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Bone & Joint Research
Vol. 11, Issue 7 | Pages 484 - 493
13 Jul 2022
Hayer S Niederreiter B Kalkgruber M Wanic K Maißner J Smolen JS Aletaha D Blüml S Redlich K

Aims. Insufficient treatment response in rheumatoid arthritis (RA) patients requires novel treatment strategies to halt disease progression. The potential benefit of combination of cytokine-inhibitors in RA is still unclear and needs further investigation. To explore the impact of combined deficiency of two major cytokines, namely interleukin (IL)-1 and IL-6, in this study double deficient mice for IL-1αβ and IL-6 were investigated in different tumour necrosis factor (TNF)-driven inflammatory bone disorders, namely peripheral arthritis and sacroiliitis, as well as systemic bone loss. Methods. Disease course, histopathological features of arthritis, and micro-CT (µCT) bone analysis of local and systemic bone loss were assessed in 15-week-old IL1-/-IL6-/-hTNFtg in comparison to IL1-/-hTNFtg, IL6-/-hTNFtg, and hTNFtg mice. µCT bone analysis of single deficient and wild-type mice was also performed. Results. Combined deficiency of IL-1/IL-6 markedly ameliorated TNF-mediated arthritis and bilateral sacroiliitis, but without additive benefits compared to single IL-1 deficiency. This finding confirms the important role of IL-1 and the marginal role of IL-6 in TNF-driven pathways of local joint damage, but questions the efficacy of potential combinatorial therapies of IL-1 and IL-6 in treatment of RA. In contrast, combined deficiency of IL-1/IL-6 led to an additive protective effect on TNF-driven systemic bone loss compared to single IL-1 and IL-6 deficiency. This finding clearly indicates a common contribution of both IL-1 and IL-6 in TNF-driven systemic bone loss, and points to a discrepancy of cytokine dependency in local and systemic TNF-driven mechanisms of inflammatory arthritis. Conclusion. Combinatorial treatments in RA might provide different benefits to inflammatory local arthritis and systemic comorbidities. Cite this article: Bone Joint Res 2022;11(7):484–493


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_7 | Pages 53 - 53
4 Apr 2023
Hipps D Dobson P Warren C Russell O Turnbull D Deehan D Lawless C
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We have developed a novel technique to analyse bone, using imaging mass cytometry (IMC) without the constraints of using immunofluorescent histochemistry. IMC can measure the expression of over 40 proteins simultaneously, without autofluorescence. We analysed mitochondrial respiratory chain (RC) protein deficiencies in human bone which are thought to contribute to osteoporosis with increasing age. Osteoporosis is characterised by reduced bone mineral density (BMD) and fragility fractures. Humans accumulate mitochondrial mutations and RC deficiency with age and this has been linked to the changing phenotype in advancing age and age-related disease. Mitochondrial mutations are detectable from the age of 30 onwards, coincidently the age BMD begins to decline. Mitochondria contain their own genome which accumulates somatic variants at around 10 times the rate of nuclear DNA. Once these mutations exceed a threshold, RC deficiency and cellular dysfunction occur. The PolgD257A/D257A mouse model expresses a proof-reading deficient version of PolgA, a mtDNA polymerase. These mice accumulate mutations 3-5 times higher than wild-type mice showing enhanced levels of age-related osteoporosis and RC deficiency in osteoblasts. Bone samples were analysed from young and old patients, developing a protocol and analysis framework for IMC in bone tissue sections to analyse osteoblasts in-situ for RC deficiency. Samples from the femoral neck of 10 older healthy volunteers aged 40 – 85 were compared with samples from young patients aged 1-19. We have identified RC complex I defect in osteoblasts from 6 of the older volunteers, complex II defects in 2 of the older volunteers, complex IV defect in just 1 older volunteer, and complex V defect in 4 of the older volunteers. These observations are consistent with the PolgD257A/D257A mouse-model and suggest that RC deficiency, due to age-related pathogenic mitochondrial DNA mutations, may play a significant role in the pathogenesis of human age-related osteoporosis


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_18 | Pages 2 - 2
1 Dec 2023
Basheer S Kwaees T Tang C Ali F Haslam P Nicolaou N
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Objectives. Congenital cruciate ligament deficiency is a rare condition that may occur in isolation or in association with longitudinal limb deficiencies such as fibular hemimelia or proximal femoral focal deficiency. Often anomalies of the menisci and their attachments can be very abnormal and impact on surgical management by standard techniques. Arthroscopic surgical knee reconstruction is undertaken to improve symptomatic instability and/or to stabilise and protect the knee for future planned limb lengthening surgery. The aim of this study is to evaluate the arthroscopic findings of patients undergoing surgery for congenital cruciate ligament deficiency, and specifically to determine the frequency and types of meniscal anatomical variations seen in these cases. Methods. Patients undergoing surgery for congenital cruciate ligament deficiency were identified from a prospectively collated database. Diagnosis was confirmed through review of the clinical notes and imaging. Operative notes and 4K saved arthroscopic images and video recordings for these cases were reviewed. Results. Over a six-year period (July 2017 – September 2023), 42 patients underwent surgery for congenital ligament deficiency and tibiofemoral instability (45 surgical episodes). Median age of patients at time of surgery was 10 years (range 4 – 17 years). The most frequent diagnosis was congenital longitudinal limb deficiency syndromes in 27 cases, with the most frequent being fibular hemimelia. Isolated congenital ligament deficiency without any other associated extra-articular manifestations occurred in 11 cases. Absence of meniscal root attachments or hypertrophy of meniscofemoral ligaments acting as ‘pseudo-cruciates’ were seen in over 25% of patients. In isolated ACL deficiency these were injured causing onset of instability symptoms and pain following trauma. Often these abnormal structures required addressing to allow surgical reconstruction. Conclusions. Our findings demonstrate that there are often meniscal variations seen in association with congenital absence or hypoplasia of the cruciate ligaments. In these patients hypertrophied meniscofemoral ligaments may act as cruciate-like structures and play a role in providing a degree of sagittal plane stability to the knee. However, when the knee becomes unstable to the point that cruciate ligament reconstruction is indicated, these meniscal variants may often require stabilisation using complex meniscal root repair techniques or variations to standard cruciate ligament reconstruction techniques to accommodate the variant anatomy


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_14 | Pages 5 - 5
10 Oct 2023
Bayram J Kanesan H Clement N
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The aims were to assess whether vitamin D deficiency influenced mortality risk for patients presenting with a hip fracture. A retrospective study was undertaken including all patients aged over 50 years that were admitted with a hip fracture to a single centre during a 24-month period. Serum vitamin D levels were assessed. Patient demographics and perioperative variables and mortality were collected. Cox regression analysis (adjusting for confounding) was utilised to determine the independent association between serum vitamin D level and patient mortality. The cohort consisted of 2075 patients with a mean age of 80.7 years and 1471 (70.9%) were female. 1510 (72.8%) patients had a serum vitamin D level taken, of which 876 (58.0%) were deficient (<50nmol/l). The median follow up was 417 (IQR 242 to 651) days. During follow up there were 464 (30.7%) deaths. Survival at 1 year was significantly (p = 0.003) lower for patients who were vitamin D deficient (71.7%, 95% confidence intervals (CI) 68.6 to 74.9) compared to those who were not (79.0%, 95% CI 75.9 to 82.3). Vitamin D deficiency was also independently associated with an increased mortality risk at 2-years (HR 1.42, 95% CI 1.17 to 1.71, p = 0.03), but not at 1-year (p = 0.08). Hip fracture patients with vitamin D deficiency had an increased mortality risk. This risk was independent of confounders at 2 years. The role of measuring vitamin D levels in these patients is unclear. Improved public health policy about vitamin D may be required to reduce deficiency in this patient population


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_6 | Pages 3 - 3
2 May 2024
Bayram JM Kanesan H Clement N
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The aims were to assess whether vitamin D deficiency influenced mortality risk for patients presenting with a hip fracture. A retrospective study was undertaken including all patients aged over 50 years that were admitted with a hip fracture to a single centre during a 24-month period. Serum vitamin D levels were assessed. Patient demographics and perioperative variables and mortality were collected. Cox regression analysis (adjusting for confounding) was utilised to determine the independent association between serum vitamin D level and patient mortality. The cohort consisted of 2075 patients with a mean age of 80.7 years and 1471 (70.9%) were female. 1510 (72.8%) patients had a serum vitamin D level taken, of which 876 (58.0%) were deficient (50nmol/l). The median follow up was 417 (IQR 242 to 651) days. During follow up there were 464 (30.7%) deaths. Survival at 1 year was significantly (p=0.003) lower for patients who were vitamin D deficient (71.7%, 95% confidence intervals (CI) 68.6 to 74.9) compared to those who were not (79.0%, 95% CI 75.9 to 82.3). Vitamin D deficiency was also independently associated with an increased mortality risk at 2-years (HR 1.25, 95% CI 1.03 to 1.53, p=0.025), but not at 1-year (p=0.057). Hip fracture patients with vitamin D deficiency had an increased mortality risk. This risk was independent of confounders at 2 years. The role of measuring vitamin D levels in these patients is unclear. Improved public health policy about vitamin D may be required to reduce deficiency in this patient population


Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_11 | Pages 22 - 22
1 Nov 2022
Tolat A Salam NA Gavai P Desai V
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Abstract. Introduction. Vitamin D deficiency in the UK is well documented − 30–40% of the population. It is an essential component of calcium metabolism and adequate levels are important for bone healing. Studies have demonstrated an overall prevalence of vitamin D deficiency/insufficiency at 77% in trauma patients aged >18, deficiency alone was 39%. Adequate vitamin D levels have a positive effect on bone mineral density and callus formation at fracture sites. Methods. We conducted a retrospective consecutive case series of all patients aged 0–50 undergoing surgical management for any fracture in October 2021 to March 2022. We assessed if vitamin D levels were checked and if patients were prescribed replacement as per local guidelines. Results. A total of 131 patients were identified, (mean 29 years; 83 male and 48 female). Most cases were upper limb fractures (n=78, 60%), as opposed to lower limb (n=53, 40%). Only 20 (15%) had their levels checked, of which 13 (65%) were insufficient/deficient (10 insufficiency, 2 deficiency, 1 severe deficiency). Of these 13 patients, only 3 (23%) were prescribed replacement therapy. Conclusions. Only a small proportion of patients had their levels checked, however the majority were insufficient/deficient. The prevalence in our study is consistent with larger epidemiology studies, which reflect a higher rate of deficiency in fracture patients compared to the general population. Thus, we propose that all patients in this age group should undergo a vitamin d level check upon time of clerking and this should be accurately treated as per trust guidance


The Bone & Joint Journal
Vol. 102-B, Issue 11 | Pages 1555 - 1559
1 Nov 2020
Sebastia-Forcada E Lizaur-Utrilla A Mahiques-Segura G Ruiz-Lozano M Lopez-Prats FA Alonso-Montero C

Aims. The purpose of this study was to determine whether there were long-term differences in outcomes of reverse shoulder arthroplasty (RSA) undertaken for acute proximal humeral fracture versus rotator cuff deficiency with a minimum follow-up of five years. Methods. This was a prospective cohort study comparing 67 patients with acute complex proximal humeral fracture and 64 patients with irreparable rotator cuff deficiency who underwent primary RSA. In the fracture group, there were 52 (77.6%) females and 15 (22.4%) males, with a mean age of 73.5 years (51 to 85), while in the arthropathy group, there were 43 (67.1%) females and 21 (32.9%) males, with a mean age of 70.6 years (50 to 84). Patients were assessed by the Constant score, University of California Los Angeles shoulder score (UCLA), short version of the Disability of the Arm Shoulder and Hand score (QuickDASH), and visual analogue scales (VAS) for pain and satisfaction. Radiological evaluation was also performed. Results. Mean follow-up was 8.4 years (5 to 11). There were no significant differences in mean absolute (p = 0.125) or adjusted (p = 0.569) Constant, UCLA (p = 0.088), QuickDASH (p = 0.135), VAS-pain (p = 0.062), or range of movement at the final follow-up. However, patient satisfaction was significantly lower in the fracture group (p = 0.002). The complication rate was 1.5% (one patient) versus 9.3% (six patients), and the revision rate was 1.5% (one patient) versus 7.8% (five patients) in the fracture and arthropathy groups, respectively. The ten-year arthroplasty survival was not significantly different (p = 0.221). Conclusion. RSA may be used not only for patients with irreparable rotator cuff deficiencies, but also for those with acute complex proximal humeral fractures. We found that RSA provided similar functional outcomes and a low revision rate for both indications at long-term. However, satisfaction is lower in patients with an acute fracture. Cite this article: Bone Joint J 2020;102-B(11):1555–1559


The Bone & Joint Journal
Vol. 95-B, Issue 3 | Pages 343 - 347
1 Mar 2013
Odak S Ivory J

Deficiency of the abductor mechanism is a well-recognised cause of pain and limping after total hip replacement (THR). This can be found incidentally at the time of surgery, or it may arise as a result of damage to the superior gluteal nerve intra-operatively, or after surgery owing to mechanical failure of the abductor muscle repair or its detachment from the greater trochanter. The incidence of abductor failure has been reported as high as 20% in some studies. The management of this condition remains a dilemma for the treating surgeon. We review the current state of knowledge concerning post-THR abductor deficiency, including the aetiology, diagnosis and management, and the outcomes of surgery for this condition. Cite this article: Bone Joint J 2013;95-B:343–7


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_15 | Pages 53 - 53
1 Dec 2021
Osinga R Eggimann M Lo S Kühl R Lunger A Ochsner PE Sendi P Clauss M Schaefer D
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Aim. Reconstruction of composite soft-tissue defects with extensor apparatus deficiency in patients with periprosthetic joint infection (PJI) of the knee is challenging. We present a single-centre multidisciplinary orthoplastic treatment concept based on a retrospective outcome analysis over 20 years. Method. One-hundred sixty-seven patients had PJI after total knee arthroplasty. Plastic surgical reconstruction of a concomitant perigenicular soft-tissue defect was indicated in 49 patients. Of these, seven presented with extensor apparatus deficiency. Results. One patient underwent primary arthrodesis and six patients underwent autologous reconstruction of the extensor apparatus. The principle to reconstruct missing tissue ‘like with like’ was thereby favoured: Two patients with a wide soft-tissue defect received a free anterolateral thigh flap with fascia lata; one patient with a smaller soft-tissue defect received a free sensate, extended lateral arm flap with triceps tendon; and three patients received a pedicled medial sural artery perforator gastrocnemius flap, of which one with Achilles tendon. Despite good functional results 1 year later, long-term follow-up revealed that two patients had to undergo knee arthrodesis because of recurrent infection and one patient was lost to follow-up. In parts, results have been published under doi: 10.7150/jbji.47018. Conclusions. A treatment concept and its rationale, based on a single-centre experience, is presented. It differentiates between various types of soft-tissue defects and shows reconstructive options following the concept to reconstruct ‘like with like’. Despite good results 1 year postoperatively, PJI of the knee with extensor apparatus deficiency remains a dreaded combination with a poor long-term outcome


The Journal of Bone & Joint Surgery British Volume
Vol. 94-B, Issue 12 | Pages 1666 - 1669
1 Dec 2012
Gulotta LV Choi D Marinello P Wright T Cordasco FA Craig EV Warren RF

Reverse total shoulder replacement (RTSR) depends on adequate deltoid function for a successful outcome. However, the anterior deltoid and/or axillary nerve may be damaged due to prior procedures or injury. The purpose of this study was to determine the compensatory muscle forces required for scapular plane elevation following RTSR when the anterior deltoid is deficient. The soft tissues were removed from six cadaver shoulders, except for tendon attachments. After implantation of the RTSR, the shoulders were mounted on a custom-made shoulder simulator to determine the mean force in each muscle required to achieve 30° and 60° of scapular plane elevation. Two conditions were tested: 1) Control with an absent supraspinatus and infraspinatus; and 2) Control with anterior deltoid deficiency. Anterior deltoid deficiency resulted in a mean increase of 195% in subscapularis force at 30° when compared with the control (p = 0.02). At 60°, the subscapularis force increased a mean of 82% (p < 0.001) and the middle deltoid force increased a mean of 26% (p = 0.04). Scapular plane elevation may still be possible following an RTSR in the setting of anterior deltoid deficiency. When the anterior deltoid is deficient, there is a compensatory increase in the force required by the subscapularis and middle deltoid. Attempts to preserve the subscapularis, if present, might maximise post-operative function


Bone & Joint Research
Vol. 11, Issue 8 | Pages 528 - 540
1 Aug 2022
Dong W Postlethwaite BC Wheller PA Brand D Jiao Y Li W Myers LK Gu W

Aims. This study investigated the effects of β-caryophyllene (BCP) on protecting bone from vitamin D deficiency in mice fed on a diet either lacking (D-) or containing (D+) vitamin D. Methods. A total of 40 female mice were assigned to four treatment groups (n = 10/group): D+ diet with propylene glycol control, D+ diet with BCP, D-deficient diet with control, and D-deficient diet with BCP. The D+ diet is a commercial basal diet, while the D-deficient diet contains 0.47% calcium, 0.3% phosphorus, and no vitamin D. All the mice were housed in conditions without ultraviolet light. Bone properties were evaluated by X-ray micro-CT. Serum levels of klotho were measured by enzyme-linked immunosorbent assay. Results. Under these conditions, the D-deficient diet enhanced the length of femur and tibia bones (p < 0.050), and increased bone volume (BV; p < 0.010) and trabecular bone volume fraction (BV/TV; p < 0.010) compared to D+ diet. With a diet containing BCP, the mice exhibited higher BV and bone mineral density (BMD; p < 0.050) than control group. The trabecular and cortical bone were also affected by vitamin D and BCP. In addition, inclusion of dietary BCP improved the serum concentrations of klotho (p < 0.050). In mice, klotho regulates the expression level of cannabinoid type 2 receptor (Cnr2) and fibroblast growth factor 23 (Fgf23) through CD300a. In humans, data suggest that klotho is connected to BMD. The expression of klotho is also associated with bone markers. Conclusion. These data indicate that BCP enhances the serum level of klotho, leading to improved bone properties and mineralization in an experimental mouse model. Cite this article: Bone Joint Res 2022;11(8):528–540


Orthopaedic Proceedings
Vol. 96-B, Issue SUPP_17 | Pages 32 - 32
1 Nov 2014
Ball T Readman H Kendal A Rogers M Sharp R Lavis G Cooke P
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Introduction:. Vitamin D plays an important role in bone turnover. Deficiency (including borderline deficiency, or insufficiency) has a known association with fractures and has been linked to delayed or nonunion of fractures. We therefore routinely test vitamin D in cases of nonunion. Noting a high rate of vitamin D deficiency in this group, we instituted a policy to routinely screen for and treat vitamin D deficiency in both post-operative and pre-operative patients. We hypothesised that, in the post-operative patients, levels would correlate with rates of union. Methods:. We sent serum vitamin D levels on consecutive post-operative patients seen in clinics between January and May 2014. They included those with an arthrodesis of the ankle, triple joint or first MTPJ. Union was deemed to have occurred when the patient was comfortable full weight bearing and radiographs showed trabeculae crossing the fusion site. Nonunions were all confirmed with computed tomography. Results:. Ten patients were treated for nonunion, and had a mean serum vitamin D of 58nmol/L. Fourteen patients (collected over a shorter time period) had confirmed union, with a mean vitamin D of 90nmol/L. This was statistically significant on a one tailed Student's t test (p=0.038). Vitamin D was deficient in five (50%) of nonunions and in three (21%) of unions, giving an odds ratio of 3.67. Conclusions:. Our early results show a significant association of serum vitamin D levels with likelihood of nonunion, and we continue to collect data. There is a high prevalence of vitamin D deficiency in our patient population. This is of concern both for the outcome of their surgery and for their lifetime fracture risk. We recommend either screening for or presumptively treating vitamin D deficiency


Orthopaedic Proceedings
Vol. 98-B, Issue SUPP_22 | Pages 46 - 46
1 Dec 2016
Engh C
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Abductor deficiency commonly contributes to total hip dislocation. Successful treatment of the deficiency can improve function, decrease pain, and decrease reliance on implants to cure recurrent dislocation. The defining physical exam findings are dependence on ambulatory assistive devices, severe limp, positive Trendelenberg sign, and inability to abduct against gravity. Three techniques have been described for chronic abductor discontinuity in which the abductors have retracted or are absent and cannot reach the greater trochanter: Vastus lateralis muscle shift, Achilles tendon allograft, and gluteus maximus muscle transfer. None of the techniques were specifically performed for dislocation. The vastus lateralis shift transfers the entire muscle proximally maintaining the neurovascular bundle. The procedure requires an incision from the hip to the knee, isolation of the neurovascular bundle, and elevation of the muscle from the femur. The authors admitted that the technique is demanding and not easily applicable to many surgeons. Repair with an Achilles allograft requires an identifiable contractile abductor mass. The allograft is looped through the abductors to bridge the gap to the trochanter. Two variations of a gluteus muscle transfer for abductor deficiency after total hip have been described. A portion of the gluteus maximus with its distal fascial portion are transferred to the greater trochanter. As far as dislocation is concerned an advantage of this technique is the use of the posterior maximus flap to fill a posterior and superior capsular defect not addressed with the other techniques. In addition the technique is easy to perform in almost all cases


Proximal femoral focal deficiency is a congenital disorder of malformation of the proximal femur and/or the acetabulum. Patients present with limb length discrepancy and clinical features along a spectrum of severity. As these patients progress through to skeletal maturity and on to adulthood, altered biomechanical demands lead to progression of arthropathy in any joint within the lower limb. Abnormal anatomy presents a challenge to surgeons and conventional approaches and implants may not necessarily be applicable. We present a case of a 62-year-old lady with unilateral proximal femoral focal deficiency (suspected Aitken Class A) who ambulated with an equinus prosthesis for her entire life. She presented with ipsilateral knee pain and instability due to knee arthritis but could not tolerate a total knee arthroplasty due to poor quadriceps control. A custom osteointegration prosthesis was inserted with a view to converting to the proximal segment to a total hip replacement if required. The patient went on to develop ipsilateral symptomatic hip arthritis but altered acetabular anatomy required a custom tri-flange component (Ossis, Christchurch, New Zealand) and a custom proximal femoral component to link with the existing osseointegration component (Osseointegration Group of Australia, Sydney, Australia) were designed and implanted. The 18 month follow up of the custom hip components showed that the patient had Oxford hip scores that were markedly improved from pre-operatively. Knee joint heights were successfully restored to equal when the patient's prosthesis was attached. The patient describes feeling like “a normal person”, walks unaided for short distances and can ambulate longer distances with crutches. Advances in design and manufacture of implants have empowered surgeons to offer life improving treatments to patients with challenging anatomy. Using a custom acetabular tri-flange and osseointegration components is one possible solution to address symptomatic ipsilateral hip and knee arthropathy in the context of PFFD in adulthood


Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_14 | Pages 78 - 78
1 Nov 2018
Geoghegan I Hoey D McNamara L
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The expression of the mechanosensor, integrin αvβ3, is reduced in osteoporotic bone cells compared to controls. MLO-Y4 osteocytes experience altered mechanotransduction under estrogen deficiency and it is unknown whether this is associated with defective αvβ3 expression or signalling. The objectives of this study are to (1) investigate αvβ3 expression and spatial organisation in osteocytes during estrogen deficiency, and (2) establish whether altered responses of osteocytes under estrogen deficiency correlate to defective αvβ3 expression and functionality. MLO-Y4 cells were cultured as follows: Ctrl (no added estradiol), E+ (10nM 17β-estradiol for 5 days), and Ew (10nM 17β-estradiol for 3 days and withdrawal for 2 days). Cells were cultured with/without 0.5µM IntegriSense750 (αvβ3 antagonist). Laminar oscillatory fluid flow of 1Pa at 0.5Hz was applied for 1hr. αvβ3 content was quantified using an ELISA. The location and quantity of αvβ3 and focal-adhesions was determined by immunocytochemistry. Estrogen withdrawal under static conditions led to lower cell and focal-adhesion area (p<0.05), compared to E+ cells. Fluid flow led to higher αvβ3 content (p<0.05) in all groups, compared to static counterparts, with αvβ3 blocking altering this response. Fluid flow on Ew cells had the highest αvβ3 levels (p<0.05), but αvβ3 did not localise at focal-adhesions sites. Cell morphologies were similar after treatment with the αvβ3 antagonist to the Ew group. These results suggest there are fewer functional focal-adhesion sites at which αvβ3 integrins localise to facilitate mechanotransduction. To further understand these results, we are analysing osteocyte mechanotransduction by quantifying PGE2 and gene expression (COX-2, RANKL, OPG, SOST)


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_8 | Pages 6 - 6
11 Apr 2023
Kronenberg D Everding J Wendler L Brand M Timmen M Stange R
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Integrin α2β1 is one of the major transmembrane receptors for fibrillary collagen. In native bone we could show that the absence of this protein led to a protective effect against age-related osteoporosis. The objective of this study was to elucidate the effects of integrin α2β1 deficiency on fracture repair and its underlying mechanisms. Standardised femoral fractures were stabilised by an intramedullary nail in 12 week old female C57Bl/6J mice (wild type and integrin α2. -/-. ). After 7, 14 and 28 days mice were sacrificed. Dissected femura were subjected to µCT and histological analyses. To evaluate the biomechanical properties, 28-day-healed femura were tested in a torsional testing device. Masson goldner staining, Alizarin blue, IHC and IF staining were performed on paraffin slices. Blood serum of the animals were measured by ELISA for BMP-2. Primary osteoblasts were analysed by in/on-cell western technology and qRT-PCR. Integrin α2β1 deficient animals showed earlier transition from cartilaginous callus to mineralized callus during fracture repair. The shift from chondrocytes over hypertrophic chondrocytes to bone-forming osteoblasts was accelerated. Collagen production was increased in mutant fracture callus. Serum levels of BMP-2 were increased in healing KO mice. Isolated integrin deficient osteoblast presented an earlier expression and production of active BMP-2 during the differentiation, which led to earlier mineralisation. Biomechanical testing showed no differences between wild-type and mutant bones. Knockout of integrin α2β1 leads to a beneficial outcome for fracture repair. Callus maturation is accelerated, leading to faster recovery, accompanied by an increased generation of extra-cellular matrix material. Biomechanical properties are not diminished by this accelerated healing. The underlying mechanism is driven by an earlier availability of BMP-2, one main effectors for bone development. Local inhibition of integrin α2β1 is therefore a promising target to accelerate fracture repair, especially in patients with retarded healing


The Journal of Bone & Joint Surgery British Volume
Vol. 93-B, Issue 11 | Pages 1440 - 1448
1 Nov 2011
Dodds AL Gupte CM Neyret P Williams AM Amis AA

This annotation considers the place of extra-articular reconstruction in the treatment of anterior cruciate ligament (ACL) deficiency. Extra-articular reconstruction has been employed over the last century to address ACL deficiency. However, the technique has not gained favour, primarily due to residual instability and the subsequent development of degenerative changes in the lateral compartment of the knee. Thus intra-articular reconstruction has become the technique of choice. However, intra-articular reconstruction does not restore normal knee kinematics. Some authors have recommended extra-articular reconstruction in conjunction with an intra-articular technique. . The anatomy and biomechanics of the anterolateral structures of the knee remain largely undetermined. Further studies to establish the structure and function of the anterolateral structures may lead to more anatomical extra-articular reconstruction techniques that supplement intra-articular reconstruction. This might reduce residual pivot shift after an intra-articular reconstruction and thus improve the post-operative kinematics of the knee.


The Journal of Bone & Joint Surgery British Volume
Vol. 92-B, Issue 4 | Pages 496 - 499
1 Apr 2010
Nawabi DH Chin KF Keen RW Haddad FS

We measured the plasma 25-hydroxyvitamin D. 3. (25(OH)D. 3. ) levels in 62 consecutive Caucasian patients undergoing total hip replacement for osteoarthritis. The patients were divided into two groups based on whether they were vitamin D sufficient or deficient. The groups were matched for age, gender and the American Society of Anaesthesiologists (ASA) grade. The prevalence of vitamin D deficiency in our patients was comparable with recent population-based studies performed in the United Kingdom. Patients with vitamin D deficiency had lower pre-operative Harris hip scores (Mann-Whitney test, p = 0.018) and were significantly less likely to attain an excellent outcome from total hip replacement (chi-squared test, p = 0.038). Vitamin D levels were found to positively correlate with both pre- and post-operative Harris hip scores. These results warrant further study of vitamin D deficiency in patients undergoing joint replacement as it is a risk factor for a suboptimal outcome which is relatively simple and cheap to correct


The Bone & Joint Journal
Vol. 95-B, Issue 6 | Pages 851 - 854
1 Jun 2013
Madhuri V Arora SK Dutt V

Slipped capital femoral epiphysis (SCFE) is uncommon in India and we routinely look for associated metabolic or endocrine abnormalities. In this study we investigated a possible association between vitamin D deficiency and SCFE. All children presenting with SCFE during the study period had their 25-hydroxyvitamin D levels measured as part of an overall metabolic, renal and endocrine status evaluation, which included measurement of body mass index (BMI). Vitamin D status was compared with age-, gender- and habitat-matched controls with acute trauma or sepsis presenting to our emergency department. A total of 15 children (12 boys and three girls) with a mean age of 13 years (. sd. 1.81; 10 to 16) presented for treatment for SCFE during a two-year period beginning in January 2010. Renal and thyroid function was within the normal range in all cases. The mean BMI was 24.9 kg/m. 2. (17.0 to 33.8), which was significantly higher than that of the controls (p = 0.006). There was a statistically significant difference between the mean values of 25-hydroxyvitamin D in the children with SCFE and the controls (11.78 ng/ml (. sd. 5.4) versus 27.06 ng/ml (. sd. 5.53), respectively; p < 0.001). We concluded that, along with high BMI, there is a significant association of vitamin D deficiency and SCFE in India. Cite this article: Bone Joint J 2013;95-B:851–4


Orthopaedic Proceedings
Vol. 101-B, Issue SUPP_5 | Pages 88 - 88
1 Apr 2019
Smulders K Rensch PV Wymenga A Heesterbeek P Groen B
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Background. The cruciate ligaments are important structures for biomechanical stability of the knee. For total knee arthroplasty (TKA), understanding of the exact function of the (PCL) and anterior (ACL) cruciate ligament during walking is important in the light of recent designs of bicruciate TKAs. However, studies evaluating in vivo function of the PCL during daily activities such as walking are scarce. We aimed to assess the role of the PCL during gait by measuring kinematics and kinetics of individuals with PCL deficiency and compare them with individuals with ACL deficiency and healthy young adults. Methods. Individuals with unilateral PCL deficiency (PCLD; n=9), unilateral ACL deficiency (n=10) and healthy young adults performed (n=10) 10 walk trials (5 for each leg) in which they walked over a force platform. Motion analysis (Vicon Motion Capture System) was used to calculate joint angles and internal moments around the knee, hip and ankle in the sagittal plane. Joint angles and moments of the injured knee (in PCLD and ACLD) or left knee (in HYA) were compared between groups at weight acceptance, mid-stance and push-off phases (see Fig. 1). Clinical assessment included passive knee laxity (Kneelax) for anterior (in 20–30° knee flexion) and posterior tibia translation (in 70–90° knee flexion) and Lysholm questionnaires. Results. Lysholm scores were significantly lower in PCLD and ACLD individuals compared to HYA (p's ≤ .001). PCLD subjects had more passive anterior (p = .001) and posterior tibia translation (p = .041) compared to HYA, but no significant differences were found in both directions between ACLD and HYA (p's > .10). During gait, knee angles at weight acceptance, late stance and around toe-off were not significantly different between the PCLD and HYA, and between ACLD and HYA (all p's > .06). However, the knee extension moment during mid-stance was significantly lower in the PCLD group when compared to the HYA group (p = .001; Fig. 2). Interestingly, the knee moment in the PCLD group remained positive (i.e. extension moment) throughout the stance phase, whereas HYA and ACLD groups created a substantial flexion moment around the knee at this instant. We did not observe any significant differences in hip and ankle joint angles and moments between groups. Discussion. We observed a difference in gait pattern in individuals with PCL deficiency compared to HYA, that was confined to an absence of knee flexion moments during the mid-stance phase. We hypothesize that this difference reflects a compensation strategy employed by individuals with PCL deficiency to avoid external knee (hyper)extension moments. Gait adaptations related to PCL deficiency might also have implications for design of total knee prosthesis and calls for careful evaluation of gait patterns after TKA with a specific focus on the role of the PCL. For any figures or tables, please contact the authors directly