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The Journal of Bone & Joint Surgery British Volume
Vol. 93-B, Issue 4 | Pages 510 - 516
1 Apr 2011
Sugata Y Sotome S Yuasa M Hirano M Shinomiya K Okawa A

Several bisphosphonates are now available for the treatment of osteoporosis. Porous hydroxyapatite/collagen (HA/Col) composite is an osteoconductive bone substitute which is resorbed by osteoclasts. The effects of the bisphosphonate alendronate on the formation of bone in porous HA/Col and its resorption by osteoclasts were evaluated using a rabbit model. Porous HA/Col cylinders measuring 6 mm in diameter and 8 mm in length, with a pore size of 100 μm to 500 μm and 95% porosity, were inserted into a defect produced in the lateral femoral condyles of 72 rabbits. The rabbits were divided into four groups based on the protocol of alendronate administration: the control group did not receive any alendronate, the pre group had alendronate treatment for three weeks prior to the implantation of the HA/Col, the post group had alendronate treatment following implantation until euthanasia, and the pre+post group had continuous alendronate treatment from three weeks prior to surgery until euthanasia. All rabbits were injected intravenously with either saline or alendronate (7.5 μg/kg) once a week. Each group had 18 rabbits, six in each group being killed at three, six and 12 weeks post-operatively. Alendronate administration suppressed the resorption of the implants. Additionally, the mineral densities of newly formed bone in the alendronate-treated groups were lower than those in the control group at 12 weeks post-operatively. Interestingly, the number of osteoclasts attached to the implant correlated with the extent of bone formation at three weeks. In conclusion, the systemic administration of alendronate in our rabbit model at a dose-for-weight equivalent to the clinical dose used in the treatment of osteoporosis in Japan affected the mineral density and remodelling of bone tissue in implanted porous HA/Col composites


The Bone & Joint Journal
Vol. 100-B, Issue 9 | Pages 1234 - 1240
1 Sep 2018
Brady J Hardy BM Yoshino O Buxton A Quail A Balogh ZJ

Aims

Little is known about the effect of haemorrhagic shock and resuscitation on fracture healing. This study used a rabbit model with a femoral osteotomy and fixation to examine this relationship.

Materials and Methods

A total of 18 male New Zealand white rabbits underwent femoral osteotomy with intramedullary fixation with ‘shock’ (n = 9) and control (n = 9) groups. Shock was induced in the study group by removal of 35% of the total blood volume 45 minutes before resuscitation with blood and crystalloid. Fracture healing was monitored for eight weeks using serum markers of healing and radiographs.


The Bone & Joint Journal
Vol. 99-B, Issue 5 | Pages 680 - 685
1 May 2017
Morris R Hossain M Evans A Pallister I

Aims

This study describes the use of the Masquelet technique to treat segmental tibial bone loss in 12 patients.

Patients and Methods

This retrospective case series reviewed 12 patients treated between 2010 and 2015 to determine their clinical outcome. Patients were mostly male with a mean age of 36 years (16 to 62). The outcomes recorded included union, infection and amputation. The mean follow-up was 675 days (403 to 952).


The Bone & Joint Journal
Vol. 97-B, Issue 7 | Pages 997 - 1003
1 Jul 2015
Papanagiotou M Dailiana ZH Karachalios T Varitimidis S Vlychou M Hantes M Malizos KN

We report the outcome of 84 nonunions involving long bones which were treated with rhBMP-7, in 84 patients (60 men: 24 women) with a mean age 46 years (18 to 81) between 2003 and 2011. The patients had undergone a mean of three previous operations (one to 11) for nonunion which had been present for a mean of 17 months (4 months to 20 years). The nonunions involved the lower limb in 71 patients and the remainder involved the upper limb. A total of 30 nonunions were septic. Treatment was considered successful when the nonunion healed without additional procedures. The relationship between successful union and the time to union was investigated and various factors including age and gender, the nature of the nonunion (location, size, type, chronicity, previous procedures, infection, the condition of the soft tissues) and type of index procedure (revision of fixation, type of graft, amount of rhBMP-7) were analysed. The improvement of the patients’ quality of life was estimated using the Short Form (SF) 12 score.

A total of 68 nonunions (80.9%) healed with no need for further procedures at a mean of 5.4 months (3 to 10) post-operatively. Multivariate logistic regression analysis of the factors affecting union suggested that only infection significantly affected the rate of union (p = 0.004).Time to union was only affected by the number of previous failed procedures (p = 0.006). An improvement of 79% and 32.2% in SF-12 physical and mental score, respectively, was noted within the first post-operative year.

Rh-BMP-7 combined with bone grafts, enabled healing of the nonunion and improved quality of life in about 80% of patients. Aseptic nonunions were much more likely to unite than septic ones. The number of previous failed operations significantly delayed the time to union.

Cite this article: Bone Joint J 2015;97-B:997–1003.


The Bone & Joint Journal
Vol. 95-B, Issue 5 | Pages 583 - 597
1 May 2013
Kurien T Pearson RG Scammell BE

We reviewed 59 bone graft substitutes marketed by 17 companies currently available for implantation in the United Kingdom, with the aim of assessing the peer-reviewed literature to facilitate informed decision-making regarding their use in clinical practice. After critical analysis of the literature, only 22 products (37%) had any clinical data. Norian SRS (Synthes), Vitoss (Orthovita), Cortoss (Orthovita) and Alpha-BSM (Etex) had Level I evidence. We question the need for so many different products, especially with limited published clinical evidence for their efficacy, and conclude that there is a considerable need for further prospective randomised trials to facilitate informed decision-making with regard to the use of current and future bone graft substitutes in clinical practice.

Cite this article: Bone Joint J 2013;95-B:583–97.


The Bone & Joint Journal
Vol. 95-B, Issue 11 | Pages 1544 - 1550
1 Nov 2013
Uchiyama S Itsubo T Nakamura K Fujinaga Y Sato N Imaeda T Kadoya M Kato H

This multicentre prospective clinical trial aimed to determine whether early administration of alendronate (ALN) delays fracture healing after surgical treatment of fractures of the distal radius. The study population comprised 80 patients (four men and 76 women) with a mean age of 70 years (52 to 86) with acute fragility fractures of the distal radius requiring open reduction and internal fixation with a volar locking plate and screws. Two groups of 40 patients each were randomly allocated either to receive once weekly oral ALN administration (35 mg) within a few days after surgery and continued for six months, or oral ALN administration delayed until four months after surgery. Postero-anterior and lateral radiographs of the affected wrist were taken monthly for six months after surgery. No differences between groups was observed with regard to gender (p = 1.0), age (p = 0.916), fracture classification (p = 0.274) or bone mineral density measured at the spine (p = 0.714). The radiographs were assessed by three independent assessors. There were no significant differences in the mean time to complete cortical bridging observed between the ALN group (3.5 months (se 0.16)) and the no-ALN group (3.1 months (se 0.15)) (p = 0.068). All the fractures healed in the both groups by the last follow-up. Improvement of the Quick-Disabilities of the Arm, Shoulder and Hand (QuickDASH) score, grip strength, wrist range of movement, and tenderness over the fracture site did not differ between the groups over the six-month period. Based on our results, early administration of ALN after surgery for distal radius fracture did not appear to delay fracture healing times either radiologically or clinically.

Cite this article: Bone Joint J 2013;95-B:1544–50.


The Bone & Joint Journal
Vol. 97-B, Issue 10 | Pages 1423 - 1427
1 Oct 2015
Rand BCC Penn-Barwell JG Wenke JC

Systemic antibiotics reduce infection in open fractures. Local delivery of antibiotics can provide higher doses to wounds without toxic systemic effects. This study investigated the effect on infection of combining systemic with local antibiotics via polymethylmethacrylate (PMMA) beads or gel delivery.

An established Staphylococcus aureus contaminated fracture model in rats was used. Wounds were debrided and irrigated six hours after contamination and animals assigned to one of three groups, all of which received systemic antibiotics. One group had local delivery via antibiotic gel, another PMMA beads and the control group received no local antibiotics. After two weeks, bacterial levels were quantified.

Combined local and systemic antibiotics were superior to systemic antibiotics alone at reducing the quantity of bacteria recoverable from each group (p = 0.002 for gel; p = 0.032 for beads). There was no difference in the bacterial counts between bead and gel delivery (p = 0.62).

These results suggest that local antibiotics augment the antimicrobial effect of systemic antibiotics. Although no significant difference was found between vehicles, gel delivery offers technical advantages with its biodegradable nature, ability to conform to wound shape and to deliver increased doses. Further study is required to see if the gel delivery system has a clinical role.

Cite this article: Bone Joint J 2015;97-B:1423–7.


The Bone & Joint Journal
Vol. 97-B, Issue 1 | Pages 109 - 114
1 Jan 2015
Haller JM Holt DC McFadden ML Higgins TF Kubiak EN

The aim of this study was to report the incidence of arthrofibrosis of the knee and identify risk factors for its development following a fracture of the tibial plateau. We carried out a retrospective review of 186 patients (114 male, 72 female) with a fracture of the tibial plateau who underwent open reduction and internal fixation. Their mean age was 46.4 years (19 to 83) and the mean follow-up was16.0 months (6 to 80).

A total of 27 patients (14.5%) developed arthrofibrosis requiring a further intervention. Using multivariate regression analysis, the use of a provisional external fixator (odds ratio (OR) 4.63, 95% confidence interval (CI) 1.26 to 17.7, p = 0.021) was significantly associated with the development of arthrofibrosis. Similarly, the use of a continuous passive movement (CPM) machine was associated with significantly less development of arthrofibrosis (OR = 0.32, 95% CI 0.11 to 0.83, p = 0.024). The effect of time in an external fixator was found to be significant, with each extra day of external fixation increasing the odds of requiring manipulation under anaesthesia (MUA) or quadricepsplasty by 10% (OR = 1.10, p = 0.030). High-energy fracture, surgical approach, infection and use of tobacco were not associated with the development of arthrofibrosis. Patients with a successful MUA had significantly less time to MUA (mean 2.9 months; sd 1.25) than those with an unsuccessful MUA (mean 4.86 months; sd 2.61, p = 0.014). For those with limited movement, therefore, performing an MUA within three months of the injury may result in a better range of movement.

Based our results, CPM following operative fixation for a fracture of the tibial plateau may reduce the risk of the development of arthrofibrosis, particularly in patients who also undergo prolonged provisional external fixation.

Cite this article: Bone Joint J 2015;97-B:109–14.


The Journal of Bone & Joint Surgery British Volume
Vol. 94-B, Issue 1 | Pages 107 - 112
1 Jan 2012
Penn-Barwell JG Murray CK Wenke JC

Most animal studies indicate that early irrigation and debridement reduce infection after an open fracture. Unfortunately, these studies often do not involve antibiotics. Clinical studies indicate that the timing of initial debridement does not affect the rate of infection but these studies are observational and fraught with confounding variables. The purpose of this study was to control these variables using an animal model incorporating systemic antibiotics and surgical treatment.

We used a rat femur model with a defect which was contaminated with Staphylococcus aureus and treated with a three-day course of systemic cefazolin (5 mg/kg 12-hourly) and debridement and irrigation, both of which were initiated independently at two, six and 24 hour time points. After 14 days the bone and hardware were harvested for separate microbiological analysis.

No animal that received antibiotics and surgery two hours after injury had detectable bacteria. When antibiotics were started at two hours, a delay in surgical treatment from two to six hours significantly increased the development of infection (p = 0.047). However, delaying surgery to 24 hours increase the rate of infection, but not significantly (p = 0.054). The timing of antibiotics had a more significant effect on the proportion of positive samples than earlier surgery. Delaying antibiotics to six or 24 hours had a profoundly detrimental effect on the infection rate regardless of the timing of surgery. These findings are consistent with the concept that bacteria progress from a vulnerable planktonic form to a treatment-resistant biofilm.


The Journal of Bone & Joint Surgery British Volume
Vol. 92-B, Issue 5 | Pages 679 - 686
1 May 2010
Das De S Setiobudi T Shen L Das De S

There have been recent reports linking alendronate and a specific pattern of subtrochanteric insufficiency fracture. We performed a retrospective review of all subtrochanteric fractures admitted to our institution between 2001 and 2007. There were 20 patients who met the inclusion criteria, 12 of whom were on long-term alendronate. Alendronate-associated fractures tend to be bilateral (Fisher’s exact test, p = 0.018), have unique radiological features (p < 0.0005), be associated radiologically with a pre-existing ellipsoid thickening of the lateral femoral cortex and are likely to be preceded by prodromal pain. Biomechanical investigations did not suggest overt metabolic bone disease. Only one patient on alendronate had osteoporosis prior to the start of therapy. We used these findings to develop a management protocol to optimise fracture healing. We also advocate careful surveillance in individuals at-risk, and present our experience with screening and prophylactic fixation in selected patients.


The Journal of Bone & Joint Surgery British Volume
Vol. 90-B, Issue 12 | Pages 1617 - 1622
1 Dec 2008
Axelrad TW Steen B Lowenberg DW Creevy WR Einhorn TA

Heterotopic ossification occurring after the use of commercially available bone morphogenetic proteins has not been widely reported. We describe four cases of heterotopic ossification in patients treated with either recombinant bone morphogenetic protein 2 or recombinant bone morphogenetic protein 7. We found that while some patients were asymptomatic, heterotopic ossification which had occurred around a joint often required operative excision with good results.


The Journal of Bone & Joint Surgery British Volume
Vol. 89-B, Issue 11 | Pages 1482 - 1487
1 Nov 2007
Gupta A

We describe a series of 20 patients with ununited fractures of the femoral neck following neglected trauma or failed primary internal fixation who were seen at a mean of 7.5 months (2 to 18) following injury. Open reduction and internal fixation of the fracture was performed in all patients, together with a myoperiosteal flap on the quadratus femoris muscle pedicle.

Union occurred at a mean of 4.9 months (2 to 10) in all patients. The mean follow-up was for 70 months (14 to 144). There was no further progression in six of seven patients with pre-operative radiological evidence of osteonecrosis of the femoral head. One patient had delayed collapse and flattening of the femoral head ten years after union of the fracture, but remained asymptomatic.

This study demonstrates the orthopaedic application of myoperiosteal grafting for inducing osteogenesis in a difficult clinical situation.