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Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_1 | Pages 30 - 30
2 Jan 2024
Procter P Hulsart-Billström G Alves A Pujari-Palmer M Wenner D Insley G Engqvist H Larsson S Pippenger B Bossard D
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Surgeons treating fractures with many small osteochondral fragments have often expressed the clinical need for an adhesive to join such fragments, as an adjunct to standard implants. If an adhesive would maintain alignment of the articular surfaces and subsequently heal it could result in improved clinical outcomes. However, there are no bone adhesives available for clinical indications and few pre-clinical models to assess safety and efficacy of adhesive biomaterial candidates. A bone adhesive candidate based on water, α-TCP and an amino acid phosphoserine was evaluated in-vivo in a novel murine bone core model (preliminary results presented EORS 2019) in which excised bone cores were glued back in place and harvested @ 0, 3, 7, 14, 28 and 42days. Adhesive pull-out strength was demonstrated 0–28 days, with a dip at 14 days increasing to 11.3N maximum. Histology 0–42 days showed the adhesive progressively remodelling to bone in both cancellous and cortical compartments with no signs of either undesirable inflammation or peripheral ectopic bone formation. These favourable results suggested translation to a large animal model.

A porcine dental extraction socket model was subsequently developed where dental implants were affixed only with the adhesive. Biomechanical data was collected @ 1, 14, 28 and 56 days, and histology at 1,14,28 and 56 days. Adhesive strength assessed by implant pull-out force increased out to 28 days and maintained out to 56 days (282N maximum) with failure only occurring at the adhesive bone interface. Histology confirmed the adhesive's biocompatibility and osteoconductive behavior. Additionally, remodelling was demonstrated at the adhesive-bone interface with resorption by osteoclast-like cells and followed by new bone apposition and substitution by bone. Whilst the in-vivo dental implant data is encouraging, a large animal preclinical model is needed (under development) to confirm the adhesive is capable of healing, for example, loaded osteochondral bone fragments.

Acknowledgements: The murine study was supported, in part, by the Swedish Foundation for Strategic Research (#RMA15-0110).


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_4 | Pages 99 - 99
1 Mar 2021
Procter P Hulsart-Billstrom G Insley G Pujari-Palmer M Wenner D Engqvist H Larsson S
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An ex vivo biomechanical test model for evaluating a novel bone adhesive has been developed. However, at day 1 in the in vivo pilot, high blood flow forced the study to halt until the solution presented here was developed.

The profuse bleeding after bone core removal affected the bond strength and was reflected in the lower mean peak value 1.53N. After considering several options, we were successful in sealing the source of blood flow by pressing adhesive into place after bone core removal. After the initial adhesive had cured additional adhesive was used to secure the bone core in place. The animals were sacrificed after 24 h and a tensile test was undertaken on the bone core to failure.

The ex vivo study produced mean peak tensile loads of 7.63N SD 2.39N (n=8, 4 rats 8 femurs). Whilst the mean peak tensile loads in the day 1 in vivo pilot were significantly lower 1.53N SD1.57 (n=8, 6 rats 8 femurs − 4 used for other tests). The subsequent layered adhesive bone cores showed a mean peak tensile force of 6.79N SD =3.13 (n=8, 4 rats 8 femurs). 7/8 failed at the bone to glue interface. This is the first successful demonstration of bonding bone in vivo for this class of adhesives.

The development of a double adhesive method of fixing a bone core in the distal femur enabled mean peak tensile forces to be achieved in vivo at 24 hours that were comparable with the ex vivo results previously demonstrated. This method supports application in further animal series and over longer time scales. Biomaterials researchers that intend to use gel or paste like preparations in distal femur defects in the rat should be aware of the risks of biomaterial displacement by local blood flow.


Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_14 | Pages 83 - 83
1 Nov 2018
Procter P Insley G Engqvist H Pujari-Palmer M Billstrom GH Larsson S
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There are clinical situations in fracture repair, e.g. osteochondral fragments, where current implant hardware is insufficient. The proposition of an adhesive enabling fixation and healing has been considered but no successful candidate has emerged thus far. The many preclinical and few clinical attempts include fibrin glue, mussel adhesive and even “Kryptonite” (US bone void filler). The most promising recent attempts are based on phosphorylating amino acids, part of a common cellular adhesion mechanism linking mussels, caddis fly larvae, and mammals. Rapid high bond strength development in the wetted fatty environment of fractured bone, that is sustained during biological healing, is challenging to prove both safety and efficacy. Additionally, there are no “predicate” preclinical animal and human models which led the authors to develop novel evaluations for an adhesive candidate “OsStictm” based on calcium salts and amino acids. Adhesive formulations were evaluated in both soft (6/12 weeks) and hard tissue (3,7,10,14 & 42 days) safety studies in murine models. The feasibility of a novel adhesiveness test, initially proven in murine cadaver femoral bone, is being assessed in-vivo (3,7,10,14 & 42 days) in bilateral implantations with a standard tissue glue as the control. In parallel an ex-vivo human bone model using freshly harvested human donor bone is under development to underwrite the eventual clinical application of such an adhesive. This is part of a risk mitigation project bridging between laboratory biomaterial characterisation and a commercial biomaterial development where safety and effectiveness have to meet today´s new medical device requirements.


Orthopaedic Proceedings
Vol. 93-B, Issue SUPP_II | Pages 184 - 184
1 May 2011
Borg T Totterman A Larsson S
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Introduction: Pelvic and acetabular fracture patients surgically treated have low patient reported outcome compared to a reference population. Our aim was to study quality of life changes during the first 2 years following injury.

Methods: All 155 patients (110 male, 45 female, age 16–83) patients with pelvic and acetabular fractures surgically treated Sept 2004-April 2007 were prospectively followed at 6, 12 and 24 months with SF-36. There were 51 pelvic and 104 acetabular fractures. 124 patients answered the questionnaire (80%), and were compared to an age-and-gender matched reference population.

Results: Pelvic fracture patients mean scores for physical function (PF) at 6–12–24 months were 59–66–74, and for role physical (RP) 28–47–62. This was below 1 SD from normative PF (mean 91, SD 28) and RP (mean 86, SD 41) at 6 months but not at 12 and 24 months. Acetabular fracture patients mean scores for PF were 51–56–61 and for RP 19–32–45. This was lower than 1 SD from normative PF (mean 85, SD 25) and RP (mean 79, SD 43) both at 6 and 12 months but not at 24 months. SF-36 scores were lower than the reference population in all domains for both fracture groups at the three time points. However mean scores were within 1 SD from normative for the other 6 domains BP, GH, VT, SF, RE and MH at all time points for both fracture groups. Hence improvement in the physical domains PF and RP was reported during the first year in both groups and during the second year for acetabular fractures.

Discussion: and Conclusion: We found significant improvement in quality of life physical domains during the first year for both pelvic and acetabular fracture patients, and also during the second year for the latter group.


The Journal of Bone & Joint Surgery British Volume
Vol. 91-B, Issue 10 | Pages 1316 - 1321
1 Oct 2009
Wallander H Larsson S Bjönness T Hansson G

The outcome in 83 patients with congenital clubfoot was evaluated at a mean age of 64 years using three validated questionnaires assessing both quality of life (short-form (SF)-36 and EQ-5D) and foot and ankle function (American Academy of Orthopaedic Surgeons (AAOS) Foot and Ankle questionnaire). In SF-36, male patients scored significantly better than male norms in seven of the eight domains, whereas female patients scored significantly worse than female norms in two of the eight. Male patients scored better than male norms in both the EQ-5D index (p = 0.027) and visual analogue scale (VAS) (p = 0.013), whereas female patients scored worse than female norms in the VAS (p < 0.001). Both male and female patients had a significantly worse outcome on the AAOS Core Scale than did norms. There was a significant correlation for both genders between the SF-36 Physical Component Summary Score and the AAOS Core Scale.

The influence on activities of daily life was limited to foot and ankle problems in all patients, and in females there was an adverse effect in physical aspects of quality of life.


The Journal of Bone & Joint Surgery British Volume
Vol. 87-B, Issue 9 | Pages 1203 - 1209
1 Sep 2005
Mattsson P Alberts A Dahlberg G Sohlman M Hyldahl HC Larsson S

We undertook a multicentre, prospective study of a series of 112 unstable trochanteric fractures in order to evaluate if internal fixation with a sliding screw device combined with augmentation using a calcium phosphate degradable cement (Norian SRS) could improve the clinical, functional and radiological outcome when compared with fractures treated with a sliding screw device alone. Pain, activities of daily living, health status (SF-36), the strength of the hip abductor muscles and radiological outcome were analysed.

Six weeks after surgery, the patients in the augmented group had significantly lower global and functional pain scores (p < 0.003), less pain after walking 50 feet (p < 0.01), and a better return to the activities of daily living (p < 0.05). At follow-up at six weeks and six months, those in the augmented group showed a significant improvement compared with the control group in the SF-36 score. No other significant differences were found between the groups. We conclude that augmentation with calcium phosphate cement in unstable trochanteric fractures provides a modest reduction in pain and a slight improvement in the quality of life during the course of healing when compared with conventional fixation with a sliding screw device alone.


The Journal of Bone & Joint Surgery British Volume
Vol. 86-B, Issue 6 | Pages 856 - 860
1 Aug 2004
Rahme H Mattsson P Larsson S

We studied the stability of cemented all-polyethylene keeled glenoid components by radiostereometric analysis (RSA) in 16 shoulders which had received a total shoulder replacement. There were 14 women (one bilateral) and one man with a mean age of 64 years. The diagnosis was osteoarthritis in eight and rheumatoid arthritis in seven. Two of the shoulders were excluded from the RSA study because of loosening of the tantalum markers.

Three tantalum markers were inserted in the glenoid socket, two in the coracoid process and two in the acromion. The polyethylene keeled glenoid component was marked with three to five tantalum markers. Conventional radiological and RSA examinations were carried out at five to seven days, at four months and at one and two years after operation. Radiolucent lines were found in all except three shoulders. Migration was most pronounced in the distal direction and exceeded 1 mm in four shoulders. In ten shoulders rotation exceeded 2° in one or more axes with retroversion/anteversion being most common. No correlation was found between migration and the presence of radiolucencies on conventional radiographs.


The Journal of Bone & Joint Surgery British Volume
Vol. 86-B, Issue 3 | Pages 457 - 461
1 Apr 2004
Sandén B Olerud C Petrén-Mallmin M Johansson C Larsson S

We examined the radiographs from a prospective clinical study of fixation by pedicle screws and those from an experimental study in a sheep model. In the clinical study, instruments were removed from 21 patients after implantation for 11 to 16 months and the extraction torques of the screws were recorded. A structured protocol was used for the radiological examinations. In the experimental study, loaded pedicle screw instrumentations were implanted in the sheep for six or 12 weeks. After radiological examination the pull-out resistance and the histological characteristics were studied.

In the clinical study, all screws with radiolucent zones had a significantly reduced mean extraction torque compared with screws without radiolucent zones (16 ± 10 Ncm v 403 ± 220 Ncm; p < 0.0001). In the experimental study the mean maximum pull-out resistance for the screws with radiolucent zones was significantly lower than for those with no radiolucency (243 ± 156 N v 2214 ± 578 N; p = 0.0006) and the mean bone-to-screw contact was reduced for screws with zones compared with those without zones (8 ± 9% v 55 ± 29%; p = 0.0002).

Our findings showed that all screws with radiolucent zones had low extraction torques or low pull-out resistance. A radiolucent zone is a good indicator of loosening of a pedicle screw.


Orthopaedic Proceedings
Vol. 86-B, Issue SUPP_III | Pages 214 - 214
1 Mar 2004
Hedin H Larsson S Hjorth K Nilsson S
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Aims: To evaluate one of the surgical options for treating femoral fractures in children.

Methods: In a consecutive and prospective study during the period 1993–2000, 96 children aged 3–15 years with 98 displaced fractures femoral fractures were treated with external fixation and early mobilization.

Results: All fractures healed. Minor complications included pin tract infections (18%) and clinical insignificant malunions. Major complications (6%) included 2 refractures after significant trauma and three plastic deformations after premature fixator removal. Malunions remodelled almost completely, overgrowth was far less than expected. Isokinetic muscle strength was tested for both hamstrings and quadriceps and showed no residual weakness.

Conclusions: External fixation of displaced femoral fractures can be used as surgical alternative in children aged 3–15 years. The treatment provides satisfactory results with a low rate of major complications. Early mobilization seems to prevent residual muscle weakness. The treatment reduces the number of days in hospital for the child and the number of days of sick leave for the parents.


The Journal of Bone & Joint Surgery British Volume
Vol. 84-B, Issue 3 | Pages 387 - 391
1 Apr 2002
Sandén B Olerud C Petrén-Mallmin M Larsson S

We investigated the effects of hydroxyapatite (HA) coating on the purchase of pedicle screws. A total of 23 consecutive patients undergoing lumbar fusion was randomly assigned to one of three treatment groups. The first received uncoated stainless-steel screws, the second screws which were partly coated with HA, and the third screws which were fully coated. The insertion torque was recorded. After 11 to 16 months, 21 screws had been extracted. The extraction torque was recorded. Radiographs were taken to assess fusion and to detect loosening of the screws.

At removal, the extraction torques exceeded the upper limit of the torque wrench (600 Ncm) for many HA-coated screws. The calculated mean extraction torque was 29 ± 36 Ncm for the uncoated group, 447 ± 114 Ncm for the partly-coated group and 574 ± 52 Ncm for the fully-coated group. There were significant differences between all three groups (p < 0.001). There were more radiolucent zones surrounding the uncoated screws than the HA-coated screws (p < 0.001). HA coating of pedicle screws resulted in improved fixation with reduced risk of loosening of the screws.


The Journal of Bone & Joint Surgery British Volume
Vol. 71-B, Issue 2 | Pages 300 - 303
1 Mar 1989
Ahlgren O Larsson S

Seventy-six patients (83 ankles) with chronic lateral instability of the ankle were treated by a simple reconstructive operation, namely, a subperiosteal release on the distal part of the lateral malleolus. The released flap, including the insertion of both the anterior talofibular and the calcaneofibular ligaments, was reattached to the malleolus more proximally. Seventy-five patients (82 ankles) were examined at a mean of 24 months (range 12 to 70) after operation. In 78 ankles (95%) the result was excellent or good. Forty-four of the 51 patients (86%) whose sporting activities were restricted before operation had no restriction at follow-up. Recurrence of instability occurred in one ankle, following a further injury two years after operation.


The Journal of Bone & Joint Surgery British Volume
Vol. 62-B, Issue 1 | Pages 86 - 92
1 Feb 1980
Lorentzon R Larsson S Boquist L

At re-examination of all osteosarcomata recorded in the Swedish Cancer Registry during the years 1958 to 1968, 11 cases of parosteal osteosarcoma were found. No case of so-called periosteal osteosarcoma was identified. The tumours constituted 1.6 per cent of all proved primary malignant bone tumours. The ages of the 11 patients (six women and five men) ranged from 17 to 62 years (average 33 years). The clinical and histopathological findings of this study and of those collected from a review of the literature suggest the occurrence of two different types of parosteal osteosarcoma: the predominant type is originally benign but has a definite malignant potential, causing metastases after long symptom-free intervals; the other type is highly malignant from the beginning. Primary amputation is recommended for the latter category of tumours, and compartmental, radical en bloc resection followed by regular review is recommended for the former.


The Journal of Bone & Joint Surgery British Volume
Vol. 61-B, Issue 4 | Pages 489 - 493
1 Nov 1979
Larsson S

Total removal of the third thoracic vertebra and partial removal of the second and fourth vertebrae together with partial lung resection were successfully performed in a twenty-two-year-old woman with a large, radioresistant, giant-cell tumour which completely surrounded the spinal cord and extended over the left lung. On admission, the patient was in her third episode of paraplegia, the two previous episodes having been temporarily relieved after decompression of the spinal cord by laminectomy and partial removal of the tumour. Three and a half months after operation she was discharged walking without support and with normal sphincter control. Two years later she is free of symptoms and the neurological status is practically normal. Clinical and radiological examinations show no signs of recurrence of the tumour.


The Journal of Bone & Joint Surgery British Volume
Vol. 61-B, Issue 2 | Pages 205 - 208
1 May 1979
Lorentzon R Larsson S Boquist L

Four cases of extra-osseous osteosarcoma were found among 242 cases recorded as osteosarcoma in the Swedish Cancer Registry during the years 1958 to 1968. The tumours occurred in middle-aged and elderly patients. Three of the tumours were situated in the proximal part of the thigh and one in the scapular region. Histopathologically, all tumours were subclassified as osteoblastic osteosarcomas. The patients were treated by primary local excision which in one case was followed by a radical en bloc excision of the entire tumour bed. All cases subjected to simple excision died of metastatic disease five to twenty-four months after diagnosis. The patient treated by en bloc excision is alive and apparently free from disease fourteen years after diagnosis.


The Journal of Bone & Joint Surgery British Volume
Vol. 58-B, Issue 4 | Pages 412 - 417
1 Nov 1976
Larsson S Lorentzon R Boquist L

The clinical records, radiographs and histopathological material of all forty-one patients recorded as suffering from fibrosarcoma of bone in the Swedish Cancer Registry for the years 1958 to 1968 have been analysed; in addition, four cases were found on histological review of a series of osteosarcomas. From this re-examination, twenty-four patients with genuine fibrosarcoma of bone were identified; twenty-two had primary neoplasms and two secondary. No sex or geographical differences were found. The tumours showed a prevalence for patients in the adult and older age groups. Half of the tumours arose from femoral or tibial metaphysial bone adjacent to a knee joint. All the tumours were of the medullary type. Almost one-third presented with a pathological fracture, and soft-tissue extension had occurred in all but three tumours. In contrast to previous reports, these tumours were more malignant than osteosarcomas and showed a five-year survival rate of only 4-2 per cent. In accessible sites, ablative surgery was used as the primary treatment, Fibrosarcoma of bone is a distinctive lesion and should be distinguished carefully from periosteal and soft-tissue fibrosarcomas because of differences in prognosis and treatment.


The Journal of Bone & Joint Surgery British Volume
Vol. 56-B, Issue 3 | Pages 534 - 540
1 Aug 1974
Larsson S Lorentzon R

1. The incidence of osteogenic sarcoma, chondrosarcoma and Ewing's sarcoma in relation to age, sex and site is analysed in a study of 832 malignant primary bone tumours diagnosed in Sweden in 1958-68. The results are compared with those in other series.

2. The adolescent incidence peak for osteogenic sarcoma is caused by tumours localised to the long bones of the lower limb. The peak incidence occurs at a mean age of twelve years for girls and sixteen years for boys and is associated with the maximum growth velocity for the adolescent growth spurt.

3. Ewing's sarcoma, showing no sex difference with regard to its incidence peak, seems not to be associated with bone growth.

4. In the adult, the incidence of osteogenic sarcoma parallels that of chondrosarcoma, thus showing a successive increase with increasing age. In Sweden, where Paget's disease is uncommon, the incidence of osteogenic sarcoma over the age of thirty is only one-third of that during adolescence.

5. In osteogenic sarcoma and chondrosarcoma but not in Ewing's sarcoma, the characteristic predominance of males over females is valid only for localisations to the long bones of the lower limb, the pelvis and the spinal column and not for other sites. Internal factors such as age, sex, bone growth and maturation and also weight-bearing seems to be of importance in modifying the response of the tissue to a causative external factor, like a common virus.