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Bone & Joint Research
Vol. 7, Issue 10 | Pages 548 - 560
1 Oct 2018
Qayoom I Raina DB Širka A Tarasevičius Š Tägil M Kumar A Lidgren L

During the last decades, several research groups have used bisphosphonates for local application to counteract secondary bone resorption after bone grafting, to improve implant fixation or to control bone resorption caused by bone morphogenetic proteins (BMPs). We focused on zoledronate (a bisphosphonate) due to its greater antiresorptive potential over other bisphosphonates. Recently, it has become obvious that the carrier is of importance to modulate the concentration and elution profile of the zoledronic acid locally. Incorporating one fifth of the recommended systemic dose of zoledronate with different apatite matrices and types of bone defects has been shown to enhance bone regeneration significantly in vivo. We expect the local delivery of zoledronate to overcome the limitations and side effects associated with systemic usage; however, we need to know more about the bioavailability and the biological effects. The local use of BMP-2 and zoledronate as a combination has a proven additional effect on bone regeneration. This review focuses primarily on the local use of zoledronate alone, or in combination with bone anabolic factors, in various preclinical models mimicking different orthopaedic conditions.

Cite this article: I. Qayoom, D. B. Raina, A. Širka, Š. Tarasevičius, M. Tägil, A. Kumar, L. Lidgren. Anabolic and antiresorptive actions of locally delivered bisphosphonates for bone repair: A review. Bone Joint Res 2018;7:548–560. DOI: 10.1302/2046-3758.710.BJR-2018-0015.R2.


Bone & Joint Research
Vol. 4, Issue 6 | Pages 99 - 104
1 Jun 2015
Savaridas T Wallace RJ Dawson S Simpson AHRW

Objectives

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.

Methods

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.


The Journal of Bone & Joint Surgery British Volume
Vol. 88-B, Issue 11 | Pages 1438 - 1440
1 Nov 2006
Niimi R Sudo A Hasegawa M Fukuda A Uchida A

Transient osteoporosis of the hip is a disorder characterised by pain, and associated with temporary osteopaenia. Although osteopaenia is the essence of the condition, data do not exist about the local bone density of the femoral neck if no medication is administered. We describe three patients who were treated with limitation of weight-bearing only. Repeated bone mineral density measurements were obtained, and that at the femoral neck was lowest two months after the onset of the condition. The mean reduction in bone mineral density when compared with an age-matched control group was 13% (3% to 24%). Spontaneous recovery was observed in all patients.


The Bone & Joint Journal
Vol. 100-B, Issue 1 | Pages 95 - 100
1 Jan 2018
Evers J Fischer M Zderic I Wähnert D Richards RG Gueorguiev B Raschke MJ Ochman S

Aims

The aim of this study was to investigate the effect of a posterior malleolar fragment (PMF), with < 25% ankle joint surface, on pressure distribution and joint-stability. There is still little scientific evidence available to advise on the size of PMF, which is essential to provide treatment. To date, studies show inconsistent results and recommendations for surgical treatment date from 1940.

Materials and Methods

A total of 12 cadaveric ankles were assigned to two study groups. A trimalleolar fracture was created, followed by open reduction and internal fixation. PMF was fixed in Group I, but not in Group II. Intra-articular pressure was measured and cyclic loading was performed.


Bone & Joint 360
Vol. 6, Issue 6 | Pages 14 - 16
1 Dec 2017


Bone & Joint Research
Vol. 7, Issue 4 | Pages 289 - 297
1 Apr 2018
Sanghani-Kerai A Osagie-Clouard L Blunn G Coathup M

Objectives

This study aimed to assess the effect of age and osteoporosis on the proliferative and differentiating capacity of bone-marrow-derived mesenchymal stem cells (MSCs) in female rats. We also discuss the role of these factors on expression and migration of cells along the C-X-C chemokine receptor type 4 (CXCR-4) / stromal derived factor 1 (SDF-1) axis.

Methods

Mesenchymal stem cells were harvested from the femora of young, adult, and osteopenic Wistar rats. Cluster of differentiation (CD) marker and CXCR-4 expression was measured using flow cytometry. Cellular proliferation was measured using Alamar Blue, osteogenic differentiation was measured using alkaline phosphatase expression and alizarin red production, and adipogenic differentiation was measured using Oil red O. Cells were incubated in Boyden chambers to quantify their migration towards SDF-1. Data was analyzed using a Student’s t-test, where p-values < 0.05 were considered significant.


The Bone & Joint Journal
Vol. 96-B, Issue 10 | Pages 1378 - 1384
1 Oct 2014
Weiser L Korecki MA Sellenschloh K Fensky F Püschel K Morlock MM Rueger JM Lehmann W

It is becoming increasingly common for a patient to have ipsilateral hip and knee replacements. The inter-prosthetic (IP) distance, the distance between the tips of hip and knee prostheses, has been thought to be associated with an increased risk of IP fracture. Small gap distances are generally assumed to act as stress risers, although there is no real biomechanical evidence to support this.

The purpose of this study was to evaluate the influence of IP distance, cortical thickness and bone mineral density on the likelihood of an IP femoral fracture.

A total of 18 human femur specimens were randomised into three groups by bone density and cortical thickness. For each group, a defined IP distance of 35 mm, 80 mm or 160 mm was created by choosing the appropriate lengths of component. The maximum fracture strength was determined using a four-point bending test.

The fracture force of all three groups was similar (p = 0.498). There was a highly significant correlation between the cortical area and the fracture strength (r = 0.804, p <  0.001), whereas bone density showed no influence.

This study suggests that the IP distance has little influence on fracture strength in IP femoral fractures: the thickness of the cortex seems to be the decisive factor.

Cite this article: Bone Joint J 2014;96-B:1378–84.


The Journal of Bone & Joint Surgery British Volume
Vol. 92-B, Issue 12 | Pages 1648 - 1653
1 Dec 2010
Cordingley R Kohan L Ben-Nissan B

The major advantage of hip resurfacing is the decreased amount of bone resection compared with a standard total hip replacement. Fracture of the femoral neck is the most common early complication and poor bone quality is a major risk factor. We undertook a prospective consecutive case control study examining the effect of bone mineral density changes in patients undergoing hip resurfacing surgery. A total of 423 patients were recruited with a mean age of 54 years (24 to 87). Recruitment for this study was dependent on pre-operative bilateral femoral bone mineral density results not being osteoporotic. The operated and non-operated hips were assessed. Bone mineral density studies were repeated over a two-year period. The results showed no significant deterioration in the bone mineral density in the superolateral region in the femoral neck, during that period.

These findings were in the presence of a markedly increased level of physical activity, as measured by the short-form 36 health survey physical function score.


Bone & Joint 360
Vol. 6, Issue 4 | Pages 23 - 25
1 Aug 2017


Bone & Joint Research
Vol. 6, Issue 10 | Pages 602 - 609
1 Oct 2017
Jin A Cobb J Hansen U Bhattacharya R Reinhard C Vo N Atwood R Li J Karunaratne A Wiles C Abel R

Objectives

Bisphosphonates (BP) are the first-line treatment for preventing fragility fractures. However, concern regarding their efficacy is growing because bisphosphonate is associated with over-suppression of remodelling and accumulation of microcracks. While dual-energy X-ray absorptiometry (DXA) scanning may show a gain in bone density, the impact of this class of drug on mechanical properties remains unclear. We therefore sought to quantify the mechanical strength of bone treated with BP (oral alendronate), and correlate data with the microarchitecture and density of microcracks in comparison with untreated controls.

Methods

Trabecular bone from hip fracture patients treated with BP (n = 10) was compared with naïve fractured (n = 14) and non-fractured controls (n = 6). Trabecular cores were synchrotron scanned and micro-CT scanned for microstructural analysis, including quantification of bone volume fraction, microarchitecture and microcracks. The specimens were then mechanically tested in compression.


Bone & Joint Research
Vol. 6, Issue 12 | Pages 640 - 648
1 Dec 2017
Xia B Li Y Zhou J Tian B Feng L

Objectives

Osteoporosis is a chronic disease. The aim of this study was to identify key genes in osteoporosis.

Methods

Microarray data sets GSE56815 and GSE56814, comprising 67 osteoporosis blood samples and 62 control blood samples, were obtained from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified in osteoporosis using Limma package (3.2.1) and Meta-MA packages. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed to identify biological functions. Furthermore, the transcriptional regulatory network was established between the top 20 DEGs and transcriptional factors using the UCSC ENCODE Genome Browser. Receiver operating characteristic (ROC) analysis was applied to investigate the diagnostic value of several DEGs.


The Journal of Bone & Joint Surgery British Volume
Vol. 87-B, Issue 10 | Pages 1344 - 1351
1 Oct 2005
Field RE Rushton N

The Cambridge Cup has been designed to replace the horseshoe-shaped articular cartilage of the acetabulum and the underlying subchondral bone. It is intended to provide physiological loading with minimal resection of healthy bone.

The cup has been used in 50 women with displaced, subcapital fractures of the neck of the femur. In 24 cases, the cup was coated with hydroxyapatite. In 26, the coating was removed before implantation in order to simulate the effect of long-term resorption.

The mean Barthel index and the Charnley-modified Merle d’Aubigné scores recovered to their levels before fracture. We reviewed 30 women at two years, 21 were asymptomatic and nine reported minimal pain. The mean scores deteriorated slightly after five years reflecting the comorbidity of advancing age. Patients with the hydroxyapatite-coated components remained asymptomatic, with no wear or loosening. The uncoated components migrated after four years and three required revision. This trial shows good early results using a novel, hydroxyapatite-coated, physiological acetabular component.


Bone & Joint Research
Vol. 6, Issue 1 | Pages 8 - 13
1 Jan 2017
Acklin YP Zderic I Grechenig S Richards RG Schmitz P Gueorguiev B

Objectives

Osteosynthesis of anterior pubic ramus fractures using one large-diameter screw can be challenging in terms of both surgical procedure and fixation stability. Small-fragment screws have the advantage of following the pelvic cortex and being more flexible.

The aim of the present study was to biomechanically compare retrograde intramedullary fixation of the superior pubic ramus using either one large- or two small-diameter screws.

Materials and Methods

A total of 12 human cadaveric hemipelvises were analysed in a matched pair study design. Bone mineral density of the specimens was 68 mgHA/cm3 (standard deviation (sd) 52). The anterior pelvic ring fracture was fixed with either one 7.3 mm cannulated screw (Group 1) or two 3.5 mm pelvic cortex screws (Group 2). Progressively increasing cyclic axial loading was applied through the acetabulum. Relative movements in terms of interfragmentary displacement and gap angle at the fracture site were evaluated by means of optical movement tracking. The Wilcoxon signed-rank test was applied to identify significant differences between the groups


Bone & Joint Research
Vol. 2, Issue 8 | Pages 140 - 148
1 Aug 2013
Gauthier L Dinh L Beaulé PE

Objectives

To quantify and compare peri-acetabular bone mineral density (BMD) between a monoblock acetabular component using a metal-on-metal (MoM) bearing and a modular titanium shell with a polyethylene (PE) insert. The secondary outcome was to measure patient-reported clinical function.

Methods

A total of 50 patients (25 per group) were randomised to MoM or metal-on-polyethlene (MoP). There were 27 women (11 MoM) and 23 men (14 MoM) with a mean age of 61.6 years (47.7 to 73.2). Measurements of peri-prosthetic acetabular and contralateral hip (covariate) BMD were performed at baseline and at one and two years’ follow-up. The Western Ontario and McMaster Universities osteoarthritis index (WOMAC), University of California, Los Angeles (UCLA) activity score, Harris hip score, and RAND-36 were also completed at these intervals.


Bone & Joint Research
Vol. 5, Issue 12 | Pages 594 - 601
1 Dec 2016
Li JJ Wang BQ Fei Q Yang Y Li D

Objectives

In order to screen the altered gene expression profile in peripheral blood mononuclear cells of patients with osteoporosis, we performed an integrated analysis of the online microarray studies of osteoporosis.

Methods

We searched the Gene Expression Omnibus (GEO) database for microarray studies of peripheral blood mononuclear cells in patients with osteoporosis. Subsequently, we integrated gene expression data sets from multiple microarray studies to obtain differentially expressed genes (DEGs) between patients with osteoporosis and normal controls. Gene function analysis was performed to uncover the functions of identified DEGs.


The Bone & Joint Journal
Vol. 98-B, Issue 6 | Pages 840 - 845
1 Jun 2016
Chesser TJS Fox R Harding K Halliday R Barnfield S Willett K Lamb S Yau C Javaid MK Gray AC Young J Taylor H Shah K Greenwood R

Aims

We wished to assess the feasibility of a future randomised controlled trial of parathyroid hormone (PTH) supplements to aid healing of trochanteric fractures of the hip, by an open label prospective feasibility and pilot study with a nested qualitative sub study. This aimed to inform the design of a future powered study comparing the functional recovery after trochanteric hip fracture in patients undergoing standard care, versus those who undergo administration of subcutaneous injection of PTH for six weeks.

Patients and Methods

We undertook a pilot study comparing the functional recovery after trochanteric hip fracture in patients 60 years or older, admitted with a trochanteric hip fracture, and potentially eligible to be randomised to either standard care or the administration of subcutaneous PTH for six weeks. Our desired outcomes were functional testing and measures to assess the feasibility and acceptability of the study.


The Bone & Joint Journal
Vol. 98-B, Issue 5 | Pages 715 - 720
1 May 2016
Mifsud M Abela M Wilson NIL

Aims

Although atlantoaxial rotatory fixation (AARF) is a common cause of torticollis in children, the diagnosis may be delayed. The condition is characterised by a lack of rotation at the atlantoaxial joint which becomes fixed in a rotated and subluxed position. The management of children with a delayed presentation of this condition is controversial. This is a retrospective study of a group of such children.

Patients and Methods

Children who were admitted to two institutions between 1988 and 2014 with a diagnosis of AARF were included. We identified 12 children (four boys, eight girls), with a mean age of 7.3 years (1.5 to 13.4), in whom the duration of symptoms on presentation was at least four weeks (four to 39). All were treated with halo traction followed by a period of cervical immobilisation in a halo vest or a Minerva jacket. We describe a simple modification to the halo traction that allows the child to move their head whilst maintaining traction. The mean follow-up was 59.6 weeks (24 to 156).


Bone & Joint Research
Vol. 5, Issue 11 | Pages 544 - 551
1 Nov 2016
Kim Y Bok DH Chang H Kim SW Park MS Oh JK Kim J Kim T

Objectives

Although vertebroplasty is very effective for relieving acute pain from an osteoporotic vertebral compression fracture, not all patients who undergo vertebroplasty receive the same degree of benefit from the procedure. In order to identify the ideal candidate for vertebroplasty, pre-operative prognostic demographic or clinico-radiological factors need to be identified. The objective of this study was to identify the pre-operative prognostic factors related to the effect of vertebroplasty on acute pain control using a cohort of surgically and non-surgically managed patients.

Patients and Methods

Patients with single-level acute osteoporotic vertebral compression fracture at thoracolumbar junction (T10 to L2) were followed. If the patients were not satisfied with acute pain reduction after a three-week conservative treatment, vertebroplasty was recommended. Pain assessment was carried out at the time of diagnosis, as well as three, four, six, and 12 weeks after the diagnosis. The effect of vertebroplasty, compared with conservative treatment, on back pain (visual analogue score, VAS) was analysed with the use of analysis-of-covariance models that adjusted for pre-operative VAS scores.


Bone & Joint Research
Vol. 2, Issue 2 | Pages 41 - 50
1 Feb 2013
Cottrell JA Keshav V Mitchell A O’Connor JP

Objectives

Recent studies have shown that modulating inflammation-related lipid signalling after a bone fracture can accelerate healing in animal models. Specifically, decreasing 5-lipoxygenase (5-LO) activity during fracture healing increases cyclooxygenase-2 (COX-2) expression in the fracture callus, accelerates chondrogenesis and decreases healing time. In this study, we test the hypothesis that 5-LO inhibition will increase direct osteogenesis.

Methods

Bilateral, unicortical femoral defects were used in rats to measure the effects of local 5-LO inhibition on direct osteogenesis. The defect sites were filled with a polycaprolactone (PCL) scaffold containing 5-LO inhibitor (A-79175) at three dose levels, scaffold with drug carrier, or scaffold only. Drug release was assessed in vitro. Osteogenesis was assessed by micro-CT and histology at two endpoints of ten and 30 days.


The Bone & Joint Journal
Vol. 98-B, Issue 7 | Pages 867 - 873
1 Jul 2016
Dalury DF

As the number of younger and more active patients treated with total knee arthroplasty (TKA) continues to increase, consideration of better fixation as a means of improving implant longevity is required. Cemented TKA remains the reference standard with the largest body of evidence and the longest follow-up to support its use. However, cementless TKA, may offer the opportunity of a more bone-sparing procedure with long lasting biological fixation to the bone. We undertook a review of the literature examining advances of cementless TKA and the reported results.

Cite this article: Bone Joint J 2016;98-B:867–73.