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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. 92-B, Issue SUPP_IV | Pages 553 - 553
1 Oct 2010
Masud S Batra S Charalambos C Ravenscroft M Sahu A Warren-Smith C
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Introduction: The Polarus nail is used in the treatment of displaced surgical neck of humerus fractures, but has been reported to have a high hardware complication rate. A recent change to 5.3 mm “non-toggling” proximal locking screws has been introduced in an attempt to minimise these complications.

The aims of this study were to determine union rates and hardware complications, and to assess whether the “non-toggle” proximal locking option prevented screw back-out.

Methods: We performed a retrospective review of case notes and radiographs of consecutive patients treated with the 150 mm length Polarus nail for acute displaced surgical neck of humerus fractures at our unit between 1st May 2002 and 29th February 2008. All patients were followed up until fracture union.

Results: Forty-nine patients were treated with the Polarus nail during the study period. Eleven patients were lost to follow-up before fracture union, so were excluded. Median age of the patients was 72 years (range: 31 to 94 years). Mean time to surgery was 10.7 days (range: two to 25 days).

Thirty-six fractures (95%) went on to unite following treatment with the Polarus nail. Of the two fractures that failed to unite one had an infective non-union and the other developed avascular necrosis with non-union of the surgical neck.

Twelve patients (32%) developed post-operative hardware complications. In nine (24%) there was backing out of the proximal locking screws, but only two patients had symptoms requiring screw removal. In five patients (13%) the nail was prominent proximally, causing impingement. In one patient (3%) the proximal screws penetrated the gleno-humeral joint, although this was asymptomatic.

There was backing-out in six of the 21 patients (29%) in which the standard 5.0 mm proximal locking screws were used. This compared with three out of 14 patients (21%) in which the 5.3 mm “non-toggling” screws were used. The difference in the rate of screw backing-out between the two groups was significant (P = 0.0474, Fisher’s Exact test). In three patients a mixture of 5.0 and 5.3 mm screws was used.

Discussion: The Polarus nail provides a stable fixation to union when used for the treatment of displaced surgical neck of humerus fractures. It is associated with a high hardware complication rate (32%), however, this is asymptomatic in the majority of cases (60%). The 5.3 mm “non-toggle” proximal locking option was found to reduce the rate of screw back-out compared with the standard 5.0 mm screw. We recommend the use of this “non-toggling” screw option for proximal locking.


Orthopaedic Proceedings
Vol. 90-B, Issue SUPP_III | Pages 499 - 499
1 Aug 2008
Khan WS Jain R Agarwal M Warren-Smith C
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Introduction: Fractures of the tuberosity heal well irrespective of the treatment instituted. Fractures distal to the tuberosity have a high incidence of delayed union and non-union. This could be due to disruption of the vascular supply that enters the bone at the metaphyseal-diaphyseal region. It has also been reported that in these injuries, stress fractures occur at a different anatomic site that is more distal to acute fractures.

We present one of the largest reported series of such fractures in which we have explored the above statements.

Materials & Methods: A retrospective review of 300 closed fractures of the base of the fifth metatarsal- 268 were tuberosity fractures (group 1) and 32 were fractures distal to the tuberosity (group 2).

The patients were followed up in the outpatients clinic for a mean period of 2 months (group 1) and 16 months (group 2).

The distance of the fracture site from the proximal tip of the metatarsal was measured on the radiographs.

Results:

All group 1 fractures healed well following symptomatic management and none required surgical intervention.

Acute fractures in group 2 did better with non-weight bearing mobilization. Stress related fractures in group 2 took longer to heal when managed non-operatively.

In group 2 patients, the difference in the site of acute & stress fractures was not statistically significant.

No statistically significant correlation between distance from the proximal tip of the fifth metatarsal to the fracture site and union.

Conclusion:

A standardized classification is important because there is great variability in the types of fractures and appropriate treatment.

Nonunion in fractures distal to the tuberosity is not related to the distance of the fracture from the metaphyseal-diaphyseal region

Acute and stress fractures distal to the tuberosity do not occur at different anatomic sites.