 1.01 ± 0.08 g) weights were increased compared to the OVX group. Biomechanical parameters were not changed. Low and medium doses did not affect bone tissue and had fewer side effects. Body weight and food intake were not affected by ligandrol; OVX led to an increase in these parameters and worsened all bone parameters. CONCLUSION: Ligandrol at high dose showed a subtle anabolic effect on structural properties without any improvement in biomechanical properties of osteoporotic bones. Considering side effects of ligandrol at this dose, its further investigation for the therapy of postmenopausal osteoporosis should be reevaluated.

Reduced Cell Adhesion on LightPLAS-Coated Implant Surfaces in a Three-Dimensional Bioreactor System.

Most implants used in trauma surgery are made of steel and remain inside the body only temporarily. The strong tissue interaction of such implants sometimes creates problems with their explantation. Modified implant surfaces, which decrease tissue attachment, might allow an easier removal and therefore a better outcome. Such a modification must retain the implant function, and needs to be biocompatible and cost-effective. Here, we used a novel VUV-light (Vacuum-Ultraviolett)-based coating technology (LightPLAS) to generate coated stainless-steel plates. The tested LightPLAS coating only had an average thickness of around 335 nm, making it unlikely to interfere with implant function. The coated plates showed good biocompatibility according to ISO 10993-5 and ISO 10993-12, and reduced cell adhesion after four different time points in a 2D cell culture system with osteoblast-like MG-63 cells. Furthermore, we could show decreased cell adhesion in our 3D cell culture system, which mimics the fluid flow above the implant materials as commonly present in the in vivo environment. This new method of surface coating could offer extended options to design implant surfaces for trauma surgery to reduce cell adhesion and implant ingrowth. This may allow for a faster removal time, resulting in shorter overall operation times, thereby reducing costs and complication rates and increasing patient wellbeing.

Psychostimulants Modafinil, Atomoxetine and Guanfacine Impair Bone Cell Differentiation and MSC Migration.

Attention deficit hyperactivity disorder (ADHD) is one of the most common worldwide mental disorders in children, young and adults. If left untreated, the disorder can continue into adulthood. The abuse of ADHD-related drugs to improve mental performance for studying, working and everyday life is also rising. The potentially high number of subjects with controlled or uncontrolled use of such substances increases the impact of possible side effects. It has been shown before that the early ADHD drug methylphenidate influences bone metabolism negatively. This study focused on the influence of three more recent cognitive enhancers, modafinil, atomoxetine and guanfacine, on the differentiation of mesenchymal stem cells to osteoblasts and on their cell functions, including migration. Human mesenchymal stem cells (hMSCs) were incubated with a therapeutic plasma dosage of modafinil, atomoxetine and guanfacine. Gene expression analyses revealed a high beta-2 adrenoreceptor expression in hMSC, suggesting it as a possible pathway to stimulate action. In bone formation assays, all three cognitive enhancers caused a significant decrease in the mineralized matrix and an early slight reduction of cell viability without triggering apoptosis or necrosis. While there was no effect of the three substances on early differentiation, they showed differing effects on the expression of osterix (OSX), receptor activator of NF-κB ligand (RANKL) and osteoprotegerin (OPG) in the later stages of osteoblast development, suggesting alternative modes of action. All three substances significantly inhibited hMSC migration. This effect could be rescued by a selective beta-blocker (Imperial Chemical Industries ICI-118,551) in modafinil and atomoxetine, suggesting mediation via beta-2 receptor stimulation. In conclusion, modafinil, atomoxetine and guanfacine negatively influence hMSC differentiation to bone-forming osteoblasts and cell migration through different intracellular pathways.

The influence of bone quality on radiological outcome in 50 consecutive acetabular fractures treated with a pre-contoured anatomic suprapectineal plate.

PURPOSE: To investigate the range of indications of an anatomical-preshaped three-dimensional suprapectineal plate and to assess the impact of the bone mass density on radiologic outcomes in different types of acetabular fractures. PATIENTS AND METHODS: A consecutive case series of 50 acetabular fractures (patient age 69 ± 23 years) treated with suprapectineal anatomic plates were analyzed in a retrospective study. The analysis included: Mechanism of injury, fracture pattern, surgical approach, need for additional total hip arthroplasty, intra- or postoperative complications, as well as bone mass density and radiological outcome on postoperative computed tomography. RESULTS: Most frequently, anterior column fracture patterns with and without hemitransverse components as well as associated two column fractures were encountered. The anterior intrapelvic approach (AIP) was used in 98% (49/50) of the cases as primary approach with additional utilization of the first window of the ilioinguinal approach in 13/50 cases (26%). Determination of bone density revealed impaired bone quality in 70% (31/44). Postoperative steps and gaps were significantly greater in this subgroup (p < 0.05). Fracture reduction quality for postoperative steps revealed anatomic results in 92% if the bone quality was normal and in 46% if impaired (p < 0.05). In seven cases (14%), the plate was utilized in combination with acute primary arthroplasty. CONCLUSION: A preshaped suprapectineal plate provides good radiological outcomes in a variety of indications in a predominantly geriatric cohort. Impaired bone quality has a significantly higher risk of poor reduction results. In cases with extensive joint destruction, the combination with total hip arthroplasty was a valuable option.

[Pipkin fractures]. / Pipkin-Frakturen.

Femoral head fractures a very rare emergency situation and occur in 4-17% of hip joint dislocations. Of femoral head dislocation fractures 3.7% occur in combination with acetabular fractures. Reduction of the dislocation should be immediately performed. Decisive for whether treatment should be conservative or surgical by resection of the fragments, reconstruction of the femoral head or prosthetic joint replacement, is the grading of the fracture type using the Pipkin classification. Surgical treatment appears to give a better outcome in Pipkin type 1 and Pipkin type 2 fractures than conservative treatment. The in-house cohort of patients showed a good long-term outcome after surgical reconstruction. The follow-up treatment is carried out with 6 weeks of floor contact and pharmaceutical ossification prophylaxis. The danger of secondary femoral head necrosis needs to be considered at all times. In patients aged > 65 years a primary endoprosthetic joint replacement is indicated.

Investigating the Microchannel Architectures Inside the Subchondral Bone in Relation to Estimated Hip Reaction Forces on the Human Femoral Head.

The interplay between articular cartilage (AC) and subchondral bone (SB) plays a pivotal role in cartilage homeostasis and functionality. As direct connective pathways between the two are poorly understood, we examined the location-dependent characteristics of the 3D microchannel network within the SB that connects the basal cartilage layer to the bone marrow (i.e. cartilage-bone marrow microchannel connectors; CMMC). 43 measuring points were defined on five human cadaveric femoral heads with no signs of osteoarthritis (OA) (age ≤ 60), and cartilage-bone cylinders with diameters of 2.00 mm were extracted for high-resolution scanning (n = 215). The micro-CT data were categorized into three groups (load-bearing region: LBR, n = 60; non-load-bearing region: NLBR, n = 60; and the peripheral rim: PR, n = 95) based on a gait analysis estimation of the joint reaction force (young, healthy cohort with no signs of OA). At the AC-SB interface, the number of CMMC in the LBR was 1.8 times and 2.2 times higher compared to the NLBR, and the PR, respectively. On the other hand, the median Feret size of the CMMC were smallest in the LBR (55.2 µm) and increased in the NLBR (73.5 µm; p = 0.043) and the PR (89.1 µm; p = 0.043). AC thickness was positively associated with SB thickness (Pearson's r = 0.48; p < 1e-13), CMMC number. (r = 0.46; p < 1e-11), and circularity index (r = 0.61; p < 1e-38). In conclusion, our data suggest that regional differences in the microchannel architecture of SB might reflect regional differences in loading.

Cortical threaded pedicle screw improves fatigue strength in decreased bone quality.

PURPOSE: Inadequate anchoring of pedicle screws in vertebrae with poor bone quality is a major problem in spine surgery. The aim was to evaluate whether a modified thread in the area of the pedicle could significantly improve the pedicle screw fatigue strength. METHODS: Fourteen human cadaveric vertebral bodies (L2 and L3) were used for in vitro testing. Bone density (BMD) was determined by quantitative computed tomography. Vertebral bodies were instrumented by standard pedicle screws with a constant double thread on the right pedicle and a partial doubling of the threads-quad thread-(cortical thread) in the area of the pedicle on the left pedicle. Pulsating sinusoidal, cyclic load (0.5 Hz) with increasing peak force (100 N + 0.1 N/cycles) was applied orthogonal to the screw axis. The baseline force remained constant (50 N). Fatigue test was terminated after exceeding 5.4-mm head displacement (~ 20° screw tilting). RESULTS: The mean fatigue load at failure was 264.9 N (1682 cycles) for the standard screws and was increased significantly to 324.7 N (2285 cycles) by the use of cortical threaded screws (p = 0.014). This effect is particularly evident in reduced BMD (standard thread 241.2 N vs. cortical thread 328.4 N; p = 0.016), whereas in the group of vertebrae with normal BMD no significant difference could be detected (standard thread 296.5 N vs. cortical thread 319.8 N; p = 0.463). CONCLUSIONS: Compared to a conventional pedicle screw, the use of a cortical threaded pedicle screw promises superior fatigue load in vertebrae with reduced bone quality.

A retrospective study about functional outcome and quality of life after surgical fixation of insufficiency pelvic ring injuries.

BACKGROUND: Fragility fractures without significant trauma of the pelvic ring in older patients were often treated conservatively. An alternative treatment is surgery involving percutaneous screw fixation to stabilize the posterior pelvic ring. This surgical treatment enables patients to be mobilized quickly and complications associated with bedrest and temporary immobility are reduced. However, the functional outcome following surgery and quality of life of the patients have not yet been investigated. Here, we present a comprehensive study addressing the long-term well-being and the quality of life of patients with fragility pelvic ring fractures after surgical treatment. METHODS: Between 2011-2019, 215 geriatric patients with pelvic ring fractures were surgically treated at the university hospital in Göttingen (Germany). Of these, 94 patients had fragility fractures for which complete sets of computer tomography (CT) and radiological images were available. Fractures were classified according to Tile and according to the FFP classification of Rommens and Hofmann. The functional outcome of surgical treatment was evaluated using the Majeed pelvic score and the Short Form Health Survey-36 (SF-36). RESULTS: Thirty five tile type C and 48 type B classified patients were included in the study. After surgery eighty-three patients scored in average 85.92 points (± 23.39) of a maximum of 100 points using the Majeed score questionnaire and a mean of 1.60 points on the numerical rating scale ranging between 0 and 10 points where 0 points refers to "no pain" and 10 means "strongest pain". Also, the SF-36 survey shows that surgical treatment positively effects patients with respect to their general health status and by restoring vitality, reducing bodily pain and an increase of their general mental health. CONCLUSIONS: Patients who received a percutaneous screw fixation of fragility fractures of the posterior pelvic ring reported an overall positive outcome concerning their long-term well-being. In particular, older patients appear to benefit from surgical treatment. TRIAL REGISTRATION: Functional outcome and quality of life after surgical treatment of fragility fractures of the posterior pelvic ring, DRKS00024768. Registered 8th March 2021 - Retrospectively registered. Trial registration number DRKS00024768 .

Extracellular Vesicles Allow Epigenetic Mechanotransduction between Chondrocytes and Osteoblasts.

MicroRNAs (miRNAs) can be transported in extracellular vesicles (EVs) and are qualified as possible messengers for cell-cell communication. In the context of osteoarthritis (OA), miR-221-3p has been shown to have a mechanosensitive and a paracrine function inside cartilage. However, the question remains if EVs with miR-221-3p can act as molecular mechanotransducers between cells of different tissues. Here, we studied the effect of EV-mediated transport in the communication between chondrocytes and osteoblasts in vitro in a rat model. In silico analysis (Targetscan, miRWalk, miRDB) revealed putative targets of miRNA-221-3p (CDKN1B/p27, TIMP-3, Tcf7l2/TCF4, ARNT). Indeed, transfection of miRNA-221-3p in chondrocytes and osteoblasts resulted in regulation of these targets. Coculture experiments of transfected chondrocytes with untransfected osteoblasts not only showed regulation of these target genes in osteoblasts but also inhibition of their bone formation capacity. Direct treatment with chondrocyte-derived EVs validated that chondrocyte-produced extracellular miR-221-3p was responsible for this effect. Altogether, our study provides a novel perspective on a possible communication pathway of a mechanically induced epigenetic signal through EVs. This may be important for processes at the interface of bone and cartilage, such as OA development, physiologic joint homeostasis, growth or fracture healing, as well as for other tissue interfaces with differing biomechanical properties.

The Interaction between microRNAs and the Wnt/ß-Catenin Signaling Pathway in Osteoarthritis.

Osteoarthritis (OA) is a chronic disease affecting the whole joint, which still lacks a disease-modifying treatment. This suggests an incomplete understanding of underlying molecular mechanisms. The Wnt/ß-catenin pathway is involved in different pathophysiological processes of OA. Interestingly, both excessive stimulation and suppression of this pathway can contribute to the pathogenesis of OA. microRNAs have been shown to regulate different cellular processes in different diseases, including the metabolic activity of chondrocytes and osteocytes. To bridge these findings, here we attempt to give a conclusive overview of microRNA regulation of the Wnt/ß-catenin pathway in bone and cartilage, which may provide insights to advance the development of miRNA-based therapeutics for OA treatment.

Influence of Hyponatremia on Spinal Bone Quality and Fractures Due to Low-Energy Trauma.

Background and Objectives: Hyponatremia is the most common electrolyte disorder in elderly and associated with increased risk of falls. Clinical studies as well as small animal experiments suggested an association between chronic hyponatremia and osteoporosis. Furthermore, it has been assumed that subtle hyponatremia may be an independent fracture risk in the elderly. Therefore, this study was designed to evaluate the possible influence of chronic hyponatremia on osteoporosis and low-energy fractures of the spine. Materials and Methods: 144 patients with a vertebral body fracture (mean age: 69.15 ± 16.08; 73 females and 71 males) due to low-energy trauma were treated in a level one trauma center within one year and were included in the study. Chronic hyponatremia was defined as serum sodium < 135 mmol/L at admission. Bone mineral density (BMD) of the spine was measured using quantitative computed tomography in each patient. Results: Overall, 19.44% (n = 28) of patients in the low-energy trauma group had hyponatremia. In the group with fractures caused by low-energy trauma, the proportion of hyponatremia of patients older than 65 years was significantly increased as compared to younger patients (p** = 0.0016). Furthermore, there was no significant gender difference in the hyponatremia group. Of 28 patients with chronic hyponatremia, all patients had decreased bone quality. Four patients showed osteopenia and the other 24 patients even showed osteoporosis. In the low-energy trauma group, the BMD correlated significantly with serum sodium (r = 0.396; p*** < 0.001). Conclusions: The results suggest that chronic hyponatremia affects bone quality. Patients with chronic hyponatremia have an increased prevalence of fractures after low-energy trauma due to a decreased bone quality. Therefore, physicians from different specialties should focus on the treatment of chronic hyponatremia to reduce the fracture rate after low-energy trauma, particularly with elderly patients.

Cage or Pelvic Graft-Study on Bony Fusion of the Ventral Thoracic and Lumbar Spine in Traumatic Vertebral Fractures.

Background and Objectives: Stabilization of the spine by cage implantation or autologous pelvic bone graft are surgical methods for the treatment of traumatic spine fractures. These methods serve to stably re-adjust the spine and to prevent late detrimental effects such as pain or increasing kyphosis. They both involve ventral interventions using interbody fusion to replace the intervertebral disc space between the vertebral bodies either by cages or autologous pelvic bone grafts. We examined which of these methods serves the patients better in terms of bone fusion and the long-term clinical outcome. Materials and Methods: Forty-six patients with traumatic fractures (12 cages; mean age: 54.08/34 pelvic bone grafts; mean age: 42.18) who received an anterior fusion in the thoracic or lumbar spine were included in the study. Postoperative X-ray images were evaluated, and fusion of the stabilized segment was inspected by two experienced spine surgeons. The time to discharge from hospital and gender differences were evaluated. Results: There was a significant difference of the bone fusion rate of patients with autologous pelvic bone grafts in favor of cage implantation (p = 0.0216). Also, the stationary phase of patients who received cage implantations was clearly shorter (17.50 days vs. 23.85 days; p = 0.0089). In addition, we observed a significant gender difference with respect to the bony fusion rate in favor of females treated with cage implantations (p < 0.0001). Conclusions: Cage implantations after spinal fractures result in better bony fusion rates as compared to autologous pelvic bone grafts and a shorter stay of the patients in the hospital. Thus, we conclude that cage implantations rather than autologous pelvic bone grafts should be the preferred surgical treatment for stabilizing the spine after fracture.

Effect of Selective Androgen Receptor Modulator Enobosarm on Bone Healing in a Rat Model for Aged Male Osteoporosis.

Enobosarm (ostarine, MK-2866, or GTx-024) is a non-steroidal selective androgen receptor modulator. This study evaluated the effect of various regimens of enobosarm (EN) on bone healing in an orchiectomized rat model for aged male osteoporosis and compared it to testosterone (T) treatment. Ninety eight-month-old male Sprague Dawley rats were either orchiectomized (Orx) or left intact (Non-Orx) and divided into groups (n = 15/group): (1) Non-Orx; (2) Orx; (3) Orx+T-th; (4) Orx+EN-th; (5) Orx+T-pr; and (6) Orx+EN-pr. Prophylaxis (Pr) treatments were applied immediately after Orx for up to 18 weeks. Therapy (Th) treatments were applied 12 weeks after Orx for up to 6 weeks. Bilateral tibia osteotomy with plate osteosynthesis was performed 12 weeks after Orx in all groups. EN and T were mixed with the diet; the daily dosage was 0.35 ± 0.06 and 41 ± 8 mg/kg BW, respectively. Both T treatments improved bone healing by increasing callus volume and area, bone volume and density, and cortical width; they had no effect on prostate or levator ani weight. EN-pr increased the callus area and callus density and decreased cortical density, but increased prostate weight. The effect of T-pr and T-th on bone was stronger than EN-pr. EN-th affected bone healing negatively by reducing callus density and area and delaying osteotomy bridging. Levator ani weight was increased in both EN groups. EN treatment after fracture is not advisable in aged males. EN-pr treatment as a therapy for bone healing in men could be further investigated; endocrinological side effects must be closely monitored.

The Selective Androgen Receptor Modulator Ostarine Improves Bone Healing in Ovariectomized Rats.

Non-steroidal selective androgen receptor modulators, including ostarine, have been developed as an alternative to steroidal hormones. Ostarine has shown a beneficial effect on bone in experimental studies, but no data regarding the effect of ostarine on bone healing have yet been reported. We investigated effects of ostarine on bone healing in ovariectomized rats. Sprague-Dawley rats (3 months old) were ovariectomized (Ovx, n = 46) or left intact (Non-Ovx, n = 10). After 8 weeks, an osteotomy of the tibia metaphysis was created in all rats, and the Ovx rats were divided into four groups: untreated Ovx (n = 10) and three Ovx groups (each of 12 rats) treated with ostarine at doses of 0.04, 0.4, or 4 mg/kg BW (OS-0.04, OS-0.4, and OS-4 groups). Five weeks later, bone healing was analyzed. The OS-4 dose enhanced callus formation, increased callus density, accelerated bridging time of the osteotomy, and elevated alkaline phosphatase gene expression in callus and its protein expression in serum. In the Ovx group, most of the callus parameters were diminished. All OS treatments increased the weight of the gastrocnemius muscle, but only partly enhanced uterus weight in OS-0.4 and OS-4. Serum cholesterol level was reduced, and serum phosphorus was elevated in OS-0.04 and OS-4. Ostarine appeared to have a positive effect on early bone healing in ovariectomized rats. Considering its favorable effect on non-osteotomized bone and muscle, this treatment could be further explored as a therapy for osteoporosis. However, possible metabolic side effects should first be evaluated.

Reduced cement volume does not affect screw stability in augmented pedicle screws.

PURPOSE: Cement augmentation of pedicle screws is able to improve screw anchorage in osteoporotic vertebrae but is associated with a high complication rate. The goal of this study was to evaluate the impact of different cement volumes on pedicle screw fatigue strength. METHODS: Twenty-five human vertebral bodies (T12-L4) were collected from donors between 73 and 97 years of age. Bone density (BMD) was determined by quantitative computed tomography. Vertebral bodies were instrumented by conventional pedicle screws, and unilateral cement augmentation was performed. Thirteen vertebrae were augmented with a volume of 1 ml and twelve with a volume of 3 ml bone cement. A fatigue test was performed using a cranial-caudal sinusoidal, cyclic load (0.5 Hz) with increasing compression force (100 N + 0.1 N/cycles). RESULTS: The load to failure was 183.8 N for the non-augmented screws and was increased significantly to 268.1 N (p < 0.001) by cement augmentation. Augmentation with 1 ml bone cement increased the fatigue load by 41% while augmentation with 3 ml increased the failure load by 51% compared to the non-augmented screws, but there was no significant difference in fatigue loads between the specimens with screws augmented with 1 ml and screws augmented with 3 ml of bone cement (p = 0.504). CONCLUSION: Cement augmentation significantly increases pedicle screw stability. The benefit of augmentation on screw anchorage was not significantly affected by reducing the applied volume of cement from 3 ml to 1 ml. Considering the high risk of cement leakage during augmentation, we recommend the usage of a reduced volume of 1 ml bone cement for each pedicle screw. These slides can be retrieved under Electronic Supplementary Material .

A bioactive nano-calcium phosphate paste for in-situ transfection of BMP-7 and VEGF-A in a rabbit critical-size bone defect: results of an in vivo study.

The aim of this study was to prepare an injectable DNA-loaded nano-calcium phosphate paste that is suitable as bioactive bone substitution material. For this we used the well-known potential of calcium phosphate in bone contact and supplemented it with DNA for the in-situ transfection of BMP-7 and VEGF-A in a critical-size bone defect. 24 New Zealand white rabbits were randomly divided into two groups: One group with BMP-7- and VEGF-A-encoding DNA on calcium phosphate nanoparticles and a control group with calcium phosphate nanoparticles only. The bone defect was created at the proximal medial tibia and filled with the DNA-loaded calcium phosphate paste. As control, a bone defect was filled with the calcium phosphate paste without DNA. The proximal tibia was investigated 2, 4 and 12 weeks after the operation. A histomorphological analysis of the dynamic bone parameters was carried out with the Osteomeasure system. The animals treated with the DNA-loaded calcium phosphate showed a statistically significantly increased bone volume per total volume after 4 weeks in comparison to the control group. Additionally, a statistically significant increase of the trabecular number and the number of osteoblasts per tissue area were observed. These results were confirmed by radiological analysis. The DNA-loaded bone paste led to a significantly faster healing of the critical-size bone defect in the rabbit model after 4 weeks. After 12 weeks, all defects had equally healed in both groups. No difference in the quality of the new bone was found. The injectable DNA-loaded calcium phosphate paste led to a faster and more sustained bone healing and induced an accelerated bone formation after 4 weeks. The material was well integrated into the bone defect and new bone was formed on its surface. The calcium phosphate paste without DNA led to a regular healing of the critical-size bone defect, but the healing was slower than the DNA-loaded paste. Thus, the in-situ transfection with BMP-7 and VEGF-A significantly improved the potential of calcium phosphate as pasty bone substitution material.

Developmental Transformation and Reduction of Connective Cavities within the Subchondral Bone.

It is widely accepted that the subchondral bone (SCB) plays a crucial role in the physiopathology of osteoarthritis (OA), although its contribution is still debated. Much of the pre-clinical research on the role of SCB is concentrated on comparative evaluations of healthy vs. early OA or early OA vs. advanced OA cases, while neglecting how pure maturation could change the SCB's microstructure. To assess the transformations of the healthy SCB from young age to early adulthood, we examined the microstructure and material composition of the medial condyle of the femur in calves (three months) and cattle (18 months) for the calcified cartilage (CC) and the subchondral bone plate (SCBP). The entire subchondral zone (SCZ) was significantly thicker in cattle compared to calves, although the proportion of the CC and SCBP thicknesses were relatively constant. The trabecular number (Tb.N.) and the connectivity density (Conn.D) were significantly higher in the deeper region of the SCZ, while the bone volume fraction (BV/TV), and the degree of anisotropy (DA) were more affected by age rather than the region. The mineralization increased within the first 250 µm of the SCZ irrespective of sample type, and became stable thereafter. Cattle exhibited higher mineralization than calves at all depths, with a mean Ca/P ratio of 1.59 and 1.64 for calves and cattle, respectively. Collectively, these results indicate that the SCZ is highly dynamic at early age, and CC is the most dynamic layer of the SCZ.