We analysed the effects of commonly used medications
on human osteoblastic cell activity in vitro, specifically proliferation
and tissue mineralisation. A list of medications was retrieved from
the records of patients aged >
65 years filed in the database of
the largest health maintenance organisation in our country (>
two
million members). Proliferation and mineralisation assays were performed
on the following drugs: rosuvastatin (statin), metformin (antidiabetic),
metoprolol (β-blocker), citalopram (selective serotonin reuptake
inhibitor [SSRI]), and omeprazole (proton pump inhibitor (PPI)).
All tested drugs significantly stimulated DNA synthesis to varying
degrees, with rosuvastatin 5 µg/ml being the most effective among
them (mean 225% ( Cite this article:
Medial open-wedge high tibial osteotomy has been gaining popularity in recent years, but adequate supporting material is required in the osteotomy gap for early weight-bearing and rapid union. The purpose of this study was to investigate whether the implantation of a polycaprolactone-tricalcium phosphate composite scaffold wedge would enhance healing of the osteotomy in a micro pig model. We carried out open-wedge high tibial osteotomies in 12 micro pigs aged from 12 to 16 months. A scaffold wedge was inserted into six of the osteotomies while the other six were left open. Bone healing was evaluated after three and six months using plain radiographs, CT scans, measurement of the bone mineral density and histological examination. Complete bone union was obtained at six months in both groups. There was no collapse at the osteotomy site, loss of correction or failure of fixation in either group. Staining with haematoxylin and eosin demonstrated that there was infiltration of new bone tissue into the macropores and along the periphery of the implanted scaffold in the scaffold group. The CT scans and measurement of the bone mineral density showed that at six months specimens in the scaffold group had a higher bone mineral density than in the control group, although the implantation of the polycaprolactone-tricalcium phosphate composite scaffold wedge did not enhance healing of the osteotomy.
The aims of this study were to evaluate the clinical and radiological
outcomes of instrumented posterolateral fusion (PLF) performed in
patients with rheumatoid arthritis (RA). A total of 40 patients with RA and 134 patients without RA underwent
instrumented PLF for spinal stenosis between January 2003 and December
2011. The two groups were matched for age, gender, bone mineral
density, the history of smoking and diabetes, and number of fusion
segments. The clinical outcomes measures included the visual analogue scale
(VAS) and the Korean Oswestry Disability Index (KODI), scored before
surgery, one year and two years after surgery. Radiological outcomes
were evaluated for problems of fixation, nonunion, and adjacent
segment disease (ASD). The mean follow-up was 36.4 months in the RA
group and 39.1 months in the non-RA group.Aims
Methods
The purpose of this study was to compare clinical
outcomes of total knee arthroplasty (TKA) after manipulation under
anaesthesia (MUA) for post-operative stiffness with a matched cohort
of TKA patients who did not requre MUA. In total 72 patients (mean age 59.8 years, 42 to 83) who underwent
MUA following TKA were identified from our prospective database
and compared with a matched cohort of patients who had undergone
TKA without subsequent MUA. Patients were evaluated for range of
movement (ROM) and clinical outcome scores (Western Ontario and
McMaster Universities Arthritis Index, Short-Form Health Survey,
and Knee Society Clinical Rating System) at a mean follow-up of
36.4 months (12 to 120). MUA took place at a mean of nine weeks
(5 to 18) after TKA. In patients who required MUA, mean flexion
deformity improved from 10° (0° to 25°) to 4.4° (0° to 15°) (p <
0.001),
and mean range of flexion improved from 79.8° (65° to 95°) to 116°
(80° to 130°) (p <
0.001). There were no statistically significant
differences in ROM or functional outcome scores at three months,
one year, or two years between those who required MUA and those
who did not. There were no complications associated with manipulation At most recent follow-up, patients requiring MUA achieved equivalent
ROM and clinical outcome scores when compared with a matched control
group. While other studies have focused on ROM after manipulation,
the current study adds to current literature by supplementing this
with functional outcome scores. Cite this article:
Effects of insulin-like growth factor 1 (IGF1), fibroblast growth
factor 2 (FGF2) and bone morphogenetic protein 2 (BMP2) on the expression
of genes involved in the proliferation and differentiation of osteoblasts
in culture were analysed. The best sequence of growth factor addition
that induces expansion of cells before their differentiation was
sought. Primary human osteoblasts in Objectives
Methods
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:
We evaluated the maturation of grafted bone in
cases of successful fusion after a one- or two-level posterior lumbar interbody
fusion (PLIF) using interbody carbon cages. We carried out a five-year
prospective longitudinal radiological evaluation of patients using
plain radiographs and CT scans. One year after surgery, 117 patients
with an early successful fusion were selected for inclusion in the
study. Radiological evaluation of interbody bone fusion was graded
on a 4-point scale. The mean grades of all radiological and CT assessments
increased in the five years after surgery, and differences compared
to the previous time interval were statistically significant for
three or four years after surgery. Because the grafted bone continues
to mature for three years after surgery, the success of a fusion
should not be assessed until at least three years have elapsed.
There were no significant differences in the longitudinal patterns
of grafted bone maturity between iliac bone and local bone. However,
iliac bone grafting may remodel faster than local bone.
The June 2014 Trauma Roundup360 looks at: BMP use increasing wound complication rates in trauma surgery; can we predict re-admission in trauma?; humeral bundle nailing; how best to treat high-angle femoral neck fractures?; hyperglycaemia and infection; simultaneous soft-tissue and bony repair in terrible triad injuries; metaphyseal malunion in the forearm leading to function restrictions; delayed fixation of the distal radius: not a bad option; and fasciotomies better with shoelaces
We present the results of 62 consecutive acetabular
revisions using impaction bone grafting and a cemented polyethylene
acetabular component in 58 patients (13 men and 45 women) after
a mean follow-up of 27 years (25 to 30). All patients were prospectively
followed. The mean age at revision was 59.2 years (23 to 82). We performed Kaplan–Meier (KM) analysis and also a Competing
Risk (CR) analysis because with long-term follow-up, the presence
of a competing event (i.e. death) prevents the occurrence of the
endpoint of re-revision. A total of 48 patients (52 hips) had died or had been re-revised
at final review in March 2011. None of the deaths were related to
the surgery. The mean Harris hip score of the ten surviving hips
in ten patients was 76 points (45 to 99). The KM survivorship at 25 years for the endpoint ‘re-revision
for any reason’ was 58.0% (95% confidence interval (CI) 38 to 73)
and for ‘re-revision for aseptic loosening’ 72.1% (95% CI 51 to
85). With the CR analysis we calculated the KM analysis overestimates
the failure rate with respectively 74% and 93% for these endpoints.
The current study shows that acetabular impaction bone grafting
revisions provide good clinical results at over 25 years. Cite this article:
We report our experience of revision total hip
replacement (THR) using the Revitan curved modular titanium fluted revision
stem in patients with a full spectrum of proximal femoral defects.
A total of 112 patients (116 revisions) with a mean age of 73.4
years (39 to 90) were included in the study. The mean follow-up
was 7.5 years (5.3 to 9.1). A total of 12 patients (12 hips) died
but their data were included in the survival analysis, and four
patients (4 hips) were lost to follow-up. The clinical outcome,
proximal bone regeneration and subsidence were assessed for 101
hips. The mean Harris Hip Score was 88.2 (45.8 to 100) after five years
and there was an increase of the mean Barnett and Nordin-Score,
a measure of the proximal bone regeneration, of 20.8 (-3.1 to 52.7).
Five stems had to be revised (4.3%), three (2.9%) showed subsidence,
five (4.3%) a dislocation and two of 85 aseptic revisions (2.3%)
a periprosthetic infection. At the latest follow-up, the survival with revision of the stem
as the endpoint was 95.7% (95% confidence interval 91.9% to 99.4%)
and with aseptic loosening as the endpoint, was 100%. Peri-prosthetic
fractures were not observed. We report excellent results with respect to subsidence, the risk
of fracture, and loosening after femoral revision using a modular
curved revision stem with distal cone-in-cone fixation. A successful
outcome depends on careful pre-operative planning and the use of
a transfemoral approach when the anatomy is distorted or a fracture
is imminent, or residual cement or a partially-secured existing
stem cannot be removed. The shortest appropriate stem should, in
our opinion, be used and secured with >
3 cm fixation at the femoral
isthmus, and distal interlocking screws should be used for additional
stability when this goal cannot be realised. Cite this article:
External fixation is widely used in orthopaedic
and trauma surgery. Infections around pin or wire sites, which are usually
localised, non-invasive, and are easily managed, are common. Occasionally,
more serious invasive complications such as necrotising fasciitis
(NF) and toxic shock syndrome (TSS) may occur. We retrospectively reviewed all patients who underwent external
fixation between 1997 and 2012 in our limb lengthening and reconstruction
programme. A total of eight patients (seven female and one male)
with a mean age of 20 years (5 to 45) in which pin/wire track infections
became limb- or life-threatening were identified. Of these, four
were due to TSS and four to NF. Their management is described. A
satisfactory outcome was obtained with early diagnosis and aggressive
medical and surgical treatment. Clinicians caring for patients who have external fixation and
in whom infection has developed should be aware of the possibility
of these more serious complications. Early diagnosis and aggressive
treatment are required in order to obtain a satisfactory outcome. Cite this article:
Small animal models of fracture repair primarily investigate
indirect fracture healing via external callus formation. We present
the first described rat model of direct fracture healing. A rat tibial osteotomy was created and fixed with compression
plating similar to that used in patients. The procedure was evaluated
in 15 cadaver rats and then Objectives
Methods
Highly active anti-retroviral therapy has transformed HIV into a chronic disease with a long-term asymptomatic phase. As a result, emphasis is shifting to other effects of the virus, aside from immunosuppression and mortality. We have reviewed the current evidence for an association between HIV infection and poor fracture healing. The increased prevalence of osteoporosis and fragility fractures in HIV patients is well recognised. The suggestion that this may be purely as a result of highly active anti-retroviral therapy has been largely rejected. Apart from directly impeding cellular function in bone remodelling, HIV infection is known to cause derangement in the levels of those cytokines involved in fracture healing (particularly tumour necrosis factor-α) and appears to impair the blood supply of bone. Many other factors complicate this issue, including a reduced body mass index, suboptimal nutrition, the effects of anti-retroviral drugs and the avoidance of operative intervention because of high rates of wound infection. However, there are sound molecular and biochemical hypotheses for a direct relationship between HIV infection and impaired fracture healing, and the rewards for further knowledge in this area are extensive in terms of optimised fracture management, reduced patient morbidity and educated resource allocation. Further investigation in this area is overdue.
There remains conflicting evidence regarding cortical bone strength
following bisphosphonate therapy. As part of a study to assess the
effects of bisphosphonate treatment on the healing of rat tibial
fractures, the mechanical properties and radiological density of
the uninjured contralateral tibia was assessed. Skeletally mature aged rats were used. A total of 14 rats received
1µg/kg ibandronate (iban) daily and 17 rats received 1 ml 0.9% sodium
chloride (control) daily. Stress at failure and toughness of the
tibial diaphysis were calculated following four-point bending tests.Objectives
Methods
Platelet-derived growth factor (PDGF) is known
to stimulate osteoblast or osteoprogenitor cell activity. We investigated
the effect of locally applied PDGF from poly- These results indicate that local application of PDGF from biodegradable
PDLLA-coated implants significantly accelerates fracture healing
in experimental animals. Further development may help fracture healing
in the clinical situation.
Failure of bone repair is a challenging problem in the management of fractures. There is a limited supply of autologous bone grafts for treating nonunions, with associated morbidity after harvesting. There is need for a better source of cells for repair. Mesenchymal stem cells (MSCs) hold promise for healing of bone because of their capacity to differentiate into osteoblasts and their availability from a wide variety of sources. Our review aims to evaluate the available clinical evidence and recent progress in strategies which attempt to use autologous and heterologous MSCs in clinical practice, including genetically-modified MSCs and those grown on scaffolds. We have compared various procedures for isolating and expanding a sufficient number of MSCs for use in a clinical setting. There are now a number of clinical studies which have shown that implantation of MSCs is an effective, safe and durable method for aiding the repair and regeneration of bone.
Biochemical markers of bone-turnover have long been used to complement the radiological assessment of patients with metabolic bone disease. Their implementation in daily clinical practice has been helpful in the understanding of the pathogenesis of osteoporosis, the selection of the optimal dose and the understanding of the progression of the onset and resolution of treatment. Since they are derived from both cortical and trabecular bone, they reflect the metabolic activity of the entire skeleton rather than that of individual cells or the process of mineralisation. Quantitative changes in skeletal-turnover can be assessed easily and non-invasively by the measurement of bone-turnover markers. They are commonly subdivided into three categories; 1) bone-resorption markers, 2) osteoclast regulatory proteins and 3) bone-formation markers. Because of the rapidly accumulating new knowledge of bone matrix biochemistry, attempts have been made to use them in the interpretation and characterisation of various stages of the healing of fractures. Early knowledge of the individual progress of a fracture could help to avoid delayed or nonunion by enabling modification of the host’s biological response. The levels of bone-turnover markers vary throughout the course of fracture repair with their rates of change being dependent on the size of the fracture and the time that it will take to heal. However, their short-term biological variability, the relatively low bone specificity exerted, given that the production and destruction of collagen is not limited to bone, as well as the influence of the host’s metabolism on their concentration, produce considerable intra- and inter-individual variability in their interpretation. Despite this, the possible role of bone-turnover markers in the assessment of progression to union, the risks of delayed or nonunion and the impact of innovations to accelerate fracture healing must not be ignored.
Soaking bone grafts in a bisphosphonate solution before implantation can prevent their resorption and increase the local bone density in rats and humans. However, recent studies suggest that pre-treatment of allografts with bisphosphonate can prevent bone ingrowth into impaction grafts. We tested the hypothesis that excessive amounts of bisphosphonate would also cause a negative response in less dense grafts. We used a model where non-impacted metaphyseal bone grafts were randomised into three groups with either no bisphosphonate, alendronate followed by rinsing, and alendronate without subsequent rinsing, and inserted into bone chambers in rats. The specimens were evaluated histologically at one week, and by histomorphometry and radiology at four weeks. At four weeks, both bisphosphonate groups showed an increase in the total bone content, increased newly formed bone, and higher radiodensity than the controls. In spite of being implanted in a chamber with a limited opportunity to diffuse, even an excessive amount of bisphosphonate improved the outcome. We suggest that the negative results seen by others could be due to the combination of densely compacted bone and a bisphosphonate. We suggest that bisphosphonates are likely to have a negative influence where resorption is a prerequisite to create space for new bone ingrowth.
In a rabbit model we investigated the efficacy of a silk fibroin/hydroxyapatite (SF/HA) composite on the repair of a segmental bone defect. Four types of porous SF/HA composites (SF/HA-1, SF/HA-2, SF/HA-3, SF/HA-4) with different material ratios, pore sizes, porosity and additives were implanted subcutaneously into Sprague-Dawley rats to observe biodegradation. SF/HA-3, which had characteristics more suitable for a bone substitite based on strength and resorption was selected as a scaffold and co-cultured with rabbit bone-marrow stromal cells (BMSCs). A segmental bone defect was created in the rabbit radius. The animals were randomised into group 1 (SF/HA-3 combined with BMSCs implanted into the bone defect), group 2 (SF/HA implanted alone) and group 3 (nothing implanted). They were killed at four, eight and 12 weeks for visual, radiological and histological study. The bone defects had complete union for group 1 and partial union in group 2, 12 weeks after operation. There was no formation of new bone in group 3. We conclude that SF/HA-3 combined with BMSCs supports bone healing and offers potential as a bone-graft substitute.