Although much has been published on the causes of slipped
Objectives. Intramedullary fixation is considered the most stable treatment for pertrochanteric fractures of the proximal femur and cut-out is one of the most frequent mechanical complications. In order to determine the role of clinical variables and radiological parameters in predicting the risk of this complication, we analysed the data pertaining to a group of patients recruited over the course of six years. Methods. A total of 571 patients were included in this study, which analysed the incidence of cut-out in relation to several clinical variables: age; gender; the AO Foundation and Orthopaedic Trauma Association classification system (AO/OTA); type of nail; cervical-diaphyseal angle; surgical wait times; anti-osteoporotic medication; complete post-operative weight bearing; and radiological parameters (namely the lag-screw position with respect to the femoral head, the Cleveland system, the tip-apex distance (TAD), and the calcar-referenced tip-apex distance (CalTAD)). Results. The incidence of cut-out across the sample was 5.6%, with a higher incidence in female patients. A significantly higher risk of this complication was correlated with lag-screw tip positioning in the
Hydroxyapatite-coated standard anatomical and customised femoral stems are designed to transmit load to the metaphyseal part of the proximal femur in order to avoid stress shielding and to reduce resorption of bone. In a randomised in vitro study, we compared the changes in the pattern of cortical strain after the insertion of hydroxyapatite-coated standard anatomical and customised stems in 12 pairs of human cadaver femora. A hip simulator reproduced the physiological loads on the proximal femur in single-leg stance and stair-climbing. The cortical strains were measured before and after the insertion of the stems. Significantly higher strain shielding was seen in Gruen zones 7, 6, 5, 3 and 2 after the insertion of the anatomical stem compared with the customised stem. For the anatomical stem, the hoop strains on the femur also indicated that the load was transferred to the cortical bone at the lower metaphyseal or
We have evaluated bone-marrow activity in the proximal femur of patients with corticosteroid-induced osteonecrosis and compared it with that of patients with osteonecrosis related to sickle-cell disease and with a control group without osteonecrosis. Bone marrow was obtained by puncture of the femoral head outside the area of necrosis and in the intertrochanteric region. The activity of stromal cells was assessed by culturing fibroblast colony-forming units (FCFUs). We found a decrease in the number of FCFUs outside the area of osteonecrosis in the
Growth plates taken from five- to 20-week-old Japanese white rabbits were immunostained for c-Myc protein. This was localised both in the proliferating zone and
Tissue engineering is an increasingly popular method of addressing pathological disorders of cartilage. Recent studies have demonstrated its clinical efficacy, but there is little information on the structural organisation and biochemical composition of the repair tissue and its relation to the adjacent normal tissue. We therefore analysed by polarised light microscopy and immunohistochemistry biopsies of repair tissue which had been taken 12 months after implantation of autologous chondrocytes in two patients with defects of articular cartilage. Our findings showed zonal heterogeneity throughout the repair tissue. The deeper zone resembled hyaline-like articular cartilage whereas the
Our aim was to evaluate the expression of transcription factors CCAAT/enhancer-binding protein-beta (C/EBP. β. ) and C/EBP-homologous protein (CHOP) in the growth plate. Proximal tibial epiphyseal growth plates from ten 15-day-old Wistar rats were used. Additionally, anti-proliferating cell nuclear antigen (PCNA), anti-5-bromo-2’-deoxyuridine (BrdU) immunostaining, terminal transferase dUTP nick end-labelling (TUNEL) and nucleolar organiser region-associated proteins (AgNOR) techniques were peformed. The histological morphology of the growth plate from C/EBP. β. knock-out mice was also analysed. The normal growth plate showed that C/EBP. β. and CHOP factors are expressed both in the germinative/
Metal-on-metal (MOM) bearings for hip arthroplasty are increasing in popularity. Concern remains, however, regarding the potential toxicological effects of the metal ions which these bearings release. The serum levels of cobalt and chromium in 22 patients who had undergone MOM resurfacing arthroplasty were compared with a matched group of 22 patients who had undergone 28 mm MOM total hip arthroplasty (THA). At a median of 16 months (7 to 56) after resurfacing arthroplasty, we found the median serum levels of cobalt and chromium to be 38 nmol/l (14 to 44) and 53 nmol/l (23 to 165) respectively. These were significantly greater than the levels after 28 mm MOM THA which were 22 nmol/l (15 to 87, p = 0.021) and 19 nmol/l (2 to 58, p <
0.001) respectively. Since the
Metaphyseal tritanium cones can be used to manage the tibial bone loss commonly encountered at revision total knee arthroplasty (rTKA). Tibial stems provide additional fixation and are generally used in combination with cones. The aim of this study was to examine the role of the stems in the overall stability of tibial implants when metaphyseal cones are used for rTKA. This computational study investigates whether stems are required to augment metaphyseal cones at rTKA. Three cemented stem scenarios (no stem, 50 mm stem, and 100 mm stem) were investigated with 10 mm-deep uncontained posterior and medial tibial defects using four loading scenarios designed to mimic activities of daily living.Aims
Methods
We studied subchondral intraosseous pressure (IOP) in an animal model during loading, and with vascular occlusion. We explored bone compartmentalization by saline injection. Needles were placed in the femoral condyle and proximal tibia of five anaesthetized rabbits and connected to pressure recorders. The limb was loaded with and without proximal vascular occlusion. An additional subject had simultaneous triple recordings at the femoral head, femoral condyle and proximal tibia. In a further subject, saline injections at three sites were carried out in turn.Objectives
Materials and Methods
Metabolic syndrome and low-grade systemic inflammation are associated with knee osteoarthritis (OA), but the relationships between these factors and OA in other synovial joints are unclear. The aim of this study was to determine if a high-fat/high-sucrose (HFS) diet results in OA-like joint damage in the shoulders, knees, and hips of rats after induction of obesity, and to identify potential joint-specific risks for OA-like changes. A total of 16 male Sprague-Dawley rats were allocated to either the diet-induced obesity group (DIO, 40% fat, 45% sucrose, n = 9) or a chow control diet (n = 7) for 12 weeks. At sacrifice, histological assessments of the shoulder, hip, and knee joints were performed. Serum inflammatory mediators and body composition were also evaluated. The total Mankin score for each animal was assessed by adding together the individual Modified Mankin scores across all three joints. Linear regression modelling was conducted to evaluate predictive relationships between serum mediators and total joint damage.Objectives
Methods
The objective of this study was to develop a test for the rapid (within 25 minutes) intraoperative detection of bacteria from synovial fluid to diagnose periprosthetic joint infection (PJI). The 16s rDNA test combines a polymerase chain reaction (PCR) for amplification of 16s rDNA with a lateral flow immunoassay in one fully automated system. The synovial fluid of 77 patients undergoing joint aspiration or primary or revision total hip or knee surgery was prospectively collected. The cohort was divided into a proof-of-principle cohort (n = 17) and a validation cohort (n = 60). Using the proof-of-principle cohort, an optimal cut-off for the discrimination between PJI and non-PJI samples was determined. PJI was defined as detection of the same bacterial species in a minimum of two microbiological samples, positive histology, and presence of a sinus tract or intra-articular pus.Objectives
Methods
Osteophytes are products of active endochondral and intramembranous ossification, and therefore could theoretically provide significant efficacy as bone grafts. In this study, we compared the bone mineralisation effectiveness of osteophytes and cancellous bone, including their effects on secretion of growth factors and anabolic effects on osteoblasts. Osteophytes and cancellous bone obtained from human patients were transplanted onto the calvaria of severe combined immunodeficient mice, with Calcein administered intra-peritoneally for fluorescent labelling of bone mineralisation. Conditioned media were prepared using osteophytes and cancellous bone, and growth factor concentration and effects of each graft on proliferation, differentiation and migration of osteoblastic cells were assessed using enzyme-linked immunosorbent assays, MTS ((3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium)) assays, quantitative real-time polymerase chain reaction, and migration assays.Objectives
Methods
All-suture anchors are increasingly used in rotator cuff repair procedures. Potential benefits include decreased bone damage. However, there is limited published evidence for the relative strength of fixation for all-suture anchors compared with traditional anchors. A total of four commercially available all-suture anchors, the ‘Y-Knot’ (ConMed), Q-FIX (Smith & Nephew), ICONIX (Stryker) and JuggerKnot (Zimmer Biomet) and a traditional anchor control TWINFIX Ultra PK Suture Anchor (Smith & Nephew) were tested in cadaveric human humeral head rotator cuff repair models (n = 24). This construct underwent cyclic loading applied by a mechanical testing rig (Zwick/Roell). Ultimate load to failure, gap formation at 50, 100, 150 and 200 cycles, and failure mechanism were recorded. Significance was set at p < 0.05.Objectives
Materials and Methods
We have previously investigated an association between the genome copy number variation (CNV) and acetabular dysplasia (AD). Hip osteoarthritis is associated with a genetic polymorphism in the aspartic acid repeat in the N-terminal region of the asporin ( Acetabular coverage of all subjects was evaluated using radiological findings (Sharp angle, centre-edge (CE) angle, acetabular roof obliquity (ARO) angle, and minimum joint space width). Genomic DNA was extracted from peripheral blood leukocytes. Agilent’s region-targeted high-density oligonucleotide tiling microarray was used to analyse 64 female AD patients and 32 female control subjects. All statistical analyses were performed using EZR software (Fisher’s exact probability test, Pearson’s correlation test, and Student’s Objectives
Methods
To elucidate the effects of age on the expression levels of the receptor activator of the nuclear factor-κB ligand (RANKL) and osteoclasts in the periodontal ligament during orthodontic mechanical loading and post-orthodontic retention. The study included 20 male Sprague-Dawley rats, ten in the young group (aged four to five weeks) and ten in the adult group (aged 18 to 20 weeks). In each rat, the upper-left first molar was subjected to a seven-day orthodontic force loading followed by a seven-day retention period. The upper-right first molar served as a control. The amount of orthodontic tooth movement was measured after seven-day force application and seven-day post-orthodontic retention. The expression levels of RANKL and the tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts were evaluated on day 7 (end of mechanical force loading) and day 14 (after seven days of post-orthodontic retention). Statistical analysis was performed using the Objectives
Materials and Methods
Cellular movement and relocalisation are important for many physiologic properties. Local mesenchymal stem cells (MSCs) from injured tissues and circulating MSCs aid in fracture healing. Cytokines and chemokines such as Stromal cell-derived factor 1(SDF-1) and its receptor chemokine receptor type 4 (CXCR4) play important roles in maintaining mobilisation, trafficking and homing of stem cells from bone marrow to the site of injury. We investigated the differences in migration of MSCs from the femurs of young, adult and ovariectomised (OVX) rats and the effect of CXCR4 over-expression on their migration. MSCs from young, adult and OVX rats were put in a Boyden chamber to establish their migration towards SDF-1. This was compared with MSCs transfected with CXCR4, as well as MSCs differentiated to osteoblasts.Objectives
Methods
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
The purpose of this study was to compare the results and complications of tibial lengthening over an intramedullary nail with treatment using the traditional Ilizarov method. In this matched case study, 16 adult patients underwent 19 tibial lengthening over nails (LON) procedures. For the matched case group, 17 patients who underwent 19 Ilizarov tibial lengthenings were retrospectively matched to the LON group.Objectives
Methods
Mechanical wear and corrosion at the head-stem junction of total hip arthroplasties (THAs) (trunnionosis) have been implicated in their early revision, most commonly in metal-on-metal (MOM) hips. We can isolate the role of the head-stem junction as the predominant source of metal release by investigating non-MOM hips; this can help to identify clinically significant volumes of material loss and corrosion from these surfaces. In this study we examined a series of 94 retrieved metal-on-polyethylene (MOP) hips for evidence of corrosion and material loss at the taper junction using a well published visual grading method and an established roundness-measuring machine protocol. Hips were retrieved from 74 male and 20 female patients with a median age of 57 years (30 to 76) and a median time to revision of 215 months (2 to 324). The reasons for revision were loosening of both the acetabular component and the stem (n = 29), loosening of the acetabular component (n = 58) and infection (n = 7). No adverse tissue reactions were reported by the revision surgeons.Objectives
Methods
This study was conducted to evaluate the cytokine-release kinetics of platelet-rich plasma (PRP) according to different activation protocols. Two manual preparation procedures (single-spin (SS) at 900 g for five minutes; double-spin (DS) at 900 g for five minutes and then 1500 g for 15 minutes) were performed for each of 14 healthy subjects. Both preparations were tested for platelet activation by one of three activation protocols: no activation, activation with calcium (Ca) only, or calcium with a low dose (50 IU per 1 ml PRP) of thrombin. Each preparation was divided into four aliquots and incubated for one hour, 24 hours, 72 hours, and seven days. The cytokine-release kinetics were evaluated by assessing PDGF, TGF, VEGF, FGF, IL-1, and MMP-9 concentrations with bead-based sandwich immunoassay.Objectives
Methods
We sought to determine if a durable bilayer implant composed of trabecular metal with autologous periosteum on top would be suitable to reconstitute large osteochondral defects. This design would allow for secure implant fixation, subsequent integration and remodeling. Adult sheep were randomly assigned to one of three groups (n = 8/group): 1. trabecular metal/periosteal graft (TMPG), 2. trabecular metal (TM), 3. empty defect (ED). Cartilage and bone healing were assessed macroscopically, biochemically (type II collagen, sulfated glycosaminoglycan (sGAG) and double-stranded DNA (dsDNA) content) and histologically.Objectives
Materials and Methods
This study tests the biomechanical properties of adjacent locked
plate constructs in a femur model using Sawbones. Previous studies
have described biomechanical behaviour related to inter-device distances.
We hypothesise that a smaller lateral inter-plate distance will
result in a biomechanically stronger construct, and that addition
of an anterior plate will increase the overall strength of the construct. Sawbones were plated laterally with two large-fragment locking
compression plates with inter-plate distances of 10 mm or 1 mm.
Small-fragment locking compression plates of 7-hole, 9-hole, and
11-hole sizes were placed anteriorly to span the inter-plate distance.
Four-point bend loading was applied, and the moment required to
displace the constructs by 10 mm was recorded.Objectives
Methods
Lengthening osteotomies of the calcaneus in children are in general
grafted with bone from the iliac crest. Artificial bone grafts have
been introduced, however, their structural and clinical durability
has not been documented. Radiostereometric analysis (RSA) is a very
accurate and precise method for measurements of rigid body movements including
the evaluation of joint implant and fracture stability, however,
RSA has not previously been used in clinical studies of calcaneal
osteotomies. We assessed the precision of RSA as a measurement tool
in a lateral calcaneal lengthening osteotomy (LCLO). LCLO was performed in six fixed adult cadaver feet. Tantalum
markers were inserted on each side of the osteotomy and in the cuboideum.
Lengthening was done with a plexiglas wedge. A total of 24 radiological
double examinations were obtained. Two feet were excluded due to
loose and poorly dispersed markers. Precision was assessed as systematic
bias and 95% repeatability limits.Objectives
Methods
Venous thromboembolism (VTE) is a major potential complication following orthopaedic surgery. Subcutaneously administered enoxaparin has been used as the benchmark to reduce the incidence of VTE. However, concerns have been raised regarding the long-term administration of enoxaparin and its possible negative effects on bone healing and bone density with an increase of the risk of osteoporotic fractures. New oral anticoagulants such as rivaroxaban have recently been introduced, however, there is a lack of information regarding how these drugs affect bone metabolism and post-operative bone healing. We measured the migration and proliferation capacity of mesenchymal stem cells (MSCs) under enoxaparin or rivaroxaban treatment for three consecutive weeks, and evaluated effects on MSC mRNA expression of markers for stress and osteogenic differentiation.Objectives
Methods
Osteoporosis and abnormal bone metabolism may prove to be significant
factors influencing the outcome of arthroplasty surgery, predisposing
to complications of aseptic loosening and peri-prosthetic fracture.
We aimed to investigate baseline bone mineral density (BMD) and
bone turnover in patients about to undergo arthroplasty of the hip
and knee. We prospectively measured bone mineral density of the hip and
lumbar spine using dual-energy X-ray absorptiometry (DEXA) scans
in a cohort of 194 patients awaiting hip or knee arthroplasty. We
also assessed bone turnover using urinary deoxypyridinoline (DPD),
a type I collagen crosslink, normalised to creatinine.Aims
Methods
Ligaments which heal spontaneously have a healing process that
is similar to skin wound healing. Menopause impairs skin wound healing
and may likewise impair ligament healing. Our purpose in this study
was to investigate the effect of surgical menopause on ligament
healing in a rabbit medial collateral ligament model. Surgical menopause was induced with ovariohysterectomy surgery
in adult female rabbits. Ligament injury was created by making a
surgical gap in the midsubstance of the medial collateral ligament.
Ligaments were allowed to heal for six or 14 weeks in the presence
or absence of oestrogen before being compared with uninjured ligaments. Molecular
assessment examined the messenger ribonucleic acid levels for collagens,
proteoglycans, proteinases, hormone receptors, growth factors and
inflammatory mediators. Mechanical assessments examined ligament
laxity, total creep strain and failure stress.Objectives
Methods
We welcome letters to the Editor concerning articles
that have recently been published. Such letters will be subject
to the usual stages of selection and editing; where appropriate the
authors of the original article will be offered the opportunity
to reply.
To assess the sensitivity and specificity of self-reported osteoporosis
compared with dual energy X-ray absorptiometry (DXA) defined osteoporosis,
and to describe medication use among participants with the condition. Data were obtained from a population-based longitudinal study
and assessed for the prevalence of osteoporosis, falls, fractures
and medication use. DXA scans were also undertaken.Objectives
Methods
This study aims to assess the correlation of CT-based structural
rigidity analysis with mechanically determined axial rigidity in
normal and metabolically diseased rat bone. A total of 30 rats were divided equally into normal, ovariectomized,
and partially nephrectomized groups. Cortical and trabecular bone
segments from each animal underwent micro-CT to assess their average
and minimum axial rigidities using structural rigidity analysis.
Following imaging, all specimens were subjected to uniaxial compression
and assessment of mechanically-derived axial rigidity.Objectives
Methods
We aimed to examine the characteristics of deep venous flow in
the leg in a cast and the effects of a wearable neuromuscular stimulator
(geko; FirstKind Ltd) and also to explore the participants’ tolerance
of the stimulator. This is an open-label physiological study on ten healthy volunteers.
Duplex ultrasonography of the superficial femoral vein measured
normal flow and cross-sectional area in the standing and supine
positions (with the lower limb initially horizontal and then elevated).
Flow measurements were repeated during activation of the geko stimulator
placed over the peroneal nerve. The process was repeated after the
application of a below-knee cast. Participants evaluated discomfort
using a questionnaire (verbal rating score) and a scoring index
(visual analogue scale).Objectives
Methods
In a study on ten fresh human cadavers we examined the change in the height of the intervertebral disc space, the angle of lordosis and the geometry of the facet joints after insertion of intervertebral total disc replacements. SB III Charité prostheses were inserted at L3-4, L4-5, and L5-S1. The changes studied were measured using computer navigation sofware applied to CT scans before and after instrumentation. After disc replacement the mean lumbar disc height was doubled (p <
0.001). The mean angle of lordosis and the facet joint space increased by a statistically significant extent (p <
0.005 and p = 0.006, respectively). By contrast, the mean facet joint overlap was significantly reduced (p <
0.001). Our study indicates that the increase in the intervertebral disc height after disc replacement changes the geometry at the facet joints. This may have clinical relevance.
The biomechanics of the patellofemoral joint can become disturbed during total knee replacement by alterations induced by the position and shape of the different prosthetic components. The role of the patella and femoral trochlea has been well studied. We have examined the effect of anterior or posterior positioning of the tibial component on the mechanisms of patellofemoral contact in total knee replacement. The hypothesis was that placing the tibial component more posteriorly would reduce patellofemoral contact stress while providing a more efficient lever arm during extension of the knee. We studied five different positions of the tibial component using a six degrees of freedom dynamic knee simulator system based on the Oxford rig, while simulating an active knee squat under physiological loading conditions. The patellofemoral contact force decreased at a mean of 2.2% for every millimetre of posterior translation of the tibial component. Anterior positions of the tibial component were associated with elevation of the patellofemoral joint pressure, which was particularly marked in flexion >
90°. From our results we believe that more posterior positioning of the tibial component in total knee replacement would be beneficial to the patellofemoral joint.
The aim of our study was to investigate whether placing of the femoral component of a hip resurfacing in valgus protected against spontaneous fracture of the femoral neck. We performed a hip resurfacing in 20 pairs of embalmed femora. The femoral component was implanted at the natural neck-shaft angle in the left femur and with a 10° valgus angle on the right. The bone mineral density of each femur was measured and CT was performed. Each femur was evaluated in a materials testing machine using increasing cyclical loads. In specimens with good bone quality, the 10° valgus placement of the femoral component had a protective effect against fractures of the femoral neck. An adverse effect was detected in osteoporotic specimens. When resurfacing the hip a valgus position of the femoral component should be achieved in order to prevent fracture of the femoral neck. Patient selection remains absolutely imperative. In borderline cases, measurement of bone mineral density may be indicated.
We carried out a cross-sectional study with analysis of the demographic, clinical and laboratory characteristics of patients with metal-on-metal hip resurfacing, ceramic-on-ceramic and metal-on-polyethylene hip replacements. Our aim was to evaluate the relationship between metal-on-metal replacements, the levels of cobalt and chromium ions in whole blood and the absolute numbers of circulating lymphocytes. We recruited 164 patients (101 men and 63 women) with hip replacements, 106 with metal-on-metal hips and 58 with non-metal-on-metal hips, aged <
65 years, with a pre-operative diagnosis of osteoarthritis and no pre-existing immunological disorders. Laboratory-defined T-cell lymphopenia was present in13 patients (15%) (CD8+ lymphopenia) and 11 patients (13%) (CD3+ lymphopenia) with unilateral metal-on-metal hips. There were significant differences in the absolute CD8+ lymphocyte subset counts for the metal-on-metal groups compared with each control group (p-values ranging between 0.024 and 0.046). Statistical modelling with analysis of covariance using age, gender, type of hip replacement, smoking and circulating metal ion levels, showed that circulating levels of metal ions, especially cobalt, explained the variation in absolute lymphocyte counts for almost all lymphocyte subsets.
This study was designed to test the hypothesis
that the sensory innervation of bone might play an important role
in sensing and responding to low-intensity pulsed ultrasound and
explain its effect in promoting fracture healing. In 112 rats a
standardised mid-shaft tibial fracture was created, supported with
an intramedullary needle and divided into four groups of 28. These
either had a sciatic neurectomy or a patellar tendon resection as
control, and received the ultrasound or not as a sham treatment.
Fracture union, callus mineralisation and remodelling were assessed using
plain radiography, peripheral quantitative computed tomography and
histomorphology. Daily ultrasound treatment significantly increased the rate of
union and the volumetric bone mineral density in the fracture callus
in the neurally intact rats (p = 0.025), but this stimulating effect
was absent in the rats with sciatic neurectomy. Histomorphology
demonstrated faster maturation of the callus in the group treated
with ultrasound when compared with the control group. The results
supported the hypothesis that intact innervation plays an important
role in allowing low-intensity pulsed ultrasound to promote fracture
healing.
Sex hormones play important roles in the regulation of the proliferation, maturation and death of chondrocytes in the epiphyseal growth plate. We have investigated the effects of male castration on the cell kinetics of chondrocytes as defined by the numbers of proliferating and dying cells. The growth plates of normal rabbits and animals castrated at eight weeks of age were obtained at 10, 15, 20 and 25 weeks of age. Our study suggested that castration led to an increase in apoptosis and a decrease in the proliferation of chondrocytes in the growth plate. In addition, the number of chondrocytes in the castrated rabbits was less than that of normal animals of the same age.
This review briefly summarises some of the definitive
studies of articular cartilage by microscopic MRI (µMRI) that were
conducted with the highest spatial resolutions. The article has
four major sections. The first section introduces the cartilage
tissue, MRI and µMRI, and the concept of image contrast in MRI.
The second section describes the characteristic profiles of three
relaxation times (T1, T2 and T1ρ)
and self-diffusion in healthy articular cartilage. The third section
discusses several factors that can influence the visualisation of
articular cartilage and the detection of cartilage lesion by MRI
and µMRI. These factors include image resolution, image analysis
strategies, visualisation of the total tissue, topographical variations
of the tissue properties, surface fibril ambiguity, deformation
of the articular cartilage, and cartilage lesion. The final section
justifies the values of multidisciplinary imaging that correlates
MRI with other technical modalities, such as optical imaging. Rather
than an exhaustive review to capture all activities in the literature,
the studies cited in this review are merely illustrative.
We describe a lateral approach to the distal humerus based on initial location of the superficial branches of the radial nerve, the inferior lateral cutaneous nerve of the arm and the posterior cutaneous nerve of the forearm. In 18 upper limbs the superficial branches of the radial nerve were located in the subcutaneous tissue between the triceps and brachioradialis muscles and dissected proximally to their origin from the radial nerve, exposing the shaft of the humerus. The inferior lateral cutaneous nerve of the arm arose from the radial nerve at the lower part of the spiral groove, at a mean of 14.2 cm proximal to the lateral epicondyle. The posterior cutaneous nerve of the forearm arose from the inferior lateral cutaneous nerve at a mean of 6.9 cm (6.0 to 8.1) proximal to the lateral epicondyle and descended vertically along the dorsal aspect of the forearm. The size and constant site of emergence between the triceps and brachioradialis muscles constitute a readily identifiable landmark to explore the radial nerve and expose the humeral shaft.
We stably transfected early passage chondrocytes with an anti-apoptotic Bcl-2 gene We conclude that NO-induced chondrocyte death involves a mechanism which appears to be subject to regulation by an anti-apoptotic Bcl-2 gene. Therefore, Bcl-2 gene therapy may prove to be of therapeutic value in protecting human articular chondrocytes.
There is no diagnostic, non-invasive method for the early detection of loosening after total hip arthroplasty. In a pilot study, we have analysed two serum markers of bone remodelling, procollagen I C-terminal extension peptide (PICP) and cross-linked N-terminal telopeptide (NTx), as well as the diagnostic performance of NTx for the assessment of osteolysis. We recruited 21 patients with loosening (group I), 18 with a well-fixed prosthesis (group II) and 17 at the time of primary arthroplasty for osteoarthritis (OA) (group III). Internal normal reference ranges were obtained from 30 healthy subjects (group IV). The serum PICP level was found to be significantly lower in patients with OA and those with loosening, when compared with those with stable implants, while the NTx level was significantly increased only in the group with loosening, suggesting that collagen degradation depended on the altered bone turnover induced by the implant. This hypothesis was reinforced by the finding that the values in the pre-surgery patients and stable subjects were comparable with the reference range of younger healthy subjects. A high specificity and positive predictive value for NTx provided good diagnostic evidence of agreement between the test and the clinical and radiological evaluations. The NTx level could be used to indicate stability of the implant. However, further prospective, larger studies are necessary.
The aim of this study was to evaluate the cultivation potential of cartilage taken from the debrided edge of a chronic lesion of the articular surface. A total of 14 patients underwent arthroscopy of the knee for a chronic lesion on the femoral condyles or trochlea. In addition to the routine cartilage biopsy, a second biopsy of cartilage was taken from the edge of the lesion. The cells isolated from both sources underwent parallel cultivation as monolayer and three-dimensional (3D) alginate culture. The cell yield, viability, capacity for proliferation, morphology and the expressions of typical cartilage genes (collagen I, COL1; collagen II, COL2; aggrecan, AGR; and versican, VER) were assessed. The cartilage differentiation indices (COL2/COL1, AGR/VER) were calculated. The control biopsies revealed a higher mean cell yield (1346 cells/mg Our results suggest that the cultivation of chondrocytes solely from the edges of the lesion cannot be recommended for use in autologous chondrocyte implantation.
Our aim was to compare the biomechanical properties of suturing methods to determine a better method for the repair of lacerated skeletal muscle. We tested Kessler stitches and the combination of Mason-Allen and perimeter stitches. Individual stitches were placed in the muscle belly of quadriceps femoris from a pig cadaver and were tensioned mechanically. The maximum loads and strains were measured and failure modes recorded. The mean load and strain for the Kessler stitches were significantly less than those for combination stitches. All five Kessler stitches tore out longitudinally from the muscle. All five combination stitches did not fail but successfully elongated. Our study has shown that the better method of repair for suturing muscle is the use of combination stitches.
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.
A complete cement mantle is important for the longevity of a total hip replacement. In the minimally-invasive direct anterior approach used at the Innsbruck University hospital, the femoral component has to be inserted into the femoral canal by an angulated movement. In a cadaver study, the quality and the extent of the cement mantle surrounding 13 Exeter femoral components implanted straight through a standard anterolateral transgluteal approach were compared with those of 13 similar femoral components implanted in an angulated fashion through a direct anterior approach. A third-generation cementing technique was used. The inner and outer contours of the cement mantles was traced from CT scans and the thickness and cross-sectional area determined. In no case was the cement mantle incomplete. The total mean thickness of the cement mantle was 3.62 mm (95% confidence interval 3.59 to 3.65). The mean thickness in the group using the minimally-invasive approach was 0.16 mm less than that in the anterolateral group. The distribution of the thickness was similar in the two groups. The mean thickness was less on the anteromedial and anterolateral aspect than on the posterior aspect of the femur. There is no evidence that the angulated introduction of Exeter femoral components in the direct anterior approach in cadavers compromises the quality, extent or thickness of the cement mantle.
The aim of this study was to determine whether exposure of human articular cartilage to hyperosmotic saline (0.9%, 600 mOsm) reduces Using confocal laser scanning microscopy, we identified a sixfold (p = 0.04) decrease in chondrocyte death following mechanical injury in the superficial zone of human articular cartilage exposed to hyperosmotic saline compared with normal saline. These data suggest that increasing the osmolarity of joint irrigation solutions used during open and arthroscopic articular surgery may reduce chondrocyte death from surgical injury and could promote integrative cartilage repair.
Repeated trauma to the radial head may be one of the causative factors in the genesis of osteochondritis dissecans of the capitellum. We measured the force, contact area and pressure across the radiocapitellar articulation of the elbow before and after radial shortening osteotomy in five fresh-frozen cadaver upper limbs with loads of 45, 90 and 135 N, respectively. Measurements were made on pressure-sensitive film placed in the radiocapitellar articulation with the forearm in the supinated, neutral and pronated positions before and after radial shortening. Radial shortening significantly reduced the mean force and contact area across the radiocapitellar articulation in all positions of the forearm.
We implanted titanium and carbon fibre-reinforced plastic (CFRP) femoral prostheses of the same dimensions into five prosthetic femora. An abductor jig was attached and a 1 kN load applied. This was repeated with five control femora. Digital image correlation was used to give a detailed two-dimensional strain map of the medial cortex of the proximal femur. Both implants caused stress shielding around the calcar. Distally, the titanium implant showed stress shielding, whereas the CFRP prosthesis did not produce a strain pattern which was statistically different from the controls. There was a reduction in strain beyond the tip of both the implants. This investigation indicates that use of the CFRP stem should avoid stress shielding in total hip replacement.
We dissected 20 cadaver hips in order to investigate the anatomy and excursion of the trochanteric muscles in relation to the posterior approach for total hip replacement. String models of each muscle were created and their excursion measured while the femur was moved between its anatomical position and the dislocated position. The position of the hip was determined by computer navigation. In contrast to previous studies which showed a separate insertion of piriformis and obturator internus, our findings indicated that piriformis inserted onto the superior and anterior margins of the greater trochanter through a conjoint tendon with obturator internus, and had connections to gluteus medius posteriorly. Division of these connections allowed lateral mobilisation of gluteus medius with minimal retraction. Analysis of the excursion of these muscles revealed that positioning the thigh for preparation of the femur through this approach elongated piriformis to a maximum of 182%, obturator internus to 185% and obturator externus to 220% of their resting lengths, which are above the thresholds for rupture of these muscles. Our findings suggested that gluteus medius may be protected from overstretching by release of its connection with the conjoint tendon. In addition, failure to detach piriformis or the obturators during a posterior approach for total hip replacement could potentially produce damage to these muscles because of over-stretching, obturator externus being the most vulnerable.
Impaction allograft is an established method of securing initial stability of an implant in arthroplasty. Subsequent bone integration can be prolonged, and the volume of allograft may not be maintained. Intermittent administration of parathyroid hormone has an anabolic effect on bone and may therefore improve integration of an implant. Using a canine implant model we tested the hypothesis that administration of parathyroid hormone may improve osseointegration of implants surrounded by bone graft. In 20 dogs a cylindrical porous-coated titanium alloy implant was inserted into normal cancellous bone in the proximal humerus and surrounded by a circumferential gap of 2.5 mm. Morsellised allograft was impacted around the implant. Half of the animals were given daily injections of human parathyroid hormone (1–34) 5 μg/kg for four weeks and half received control injections. The two groups were compared by mechanical testing and histomorphometry. We observed a significant increase in new bone formation within the bone graft in the parathyroid hormone group. There were no significant differences in the volume of allograft, bone-implant contact or in the mechanical parameters. These findings suggest that parathyroid hormone improves new bone formation in impacted morsellised allograft around an implant and retains the graft volume without significant resorption. Fixation of the implant was neither improved nor compromised at the final follow-up of four weeks.
Surgical reconstruction of articular surfaces by transplantation of osteochondral autografts has shown considerable promise in the treatment of focal articular lesions. During mosaicplasty, each cylindrical osteochondral graft is centred over the recipient hole and delivered by impacting the articular surface. Impact loading of articular cartilage has been associated with structural damage, loss of the viability of chondrocytes and subsequent degeneration of the articular cartilage. We have examined the relationship between single-impact loading and chondrocyte death for the specific confined-compression boundary conditions of mosaicplasty and the effect of repetitive impact loading which occurs during implantation of the graft on the resulting viability of the chondrocytes. Fresh bovine and porcine femoral condyles were used in this experiment. The percentage of chondrocyte death was found to vary logarithmically with single-impact energy and was predicted more strongly by the mean force of the impact rather than by the number of impacts required during placement of the graft. The significance of these results in regard to the surgical technique and design features of instruments for osteochondral transplantation is discussed.
Using the transverse processes of fresh porcine lumbar spines as an experimental model we evaluated the heat generated by a rotating burr of a high-speed drill in cutting the bone. The temperature at the drilled site reached 174°C with a diamond burr and 77°C with a steel burr. With water irrigation at a flow rate of 540 ml/hr an effective reduction in the temperature was achieved whereas irrigation with water at 180 ml/hr was much less effective. There was a significant negative correlation between the thickness of the residual bone and the temperature measured at its undersurface adjacent to the drilling site (p <
0.001). Our data suggest that tissues neighbouring the drilled bone, especially nerve roots, can be damaged by the heat generated from the tip of a high-speed drill. Nerve-root palsy, one of the most common complications of cervical spinal surgery, may be caused by thermal damage to nerve roots arising in this manner.
We compared the quality of debridement of chondral lesions performed by four arthroscopic (SH, shaver; CU, curette; SHCU, shaver and curette; BP, bipolar electrodes) and one open technique (OPEN, scalpel and curette) which are used prior to autologous chondrocyte implantation (ACI). The The most vertical walls with the least adjacent damage to cartilage were obtained with the OPEN technique. The CU and SHCU methods gave inferior, but still acceptable results whereas the SH technique alone resulted in a crater-like defect and the BP method undermined the cartilage wall. The subchondral bone was severely violated in all the equine samples which might have been peculiar to this model. The predominant depth of the debridement in the adult human samples was at the level of the calcified cartilage. Some minor penetrations of the subchondral end-plate were induced regardless of the instrumentation used. Our study suggests that not all routine arthroscopic instruments are suitable for the preparation of a defect for ACI. We have shown that the preferred debridement technique is either open or arthroscopically-assisted manual curettage. The use of juvenile equine stifles was not appropriate for the study of the cartilage-subchondral bone interface.
Platelet-leucocyte gel (PLG), a new biotechnological blood product, has hitherto been used primarily to treat chronic ulcers and to promote soft-tissue and bone regeneration in a wide range of medical fields. In this study, the antimicrobial efficacy of PLG against Staphylococcus aureus (ATCC 25923) was investigated in a rabbit model of osteomyelitis. Autologous PLG was injected into the tibial canal after inoculation with Staph. aureus. The prophylactic efficacy of PLG was evaluated by microbiological, radiological and histological examination. Animal groups included a treatment group that received systemic cefazolin and a control group that received no treatment. Treatment with PLG or cefazolin significantly reduced radiological and histological severity scores compared to the control group. This result was confirmed by a significant reduction in the infection rate and the number of viable bacteria. Although not comparable to cefazolin, PLG exhibited antimicrobial efficacy in vivo and therefore represents a novel strategy to prevent bone infection in humans.
We used a biodegradable mesh to convert an acetabular defect into a contained defect in six patients at total hip replacement. Their mean age was 61 years (46 to 69). The mean follow-up was 32 months (19 to 50). Before clinical use, the strength retention and hydrolytic in vitro degradation properties of the implants were studied in the laboratory over a two-year period. A successful clinical outcome was determined by the radiological findings and the Harris hip score. All the patients had a satisfactory outcome and no mechanical failures or other complications were observed. No protrusion of any of the impacted grafts was observed beyond the mesh. According to our preliminary laboratory and clinical results the biodegradable mesh is suitable for augmenting uncontained acetabular defects in which the primary stability of the implanted acetabular component is provided by the host bone. In the case of defects of the acetabular floor this new application provides a safe method of preventing graft material from protruding excessively into the pelvis and the mesh seems to tolerate bone-impaction grafting in selected patients with primary and revision total hip replacement.
This study compared the effect of a computer-assisted and a traditional surgical technique on the kinematics of the glenohumeral joint during passive abduction after hemiarthroplasty of the shoulder for the treatment of fractures. We used seven pairs of fresh-frozen cadaver shoulders to create simulated four-part fractures of the proximal humerus, which were then reconstructed with hemiarthroplasty and reattachment of the tuberosities. The specimens were randomised, so that one from each pair was repaired using the computer-assisted technique, whereas a traditional hemiarthroplasty without navigation was performed in the contralateral shoulder. Kinematic data were obtained using an electromagnetic tracking device. The traditional technique resulted in posterior and inferior translation of the humeral head. No statistical differences were observed before or after computer-assisted surgery. Although it requires further improvement, the computer-assisted approach appears to allow glenohumeral kinematics to more closely replicate those of the native joint, potentially improving the function of the shoulder and extending the longevity of the prosthesis.
We assessed the predictive value of the macroscopic and detailed microscopic appearance of the coracoacromial ligament, subacromial bursa and rotator-cuff tendon in 20 patients undergoing subacromial decompression for impingement in the absence of full-thickness tears of the rotator cuff. Histologically, all specimens had features of degenerative change and oedema in the extracellular matrix. Inflammatory cells were seen, but there was no evidence of chronic inflammation. However, the outcome was not related to cell counts. At three months the mean Oxford shoulder score had improved from 29.2 (20 to 40) to 39.4 (28 to 48) (p <
0.0001) and at six months to 45.5 (36 to 48) (p <
0.0001). At six months, although all patients had improved, the seven patients with a hooked acromion had done so to a less extent than those with a flat or curved acromion judged by their mean Oxford shoulder scores of 43.5 and 46.5 respectively (p = 0.046). All five patients with partial-thickness tears were within this group and demonstrated less improvement than the patients with no tear (mean Oxford shoulder scores 43.2 and 46.4, respectively, p = 0.04). These findings imply that in the presence of a partial-thickness tear subacromial decompression may require additional specific treatment to the rotator cuff if the outcome is to be improved further.
Surgery is considered to be the most effective treatment for cartilaginous tumours. In recent years, a trend has emerged for patients with low-grade tumours to be treated less invasively using curettage followed by various forms of adjuvant therapy. We investigated the potential for phenol to be used as an adjuvant. Using a human chondrosarcoma-derived cartilage-producing cell line OUMS-27 as an in vitro model we studied the cytotoxic effect of phenol and ethanol. Since ethanol is the standard substance used to rinse phenol out of a bone cavity, we included an assessment of ethanol to see whether this was an important secondary factor with respect to cell death. The latter was assessed by flow cytometry. A cytotoxic effect was found for concentrations of phenol of 1.5% and of ethanol of 42.5%. These results may provide a clinical rationale for the use of both phenol and ethanol as adjuvant therapy after intralesional curettage in low-grade central chondrosarcoma and justify further investigation.
We compared time-dependent changes in the biomechanical properties of single-and double-row repair of a simulated acute tear of the rotator cuff in rabbits to determine the effect of the fixation techniques on the healing process. A tear of the supraspinatus tendon was created in 80 rabbits which were separated into two equal groups. A single-row repair with two suture anchors was conducted in group 1 and a double-row repair with four suture anchors in group 2. A total of ten intact contralateral shoulder joints was used as a control group. Biomechanical testing was performed immediately post-operatively and at four and eight weeks, and histological analysis at four and eight weeks. The mean load to failure in group 2 animals was greater than in group 1, but both groups remained lower than the control group at all intervals. Histological analysis showed similar healing properties at four and eight weeks in both groups, but a significantly larger number of healed tendon-bone interfaces were identified in group 2 than in group 1 at eight weeks (p <
0.012). The ultimate load to failure increased with the number of suture anchors used immediately post-operatively, and at four and eight weeks. The increased load to failure at eight weeks seemed to be related to the increase in the surface area of healed tendon-to-bone in the double-row repair group.
We compared the bulking and tensile strength of the Pennington modified Kessler, Cruciate and the Savage repairs in an
Platelet-rich plasma is a new inductive therapy which is being increasingly used for the treatment of the complications of bone healing, such as infection and nonunion. The activator for platelet-rich plasma is a mixture of thrombin and calcium chloride which produces a platelet-rich gel. We analysed the antibacterial effect of platelet-rich gel Zones of inhibition produced by platelet-rich gel ranged between 6 mm and 24 mm (mean 9.83 mm) in diameter. Platelet-rich gel inhibited the growth of
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.
Different calcaneal plates with locked screws were compared in an experimental model of a calcaneal fracture. Four plate models were tested, three with uniaxially-locked screws (Synthes, Newdeal, Darco), and one with polyaxially-locked screws (90° ± 15°) (Rimbus). Synthetic calcanei were osteotomised to create a fracture model and then fixed with the plates and screws. Seven specimens for each plate model were subjected to cyclic loading (preload 20 N, 1000 cycles at 800 N, 0.75 mm/s), and load to failure (0.75 mm/s). During cyclic loading, the plate with polyaxially-locked screws (Rimbus) showed significantly lower displacement in the primary loading direction than the plates with uniaxially-locked screws (mean values of maximum displacement during cyclic loading: Rimbus, 3.13 mm ( The increased stability of a plate with polyaxially-locked screws demonstrated during cyclic loading compared with plates with uniaxially-locked screws may be beneficial for clinical use.
Systemic factors are believed to be pivotal for the development of heterotopic ossification in severely-injured patients. In this study, cell cultures of putative target cells (human fibroblastic cells, osteoblastic cells (MG-63), and bone-marrow stromal cells (hBM)) were incubated with serum from ten consecutive polytraumatised patients taken from post-traumatic day 1 to day 21 and with serum from 12 healthy control subjects. The serum from the polytraumatised patients significantly stimulated the proliferation of fibroblasts, MG-63 and of hBM cells. The activity of alkaline phosphatase in MG-63 and hBM cells was significantly decreased when exposed to the serum of the severely-injured patient. After three weeks in 3D cell cultures, matrix production and osteogenic gene expression of hBM cells were equal in the patient and control groups. However, the serum from the polytraumatised patients significantly decreased apoptosis of hBM cells compared with the control serum (4.3% Increased proliferation of osteoblastic cells and reduced apoptosis of osteoprogenitors may be responsible for increased osteogenesis in severely-injured patients.
The ability to predict load-bearing capacity during the consolidation phase in distraction osteogenesis by non-invasive means would represent a significant advance in the management of patients undergoing such treatment. Measurements of stiffness have been suggested as a promising tool for this purpose. Although the multidimensional characteristics of bone loading in compression, bending and torsion are apparent, most previous experiments have analysed only the relationship between maximum load-bearing capacity and a single type of stiffness. We have studied how compressive, bending and torsional stiffness are related to the torsional load-bearing capacity of healing callus using a common set of samples of bone regenerate from 26 sheep treated by tibial distraction osteogenesis. Our findings showed that measurements of torsional, bending and compressive stiffness were all suitable as predictors of the load-bearing capacity of healing callus. Measurements of torsional stiffness performed slightly better than those of compressive and bending stiffness.
Recently, femoroacetabular impingement has been recognised as a cause of early osteoarthritis. There are two mechanisms of impingement: 1) cam impingement caused by a non-spherical head and 2) pincer impingement caused by excessive acetabular cover. We hypothesised that both mechanisms result in different patterns of articular damage. Of 302 analysed hips only 26 had an isolated cam and 16 an isolated pincer impingement. Cam impingement caused damage to the anterosuperior acetabular cartilage with separation between the labrum and cartilage. During flexion, the cartilage was sheared off the bone by the non-spherical femoral head while the labrum remained untouched. In pincer impingement, the cartilage damage was located circumferentially and included only a narrow strip. During movement the labrum is crushed between the acetabular rim and the femoral neck causing degeneration and ossification. Both cam and pincer impingement lead to osteoarthritis of the hip. Labral damage indicates ongoing impingement and rarely occurs alone.
The reduced stability of hydroxyapatite (HA)-coated implants in osteopenic conditions is considered to be a major problem. We therefore developed a model of a boosted cementless implantation in osteopenic rats. Twelve-week-old rats were either ovariectomised (OVX) or sham-operated (SO), and after 24 weeks plain or HA-coated implants were inserted. They were treated with either a prostaglandin EP4 receptor agonist (ONO-4819) or saline for one month. The EP4 agonist considerably improved the osteoporosis in the OVX group. Ultrastructural analysis and mechanical testing showed an improvement in the implant-bone attachment in the HA-coated implants, which was further enhanced by the EP4 agonist. Although the stability of the HA-coated implants in the saline-treated OVX rats was less than in the SO normal rats, the administration of the EP4 agonist significantly compensated for this shortage. Our results showed that the osteogenic effect of the EP4 agonist augmented the osteoconductivity of HA and significantly improved the stability of the implant-bone attachment in the osteoporotic rat model.