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.

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 .

Perioperative and posttraumatic anti-edematous decongestive device-based negative pressure treatment for anti-edematous swelling treatment of the lower extremity - a prospective quality study.

BACKGROUND: The perioperative management of trauma cases and orthopedic procedures is negatively influenced by tissue swelling and edema. They delay surgical treatment, extend stay in hospital and prolong the overall time of convalescence. In case of traumatic or postoperative edema the limited transport capacity (missing muscle pump and destruction of lymphatic channels) is casual. Edema mostly results in pain, limited function of the extremity, change in shape, higher infection rate and wound disorders. Manual lymph drainage (MLD) is a treatment option with respect to the complex physical decongestion (CPD). OBJECTIVE: To evaluate whether a device-based negative pressure lymph drainage (NPLD) is capable of reducing posttraumatic and perioperative swelling of the lower extremity effectively and sustainably. METHODS: Prospective quality study submitted to the Ethics Committee. The patients only received the procedures after signing the informed consent. The negative pressure was applied locally by using LymphaTouch® device (LT) (FDA approved) with a silicone-coated applicator. The lymphatic drainage had been either applied by a local stationary manner or by using the "Lift + Twist" technique. A negative pressure has been adjusted between 50-250 mm Hg depending on the skin and tissue texture. The frequency was chosen between 90-70 Hz. Type of application: pulsed or continuous negative pressure treatment. The procedure always began in the supraclavicular fossa and continued until reaching the area of surgery in the lower extremity. Duration approx. 30 min. The patient was encouraged to drink fluids after the LymphaTouch treatment (LTT). The results were documented by measurement of the girth and movement according to neutral-zero-method (NZM) and photographs. STATISTICS: Multi-variance, Wilcoxon test non-parametric. INCLUSION CRITERIA: Patients with injury to the lower extremity (LE), elective patients, age > 18 years, signed informed consent. RESULTS: 101 patients with injuries/surgical interventions to the lower extremity, age: 64.9 ± 13.17 years. The swelling was more pronounced at the knee. After 4 treatments, there was a measurable decrease in swelling of 11.6% at the lower extremity. In patients with trauma to the hip joint or hip interventions, the swelling at the femur was reduced by 8.6% between LTT 0 vs. 4. In patients with trauma to the knee joint and surgical interventions, significantly more female patients showed a positive effect to LTT. The mobility improved substantially, while the level of pain decreased. The patients reported immediate pain relief. No complications occurred. CONCLUSION: The perioperative and posttraumatic swelling at the lower extremity can be positively affected by the LT-NPLD within the first days. The preoperative duration until surgical intervention was decreased. The postoperative stage of wound and soft tissue swelling was reduced.

Reduction of postoperative swelling with a negative pressure treatment-A prospective study.

PURPOSE: Perioperative swelling and edema are the main factors that influence the time to definitive operative care, healing rate, as well as postoperative infection rate. Device-based negative pressure treatment is a new method to reduce post-traumatic and postoperative swelling of the upper extremities. The objective of this study was to evaluate a new negative pressure treatment with LymphaTouch® (Helsinki, Finland) to reduce perioperative swelling in upper extremity injuries. METHODS: We analyzed 45 patients (26 female and 19 male) after operative treatment of upper extremity injuries. A predefined treatment algorithm of 30 min using LymphaTouch® was performed on the patients every day for five consecutive days. Swelling was measured according to the neutral-zero method with six points of measurement. RESULTS: A total of 16 patients underwent an operation on their upper arm. An average of 3.5 measurements was performed per patient, with the start of therapy at a mean of 5.13 days after the operation. All of the measured circumferences except the elbow and 10 cm below the elbow were reduced from day 0 to 3. The percent reduction of swelling (relative to day 0) was 10.36%, 11.35%, 17.34%, and 3.25% for days 1-4, respectively. The greatest reduction of circumference was obtained in the metacarpus (-51.6%) and wrist (-33.1%). CONCLUSION: The LymphaTouch® system and a 30-min treatment program can reduce postoperative swelling of the upper arm, wrist, and hand on the first 5 days after surgery. The ease of learning and self-applicability of LymphaTouch® makes it interesting for further controlled randomized trials.

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 .

[Infiltration anesthesia]. / Infiltrationsanästhesie.

OBJECTIVE: Complete anesthesia of any skin and soft tissue area by intradermal, subcutaneous, or intramuscular injections. INDICATIONS: Small injuries or incisions in limbs or trunk, minor surgery on the face/jaw (e.g., on the teeth), or postoperative analgesia (local infiltration anesthesia, LIA). CONTRAINDICATIONS: Local infections at the injection site. SURGICAL TECHNIQUE: By means of intradermal, subcutaneous or intramuscular administration, a grandeur arises, here the local anesthetic blocks nerve transmission. If anesthetized distal to end arteries, vasoconstrictors (e.g., epinephrine) should be avoided. Proximal to end arteries, localized ischemia may facilitate operative care. POSTOPERATIVE MANAGEMENT: The effect of local anesthesia is self-limiting. RESULTS: By means of infiltration anesthesia or "field block", larger areas of skin are easily accessible for surgical treatment. The amount to be applied has to be adapted to the extent of the operation and the maximal dose. Postoperatively, after knee or hip arthroplasty, analgesia consumption can be reduced, and early mobilization promoted using LIA.

[Oberst's block anesthesia]. / Leitungsanästhesie nach Oberst.

OBJECTIVE: Complete anesthesia of the phalanges of the fingers and toes. INDICATIONS: All lesions distal to the metacarpophalangeal/metatarsophalangeal joint. CONTRAINDICATIONS: Local infections at the injection site. Lesions proximal to the metacarpophalangeal/metatarsophalangeal joint. TECHNIQUE: A subcutaneous deposit of a 0.5-2% local anesthetic is administered dorsoradially and dorsoulnarly at the base of the metacarpophalangeal/metatarsophalangeal joint. With the cannula advanced to palmar, an additional 0.5-1.5 ml is then administered to achieve complete anesthesia. POSTOPERATIVE MANAGEMENT: The effect of the local anesthesia is self-limiting. RESULTS: The Oberst block results in reliable anesthesia of the finger and toe. All surgical procedures distal to the metacarpophalangeal/metatarsophalangeal joint can be performed without pain.

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.

Time to augment?! Impact of cement augmentation on pedicle screw fixation strength depending on bone mineral density.

PURPOSE: Cement augmentation of pedicle screws is known to increase their mechanical strength. Aim was to evaluate the impact of cement augmentation on pedicle screw fatigue strength in dependence of the bone mineral density (BMD). METHODS: Twenty-one human L2 vertebral bodies from donors between 19 and 96 years of age were used for in vitro experiments. BMD was measured using quantitative computed tomography (QCT). Two pedicle screws were inserted in each specimen and unilaterally augmented with bone cement. Fatigue testing was performed using a cranio-caudal sinusoidal, cyclic load (0.5 Hz) with increasing compression force (100 N + 0.1 N/cycles). Results were evaluated for the BMD groups: normal: BMD > 120 mg/cm3, osteopenic: BMD 80-120 mg/cm3, and osteoporotic: BMD < 80 mg/cm3 bone mass. RESULTS: There was a significant correlation between fatigue force and BMD for the non-augmented and augmented screws (non-augmented R2 = 0.839, p < 0.001; augmented R2 = 0.551, p < 0.001). There was a significantly increased fatigue strength of the augmented screws over the non-augmented screws in the osteoporotic group (p = 0.001), while the differences in the other groups were not significant (normal p = 0.818/osteopenic p = 0.132). CONCLUSIONS: The benefit of pedicle screw cement augmentation significantly depends on the bone mineral density and has the greatest extent of increased fatigue strength in osteoporotic vertebrae. Preoperative measurement of the BMD is strongly recommended to predict the benefit of augmentation and reinforce the decision for cement augmentation. These slides can be retrieved under Electronic Supplementary Material.