Nis Nissen

Increased RANKL/OPG mRNA Ratio in Iliac Bone Biopsies From Women with Hip Fractures

RANKL (receptor activator of NF-κB) is a potent physiological inducer of osteoclastogenesis. Its actions are blocked by the decoy receptor osteoprotegerin (OPG), and treatment with OPG blocks bone resorption in postmenopausal women. Both positive and negative associations between serum OPG and bone mineral density (BMD) have been reported in the literature. We hypothesized that decreased OPG production relative to RANKL within bone itself could lead to increased risk of osteoporotic fracture. We included ten women with hip fracture (age 76.3 ± 8.0 years, N.S, hip BMD 0.686 ± 1.3 g/cm2, P < 0.05) and 24 women with osteoarthrosis of the hip (age 72.8 ± 7.2 years, hip BMD 0.832 ± 1.1 g/cm2). Transiliac biopsies were obtained at the time of surgery. Total RNA was extracted from biopsies and reverse-transcribed. Real-time quantification of mRNA was performed with a SYBR Green I real time PCR assay, calculating relative gene expession with normalization of results for β actin mRNA. Actin normalized mRNA levels for OPG and interleukin (IL)-6 were significantly lower in fracture patients, with a significantly higher RANKL/OPG ratio in patients with fractures. There was no significant difference in tumor necrosis factor (TNF), IL-1, IL-1ra, or IL-7 expression. IL-6 mRNA levels were lower in fracture patients (P < 0.05). The effect of increased RANKL/OPG ratio (Z = 2.08, P < 0.05) on fracture risk was additive to that of hip BMD T score (Z = −1.95, P < 0.05) when assessed using logistic regression. Elderly women with hip fractures exhibit an increased RANKL/OPG mRNA content of iliac bone. This is associated with increased fracture susceptibility, which is not in itself explained by low BMD.

Patient reported outcomes in patients undergoing arthroscopic partial meniscectomy for traumatic or degenerative meniscal tears: comparative prospective cohort study

Objectives To compare patient reported outcomes from before surgery to 52 weeks after surgery between individuals undergoing arthroscopic partial meniscectomy for traumatic meniscal tears and those for degenerative meniscal tears. Design Comparative prospective cohort study. Setting Four public orthopaedic departments in the Region of Southern Denmark. Participants were recruited between 1 February 2013 and 31 January 2014, and at one of the original four hospitals from 1 February 2014 to 31 January 2015. Participants Individuals selected from Knee Arthroscopy Cohort Southern Denmark, aged 18-55, and undergoing arthroscopic partial meniscectomy for a traumatic or degenerative meniscal tear (defined by a combination of age and symptom onset). Interventions Both participant groups underwent arthroscopic partial meniscectomy for a meniscal tear, with operating surgeons recording relevant information on knee pathology. Patient reported outcomes were recorded via online questionnaires. Main outcome measures Primary outcome was the average between-group difference in change on four of five subscales of the knee injury and osteoarthritis outcome score (KOOS). The four subscales covered pain, symptoms, sport and recreational function, and quality of life (KOOS4). A 95% confidence interval excluding differences greater than 10 KOOS points between groups was interpreted as absence of a clinically meaningful difference. Analyses adjusted for age, sex, and body mass index. Results 397 eligible adults (42% women) with a traumatic or degenerative meniscal tear (n=141, mean age 38.7 years (standard deviation 10.9); n=256, 46.6 years (6.4); respectively) were included in the main analysis. At 52 weeks after arthroscopic partial meniscectomy, 55 (14%) patients were lost to follow-up. Statistically, participants with degenerative meniscal tears had a significantly larger improvement in KOOS4 scores than those with traumatic tears (adjusted between-group difference −5.1 (95% confidence interval −8.9 to −1.3); P=0.008). In the analysis including KOOS4 score at all time points, a significant time-by-group interaction was observed in both the unadjusted (P=0.025) and adjusted analysis (P=0.024), indicating better self-reported outcomes in participants with degenerative tears. However, the difference between groups was at no time point considered clinically meaningful. Conclusions These results question the current tenet that patients with traumatic meniscal tears experience greater improvements in patient reported outcomes after arthroscopic partial meniscectomy than patients with degenerative tears. Trial registration ClinicalTrials.gov identifier NCT01871272.

Structural pathology is not related to patient-reported pain and function in patients undergoing meniscal surgery

Background The relationship between meniscal tears and other joint pathologies with patient-reported symptoms is not clear. We investigated associations between structural knee pathologies identified at surgery with preoperative knee pain and function in patients undergoing arthroscopic meniscal surgery. Methods This study included 443 patients from the Knee Arthroscopy Cohort Southern Denmark (KACS), a prospective cohort following patients 18 years or older undergoing arthroscopic meniscal surgery at 4 hospitals between 1 February 2013 and 31 January 2014. Patient-reported outcomes, including the Knee Injury and Osteoarthritis Outcome Score (KOOS), were obtained by online questionnaires prior to surgery. Knee pathology was assessed by the operating surgeons using a modified version of the International Society of Arthroscopy, Knee Surgery and Orthopaedic Sports Medicine (ISAKOS) classification of meniscal tears questionnaire, supplemented with information extracted from surgery reports. Following hypothesis-driven preselection of candidate variables, backward elimination regressions were performed to investigate associations between patient-reported outcomes and structural knee pathologies. Results Regression models only explained a small proportion of the variability in self-reported pain and function (adjusted R2=0.10−0.12) and this association was mainly driven by age, gender and body mass index. Conclusions Specific meniscal pathology and other structural joint pathologies found at meniscal surgery were not associated with preoperative self-reported pain and function in patients with meniscal tears questioning inferences made about a direct relationship between these. Our findings question the role of arthroscopic surgery to address structural pathology as a means to improve patient-reported outcomes in patients having surgery for a meniscal tear.

Changes in bone mineral density (BMD) around the cemented Exeter stem: A prospective study in 18 women with 5 years follow‐up

Background and purpose THA changes the pattern of strain distribution in the proximal femur. We quantified the changes in BMD for 5 years after insertion of the cemented Exeter stem in women. Methods 18 women aged 55–79 years, undergoing unilateral THA with the cemented Exeter stem, were included in the study. The BMD was measured in 7 femoral regions of interest according to Gruen, and the contralateral hip and spine using dual‐energy X‐ray absorptiometry postoperatively, at 18 and at 60 months of follow‐up. Results were tested using Wilcoxon matched‐pairs signed‐rank test. Results During the first 18 months, a significant decrease in BMD was seen in zones 2, 3, 6, and 7. No significant changes were seen in zones 4 and 5, in the contralateral hip, or at the spine. In zone 1, there was a small but significant rise in BMD. From 18 to 60 months, we observed a statistically significant rise in BMD in all zones except 4 and 7. Despite this, the total periprosthetic BMD decreased during the follow‐up relative to the immediate postoperative situation. There was no significant reduction in BMD in the contralateral hip. In the spine, we observed a significant rise in BMD. Interpretation 18 months after THA, BMD had decreased in Gruen zones 2, 3, 6, and 7. The bone loss was similar to that seen after other implants and appears to be related to the changes in stress pattern within the proximal femur. At 5 years, BMD had increased again in these zones. It remained lower than baseline, however.

When should densitometry be repeated in healthy peri- and postmenopausal women: the Danish osteoporosis prevention study.

Intervention should be considered in postmenopausal women with bone mineral density (BMD) ≥1 SD below the reference (T or Z score < −1). However, it is unclear when densitometry should be repeated. This study aimed at determining the need for repeat DXA within 5 years in untreated peri‐/postmenopausal women to detect declines of T or Z score to below −1 with 85% confidence. A cohort of 925 healthy women (aged 51.2 ± 2.9 years) were followed within the Danish Osteoporosis Prevention Study (DOPS) for 5 years without hormone‐replacement therapy (HRT). DXA of spine, hip, and forearm was done at 0,1, 2, 3, and 5 years (Hologic QDR‐1000/2000). The annual loss in SD units was 0.12 ± 0.10 at the spine (1.3%), 0.10 ± 0.09 at the femoral neck (1.2%), and 0.07 ± 0.09 at the ultradistal (UD) forearm (1.0%). Accordingly, T scores below −1 developed earlier at the spine. The need for a future DXA scan to predict declines of T and Z scores below −1 depended strongly on baseline BMD. In subjects with a positive T score, the risk of developing T < −1 remained at <15% for 5 years at all measured sites. A new scan was needed after 1 year if the T score was below −0.5, and after 3 years if the T score was between 0 and −0.5. Slightly longer intervals apply if Z scores are used. Follow‐up densitometry in untreated women should be individually targeted from baseline BMD rather than scheduled at fixed time intervals. An algorithm for planning repeat densitometry in perimenopausal women is provided.

Knee Arthroscopy Cohort Southern Denmark (KACS): protocol for a prospective cohort study

Background Meniscus surgery is a high-volume surgery carried out on 1 million patients annually in the USA. The procedure is conducted on an outpatient basis and the patients leave the hospital a few hours after surgery. A critical oversight of previous studies is their failure to account for the type of meniscal tears. Meniscus tears can be categorised as traumatic or non-traumatic. Traumatic tears (TT) are usually observed in younger, more active individuals in an otherwise ‘healthy’ meniscus and joint. Non-traumatic tears (NTT) (ie, degenerative tears) are typically observed in the middle-aged (35–55 years) and older population but the aetiology is largely unclear. Knowledge about the potential difference of the effect of arthroscopic meniscus surgery on patient symptoms between patients with traumatic and NTT is sparse. Furthermore, little is known about the natural time course of patient perceived pain, function and quality of life after meniscus surgery and factors affecting these outcomes. The aim of this prospective cohort study is to investigate the natural time course of patient-reported outcomes in patients undergoing meniscus surgery, with particular emphasis on the role of type of symptom onset. Methods/design This prospective cohort study enrol patients assigned for meniscus surgery. At the baseline (PRE surgery), patient characteristics are assessed using an email-based questionnaire also comprising several validated questionnaires assessing general health, knee-specific characteristics and patients expectations of the surgery. Follow-up will be conducted at 12 and 52 weeks after meniscus surgery. The major outcomes will be differences in changes, from before to 52 weeks after surgery, in each of the five domains on the Knee injury and Osteoarthritis Outcome Score (KOOS) between patients undergoing surgery for traumatic compared with non-traumatic meniscus tears. Dissemination The study findings will be disseminated in peer-reviewed journals and presented at national and international conferences. Trial registration number ClinicalTrials.gov Identifier: NCT01871272.

Disproportional geometry of the proximal femur in patients with Turner syndrome: a cross-sectional study.

Objective  Patients with Turner syndrome (TS) have altered growth and increased risk of osteoporosis due to oestrogen deficiency and possibly a host of other factors. Thus, TS patients have a 4·9‐fold increased risk of femoral neck fractures. Most patients are treated with oestrogen during puberty and adolescence to facilitate pubertal development and prevent secondary osteoporosis. The geometry of the hip is a predictor for hip fractures independent of bone mineral density (BMD). The purpose of the present study was to investigate the variation of the geometry of the hip in patients with TS in comparison with healthy controls.

Signs of knee osteoarthritis common in 620 patients undergoing arthroscopic surgery for meniscal tear

Background and purpose — Recent evidence has questioned the effect of arthroscopic knee surgery for middle-aged and older patients with degenerative meniscal tears with or without concomitant radiographic knee osteoarthritis (OA). We investigated the prevalence of early or more established knee OA and patients’ characteristics in a cohort of patients undergoing arthroscopic surgery for a meniscal tear. Patients and methods — 641 patients assigned for arthroscopy on suspicion of meniscus tear were consecutively recruited from February 2013 through January 2015. Of these, 620 patients (mean age 49 (18–77) years, 57% men) with full datasets available were included in the present study. Prior to surgery, patients completed questionnaires regarding onset of symptoms, duration of symptoms, and mechanical symptoms along with the knee injury and osteoarthritis outcome score (KOOS). At arthroscopy, the operating surgeon recorded information about meniscal pathology and cartilage damage. Early or more established knee OA was defined as the combination of self-reported frequent knee pain, cartilage damage, and the presence of degenerative meniscal tissue. Results — 43% of patients (269 of 620) had early or more established knee OA. Of these, a large proportion had severe cartilage lesions with almost half having a severe cartilage lesion in at least 1 knee compartment. Interpretation — Based on a definition including frequent knee pain, cartilage damage, and degenerative meniscal tissue, early or more established knee OA was present in 43% of patients undergoing knee arthroscopy for meniscal tear.

Over-optimistic patient expectations of recovery and leisure activities after arthroscopic meniscus surgery

Background and purpose — Patients’ expectations of outcomes following arthroscopic meniscus surgery are largely unknown. We investigated patients’ expectations concerning recovery and participation in leisure-time activities after arthroscopic meniscus surgery and the postoperative fulfillment of these. Patients and methods — The study sample consisted of 491 consecutively recruited patients (mean age 50 (SD 13) years, 55% men) who were assigned for arthroscopy on suspicion of meniscus injury and later verified by arthroscopy. Before surgery, patients completed questionnaires regarding their expectations of recovery time and postoperative participation in leisure activities. 3 months after surgery, the patients completed questionnaires on their actual level of leisure activity and their degree of satisfaction with their current knee function. We analyzed differences between the expected outcome and the actual outcome, and between fulfilled/exceeded expectations and satisfaction with knee function. Results — 478 patients (97%) completed the follow-up. 91% had expected to be fully recovered within 3 months. We found differences between patients’ preoperative expectations of participation in leisure activities postoperatively and their actual participation in these, with 59% having unfulfilled expectations (p < 0.001). Satisfaction with current knee function was associated with expectations of leisure activities being fulfilled/exceeded. Interpretation — In general, patients undergoing arthroscopic meniscus surgery were too optimistic regarding their recovery time and postoperative participation in leisure activities. This highlights the need for shared decision making which should include giving the patient information on realistic expectations of recovery time and regarding participation in leisure-time activities after meniscal surgery.

The effect of targeted exercise on knee-muscle function in patients with persistent hamstring deficiency following ACL reconstruction – study protocol for a randomized controlled trial

BackgroundAnterior cruciate ligament (ACL) reconstruction, using hamstring auto-graft is a common surgical procedure, which often leads to persistent hamstring muscle-strength deficiency and reduced function. The purpose of this randomized controlled trial (RCT) is to investigate the effect of a combined, progressive, strength and neuromuscular exercise intervention on knee muscle strength, functional capacity and hamstring muscle-tendon morphology in ACL-reconstructed patients with persistent hamstring muscle-strength deficiency compared with controls.Methods/designThe study is designed as a multicenter, parallel-group RCT with balanced randomization (1:1) and blinded outcome assessments (level of evidence: II) and will be reported in accordance with the CONSORT Statement. Fifty ACL-reconstructed patients (hamstring auto-graft) with persistent limb-to-limb knee-flexor muscle-strength asymmetry at 12–24 months’ post surgery, will be recruited through outpatient clinics and advertisements. Patients will be randomized to a 12-week progressive, strength and neuromuscular exercise group (SNG) with supervised training twice weekly or a control intervention (CON) consisting of a home-based, low-intensity exercise program. Outcome measures include between-group change in maximal isometric knee-flexor strength (primary outcome) and knee-extensor muscle strength, hamstring-to-quadriceps strength ratios of the leg that has been operated on and Knee injury and Osteoarthritis Outcome Score (KOOS) (secondary outcomes).In addition, several explorative outcomes will be investigated: The International Knee Documentation Committee Subjective Knee Form (IKDC), the Tegner Activity Score, rate of force development (RFD) for the knee flexors and extensors, tendon regeneration and potential muscle hypertrophy at graft harvest site evaluated by magnetic resonance imaging (MRI), postural control, kinetic/kinematic gait characteristics and knee-related functional capacity.DiscussionThis RCT is designed to investigate the effect of combined, progressive-resistance and neuromuscular exercises on knee-flexor/extensor strength, in the late rehabilitation phase following ACL reconstruction. Reduced hamstring strength represents a potential risk factor for secondary ACL rupture and accelerated progression of osteoarthritis. If deemed effective, the intervention paradigm introduced in this study may help to improve current treatment strategies in ACL-reconstructed patients.Trial registrationClinicalTrials.gov, ID: NCT02939677 (recruiting). Registered on 20 October 2016.