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
We have studied prospectively the effect of indomethacin on the development of heterotopic ossification (HO) after the internal fixation of acetabular fractures. After operation 107 patients randomly received either a six-week course of indomethacin or no treatment against HO. Plain radiographs of 101 patients at a mean of 7.9 months after surgery showed HO in 47.4% of the 57 patients who received indomethacin and in 56.8% of the 44 who did not. This difference was not statistically significant. Heterotopic ossification of Brooker class II or more was seen in four patients (7%) with prophylaxis and in one without (p = 0.51). Measurements of the volume of HO on 3-D CT reconstructions showed a median value of 1.5 cm. 3. in patients with indomethacin and 4.0 cm. 3. in those without (p = 0.28). When only the 57 patients in whom the operation was carried out through either a Kocher-Langenbeck or an extended iliofemoral approach were included the indomethacin group showed a median volume of 1.7 cm. 3. compared with 3.6 cm. 3. On plain radiographs Brooker class II or above was seen in 9.4% of the patients receiving indomethacin and in 4.8% of those who did not. Indomethacin was therefore not effective in preventing ectopic
In patients with traumatic brain injury and fractures
of long bones, it is often clinically observed that the rate of bone
healing and extent of callus formation are increased. However, the
evidence has been unconvincing and an association between such an
injury and enhanced fracture healing remains unclear. We performed
a retrospective cohort study of 74 young adult patients with a mean
age of 24.2 years (16 to 40) who sustained a femoral shaft fracture
(AO/OTA type 32A or 32B) with or without a brain injury. All the
fractures were treated with closed intramedullary nailing. The main
outcome measures included the time required for bridging callus
formation (BCF) and the mean callus thickness (MCT) at the final
follow-up. Comparative analyses were made between the 20 patients
with a brain injury and the 54 without brain injury. Subgroup comparisons
were performed among the patients with a brain injury in terms of
the severity of head injury, the types of intracranial haemorrhage
and gender. Patients with a brain injury had an earlier appearance
of BCF
(p <
0.001) and a greater final MCT value (p <
0.001) than
those without. There were no significant differences with respect
to the time required for BCF and final MCT values in terms of the
severity of head injury (p = 0.521 and p = 0.153, respectively),
the types of intracranial haemorrhage (p = 0.308 and p = 0.189,
respectively) and gender (p = 0.383 and
p = 0.662, respectively). These results confirm that an injury to the brain may be associated
with accelerated fracture healing and enhanced callus formation.
However, the severity of the injury to the brain, the type of intracranial
haemorrhage and gender were not statistically significant factors
in predicting the rate of bone healing and extent of final callus formation.
Neurogenic heterotopic ossification (NHO) is
a disorder of aberrant
The aim of this study was to assess the safety and clinical outcome of patients with a femoral shaft fracture and a previous complex post-traumatic femoral malunion who were treated with a clamshell osteotomy and fixation with an intramedullary nail (IMN). The study involved a retrospective analysis of 23 patients. All had a previous, operatively managed, femoral shaft fracture with malunion due to hardware failure. They were treated with a clamshell osteotomy between May 2015 and March 2020. The mean age was 42.6 years (26 to 62) and 15 (65.2%) were male. The mean follow-up was 2.3 years (1 to 5). Details from their medical records were analyzed. Clinical outcomes were assessed using the quality of correction of the deformity, functional recovery, the healing time of the fracture, and complications.Aims
Methods
We evaluated the effect of low-intensity pulsed ultrasound stimulation (LIPUS) on the remodelling of callus in a rabbit gap-healing model by bone morphometric analyses using three-dimensional quantitative micro-CT. A tibial osteotomy with a 2 mm gap was immobilised by rigid external fixation and LIPUS was applied using active translucent devices. A control group had sham inactive transducers applied. A region of interest of micro-CT was set at the centre of the osteotomy gap with a width of 1 mm. The morphometric parameters used for evaluation were the volume of mineralised callus (BV) and the volumetric bone mineral density of mineralised tissue (mBMD). The whole region of interest was measured and subdivided into three zones as follows: the periosteal callus zone (external), the medullary callus zone (endosteal) and the cortical gap zone (intercortical). The BV and mBMD were measured for each zone. In the endosteal area, there was a significant increase in the density of newly formed callus which was subsequently diminished by bone resorption that overwhelmed
Osteopetrosis (OP) is a rare hereditary disease that causes reduced bone resorption and increased bone density as a result of osteoclastic function defect. Our aim is to review the difficulties, mid-term follow-up results, and literature encountered during the treatment of OP. This is a retrospective and observational study containing data from nine patients with a mean age of 14.1 years (9 to 25; three female, six male) with OP who were treated in our hospital between April 2008 and October 2018 with 20 surgical procedures due to 17 different fractures. Patient data included age, sex, operating time, length of stay, genetic type of the disease, previous surgery, fractures, complications, and comorbidity.Aims
Methods
The aim of this study was to evaluate the diagnostic value of preoperative serum CRP, white blood cell count (WBC), percentage of neutrophils (%N), and neutrophil to lymphocyte ratio (NLR) when using the fracture-related infection (FRI) consensus definition. A cohort of 106 patients having surgery for suspected septic nonunion after failed fracture fixation were studied. Blood samples were collected preoperatively, and the concentration of serum CRP, WBC, and differential cell count were analyzed. The areas under the curve (AUCs) of diagnostic tests were compared using the z-test. Regression trees were constructed and internally cross-validated to derive a simple diagnostic decision tree.Aims
Methods
We have reviewed retrospectively 80 patients who were treated for traumatic fractures of the femur with a Grosse-Kempf nail to assess the incidence and causes of persisting pain in the proximal thigh. At a mean of 21 months after operation 33 patients had residual pain severe enough to interfere with their lifestyle or mobility. This was in the region of the scar on the greater trochanter in three-quarters of the patients. Only four showed no radiological abnormality. There was nonunion of the fracture in two, Paget’s disease in one, breakage of the nail in two and prominence of the proximal locking screw in five, although we found no correlation between prominence of the nail and pain. There was a strong relationship between pain and heterotopic ossification at the proximal end of the implant; this was present in 64% of the patients with pain as compared with those without pain (p <
0.001, Mann-Whitney U test). Of the 80 patients, 27 had the implant removed after 18 months, 17 of them because of pain. In six of these 17, the pain was not relieved. Prominence of the nail proximally was not associated with pain, but protuberance of laterally-based proximal locking screws caused problems. We found a strong association between heterotopic
Many authors have reported a shorter treatment time when using trifocal bone transport (TFT) rather than bifocal bone transport (BFT) in the management of long segmental tibial bone defects. However, the difference in the incidence of additional procedures, the true complications, and the final results have not been investigated. A total of 86 consecutive patients with a long tibial bone defect (≥ 8 cm), who were treated between January 2008 and January 2015, were retrospectively reviewed. A total of 45 were treated by BFT and 41 by TFT. The median age of the 45 patients in the BFT group was 43 years (interquartile range (IQR) 23 to 54).Aims
Patients and Methods
The aim of this study was to evaluate the outcomes of a salvage procedure using a 95° angled blade plate for failed osteosynthesis of atypical subtrochanteric femoral fractures associated with the long-term use of bisphosphonates. These were compared with those for failed osteosynthesis of subtrochanteric fractures not associated with bisphosphonate treatment. Between October 2008 and July 2016, 14 patients with failed osteosynthesis of an atypical subtrochanteric femoral fracture were treated with a blade plate (atypical group). Their mean age was 67.8 years (60 to 74); all were female. During the same period, 21 patients with failed osteosynthesis of a typical subtrochanteric fracture underwent restabilization using a blade plate (typical group). Outcome variables included the time of union, postoperative complications, Harris Hip Score, and Sanders functional rating scale.Aims
Patients and Methods
This article presents a unified clinical theory
that links established facts about the physiology of bone and homeostasis,
with those involved in the healing of fractures and the development
of nonunion. The key to this theory is the concept that the tissue
that forms in and around a fracture should be considered a specific
functional entity. This ‘bone-healing unit’ produces a physiological
response to its biological and mechanical environment, which leads
to the normal healing of bone. This tissue responds to mechanical
forces and functions according to Wolff’s law, Perren’s strain theory
and Frost’s concept of the “mechanostat”. In response to the local
mechanical environment, the bone-healing unit normally changes with
time, producing different tissues that can tolerate various levels
of strain. The normal result is the formation of bone that bridges
the fracture – healing by callus. Nonunion occurs when the bone-healing
unit fails either due to mechanical or biological problems or a
combination of both. In clinical practice, the majority of nonunions
are due to mechanical problems with instability, resulting in too
much strain at the fracture site. In most nonunions, there is an
intact bone-healing unit. We suggest that this maintains its biological
potential to heal, but fails to function due to the mechanical conditions.
The theory predicts the healing pattern of multifragmentary fractures
and the observed morphological characteristics of different nonunions.
It suggests that the majority of nonunions will heal if the correct
mechanical environment is produced by surgery, without the need
for biological adjuncts such as autologous bone graft. Cite this article:
Demineralised bone matrix (DBM) is rarely used for the local
delivery of prophylactic antibiotics. Our aim, in this study, was
to show that a graft with a bioactive glass and DBM combination,
which is currently available for clinical use, can be loaded with
tobramycin and release levels of antibiotic greater than the minimum
inhibitory concentration for Antibiotic was loaded into a graft and subsequently evaluated
for drug elution kinetics and the inhibition of bacterial growth.
A rat femoral condylar plug model was used to determine the effect
of the graft, loaded with antibiotic, on bone healing.Aims
Materials and Methods
To evaluate the effect of a single early high-dose vitamin D
supplement on fracture union in patients with hypovitaminosis D
and a long bone fracture. Between July 2011 and August 2013, 113 adults with a long bone
fracture were enrolled in a prospective randomised double-blind
placebo-controlled trial. Their serum vitamin D levels were measured
and a total of 100 patients were found to be vitamin D deficient
(<
20 ng/ml) or insufficient (<
30 ng/mL). These were then
randomised to receive a single dose of vitamin D3 orally
(100 000 IU) within two weeks of injury (treatment group, n = 50)
or a placebo (control group, n = 50). We recorded patient demographics,
fracture location and treatment, vitamin D level, time to fracture
union and complications, including vitamin D toxicity. Outcomes included union, nonunion or complication requiring an
early, unplanned secondary procedure. Patients without an outcome
at 15 months and no scheduled follow-up were considered lost to
follow-up. The Aims
Patients and Methods
The biomembrane (induced membrane) formed around polymethylmethacrylate (PMMA) spacers has value in clinical applications for bone defect reconstruction. Few studies have evaluated its cellular, molecular or stem cell features. Our objective was to characterise induced membrane morphology, molecular features and osteogenic stem cell characteristics. Following Institutional Review Board approval, biomembrane specimens were obtained from 12 patient surgeries for management of segmental bony defects (mean patient age 40.7 years, standard deviation 14.4). Biomembranes from nine tibias and three femurs were processed for morphologic, molecular or stem cell analyses. Gene expression was determined using the Affymetrix GeneChip Operating Software (GCOS). Molecular analyses compared biomembrane gene expression patterns with a mineralising osteoblast culture, and gene expression in specimens with longer spacer duration (> 12 weeks) with specimens with shorter durations. Statistical analyses used the unpaired student Objectives
Methods
The aim of this systematic literature review was to assess the clinical level of evidence of commercially available demineralised bone matrix (DBM) products for their use in trauma and orthopaedic related surgery. A total of 17 DBM products were used as search terms in two available databases: Embase and PubMed according to the Preferred Reporting Items for Systematic Reviews and Meta Analyses statement. All articles that reported the clinical use of a DBM-product in trauma and orthopaedic related surgery were included.Objectives
Methods
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:
MicroRNAs (miRNAs ) are small non-coding RNAs
that regulate gene expression. We hypothesised that the functions
of certain miRNAs and changes to their patterns of expression may
be crucial in the pathogenesis of nonunion. Healing fractures and
atrophic nonunions produced by periosteal cauterisation were created
in the femora of 94 rats, with 1:1 group allocation. At post-fracture
days three, seven, ten, 14, 21 and 28, miRNAs were extracted from
the newly generated tissue at the fracture site. Microarray and
real-time polymerase chain reaction (PCR) analyses of day 14 samples
revealed that five miRNAs, miR-31a-3p, miR-31a-5p, miR-146a-5p,
miR-146b-5p and miR-223-3p, were highly upregulated in nonunion.
Real-time PCR analysis further revealed that, in nonunion, the expression
levels of all five of these miRNAs peaked on day 14 and declined
thereafter. Our results suggest that miR-31a-3p, miR-31a-5p, miR-146a-5p,
miR-146b-5p and miR-223-3p may play an important role in the development
of nonunion. These findings add to the understanding of the molecular mechanism
for nonunion formation and may lead to the development of novel
therapeutic strategies for its treatment. Cite this article:
Fracture repair occurs by two broad mechanisms:
direct healing, and indirect healing with callus formation. The effects
of bisphosphonates on fracture repair have been assessed only in
models of indirect fracture healing. A rodent model of rigid compression plate fixation of a standardised
tibial osteotomy was used. Ten skeletally mature Sprague–Dawley
rats received daily subcutaneous injections of 1 µg/kg ibandronate
(IBAN) and ten control rats received saline (control). Three weeks
later a tibial osteotomy was rigidly fixed with compression plating.
Six weeks later the animals were killed. Fracture repair was assessed
with mechanical testing, radiographs and histology. The mean stress at failure in a four-point bending test was significantly
lower in the IBAN group compared with controls (8.69 Nmm-2 ( Bisphosphonate treatment in a therapeutic dose, as used for risk
reduction in fragility fractures, had an inhibitory effect on direct
fracture healing. We propose that bisphosphonate therapy not be
commenced until after the fracture has united if the fracture has
been rigidly fixed and is undergoing direct osteonal healing. Cite this article:
Tibial nonunion represents a spectrum of conditions
which are challenging to treat, and optimal management remains unclear
despite its high rate of incidence. We present 44 consecutive patients
with 46 stiff tibial nonunions, treated with hexapod external fixators
and distraction to achieve union and gradual deformity correction.
There were 31 men and 13 women with a mean age of 35 years (18 to
68) and a mean follow-up of 12 months (6 to 40). No tibial osteotomies
or bone graft procedures were performed. Bony union was achieved
after the initial surgery in 41 (89.1%) tibias. Four persistent
nonunions united after repeat treatment with closed hexapod distraction,
resulting in bony union in 45 (97.8%) patients. The mean time to
union was 23 weeks (11 to 49). Leg-length was restored to within
1 cm of the contralateral side in all tibias. Mechanical alignment
was restored to within 5° of normal in 42 (91.3%) tibias. Closed
distraction of stiff tibial nonunions can predictably lead to union
without further surgery or bone graft. In addition to generating
the required distraction to achieve union, hexapod circular external
fixators can accurately correct concurrent deformities and limb-length
discrepancies. Cite this article: