Calcitonin treatment for osteoarthritis and rheumatoid arthritis - a systematic review and meta-analysis of preclinical data.

Purpose: The aim of this study was to investigate the efficacy of calcitonin (CT) in animal models of experimental osteoarthritis (OA) and rheumatoid arthritis (RA), as new stabilized CT formulations are currently being introduced. Methods: A comprehensive and systemic literature search was conducted in PubMed/MEDLINE and Embase databases to identify articles with original data on CT treatment of preclinical OA and RA. Methodological quality was assessed using the Systematic Review Centre for Laboratory Animal Experimentation's risk of bias tool for animal intervention studies. To provide summary estimates of efficacy, a meta-analysis was conducted for outcomes reported in four or more studies, using a random-effects model. Subgroup analyses were employed to correct for study specifics. Results: Twenty-six studies were ultimately evaluated and data from 16 studies could be analyzed in the meta-analysis, which included the following outcomes: bone mineral density, bone volume, levels of cross-linked C-telopeptide of type I collagen, histopathological arthritis score, and mechanical allodynia. For all considered outcome parameters, CT-treated groups were significantly superior to control groups (P = 0.002; P = 0.01; P < 0.00001; P < 0.00001; P = 0.04). For most outcomes, effect sizes were significantly greater in OA than in RA (P ≤ 0.025). High in-between study heterogeneity was detected. Conclusion: There is preclinical evidence for an antioxidant, anti-inflammatory, antinociceptive, cartilage- and bone-protective effect of CT in RA and OA. Given these effects, CT presents a promising agent for the treatment of both diseases, although the potential seems to be greater in OA.

Periacetabular Osteotomy with a Modified Fixation Technique Using K-Wires Shows Clinical Results Comparable to Screw Fixation at Mid-Term Follow-Up.

BACKGROUND: The optimal fixation technique in periacetabular osteotomy (PAO) remains controversial. Modified fixation with Kirschner wires (K-wires) was described as a feasible and safe alternative. However, clinical follow-up of patients treated with this technique is lacking. AIMS: To assess patient-reported outcomes (PROMs) in patients treated with PAO with the K-wire fixation technique and to compare it with the screw fixation technique. METHODS: We conducted an analysis of 202 consecutive PAOs at a single university center between January 2015 and June 2017. A total of 120 cases with complete datasets were included in the final analysis. PAOs with K-wire fixation (n = 63) were compared with screw fixation (n = 57). Mean follow-up was 63 ± 10 months. PROMs assessed included the International Hip Outcome Tool (iHOT 12), Subjective Hip Value (SHV), and UCLA activity score (UCLA). Pain and patient satisfaction (NRS) were evaluated. Joint preservation was defined as non-conversion to total hip arthroplasty (THA). RESULTS: Preoperative baseline PROMs in both fixation groups were similar. In both groups, PROMs (p = <0.001) and pain (p = <0.001) improved significantly. Postoperative functional outcome was similar in both groups: iHOT 12 (71.8 ± 25.1 vs. 73 ± 21.1; p = 0.789), SHV (77.9 ± 21.2 vs. 82.4 ± 13.1; p = 0.192), UCLA (6.9 ± 1.6 vs. 6.9 ± 1.9; p = 0.909), and pain (2.4 ± 2.1 vs. 2.0 ± 2.1; p = 0.302). Patient satisfaction did not differ significantly (7.6 ± 2.6 vs. 8.2 ± 2.2; p = 0.170). Conversion to THA was low in both groups (two vs. none; p = 0.497). CONCLUSION: Periacetabular osteotomy with K-wire fixation provided good clinical results at mid-term follow-up, comparable to those of screw fixation. The technique can therefore be considered a viable option when deciding on the fixation technique in PAO.

Impact of Individual Spinopelvic Anatomy on the Localization and Severity of Symptomatic Isthmic Spondylolisthesis.

STUDY DESIGN: Retrospective analysis of prospectively collected data. OBJECTIVES: Isthmic spondylolisthesis (iSPL) occurs most commonly in L5/S1 and L4/5. This study investigates the association between spinopelvic anatomy and the pathogenesis of iSPL. METHODS: Spinopelvic parameters as well as severity of slip grade were measured in sagittal spine radiographs of symptomatic patients with iSPL in segments L4/5 and L5/S1. Means were calculated and differences between both groups were analyzed. A correlation between the analyzed parameters and degree of slippage was performed. RESULTS: We included 73 subjects in this study; 11 in L4/5 group and 62 in L5/S1 group. Pelvic anatomy significantly differed between L4/5 and L5/S1 iSPL (Pelvic Incidence (PI) 54.8° vs 66.3°, P value = .006; Pelvic Radius (PR) 124.4 mm vs 137.4 mm; P value = .005 and Sacral Table Angle (STA) 101.0° vs 92.2°, P value < .001). The relative degree of slippage was significantly higher in the L5/S1 group (L4/5 29.1% vs L5/S1 40.1%, P value .022). We also observed a significant correlation between pelvic anatomy and the severity of the slip in iSPL at the L5/S1 level. CONCLUSIONS: Pelvic parameters PI and STA play an important role concerning the level of occurrence and severity of iSPL. Spinopelvic anatomy determines the pathogenesis of iSPL.

Fixation stability and implant-associated complications in periacetabular osteotomy: a comparison of screw and K-wire fixation.

AIMS: The aim of this study was to compare the fixation stability and complications in patients undergoing periacetabular osteotomy (PAO) with either K-wire or screw fixation. PATIENTS AND METHODS: We performed a retrospective study to analyze a consecutive series of patients who underwent PAO with either screw or K-wire fixation. Patients who were treated for acetabular retroversion or had previous surgery on the ipsilateral hip joint were excluded. 172 patients (191 hips: 99 K-wire/92 screw fixation) were included. The mean age at the time of PAO was 29.3 years (16-48) in the K-wire group and 27.3 (15-45) in the screw group and 83.9% were female. Clinical parameters including duration of surgery, minor complications (soft tissue irritation and implant migration) and major complications (implant failure and non-union) were evaluated. Radiological parameters including LCE, TA and FHEI were measured preoperatively, postoperatively and at 3-months follow-up. RESULTS: Duration of surgery was significantly reduced in the K-wire group with 88.2 min (53-202) compared to the screw group with 119.7 min (50-261) (p < 0.001). Soft tissue irritation occurred significantly more often in the K-wire group (72/99) than in the screw group (36/92) (p < 0.001). No group showed significantly more implant migration than the other. No major complications were observed in either group. Postoperative LCE, TA and FHEI were improved significantly in both groups for all parameters (p = < 0.0001). There was no significant difference for initial or final correction for the respective parameters between the two groups. Furthermore, no significant difference in loss of correction was observed between the two groups for the respective parameters. CONCLUSION: K-wire fixation is a viable and safe option for fragment fixation in PAO with similar stability and complication rates as screw fixation. An advantage of the method is the significantly reduced operative time. A disadvantage is the significantly higher rate of implant-associated soft tissue irritation, necessitating implant removal. LEVEL OF EVIDENCE: III, retrospective trial.

Transversus Abdominis Plane Block Reduces Intraoperative Opioid Consumption in Patients Undergoing Periacetabular Osteotomy.

BACKGROUND: Administering intraoperative analgesia in patients undergoing periacetabular osteotomy (PAO) is challenging due to both the relevant surgical approach and osteotomies, which are associated with pain. The aim of this study was to assess the effect of the transversus abdominis plane block (TAPb) on intraoperative opioid consumption and circulation parameters in PAO patients. PATIENTS AND METHODS: We conducted a two-group randomized-controlled trial involving 42 consecutive patients undergoing PAO for symptomatic developmental dysplasia of the hip (DDH) in our department. Patients assigned to the study group received an ultrasound-guided TAPb with 0.75% ropivacaine before the beginning of the surgery and after general anesthesia induction. Patients assigned to the control group did not receive a TAPb. General anesthesia was conducted according to a defined study protocol. The primary endpoint of the study was the intraoperative opioid consumption, measured in morphine equivalent dose (MED). Secondary endpoints were the assessment of intraoperative heart rate, mean arterial pressure (MAP), need for hypotension treatment, and length of hospital stay (LOHS). A total of 41 patients (n = 21 TAPb group, n = 20 control group) completed the study; of these, 33 were women (88.5%) and 8 were men (19.5%). The mean age at the time of surgery was 28 years (18-43, SD ± 7.4). All operations were performed by a single high-volume surgeon and all TAPb procedures were performed by a single experienced senior anesthesiologist. RESULTS: We observed a significantly lower intraoperative opioid consumption in the TAPb group compared to the control group (930 vs. 1186 MED per kg bodyweight; p = 0.016). No significant differences were observed in the secondary outcome parameters. We observed no perioperative complications. CONCLUSION: Ultrasound-guided TAPb significantly reduces intraoperative opioid consumption in patients undergoing PAO.

Correction of severe valgus osteoarthritis by total knee arthroplasty is associated with increased postoperative ankle symptoms.

PURPOSE: The aim of this study was to assess the mid-term clinical outcome of the ankle joint after total knee arthroplasty (TKA) in high-grade valgus osteoarthritis. METHODS: In this case-control study, n = 36 patients with a preoperative mechanical tibiofemoral angle (mTFA) ≥ 15° who underwent TKA between December 2002 and December 2012 were included. The control group (mTFA < 15°) of n = 60 patients was created using case matching. Radiological [mechanical tibiofemoral angle (mTFA) and ankle joint orientation to the ground (G-AJLO)] and clinical parameters [Foot Function Index (FFI), Knee Society Score, Forgotten Joint Score, and Range of Motion (ROM)] were analysed. The mean follow-up time was 59 months (IQR [56, 62]). RESULTS: The degree of correcting the mTFA by TKA significantly correlated with the postoperative FFI (R = 0.95, p < 0.05), although the knee and ankle joint lines were corrected to neutral orientations. A cut-off value of 16.5° [AUC 0.912 (0.85-0.975 95% CI), sensitivity = 0.8, specificity = 0.895] was calculated, above which the odds ratio (OR) for developing ankle symptoms increased vastly [OR 34.0 (9.10-127.02 95% CI)]. ROM restrictions of the subtalar joint displayed a strong significant correlation with the FFI (R = 0.74, p < 0.05), demonstrating that decreased ROM of the subtalar joint was associated with aggravated outcomes of the ankle joint. CONCLUSIONS: In this study, higher degrees of leg axis correction in TKA were associated with increased postoperative ankle symptoms. When TKA is performed in excessive valgus knee osteoarthritis, surgeons should be aware that this might trigger the onset or progression of ankle symptoms, particularly in cases of a stiff subtalar joint. LEVEL OF EVIDENCE: III.

Weight-bearing radiography depends on limb loading.

PURPOSE: The mechanical axis of the lower limb has shown to vary between different weight-bearing conditions and change after total knee arthroplasty (TKA). The purpose of this study was to investigate the correlation between mechanical axis alignment in standing long-leg radiographs and limb loading after TKA. METHODS: Mechanical axis of the lower limb and limb loading have been prospectively evaluated in 115 patients 10 days and 3 months after TKA. By the moment of standing long-leg radiography for analysis of the mechanical leg axis, two digital scales separately captured the load of each limb. RESULTS: Mechanical axis changed from an initial - 1° ± 2° valgus alignment to a varus axis of + 1° ± 2° (p < 0.01). This change in alignment was associated with an increase of limb loading from 89.9 ± 10.7 to 93.0 ± 7.0% (p < 0.01). The mechanical axis strongly correlated with relative limb loading at the first and second measurements (r = 0.804, p < 0.001, respectively, r = 0.562, p < 0.001). A significant change in the rate of outliers was registered within the observation period. These alterations and distinctions were much more pronounced in patients with postoperative incomplete extension (n = 15). CONCLUSIONS: The postoperative mechanical axis correlates with limb loading. A clinical relevant change in frontal alignment of the lower limb is associated with increased limb loading after TKA. The actual mechanical axis can only be assessed at physiological limb loading in long-leg radiographs with complete extension at full weight bearing. LEVEL OF EVIDENCE: Diagnostic study, Level II.

Postoperative Increased Loading Leads to an Alteration in the Radiological Mechanical Axis After Total Knee Arthroplasty.

BACKGROUND: Standing long-leg radiographs allow assessment of the mechanical axis in the frontal plane before and after total knee arthroplasty (TKA). An alteration in loading, and hence in the forces acting on the knee joint, occurs postoperatively. We therefore postulated that the mechanical axis measured in the long-leg standing radiograph would change within the first year after TKA. METHODS: Standing long-leg radiographs of 156 patients were performed 7 days, 3 months, and 12 months after TKA with determination of mechanical axis of the lower limb. RESULTS: Seven days after surgery, the mechanical axis amounted 0.8° ± 1.7° valgus. Three months after the operation, at 1.3° ± 1.3° varus, it was significantly different (P < .001) from the primary measurement. No further alteration in the mechanical axis occurred during the first year after TKA. This difference was even more pronounced (P < .001) in patients with a postoperative lack of complete extension. Seven days after surgery, they had a valgus axis deviation of 1.6° ± 1.6°; after 3 months, the measurement amounted 1.2° ± 1.3° varus. CONCLUSION: Measured by a standing long-leg radiograph, the frontal mechanical axis after TKA changes over time. The predictive power of a standing long-leg radiograph in the first week after surgery is limited because limb loading is altered because of pain and is therefore nonphysiological. The actual mechanical axis resulting after TKA can only be assessed in a standing long-leg radiograph at physiological loading.

Reduced ictogenic potential of 4-aminopyridine in the hippocampal region in the pilocarpine model of epilepsy.

It was previously shown that the ictogenic potential of 4-aminopyridine (4-AP) was reduced in the parahippocampal region of kainate treated chronic epileptic rats. In the actual study we investigated the potential of 4-aminopyridine (50 and 100µM) to induce seizure like events (SLEs) in combined entorhinal cortex hippocampal slices from Wistar rats following pilocarpine induced status epilepticus. The potential of 4-AP to induce SLEs in the entorhinal cortex was reduced in the latent period and in slices of chronic epileptic animals with a high seizure incidence in vivo (>2seizures/24h). 4-AP induced SLEs in slices from animals with a low incidence of seizures in vivo (<2seizures/24h) in a similar manner as compared to controls. The hippocampal formation displayed no SLEs, instead short recurrent epileptiform discharges (REDs) were evoked by application of 4-AP in areas CA3 and CA1. The incidence of REDs was largest in slices from control animals. This study shows that the reduced ictogenic potential of 4-AP is not restricted to kainate treated chronic epileptic animals as it can be found in the pilocarpine model as well. The underlying mechanisms may relate to altered expression and editing of voltage gated potassium channels.

A contoured locking plate for distal fibular fractures in osteoporotic bone: a biomechanical cadaver study.

OBJECTIVE: Fixation of ankle fractures in elderly patients is associated with reduced stability conditioned by osteoporotic bone. Therefore, fixation with implants providing improved biomechanical features could allow a more functional treatment, diminish implant failure and avoid consequences of immobilisation. MATERIALS AND METHODS: In the actual study, we evaluated a lateral conventional contoured plate with a locking contoured plate stabilising experimentally induced distal fibular fractures in human cadavers from elderly. Ankle fractures were induced by the supination-external rotation mechanism according to Lauge-Hansen. Stage II fractures (AO 44-B1) were fixed with the 2 contoured plates and a torque to failure test was performed. Bone mineral density (BMD) was measured by quantitative computed tomography to correlate the parameters of the biomechanical experiments with bone quality. RESULTS: The locking plate showed a higher torque to failure, angle at failure, and maximal torque compared to the conventional plate. In contrast to the nonlocking system, fixation with the locking plate was independent of BMD. CONCLUSION: Fixation of distal fibular fractures in osteoporotic bone with the contoured locking plate may be advantageous as compared to the nonlocking contoured plate. The locking plate with improved biomechanical attributes may allow a more functional treatment, reduce complications and consequences of immobilisation.