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.
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 August 2013 Research Roundup360 looks at: passive smoking and bone substitutes; platelet-rich plasma and osteogenesis; plantar fasciitis and platelet-rich plasma: a match made in heaven?; MRSA decolonisation decreases infection rates; gums, bisphosphonates and orthopaedics; PRAISE and partner violence; blunt impact and post-traumatic OA; and IDEAL research and implants
The haematoma occurring at the site of a fracture is known to play an important role in bone healing. We have recently shown the presence of progenitor cells in human fracture haematoma and demonstrated that they have the capacity for multilineage mesenchymal differentiation. There have been many studies which have shown that low-intensity pulsed ultrasound (LIPUS) stimulates the differentiation of a variety of cells, but none has investigated the effects of LIPUS on cells derived from human fracture tissue including human fracture haematoma-derived progenitor cells (HCs). In this
We have evaluated the effect of the short-term administration of low therapeutic doses of modern COX-2 inhibitors on the healing of fractures. A total of 40 adult male New Zealand rabbits were divided into five groups. A mid-diaphyseal osteotomy of the right ulna was performed and either normal saline, prednisolone, indometacin, meloxicam or rofecoxib was administered for five days. Radiological, biomechanical and histomorphometric evaluation was performed at six weeks. In the group in which the highly selective anti-COX-2 agent, rofecoxib, was used the incidence of radiologically-incomplete union was similar to that in the control group. All the biomechanical parameters were statistically significantly lower in both the prednisolone and indometacin (p = 0.01) and in the meloxicam (p = 0.04) groups compared with the control group. Only the fracture load values were found to be statistically significantly lower (p = 0.05) in the rofecoxib group. Histomorphometric parameters were adversely affected in all groups with the specimens of the rofecoxib group showing the least negative effect. Our findings indicated that the short-term administration of low therapeutic doses of a highly selective COX-2 inhibitor had a minor negative effect on bone healing.
We have examined the deterioration of implant fixation after withdrawal of parathyroid hormone (PTH) in rats. First, the pull-out force for stainless-steel screws in the proximal tibia was measured at different times after withdrawal. The stimulatory effect of PTH on fixation was lost after 16 days. We then studied whether bisphosphonates could block this withdrawal effect. Mechanical and histomorphometric measurements were conducted for five weeks after implantation. Subcutaneous injections were given daily. Specimens treated with either PTH or saline during the first two weeks showed no difference in the mechanical or histological results (pull-out force 76 N
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:
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 ( Cite this article:
We hypothesised that the use of tantalum (Ta)
acetabular components in revision total hip arthroplasty (THA) was protective
against subsequent failure due to infection. We identified 966 patients
(421 men, 545 women and 990 hips) who had undergone revision THA
between 2000 and 2013. The mean follow up was 40.2 months (3 months
to 13.1 years). The mean age of the men and women was 62.3 years
(31 to 90) and 65.1 years (25 to 92), respectively. Titanium (Ti) acetabular components were used in 536 hips while
Ta components were used in 454 hips. In total, 73 (7.3%) hips experienced
subsequent acetabular failure. The incidence of failure was lower
in the Ta group at 4.4% (20/454) compared with 9.9% (53/536) in
the Ti group (p <
0.001, odds ratio 2.38; 95% CI 1.37 to 4.27).
Among the 144 hips (64 Ta, 80 Ti) for which revision had been performed
because of infection, failure due to a subsequent infection was
lower in the Ta group at 3.1% (2/64) compared with 17.5% (14/80)
for the Ti group (p = 0.006). Thus, the use of Ta acetabular components during revision THA
was associated with a lower incidence of failure from all causes
and Ta components were associated with a lower incidence of subsequent
infection when used in patients with periprosthetic joint infection. Cite this article:
The major problem with repair of an articular cartilage injury
is the extensive difference in the structure and function of regenerated,
compared with normal cartilage. Our work investigates the feasibility
of repairing articular osteochondral defects in the canine knee
joint using a composite lamellar scaffold of nano-ß-tricalcium phosphate
(ß-TCP)/collagen (col) I and II with bone marrow stromal stem cells
(BMSCs) and assesses its biological compatibility. The bone–cartilage scaffold was prepared as a laminated composite,
using hydroxyapatite nanoparticles (nano-HAP)/collagen I/copolymer
of polylactic acid–hydroxyacetic acid as the bony scaffold, and
sodium hyaluronate/poly(lactic-co-glycolic acid) as the cartilaginous
scaffold. Ten-to 12-month-old hybrid canines were randomly divided
into an experimental group and a control group. BMSCs were obtained
from the iliac crest of each animal, and only those of the third
generation were used in experiments. An articular osteochondral
defect was created in the right knee of dogs in both groups. Those
in the experimental group were treated by implanting the composites
consisting of the lamellar scaffold of ß-TCP/col I/col II/BMSCs.
Those in the control group were left untreated.Objectives
Methods
Conventional cemented acetabular components are
reported to have a high rate of failure when implanted into previously
irradiated bone. We recommend the use of a cemented reconstruction
with the addition of an acetabular reinforcement cross to improve
fixation. We reviewed a cohort of 45 patients (49 hips) who had undergone
irradiation of the pelvis and a cemented total hip arthroplasty
(THA) with an acetabular reinforcement cross. All hips had received
a minimum dose of 30 Gray (Gy) to treat a primary nearby tumour
or metastasis. The median dose of radiation was 50 Gy (Q1 to Q3:
45 to 60; mean: 49.57, 32 to 72). The mean follow-up after THA was 51 months (17 to 137). The cumulative
probability of revision of the acetabular component for a mechanical
reason was 0% (0 to 0%) at 24 months, 2.9% (0.2 to 13.3%) at 60
months and 2.9% (0.2% to 13.3%) at 120 months, respectively. One
hip was revised for mechanical failure and three for infection. Cemented acetabular components with a reinforcement cross provide
good medium-term fixation after pelvic irradiation. These patients
are at a higher risk of developing infection of their THA. Cite this article:
Florid reactive periostitis is a pronounced periosteal reaction, usually affecting the hands and feet, for which there is no obvious cause. It is rare in children and in long bones. We report an unusual case of florid reactive periostitis in a ten-year-old girl that involved both bones of the forearm. The lesion resolved over a period of one year, leaving a residual exostosis. She developed a physeal bar in the distal ulna in the region of the lesion at one-year follow-up. This was thought to be a complication of the biopsy procedure and was treated by resection and proximal ulnar lengthening.
Cancellous allograft bone chips are commonly
used in the reconstruction of defects in bone after removal of benign tumours.
We investigated the MRI features of grafted bone chips and their
change over time, and compared them with those with recurrent tumour.
We retrospectively reviewed 66 post-operative MRIs from 34 patients
who had undergone curettage and grafting with cancellous bone chips
to fill the defect after excision of a tumour. All grafts showed
consistent features at least six months after grafting: homogeneous
intermediate or low signal intensities with or without scattered
hyperintense foci (speckled hyperintensities) on T1 images; high
signal intensities with scattered hypointense foci (speckled hypointensities)
on T2 images, and peripheral rim enhancement with or without central
heterogeneous enhancements on enhanced images. Incorporation of
the graft occurred from the periphery to the centre, and was completed
within three years. Recurrent lesions consistently showed the same signal
intensities as those of pre-operative MRIs of the primary lesions.
There were four misdiagnoses, three of which were chondroid tumours. We identified typical MRI features and clarified the incorporation
process of grafted cancellous allograft bone chips. The most important
characteristics of recurrent tumours were that they showed the same
signal intensities as the primary tumours. It might sometimes be
difficult to differentiate grafted cancellous allograft bone chips
from a recurrent chondroid tumour. Cite this article:
This paper reviews the current literature concerning the main clinical factors which can impair the healing of fractures and makes recommendations on avoiding or minimising these in order to optimise the outcome for patients. The clinical implications are described.
Curettage and packing with polymethylmethacrylate cement is a routine treatment for giant-cell tumour (GCT) of bone. We performed an We found that the cytotoxic effect of eluted drugs depended on their concentration and the time interval, with even the lowest dose of each drug demonstrating an acceptable rate of cytotoxicity. Even in low doses, cytotoxic drugs mixed with polymethylmethacrylate cement could therefore be considered as effective local adjuvant treatment for GCTs.
A silver-containing hydroxyapatite (Ag-HA) coating has been developed using thermal spraying technology. We evaluated the osteoconductivity of this coating on titanium (Ti) implants in rat tibiae in relation to bacterial infection in joint replacement. At 12 weeks, the mean affinity indices of bone formation of a Ti, an HA, a 3%Ag-HA and a 50%Ag-HA coating were 97.3%, 84.9%, 81.0% and 40.5%, respectively. The mean affinity indices of bone contact of these four coatings were 18.8%, 83.7%, 77.2% and 40.5%, respectively. The indices of bone formation and bone contact around the implant of the 3%Ag-HA coating were similar to those of the HA coating, and no significant differences were found between them (bone formation, p = 0.99; bone contact, p = 0.957). However, inhibition of bone formation was observed with the 50%Ag-HA coating. These results indicate that the 3%Ag-HA coating has low toxicity and good osteoconductivity, and that the effect of silver toxicity on osteoconductivity depends on the dose.
The literature on fracture repair has been reviewed. The traditional concepts of delayed and nonunion have been examined in terms of the phased and balanced anabolic and catabolic responses in bone repair. The role of medical manipulation of these inter-related responses in the fracture healing have been considered.
We compared the clinical and radiographic results
of total ankle replacement (TAR) performed in non-diabetic and diabetic
patients. We identified 173 patients who underwent unilateral TAR
between 2004 and 2011 with a minimum of two years’ follow-up. There
were 88 male (50.9%) and 85 female (49.1%) patients with a mean
age of 66 years ( The mean AOS and AOFAS scores were significantly better in the
non-diabetic group (p = 0.018 and p = 0.038, respectively). In all,
nine TARs (21%) in the diabetic group had clinical failure at a
mean follow-up of five years (24 to 109), which was significantly
higher than the rate of failure of 15 (11.6%) in the non-diabetic
group (p = 0.004). The uncontrolled diabetic subgroup had a significantly
poorer outcome than the non-diabetic group (p = 0.02), and a higher
rate of delayed wound healing. The incidence of early-onset osteolysis was higher in the diabetic
group than in the non-diabetic group (p = 0.02). These results suggest
that diabetes mellitus, especially with poor glycaemic control,
negatively affects the short- to mid-term outcome after TAR. Cite this article:
Although mechanical stabilisation has been a hallmark of orthopaedic surgical management, orthobiologics are now playing an increasing role. Platelet-rich plasma (PRP) is a volume of plasma fraction of autologous blood having platelet concentrations above baseline. The platelet α granules are rich in growth factors that play an essential role in tissue healing, such as transforming growth factor-β, vascular endothelial growth factor, and platelet-derived growth factor. PRP is used in various surgical fields to enhance bone and soft-tissue healing by placing supraphysiological concentrations of autologous platelets at the site of tissue damage. The easily obtainable PRP and its possible beneficial outcome hold promise for new regenerative treatment approaches. The aim of this literature review was to describe the bioactivities of PRP, to elucidate the different techniques for PRP preparation, to review animal and human studies, to evaluate the evidence regarding the use of PRP in trauma and orthopaedic surgery, to clarify risks, and to provide guidance for future research.