Previously, we reported impaired biomechanical bone properties and inferior bone matrix quality in tachykinin1 (Tac1)-deficient mice lacking the sensory neuropeptide substance P (SP). Additionally, fracture callus development is affected by the absence of SP indicating a critical effect of sensory nerve fibers on bone health and regeneration. For α-calcitonin gene-related peptide (α-CGRP)-deficient mice, a profound distortion of bone microarchitecture has also been described. We hypothesize that SP and α-CGRP modulate inflammatory as well as pain-related processes and positively affect bone regeneration during impaired fracture healing under osteoporotic conditions. Therefore, this study investigates the effects of SP and α-CGRP on fracture healing and fracture-related pain processes under conditions of experimental osteoporosis using SP- and α-CGRP-deficient mice and WT controls. We ovariectomized female WT, Tac1−/− and α-CGRP−/− mice (age 10 weeks, all strains on C57Bl/6J background) and set intramedullary fixed femoral fractures in the left femora 28 days later. We analyzed pain threshold (Dynamic Plantar Aesthesiometer Test) and locomotion (recorded at day and night, each for 1 hour, EthoVision®XT, Noldus) at 5, 9, 13, 16 and 21 days after fracture. At each time point, fractured femora were prepared for histochemical analysis of callus tissue composition (alcian blue/sirius red staining). Pain threshold is significantly higher in Tac1−/− mice 13 days after fracture and tends to be higher after 21 days compared to WT controls. In contrast, touch sensibility was similar in α-CGRP−/− mice and WT controls but compared to Tac1−/− mice pain threshold was significantly lower in α-CGRP−/− mice 13 and 16 days and tends to be lower 21 days after fracture. Locomotion of Tac1−/− mice during daylight was by trend higher 9 days after fracture and significantly higher 16 days after fracture whereas nightly locomotion is reduced compared to WT mice. Analysis of locomotion during daylight or night revealed no differences between α-CGRP−/− and WT mice. During early fracture healing phase, 5 and 9 days after fracture, transition of mesenchymal to cartilaginous callus tissue tends to be faster in Tac1−/− mice compared to WT controls whereas no difference was observed during late stage of fracture healing, 13, 16 and 21 days after fracture. In contrast, callus tissue maturation seems to be similar in α-CGRP−/− and WT mice. Our data indicate different effects of SP and α-CGRP on fracture healing under conditions of experimental osteoporosis as a model for impaired bone tissue. Lack of α-CGRP seems to have no effects, but loss of SP affects locomotion throughout osteoporotic fracture healing and fracture-related pain processes during late phases of osteoporotic fracture healing. This indicates a modified role of SP during fracture healing under impaired versus healthy conditions, where SP changed early fracture-related pain processes and had no influence on callus tissue composition

To consider bilateral simultaneous knee replacement, both knees must have significant structural damage. It is best if the patient can't decide which knee is more bothersome. In borderline cases, ask the patient to pretend that the worse knee is normal and if so, would they be seeing you for consideration of knee replacement on the less involved side. If the answer to this question is “yes,” consider the patient a potential candidate for bilateral knee replacement. If the answer is “no,” recommend operating only on the worse knee, and expect that the operation on the second knee can probably be delayed for a considerable period of time. Strong indications for bilateral simultaneous TKA are bilateral severe angular deformity, bilateral severe flexion contracture, and anesthesia difficulties, i.e., patients who are anatomically or medically difficult to anesthetise, such as some adult or juvenile rheumatoid arthritis patients or patients with severe ankylosing spondylitis. Relative indications for bilateral simultaneous TKA include the need for multiple additional surgical procedures to achieve satisfactory function and financial or social considerations for the patient. Contraindications to bilateral TKA include medical infirmity (especially cardiac), a reluctant patient, and a patient with a very low pain threshold. When performing bilateral simultaneous TKA, both limbs are prepped and draped at the same time. An initial dose of an intravenous antibiotic is given (usually 1g of a cephalosporin) before inflation of the tourniquet. Surgery begins on the more symptomatic side or on either side if neither knee is significantly worse than the other. The reason for starting on the more symptomatic side is in case surgery has to be discontinued after only one procedure owing to anesthetic considerations. After the components have been implanted on the first side, the tourniquet is deflated and a second dose of intravenous antibiotic is administered (usually 500mg of a cephalosporin). After the joint capsule is closed and flexion against gravity is measured, one team completes the subcutaneous and skin closure on the first side while the other team inflates the second tourniquet and begins the exposure of the second side. When the second tourniquet is deflated, a third dose of antibiotic is given (usually 500mg of a cephalosporin for a total dose of 2g for both knees). Because of concern about the potential for cross-contamination of the knee wounds when instruments used during the final stages of skin closure on the first knee are maintained on the field and used on the second knee, they should probably be handed off the field and outer surgical gloves changed. Most patients will report after their complete recovery that they are glad they did both knees at the same time. A patient who has any uncertainty about proceeding with bilateral surgery should have only one knee done at a time. In many cases, the second side receives a “reprieve,” becoming more tolerable after the first side has been operated on

To consider bilateral simultaneous knee replacement, both knees must have significant structural damage. It is best if the patient can't decide which knee is more bothersome. In borderline cases, ask the patient to pretend that the worse knee is normal and if so, would they be seeing you for consideration of knee replacement on the less involved side. If the answer to this question is “yes,” consider the patient a potential candidate for bilateral knee replacement. If the answer is “no,” recommend operating only on the worse knee, and expect that the operation on the second knee can probably be delayed for a considerable period of time. Strong indications for bilateral simultaneous TKA are bilateral severe angular deformity, bilateral severe flexion contracture, and anesthesia difficulties, i.e., patients who are anatomically or medically difficult to anesthetise, such as some adult or juvenile rheumatoid arthritis patients or patients with severe ankylosing spondylitis. Relative indications for bilateral simultaneous TKA include the need for multiple additional surgical procedures to achieve satisfactory function and financial or social considerations for the patient. Contraindications to bilateral TKA include medical infirmity (especially cardiac), a reluctant patient, and a patient with a very low pain threshold. When performing bilateral simultaneous TKA, both limbs are prepped and draped at the same time. An initial dose of an intravenous antibiotic is given (usually 1 gram of a cephalosporin) before inflation of the tourniquet. Surgery begins on the more symptomatic side or on either side if neither knee is significantly worse than the other. The reason for starting on the more symptomatic side is in case surgery has to be discontinued after only one procedure owing to anesthetic considerations. After the components have been implanted on the first side, the tourniquet is deflated and a second dose of intravenous antibiotic is administered (usually 500 mg of a cephalosporin). After the joint capsule is closed and flexion against gravity is measured, one team completes the subcutaneous and skin closure on the first side while the other team inflates the second tourniquet and begins the exposure of the second side. When the second tourniquet is deflated, a third dose of antibiotic is given (usually 500 mg of a cephalosporin for a total dose of 2 g for both knees). Because of concern about the potential for cross-contamination of the knee wounds when instruments used during the final stages of skin closure on the first knee are maintained on the field and used on the second knee, they should probably be handed off the field and outer surgical gloves changed. Most patients will report after their complete recovery that they are glad they did both knees at the same time. A patient who has any uncertainty about proceeding with bilateral surgery should have only one knee done at a time. In many cases, the second side receives a “reprieve,” becoming more tolerable after the first side has been operated on

Anterior knee pain is one of the most frequently reported musculoskeletal complaints in all age groups. However, patient's complaints are often nonspecific, leading to difficulty in properly diagnosing the condition. One of the causes of pain is the degeneration of the articular cartilage. As the cartilage deteriorates, its ability to distribute the joint reaction forces decreases and the stresses may exceed the pain threshold. Unfortunately, the assessment of the cartilage condition is often limited to a detailed interview with the patient, careful physical examination and x-ray imaging. The X-ray screening may reveal bone degeneration, but does not carry sufficient information of the soft tissues' conditions. More advanced imaging tools such as MRI or CT are available, but these are expensive, time consuming and are only suitable for detection of advanced arthritis. Arthroscopic surgery is often the only reliable option, however due to its semi-invasive nature, it cannot be considered as a practical diagnostic tool. However, as the articular cartilage degenerates, the surfaces become rougher, they produce higher vibrations than smooth surfaces due to higher friction during the interaction. Therefore, it was proposed to detect vibrations non-invasively using accelerometers, and evaluate the signals for their potential diagnostic applications. Vibration data was collected for 75 subjects; 23 healthy and 52 subjects suffering from knee arthritis. The study was approved by the IRB and an Informed Consent was obtained prior to data collection. Five accelerometers were attached to skin around the knee joint (at the patella, medial and lateral femoral condyles, tibial tuberosity and medial tibial plateau). Each subject performed 5 activities; (1) flexion-extension, (2) deep knee bend, (3) chair rising, (4) stair climbing and (5) stair descent. The vibration and motion components of the signals were separated by a high pass filter. Next, 33 parameters of the signals were calculated and evaluated for their discrimination effectiveness (Figure 1). Finally the pattern recognition method based on Baysian classification theorem was used for classify each signal to either healthy or arthritic group, assuming equal prior probabilities. The variance and mean of the vibration signals were significantly higher in the arthritic group (p=2.8e-7 and p=3.7e-14, respectively), which confirms the general hypothesis that the vibration magnitudes increase as the cartilage degenerates. Other signal features providing good discrimination included the 99. th. quantile, the integral of the vibration signal envelope, and the product of the signal envelope and the activity duration. The pattern classification yielded excellent results with the success rate of up to 92.2% using only 2 features, up to 94.8% using 3 (Figure 2), and 96.1% using 4 features. The current study proved that the vibrations can be studied non-invasively using a low-cost technology. The results confirmed the hypothesis that the degeneration of the cartilage increases the vibration of the articulating bones. The classification rate obtained in the study is very encouraging, providing over 96% accuracy. The presented technology has certainly a potential of being used as an additional screening methodology enhancing the assessment of the articular cartilage condition