Calcified cartilage differs in patients with end-stage primary osteoarthritis and secondary osteoarthritis due to rheumatoid arthritis of the hip joint.

OBJECTIVES: Despite distinct aetiologies, the end-stages of primary osteoarthritis (OA) and secondary OA are described by common radiological features. However, the morphology of the bone-cartilage unit may differ depending on the pathogenesis. In this cross-sectional study, we aimed to investigate the histological differences in the bone-cartilage unit of the femoral head between patients with primary OA and secondary OA due to rheumatoid arthritis (RA). METHOD: Femoral heads were obtained from 12 patients with primary OA, six patients with secondary OA due to RA, and 12 control subjects. The femoral heads were investigated using stereological methods to ensure unbiased quantification. RESULTS: The volume (mean difference [95% confidence interval]) (2.1 [0.5;3.8] cm3, p = 0.016) and thickness (413 [78.9;747] µm, p = 0.029) of the articular cartilage and the thickness of the calcified cartilage (56.4 [0.4;113] µm, p = 0.017) were larger in patients with primary OA than in patients with secondary OA due to RA. Femoral head volume (1.2 [-3.6;6.1] cm3, p = 0.598), bone volume fraction (-1.1 [-2.8;5.1] cm3, p = 0.553), subchondral bone thickness (-2.5 [-212;207] µm, p = 0.980), and osteophyte area (25.3 [-53.6;104] cm2, p = 0.506) did not differ between patients. CONCLUSION: The thicker calcified cartilage in primary OA preceding the loss of articular cartilage can be attributed to endochondral ossification. Patients with secondary OA due to RA had severely thinner calcified cartilage as the pathogenesis is driven by inflammation and is characterized by a generalized and more severe loss of articular cartilage.

Development of a multivariable prediction model for early revision of total knee arthroplasty - The effect of including patient-reported outcome measures.

BACKGROUND: Revision TKA is a serious adverse event with substantial consequences for the patient. As revision is becoming increasingly common in patients under 65 years, the need for improved preoperative patient selection is imminently needed. Therefore, this study aimed to identify the most important factors of early revision and to develop a prediction model of early revision including assessment of the effect of incorporating data on patient-reported outcome measures (PROMs). MATERIAL AND METHODS: A cohort of 538 patients undergoing primary TKA was included. Multiple logistic regression using forward selection of variables was applied to identify the best predictors of early revision and to develop a prediction model. The model was internally validated with stratified 5-fold cross-validation. This procedure was repeated without including data on PROMs to develop a model for comparison. The models were evaluated on their discriminative capacity using area under the receiver operating characteristic curve (AUC). RESULTS: The most important factors of early revision were age (OR 0.63 [0.42, 0.95]; P = 0.03), preoperative EQ-5D (OR 0.07 [0.01, 0.51]; P = 0.01), and number of comorbidities (OR 1.01 [0.97, 1.25]; P = 0.15). The AUCs of the models with and without PROMs were 0.65 and 0.61, respectively. The difference between the AUCs was not statistically significant (P = 0.32). CONCLUSIONS: Although more work is needed in order to reach a clinically meaningful quality of the predictions, our results show that the inclusion of PROMs seems to improve the quality of the prediction model.

Cost-effectiveness of 12 weeks of supervised treatment compared to written advice in patients with knee osteoarthritis: a secondary analysis of the 2-year outcome from a randomized trial.

OBJECTIVE: To assess the 24-month cost-effectiveness of supervised treatment compared to written advice in knee osteoarthritis (OA). DESIGN: 100 adults with moderate-severe OA not eligible for total knee replacement (TKR) randomized to a 12-week individualized, supervised treatment (exercise, education, diet, insoles and pain medication) or written advice. Effectiveness was measured as change in quality-adjusted life years (QALYs) from baseline to 24 months, including data from baseline, 3, 6, 12 and 24 months, while healthcare costs and transfer payments were derived from national registries after final follow-up. Incremental costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs) were calculated. A sensitivity analysis resampling existing data was conducted and the probability of cost-effectiveness was estimated using a 22,665 Euros/QALY threshold. In a sensitivity analysis, cost-effectiveness was calculated for different costs of the supervised treatment (actual cost in study; cost in private practice; and in-between cost). RESULTS: Average costs were similar between groups (6,758 Euros vs 6,880 Euros), while the supervised treatment were close to being more effective (incremental effect (95% CI) of 0.075 (-0.005 to 0.156). In the primary analysis excluding deaths, this led the supervised treatment to be cost-effective, compared to written advice. The sensitivity analysis demonstrated that the results were sensitive to changes in the cost of treatment, but in all scenarios the supervised treatment was cost-effective (ICERs of 6,229 to 20,688 Euros/QALY). CONCLUSIONS: From a 24-month perspective, a 12-week individualized, supervised treatment program is cost-effective compared to written advice in patients with moderate-severe knee OA not eligible for TKR. TRIAL REGISTRATION: ClinicalTrials.gov number: NCT01535001.

Mismatch 'never events' in hip and knee arthroplasty: a cohort and intervention study.

AIMS: The aim of this study was to give estimates of the incidence of component incompatibility in hip and knee arthroplasty and to test the effect of an online, real-time compatibility check. MATERIALS AND METHODS: Intraoperative barcode registration of arthroplasty implants was introduced in Denmark in 2013. We developed a compatibility database and, from May 2017, real-time compatibility checking was implemented and became part of the registration. We defined four classes of component incompatibility: A-I, A-II, B-I, and B-II, depending on an assessment of the level of risk to the patient (A/B), and on whether incompatibility was knowingly accepted (I/II). RESULTS: A total of 26 524 arthroplasties were analyzed. From 12 307 procedures that were undertaken before implementation of the compatibility check, 21 class A incompatibilities were identified (real- or high-risk combinations; 0.17%; 95% confidence interval (CI) 0.11 to 0.26). From 5692 hip and 6615 knee procedures prior to implementation of the compatibility check, we found rates of class A-I incompatibility (real- or high-risk combinations unknowingly inserted) of 0.14% (95% CI 0.06 to 0.28) and 0.17% (95% CI 0.08 to 0.30), respectively. From 14 217 procedures after the introduction of compatibility checking (7187 hips and 7030 knees), eight class A incompatibilities (0.06%; 95% CI 0.02 to 0.11) were identified. This difference was statistically significant (p = 0.008). CONCLUSION: Our data presents validated estimates of the baseline incidence of incompatibility events for hip and knee arthroplasty procedures and shows that a significant reduction in class A incompatibility events is possible using a web-based recording system. Cite this article: Bone Joint J 2019;101-B:960-969.

Evaluation of vitamin E-diffused highly crosslinked polyethylene wear and porous titanium-coated shell stability: a seven-year randomized control trial using radiostereometric analysis.

AIMS: Vitamin E-diffused, highly crosslinked polyethylene (VEPE) and porous titanium-coated (PTC) shells were introduced in total hip arthroplasty (THA) to reduce the risk of aseptic loosening. The purpose of this study was: 1) to compare the wear properties of VEPE to moderately crosslinked polyethylene; 2) to assess the stability of PTC shells; and 3) to report their clinical outcomes at seven years. PATIENTS AND METHODS: A total of 89 patients were enrolled into a prospective study. All patients received a PTC shell and were randomized to receive a VEPE liner (n = 44) or a moderately crosslinked polyethylene (ModXLPE) liner (n = 45). Radiostereometric analysis (RSA) was used to measure polyethylene wear and component migration. Differences in wear were assessed while adjusting for body mass index, activity level, acetabular inclination, anteversion, and head size. Plain radiographs were assessed for radiolucency and patient-reported outcome measures (PROMs) were administered at each follow-up. RESULTS: In total, 73 patients (82%) completed the seven-year visit. Mean seven-year linear proximal penetration was -0.07 mm (sd 0.16) and 0.00 mm (sd 0.22) for the VEPE and ModXLPE cohorts, respectively (p = 0.116). PROMs (p = 0.310 to 0.807) and radiolucency incidence (p = 0.330) were not different between the polyethylene cohorts. The mean proximal shell migration rate was 0.04 mm per year (sd 0.09). At seven years, patients with radiolucency (34%) demonstrated greater migration (mean difference: 0.6 mm (sd 0.2); p < 0.001). PROMs were lower for patients with radiolucency and greater proximal migration (p = 0.009 to p = 0.045). No implants were revised for aseptic loosening. CONCLUSION: This is the first randomized controlled trial to report seven-year RSA results for VEPE. All wear rates were below the previously reported osteolysis threshold (0.1 mm per year). PTC shells demonstrated acceptable primary stability through seven years, as indicated by low migration and lack of aseptic loosening. However, patients with acetabular radiolucency were associated with higher shell migration and lower PROM scores. Cite this article: Bone Joint J 2019;101-B:760-767.

Initial metal-metal bond breakage detected by fs X-ray scattering in the photolysis of Ru3(CO)12 in cyclohexane at 400 nm.

Using femtosecond resolution X-ray solution scattering at a free electron laser we were able to directly observe metal-metal bond cleavage upon photolysis at 400 nm of Ru3(CO)12, a prototype for the photochemistry of transition metal carbonyls. This leads to the known single intermediate Ru3(CO)11(µ-CO)*, with a bridging ligand (µCO) and where the asterisk indicates an open Ru3-ring. This loses a CO ligand on a picosecond time scale yielding a newly observed triple bridge intermediate, Ru3(CO)8(µ-CO)3*. This loses another CO ligand to form the previously observed Ru3(CO)10, which returns to Ru3(CO)12via the known single-bridge Ru3(CO)10(µ-CO). These results indicate that contrary to long standing hypotheses, metal-metal bond breakage is the only chemical reaction immediately following the photolysis of Ru3(CO)12 at 400 nm. Combined with previous picosecond resolution X-ray scattering data and time resolved infrared spectroscopy these results yield a new mechanism for the photolysis of Ru3(CO)12.

Increased postural stiffness during challenging postural tasks in patients with knee osteoarthritis with high pain sensitization.

BACKGROUND: Postural stability is affected in knee osteoarthritis patients who present with pain but the link to pain sensitization is unclear. METHODS: Patients with knee osteoarthritis completed the Knee Injury and Osteoarthritis Outcome Score and pressure pain thresholds were assessed bilaterally at the knee, lower leg and forearm prior to standing quietly (1 min) on a force platform in four conditions: Firm surface with open eyes, firm surface with closed eyes, soft surface with open eyes, and soft surface with closed eyes. Pain intensity during standing was assessed via numerical rating scale. Postural stability was assessed by the range, velocity, and standard deviation of the Center of Pressure (CoP) extracted from the force platform. The means of three repeated measures per standing condition were analysed. High-sensitization and low-sensitization groups were defined based on bilateral pressure pain thresholds from leg and arm. FINDINGS: Fifty-six patients were included. Compared with the low-sensitization group, the high-sensitization group demonstrated 1) smaller pressure pain thresholds at the knee (P < 0.05) although the Knee Injury and Osteoarthritis Outcome Score and pain intensity were not significantly different between groups, and 2) smaller range of the CoP in the anterior-posterior direction during the soft surface with closed eyes condition (P < 0.05). INTERPRETATION: Smaller CoP range suggest that patients with more widespread pain sensitivity have increased postural stiffness compared with the low-sensitization group. The greater stiffness found in high-sensitization patients under sensory restrictions (closed eyes and reduced proprioception) might relate to restricted integration of sensory information due to widespread pain sensitization.

Evaluation of in vivo wear of vitamin E-diffused highly crosslinked polyethylene at five years: a multicentre radiostereometric analysis study.

AIMS: The primary aim of this study was to compare the wear properties of vitamin E-diffused, highly crosslinked polyethylene (VEPE) and one formulation of moderately crosslinked and mechanically annealed ultra-high molecular weight polyethylene (ModXLPE) in patients five years after primary total hip arthroplasty (THA). The secondary aim was to assess the clinical results of patients treated with VEPE by evaluating patient-reported outcome measures (PROMs), radiological evidence of fixation, and the incidence of mechanical failure. PATIENTS AND METHODS: A total of 208 patients (221 THAs) from four international centres were recruited into a prospective study involving radiostereometric analysis (RSA) and the assessment of clinical outcomes. A total of 193 hips (87%) were reviewed at the five-year follow-up. Of these, 136 (70%) received VEPE (vs ModXLPE) liners and 68 (35%) received ceramic (vs metal) femoral heads. PROMs and radiographs were collected preoperatively and at one, two, and five years postoperatively. In addition, RSA images were collected to measure PE wear postoperatively and at one, two, and five years after surgery. RESULTS: We observed similar bedding in one year postoperatively and wear two years postoperatively between the two types of liner. However, there was significantly more penetration of the femoral head in the ModXLPE cohort compared with the VEPE cohort five years postoperatively (p < 0.001). The only variables independently predictive of increased wear were ModXLPE (vs VEPE) liner type (ß = 0.22, p = 0.010) and metal (vs ceramic) femoral head (ß = 0.21, p = 0.013). There was no association between increased wear and the development of radiolucency (p = 0.866) or PROMs. No patient had evidence of osteolysis. CONCLUSION: Five years postoperatively, patients with VEPE (vs ModXLPE) and ceramic (vs metal) femoral heads had decreased wear. The rates of wear for both liners were very low and have not led to any osteolysis or implant failure due to aseptic loosening.

Total knee replacement and non-surgical treatment of knee osteoarthritis: 2-year outcome from two parallel randomized controlled trials.

OBJECTIVES: To compare 2-year outcomes of total knee replacement (TKR) followed by non-surgical treatment to that of non-surgical treatment alone and outcomes of the same non-surgical treatment to that of written advice. DESIGN: In two randomized trials, 200 (mean age 66) adults with moderate to severe knee osteoarthritis (OA), 100 eligible for TKR and 100 not eligible for TKR, were randomized to TKR followed by non-surgical treatment, non-surgical treatment alone, or written advice. Non-surgical treatment consisted of 12 weeks of supervised exercise, education, dietary advice, use of insoles, and pain medication. The primary outcome was the mean score of the Knee Injury and Osteoarthritis Outcome Score (KOOS) subscales, covering pain, symptoms, activities of daily living (ADL), and quality of life (QOL). RESULTS: Patients randomized to TKR had greater improvements than patients randomized to non-surgical treatment alone (difference of 18.3 points (95% CI; 11.3 to 25.3)), who in turn improved more than patients randomized to written advice (difference of 7.0 points (95% CI; 0.4 to 13.5)). Among patients eligible for TKR, 16 (32%) from the non-surgical group underwent TKR during 2 years and among those initially ineligible, seven patients (14%) from the non-surgical group and ten (20%) from the written advice group underwent TKR. CONCLUSIONS: TKR followed by non-surgical treatment is more effective on pain and function than non-surgical treatment alone, which in turn is more effective than written advice. Two out of three patients with moderate to severe knee OA eligible for TKR delayed surgery for at least 2 years following non-surgical treatment. TRIAL REGISTRATION: ClinicalTrials.gov numbers NCT01410409 and NCT01535001.

Incidence and related factors for intraoperative failed spinal anaesthesia for lower limb arthroplasty.

BACKGROUND: Spinal anaesthesia is the preferred choice for total hip- and knee arthroplasty (THA/TKA), due to the claimed superior outcome profile, relative simple technique and without the need for advanced airway support. However, choosing and informing about spinal anaesthesia should also include the risk for intraoperative failed spinal anaesthesia with associated pain, discomfort and suboptimal settings for airway management. Small-scale studies suggest incidences from 1 to 17%; however, no multi-institutional large data exists on failed spinal incidence and related factors during THA/TKA, hindering evidence-based information and potential anaesthesia stratification. METHODS: In a sub-analysis, data from a prospective study on spinal anaesthesia for THA/TKA were examined for incidence of intraoperative conversion to general anaesthesia. Potential perioperative factors (age, gender, American Society of Anaesthesiologist (ASA) score, height, weight, BMI, procedure, bupivacaine dosage and duration of time from spinal administration until end of surgery) were analysed with logistic regression for relation to failed spinal anaesthesia. RESULTS: In all, 1451 patients were included for analysis, whereof 57 (3.9%) had failed spinal anaesthesia. Spinal failure patients were significantly younger (61 vs. 67 years, P = 0.003), and operation time longer in the failed spinal group vs no-failure, respectively (133 vs. 89 min, P < 0.001). No significant differences were found with regard to bupivacaine volume, gender, ASA-score, height, weight, BMI or THA vs. TKA. CONCLUSION: Failed spinal anaesthesia for THA and TKA is a relatively frequent occurrence and identification of risk patients is not feasible. These results should be considered when choosing anaesthesia and included in the information to patients.

Pain and sensitization after total knee replacement or nonsurgical treatment in patients with knee osteoarthritis: Identifying potential predictors of outcome at 12 months.

BACKGROUND: This study is a secondary analysis of 12-month follow-ups from two parallel, randomized controlled trials (RCT) in painful knee osteoarthritis patients. RCT1: Total knee replacement (TKR) followed by nonsurgical treatment compared with nonsurgical treatment. RCT2: Nonsurgical treatment compared with usual care. The aims were to investigate (1) possible predictors of treatment outcome after TKR and nonsurgical interventions at 12 months, (2) associations between pain intensity and pressure pain thresholds (PPTs) (pain sensitization) at baseline and after 12 months and (3) possible gender differences. METHOD: Each RCT included 100 patients. Pain intensities, PPTs and number of painful sites were assessed at baseline and after 12 months. RESULTS: In all groups, pain improved and pain sensitization decreased. In RCT1, the TKR group had the greatest improvements in pain. In RCT2 the nonsurgical group had the greatest improvement, with no between-group differences in PPTs. Lower PPTs at baseline predicted higher pain after TKR. Baseline pain intensity and PPT levels were associated with the number of painful sites. Subjects with the highest pain and lowest PPTs at baseline showed the largest relative improvement in pain and sensitization but were still experiencing highest absolute pain and lowest PPTs after 12 months (combined cohorts). CONCLUSION: Low PPTs at baseline predicted worse pain outcome after TKR, but did not predict outcome after nonsurgical interventions. The number of painful sites was weakly associated with pain and PPTs, and the higher pain/lower PPTs, the higher pain/lower PPTs at 12 months with females showing the lowest PPT values. SIGNIFICANCE: Human experimental pain assessment was used to assess the degree of pain sensitization in patients with painful knee osteoarthritis. High sensitization before TKR predicted worse outcome. Outcome after nonsurgical interventions could not be predicted.

Vitamin E diffused highly cross-linked polyethylene in total hip arthroplasty at five years: a randomised controlled trial using radiostereometric analysis.

AIMS: The objective of this five-year prospective, blinded, randomised controlled trial (RCT) was to compare femoral head penetration into a vitamin E diffused highly cross-linked polyethylene (HXLPE) liner with penetration into a medium cross-linked polyethylene control liner using radiostereometric analysis. PATIENTS AND METHODS: Patients scheduled for total hip arthroplasty (THA) were randomised to receive either the study E1 (32 patients) or the control ArComXL polyethylene (35 patients). The median age (range) of the overall cohort was 66 years (40 to 76). RESULTS: The five-year median (interquartile range) proximal femoral head penetration into the E1 was -0.05 mm (-0.13 to -0.02) and 0.07 mm (-0.03 to 0.16) for ArComXL. At three and five years, the penetration was significantly greater in the ArComXL group compared with the E1 group (p = 0.029 and p = 0.019, respectively). All patient-reported outcomes (PROs) improved significantly from the pre-operative interval compared with those at one year, and remained favourable at five years. There were no differences between the two groups at any interval. CONCLUSION: The five-year results showed that E1 polyethylene does not wear more than the control, ArComXL. This is the longest-term RCT comparing the wear performance and clinical outcome of vitamin E diffused HXLPE with a previous generation of medium cross-linked polyethylene. Cite this article: Bone Joint J 2017;99-B:577-84.

The effects of total knee replacement and non-surgical treatment on pain sensitization and clinical pain.

BACKGROUND: The objective was to compare the effect of total knee replacement (TKR) followed by a 3-month non-surgical treatment with the non-surgical treatment alone in reducing pain sensitization and other pain-related measures in patients with knee osteoarthritis. METHODS: One hundred patients were randomized to (1) TKR followed by a non-surgical treatment of neuromuscular exercise, education, diet, insoles and pain medication or (2) the non-surgical treatment alone. Outcomes assessed at baseline and after 3 months were as follows: (1) pain sensitization assessed as pressure-pain thresholds (PPTs) at the knee (localized sensitization) and the lower leg (spreading sensitization), (2) peak pain intensity during the previous 24 h, (3) pain intensity after 30 min of walking, (4) pain location and pattern, (5) spreading of pain on a region-divided body chart and (6) the usage of pain medication. RESULTS: There was a statistical significant mean difference (95% CI) in change in PPTs from baseline to 3 months between groups in the crude analysis of 71 kPa (21-121) and of 75 kPa (33-117) when adjusting for baseline PPT, age, gender and body mass index, favouring the group having TKR. There were no significant between-group differences in change in the pain-related measures from baseline to 3 months (p = 0.15-0.27). Both groups improved in most of the pain-related measures (p < 0.05). CONCLUSIONS: At 3 months, TKR followed by non-surgical treatment is more effective in reducing localized and spreading pain sensitization than non-surgical treatment alone. Both treatments are equally efficacious in reducing the pain-related measures of this study. WHAT DOES THIS STUDY ADD?: Knee replacement followed by non-surgical treatment is more effective in reducing pain sensitization, but not other pain-related measures, as compared to non-surgical treatment alone at 3 months.

The efficacy of non-surgical treatment on pain and sensitization in patients with knee osteoarthritis: a pre-defined ancillary analysis from a randomized controlled trial.

OBJECTIVE: To report the efficacy of a 3-month treatment program consisting of neuromuscular exercise, education, diet, insoles and pain medication (MEDIC-treatment) compared to usual care (two leaflets with information and treatment advice) in reducing pain-related measures and sensitization in patients with knee osteoarthritis (OA) not eligible for total knee replacement (TKR). METHOD: A pre-defined ancillary analysis of the results at 3 months of a randomized controlled trial (RCT) of 100 patients randomized to MEDIC-treatment or usual care. TRIAL REGISTRATION: ClinicalTrials.gov (NCT01535001). Outcomes were sensitization assessed at the knee, the lower leg and forearm using a handheld algometer, peak pain intensity in the previous 24 h, pain intensity after 30 min of walking, pain location and pattern, spreading of pain (a region-divided body chart) and the usage of pain medication. RESULTS: The MEDIC group had larger improvements from baseline to 3 months in peak pain intensity (P = 0.02) and pain after 30 min of walking (P < 0.001) and in the number of body sites with pain (P = 0.04). There was no difference in the change in sensitization from baseline to 3 months between groups (P = 0.87), but sensitization decreased in both groups (P < 0.001). CONCLUSION: A non-surgical treatment program is more efficacious in reducing pain-related measures than usual care, while both are equally efficacious in reducing sensitization, indicating that mechanisms other than pain sensitization contribute to the perceived pain. The patients did not have severe symptomatic knee OA and hence pain sensitization may not yet have developed into a clinically relevant parameter or subgroups with less sensitization may exist.

Subchondral bone turnover, but not bone volume, is increased in early stage osteoarthritic lesions in the human hip joint.

OBJECTIVE: The pathogenesis of osteoarthritis (OA) is not fully understood, but bone changes are suggested to be important. Bone turnover and bone volume (BV) in human hip OA were investigated in relation to the overlying cartilage degeneration using design-based stereological estimators. MATERIALS AND METHODS: Femoral heads were obtained from 25 end-stage OA patients and 24 controls (CTL). Design-based stereological methods were used for sampling and quantification to obtain absolute estimates of volume and surface in the central trabecular and the subarticular bone region. The subarticular bone was further subdivided into regions according to the OARSI-score of the overlying articular cartilage in which erosion and osteoid surfaces were estimated. RESULTS: In the subarticular region, bone volume (BV/TV) was 15.0% higher in OA patients compared to CTL; The fraction of erosive (ES/BS) and osteoid surfaces (OS/BS) were 56.2% and 72.8% higher in OA compared to CTL. In subarticular regions with none to mild cartilage degeneration (OARSI grade 0-2), ES/BS and OS/BS were 48.6% and 59.9% higher in OA compared to CTL, whereas BV/TV did not differ between OA and CTL. CONCLUSION: In human end-stage hip OA, BV and bone turnover correlate with the degree of local cartilage degeneration. Subarticular bone sclerosis was only present in regions corresponding to end-stage OA. However, in regions with only none to mild cartilage degeneration the underlying bone had significantly higher turnover in OA patients compared to the control group, suggesting that high bone turnover may contribute to the early pathogenesis of OA.

The efficacy of 12 weeks non-surgical treatment for patients not eligible for total knee replacement: a randomized controlled trial with 1-year follow-up.

OBJECTIVE: To compare the efficacy of a 12-week non-surgical treatment program with usual care in patients with knee osteoarthritis (OA) not eligible for total knee replacement (TKR). METHOD: This two-arm parallel group assessor-blinded randomized controlled trial (RCT) included 100 adults from secondary care with knee OA, confirmed by radiography (Kellgren-Lawrence grade ≥1), but not eligible for a TKR. The 12-week non-surgical treatment program consisted of individualized progressed neuromuscular exercise, patient education, insoles, dietary advice and prescription of pain medication if indicated, while usual care comprised two leaflets with information and advice on knee OA and recommended treatments. The primary outcome was the change from baseline to 12 months in the Knee injury and Osteoarthritis Outcome Score (KOOS)4 defined as the average score for the KOOS subscales of pain, symptoms, activities of daily living (ADL), and quality of life (QOL). RESULTS: 91% of the patients completed the 12 months follow-up on the primary outcome. Compared with usual care, patients undergoing the treatment program improved more in KOOS4 (adjusted mean difference (95% CI) of 9.6 (4.4-14.8)) with no serious treatment-related adverse events (AE). The number needed to treat (NNT), defined as the number of patients needed to treat for one person to improve 15% was 7.2. Secondary outcomes supported the primary findings. CONCLUSION: In patients with mostly moderate to severe knee OA not eligible for TKR, a 12-week individualized, non-surgical treatment program is more efficacious at 12 months compared with usual care and has few treatment-related AE. TRIAL REGISTRATION: ClinicalTrials.gov (NCT01535001).

Multi-level synchrotron radiation-based microtomography of the dental alveolus and its consequences for orthodontics.

Multilevel synchrotron radiation-based microtomography has been performed on a human jaw segment obtained at autopsy by cutting increasingly smaller samples from the original segment. The focus of this study lay on the microstructure of the interface between root, periodontal ligament (PDL) and alveolar bone in order to find an answer to the question why alveolar bone remodels during orthodontic loading, when the associated stress and strain levels calculated with finite element analyses are well below the established threshold levels for bone remodeling. While the inner surface of the alveolus appears to be rather smooth on the lower resolution scans, detailed scans of the root-PDL-bone interface reveal that on a microscopical scale it is actually quite rough and uneven with bony spiculae protruding into the PDL space. Any external (orthodontic) loading applied to the root, when transferred through the PDL to the alveolar bone, will cause stress concentrations in these spiculae, rather than be distributed over a "smooth surface". As osteocyte lacunae are shown to be present in these spiculae, the local amplified stresses and strain can well be registered by the mechano-sensory network of osteocytes. In addition, a second stress amplification mechanism, due to the very presence of the lacunae themselves, is evidence that stresses and strains calculated with FE analyses, based on macroscopical scale models of teeth and their supporting structures, grossly underestimate the actual mechanical loading of alveolar bone at tissue level. It is therefore hypothesized that remodeling of alveolar bone is subject to the same biological regulatory process as remodeling in other bones.

Facilitation of pain sensitization in knee osteoarthritis and persistent post-operative pain: a cross-sectional study.

BACKGROUND: Around 20% of patients with osteoarthritis (OA) have chronic post-operative pain after total knee arthroplasty (TKA) and often undergo revision surgery with unfavourable pain outcome. This study compared sensitization in pain patients with knee OA and after revision TKA (re-TKA). METHODS: Median pressure pain thresholds (PPTs) assessed from the most affected knee (localized sensitization) were used to subgroup 53 patients with OA pain and 20 patients with pain after re-TKA: group 1: OA and high-knee PPT; group 2: OA and low-knee PPT; group 3: re-TKA and high-knee PPT; group 4: re-TKA and low-knee PPT. Clinical pain intensity was assessed using a visual analogue scale (VAS). Bilateral PPTs were measured from the lower leg and forearm (spreading sensitization). Furthermore, the pain intensities evoked by 10 repeated pressure pain stimuli (temporal summation) at the knee and lower leg were assessed on an electronic VAS. RESULTS: The mean clinical pain intensity was not significantly different between groups. The PPTs from both lower leg and forearm were significantly lower in group 4 compared to groups 1, 2, and 3 and in groups 2 and 3 compared to group 1 (p < 0.05). Temporal summations from the knee and lower leg were significantly facilitated in groups 3 and 4 compared to groups 1 and 2 (p < 0.05). CONCLUSIONS: Despite similar pain intensities, facilitated temporal summation is worse in re-TKA than in OA and patients with high local knee hyperalgesia show more prominent spreading sensitization. The study suggests that sensitization should be considered in knee OA especially before re-TKA.