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Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_8 | Pages 119 - 119
11 Apr 2023
Peffers M Anderson J Jacobsen S Walters M Bundgaard L Hackle M James V
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Joint tissues release extracellular vesicles (EVs) that potentially sustain joint homeostasis and contribute to osteoarthritis (OA) pathogenesis. EVs are putative novel therapeutics for OA, and transport biologically active molecules (including small non-coding RNAs (SNCRNAs)) between cells. This study identified altering SNCRNA cargo in EVs in OA which may act as early diagnostic markers and treatment targets.

OA was surgically induced in four skeletally mature Standardbred horses using an osteochondral fragment model in the left middle carpal joint. The right joint underwent sham surgery. Synovial fluid (SF) and plasma were obtained weekly throughout the 70-day study. EVs were isolated using size exclusion chromatography and characterised using nanoparticle tracking (Nanosight), and exosome fluorescence detection and tetraspanin phenotyping (Exoview). RNA was extracted from EVs derived from SF (sham and OA joints) and plasma collected at days 10, 35, 42, 49, 56, 63, and subjected to small RNA sequencing on a NovaSeq SP100 flow cell (Illumina).

Nanosight-derived EV characteristics of size and concentration were not significantly different following disease induction. The diameter of the temporal population of plasma and SF-derived exosomes changed significantly for CD9 and CD81 following OA induction with significant temporal, and disease-related changes in CD63 and CD81 protein expressin in plasma and SF.

In SF and plasma-derived EVs snoRNAs, snRNAs, tRNAs, lncRNA, y-RNA, piRNAs and scRNA were found. Following pairwise analysis of all-time points we identified 27 miRs DE in plasma and 45 DE miRs in SF. Seven were DE in plasma and SF; miR-451, miR-25, miR-215, miR-92a, miR-let-7c, miR-486-5p, miR-23a. In plasma and SF 35 and 21 snoRNAs were DE with four DE in plasma and SF; U3, snord15, snord46, snord58.

This work has identified alterations to OA EV sncRNAs in plasma and SF providing a greater understanding of the role of EVs in early OA.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXXVII | Pages 309 - 309
1 Sep 2012
Palm H Krasheninnikoff M Holck K Lemser T Foss N Jacobsen S Kehlet H Gebuhr P
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Introduction

We implemented an exhaustive operative and supervision algorithm for surgical treatment of hip fractures primarily based on own previously published literature. The purpose was to improve supervision and reduce the rate of reoperations.

Materials and methods

2000 consecutive unselected patients above 50 years admitted with a hip fracture were included, 1000 of these prospectively after implementation of the algorithm. Demographic parameters, hospital treatment and reoperations within the first postoperative year were assessed from patient records.

The algorithm dictated the surgical treatment based on three objective patient parameters: age, new mobility score and fracture classification on pre-operative anterior-posterior and axial radiographs. Intra capsular fractures were treated with two parallel implants, a sliding hip screw, an arthroplasty or resection of the femoral head. Extra capsular fractures were treated with a sliding hip screw or an intramedullary nail. Supervision of junior registrars was mandatory for the prosthesis and intramedullary nail procedures.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_I | Pages 2 - 2
1 Jan 2012
Petersen T Larsen K Nordsteen J Olsen S Fournier G Jacobsen S
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Purpose

To compare the effectiveness of the McKenzie method and spinal manipulation when used adjunctive to information and advice for patients with clinical signs suggestive of disc-related symptoms for duration of more than 6 Weeks.

Background

The conclusions drawn from previous randomised studies have been contradictory. The need for studies testing treatment strategies to specific diagnostic subgroups has been emphasised.


Orthopaedic Proceedings
Vol. 93-B, Issue SUPP_II | Pages 138 - 138
1 May 2011
Palm H Lysén C Krasheninnikoff M Holck K Jacobsen S Gebuhr P
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Introduction: The use of intramedullary nailing (IMHS) has increased at the expense of the dynamic hip screw (DHS), although the outcome is not different in the studies of pertrochanteric fractures (PTF), known as AO/OTA type 31A1-2 fractures with a preoperative intact lateral femoral wall. We therefore investigated the two implants in the subgroup of PTF with a fractured greater trochanter.

Materials and Methods: Six hundred thirty-five consecutive patients with PTF fixated by a short IMHS or by a DHS mounted on a four hole lateral plate were prospectively included between 2002 and 2008. The fractures were preoperatively classified according to AO/OTA classification system, including status of the greater and lesser trochanter. The integrity of the lateral femoral wall, fracture reduction and implant positioning were assessed postoperatively. Reoperations due to technical failures were recorded for one year.

Results: Among the 311 patients sustaining a PTF with a fractured greater trochanter, 4% (6/158) operated with an IMHS were reoperated compared to 14% (22/153) with a DHS (p=0.001). Multivariate logistic regression analysis combining demographic and biomechanical parameters showed the IMHS to have a lower rate of reoperation (p=0.002).

During the operative procedure, the lateral femoral wall was fractured in 6% (9/158) of patients, in which an IMHS was performed versus 28% (42/153) operated with a DHS (p< 0.001). Among the DHS, a fractured lateral femoral wall was confirmed to be a predictor of a reoperation (31% (13/42) of patients with a fractured lateral femoral wall versus 8% (9/111) with an intact lateral femoral wall, p< 0.001).

As in other studies, the different reoperation rate would have been overseen in the main group of AO/ OTA type 31A1-2 PTF fractures (4% (6/164) IMHS versus 6% (30/471) DHS, p=0.196).

Conclusion: The IMHS seems to have a lower reoperation rate than the DHS in the subgroup of PTF with a fractured greater trochanter. In contrast to the DHS, the IMHS presumably keeps the integrity of the lateral femoral wall. In future studies, PTF should be divided into subgroups.


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_II | Pages 307 - 307
1 May 2010
Palm H Krasheninnikoff M Holck K Lemser T Foss N Kehlet H Jacobsen S Sonneholm S Gebuhr P
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Introduction: We derived an exhaustive operative and supervision guideline for the treatment of hip fractures from the current international and own published literature, and implemented the guidelines in our department.

Methods: 1274 unselected consecutive patients admitted with a hip fracture were included, 336 of these prospectively after implementation of the new guideline. Demographic parameters, hospital treatment and re-operations were assessed from patient journals. Re-operations were recorded after six months.

Results: 95% (320/336) of operative procedures were found to have followed the new guideline treatment compared to 78% (733/938) prior to its introduction (p< 0.001 X2). Retrospectively we found that only 12% (121/1053) of operative procedures performed as the new guideline prescribes were re-operated compared to 24% (53/221) of operative procedures performed with other methods (p< 0.001 X2). In logistic regression analysis combining sex, age, ASA score, cognitive function, new mobility score, time from admission to operation and level of surgeon’s experience, not following the guideline was the only significant predictor for re-operation (p< 0.001 log. reg.)

After implementing the guideline, the rate of unsupervised junior registrars performing operations declined from 20% (188/938) to 6% (21/336, p< 0.001 X2). The rate of reoperations declined from 15% (139/938) to 10% (35/336, p=0.044 X2, p=0.043 log.reg.), with a 20% (85/436) to 13% (23/174) decline for intracapsulary and an 11% (54/502) to 7% (12/162) decline for extracapsulary fractures.

Conclusion: An exhaustive operative guideline for hip fracture treatment can be implemented. In our case, the guideline both raised the rate of supervision and reduced the rate of reoperations.


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_II | Pages 357 - 357
1 May 2010
Gosvig K Jacobsen S Sonne-holm S Palm H Magnusson E
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Introduction: Cam-type femoroacetabular impingement (FAI) is a pre-osteoarthritic condition causing premature joint degeneration. Cam-deformities are characterised by decreased cranial offset of the femoral head/neck junction and aspherity of the femoral head causing delamination of the acetabular cartilage and detachment of the acetabular labrum. To asses the epidemiological aspects of cam-type FAI we evaluated Nötzlis alpha angle and our own Triangular Index (TI) for use on plain AP pelvic radiographs.

Materials and Methods: Cam malformation was assessed in 2.803 pelvic radiographs by the alpha (α) angle and the TI to define pathological cut off values. The α-angle and TI were assessed in AP and lateral hip radiographs of 164 patients scheduled for THR and the influence of varying rotation on the α-angle and TI was assessed in femoral specimens. The distribution of Cam-deformities was assessed in 3.712 standardized AP pelvic radiographs using the α-angle and TI.

Results: Mean AP α-angle male/female was 55°/45°. The α-angle and TI was highly interrelated, OR 8.6–35 (p< 0.001). Almost all cam-malformations were identifiable in AP projections, sensitivity 88–94% compared to axial view. The TI proved robust for cam identification during rotation (± 20°) compared to the α-angle (−10° to +20°). The distribution of pathologic TI and α-angle (Right/Left) were 11.6/12.5% and 6.1/7.4% in males and 2.2/3.2% and 2.1/3.8% in females. We found a pronounced sexrelated difference in cam-deformity distribution, OR 2.0–6.3 (p< 0.001).

Conclusion: The triangular index and the α-angle were found reliable for epidemiological purpose. Overall prevalence of definite cam-deformity was app. 10% in men and 2,5% in women.


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_II | Pages 338 - 338
1 May 2010
Bencke J Curtis D Jacobsen S Munk K Bandholm T
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Introduction: Single leg hop for distance is a test often used as a measure of knee performance and stability during rehabilitation after knee surgery or injury. Both distance hopped and qualitative assessment of stability in landing is widely used as parameters of knee joint control. While hop distance is reported as highly reliable, no investigations have studied the reliability of the biomechanical parameters expressing the quality of the landing after a single leg hop. The aim of the present study was to investigate the reliability of hop distance and biomechanical landing parameters during a single leg hop test.

Methods: The study was designed as an intra-tester, inter-day test-retest reliability study. Fourteen (7 males, 7 females) physically active, healthy subjects volunteered to participate. The subjects performed 5 maximal single leg hops for distance including 2 trial jumps, and the mean of the last 3 hops was used for analysis. The test session was repeated after 1 week. In both sessions the same tester placed markers on the lower body (Helen Hayes model) and the subjects landed after maximal hopping on a force plate. The hops were recorded using an 8 camera Vicon 612 system filming at 200 Hz. Kinematic and kinetic data were calculated using inherent Vicon software. Intraclass Correlation Coefficient (2,1) was used for analysis of reliability on selected kinematic and kinetic knee joint parameters.

Results: The ICC of the maximal hop distance was excellent (0.93, p< 0.001). The reliability of the maximal knee joint flexion during landing was poor and non-significant, and also peak knee extensor moment during landing showed poor reliability (ICC: 0.48, p=0.037). The maximal external knee joint varus moment and the relative eccentric power production of the knee joint in comparison to the hip and ankle joints were moderately reliable (ICC: 0.56, p=0.015, and ICC: 0.64, p=0.005, respectively).

Conclusions: This study shows, that in healthy subjects the reliability of the maximal hop distance is excellent, however the underlying biomechanical parameters controlling the knee joint during landing is only moderately or poorly reliable. This may imply, that the subjects use slightly different strategies during landing from the hop and evaluation of knee joint performance based on landing biomechanics may be done with caution. Future reliability and validation studies of the take-off biomechanics may further reveal if the single leg hop test is reliable and valid as a measure of knee joint performance.


The Journal of Bone & Joint Surgery British Volume
Vol. 91-B, Issue 6 | Pages 797 - 802
1 Jun 2009
Jacobsen S Hansson G Nathorst-Westfelt J

We reviewed the clinical and radiological results of six patients who had sustained traumatic separation of the distal epiphysis of the humerus at birth.

The correct diagnosis was made from plain radiographs and often supplemented with ultrasonography, MRI and arthrography. An orthopaedic surgeon saw two patients within two days of birth, and the other four were seen at between nine and 30 days. The two neonates underwent unsuccessful attempts at closed reduction. In the remaining patients, seen after the age of eight days, no attempt at reduction was made. All six displaced fractures were immobilised in a cast with the elbow at 90° of flexion and the forearm pronated.

When seen at a mean of 58 months (16 to 120) after injury, the clinical and radiological results were excellent in five patients, with complete realignment of the injury. In one patient the forearm lay in slightly reduced valgus with the elbow in full extension.

Traumatic separation of the distal epiphysis of the humerus may be missed on the maternity wards and not diagnosed until after discharge from hospital. However, even when no attempt is made to reduce the displaced epiphysis, a good clinical result can be expected.


Orthopaedic Proceedings
Vol. 91-B, Issue SUPP_I | Pages 87 - 87
1 Mar 2009
Palm H Jacobsen S Sonne-Holm S Krasheninnikoff M Gebuhr P
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Introduction: Re-operations after intertrochanteric fractures (ITF) are often caused by fracture displacement following postoperative mobilisation. The biomechanical complexity of the fracture, implant position, and the patient’s characteristics are known to influence postoperative outcome significantly. We investigated the importance of an intact lateral femoral wall (LFW) for the postoperative displacement after fixation by a sliding compression hip screw (SHS).

Methods: Two hundred and fourteen consecutive patients with ITF fixated by 135° SHS mounted on four hole lateral plates were included between 2002 and 2004. The fractures were preoperatively classified according to the AO/OTA classification system. The status of the greater and lesser trochanter, the integrity of the LFW and implant positioning were assessed postoperatively. Re-operations due to technical failure were recorded for six months.

Results: Only three percent of patients (5/168) with postoperatively intact LFW’s were re-operated within six months, while twenty-two percent (10/46) of patients with fractured LFW’s had been re-operated (p < 0.001). In multivariate logistic regression analyses combining demographic and biomechanical parameters, a compromised LFW was a significant predictor for reoperation (p = 0.010). Seventy-four percent (34/46) of the LFW fractures occurred during the operative procedure itself. Peri-operative LFW fractures only occurred in three percent (3/103) of the AO/OTA type 31A1–A2.1 ITF fractures, compared to thirty-one percent (31/99) of the AO/OTA type 31A2.2–A2.3 fractures (p < 0.001).

Conclusions: A postoperative fractured LFW was found to be the main predictor for reoperation after ITF. Consequently we conclude that patients with pre- or potential postoperative LFW fractures are not treated adequately by SHS. ITF should therefore be classified according to the integrity of the LFW, especially in regard to randomized trials comparing fracture implants.


Orthopaedic Proceedings
Vol. 91-B, Issue SUPP_I | Pages 70 - 70
1 Mar 2009
Sonne-Holm S Jacobsen S Jensen T Hyldstrup L Rovsing H Rovsing H
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Background: The epidemiology of Schmorl nodes is based on post-mortem investigations. The proposed pathogenesis of the focal nodes is a bulging of the disc into the vertebral body depending of the degree of osteoporosis. Secondar peripheral osteophytes are formed at the annular insertion.

Study design: A cross sectional epidemiological study of 4151 participants of the Copenhagen Osteoarthritis Study in 1993 with a 13 years follow with the Roland-Morris (R-MQ) back pain questionnaire.

In 1993 standardized, lateral radiographs of the lumbar spine were recorded and the bone mineral density (BMD) was estimated by digital x-ray radiogrammetry of standardised hand x-rays.

Methods: Statistical correlations were made between Schmorl nodes and low back pain in 1993, the R-MQ score, BMD and the presence of osteophytes, disc degeneration and endplate sclerosis.

Results: There were 2610 women and 1538 men. At follow up 1190 women and 674 responded. In 196 cases one or more Schmorl nodes in the lumbar spine were found (women 3.7 %, men 6.5 %). A decreasing prevalence of Schmorl nodes by ages was found in both genders (p< 0.000). At the time of the radiographic examination participants with Schmorl nodes clamed of low back pain (p=0.003). The presence of nodes was without relation to osteophytosis, intervertebral disc degeneration or sclerosis of endplates (p> 0.14) in 1993. Neither was the R-MQ score at follow-up related to Schmorls nodes(p> 0.26). The presence of nodes was associated with higher BMD (mean 0.50 (SD 0.079) versus 0.53 (SD 0.081)(p=0.000), however the difference disappeared taking into account age at examination.

Conclusion: This large scaled epidemiological study cannot confirm the hitherto hold opinion of the implication of the Schmorls nodes. The nodes are not associated with radiological degeneration and osteoporosis neither are they a predictor of lower back pain later in life.


Orthopaedic Proceedings
Vol. 91-B, Issue SUPP_I | Pages 153 - 153
1 Mar 2009
Jacobsen S Jensen T Bach-Mortensen P Sonne-Holm S Hyldstrup L
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Background/Objective: Since estrogen receptors (ERα/ERβ) were identified in human chondrocytes, animal-and experimental studies have demonstrated the importance of continued estrogen production for the integrity of articular cartilage. However, human epidemiological support of the hypothesis has been inconclusive. The present study investigated the relationship between reduced bone mineral densities (BMD), as a surrogate parameter of endogenous estrogen status – assessed by digital x-ray radiogrammetry (DXR), and reduced minimum hip joint space width (JSW).

Methods: Standardised hand radiographs of the Copenhagen Osteoarthritis Study cohort of 3.913 adults (1.470M/2.443F) with a mean age of 60 years (range, 18–92), were analysed by the X-Posure digital software v. 2.0 (Sectra-Pronosco). The system is operator independent. From 1.200 individual measurements per radiograph mean BMD was calculated. Minimum hip joint JSW was assessed in standardized, pelvic radiographs.

Results: DXR-BMD decreased in both men and women after the age of 45 years, progressively more so in women. While minimum hip JSW in men remained relatively unaltered throughout life, a marked decline in female minimum hip JSW after 45 years was observed. We found moderate, but highly significant relationships between reduced BMD and reduced hip JSW in women (p < 0.001), adjusted for age and dysplastic joint incongruity.

Conclusion: We believe that the present study supports the hypothetical relationship between reduced estrogen levels and hip joint space width reduction in women.


The Journal of Bone & Joint Surgery British Volume
Vol. 89-B, Issue 10 | Pages 1309 - 1316
1 Oct 2007
Gosvig KK Jacobsen S Palm H Sonne-Holm S Magnusson E

Femoroacetabular cam impingement is thought to be a cause of premature osteoarthritis of the hip.

The presence of cam malformation was determined in 2803 standardised anteroposterior (AP) pelvic radiographs from the Copenhagen Osteoarthritis Study by measuring the alpha (α) angle and the triangular index, a new measure of asphericity of the femoral head. In addition, the α-angle and the triangular index were assessed on the AP and lateral hip radiographs of 82 men and 82 women randomly selected from patients scheduled for total hip replacement (THR). The influence of varying femoral rotation on the α angle and the triangular index was also determined in femoral specimens under experimental conditions.

From the 2803 radiographs the mean AP α-angle was 55° (30° to 100°) in men and 45° (34° to 108°) in women. Approximately 6% of men and 2% of women had cam malformation. The α-angle and triangular index were highly inter-related. Of those patients scheduled for THR, 36 men (44%) and 28 women (35%) had cam malformation identifiable on the AP radiographs. The triangular index proved to be more reliable in detecting cam malformation when the hip was held in varying degrees of rotation.

The combination of the α-angle and the triangular index will allow examination of historical radiographs for epidemiological purposes in following the natural history of the cam deformity.


The Journal of Bone & Joint Surgery British Volume
Vol. 87-B, Issue 4 | Pages 471 - 477
1 Apr 2005
Jacobsen S Sonne-Holm S Søballe K Gebuhr P Lund B

In a longitudinal case-control study, we followed 81 subjects with dysplasia of the hip and 136 control subjects without dysplasia for ten years assessing radiological evidence of degeneration of the hip at admission and follow-up. There were no cases of subluxation in the group with dysplasia. Neither subjects with dysplasia nor controls had radiological signs of ongoing degenerative disease at admission. The primary radiological discriminator of degeneration of the hip was a change in the minimum joint space width over time. There were no significant differences between these with dysplasia and controls in regard to age, body mass index or occupational exposure to daily repeated lifting at admission.

We found no significant differences in the reduction of the joint space width at follow-up between subjects with dysplasia and the control subjects nor in self-reported pain in the hip. The association of subluxation and/or associated acetabular labral tears with dysplasia of the hip may be a conditional factor for the development of premature osteoarthritis in mildly to moderately dysplastic hips.