Intermittently administered parathyroid hormone (PTH 1-34) has been shown to promote bone formation in both human and animal studies. The hormone and its analogues stimulate both bone formation and resorption, and as such at low doses are now in clinical use for the treatment of severe osteoporosis. By varying the duration of exposure, parathyroid hormone can modulate genes leading to increased bone formation within a so-called ‘anabolic window’. The osteogenic mechanisms involved are multiple, affecting the stimulation of osteoprogenitor cells, osteoblasts, osteocytes and the stem cell niche, and ultimately leading to increased osteoblast activation, reduced osteoblast apoptosis, upregulation of Wnt/β-catenin signalling, increased stem cell mobilisation, and mediation of the RANKL/OPG pathway. Ongoing investigation into their effect on bone formation through ‘coupled’ and ‘uncoupled’ mechanisms further underlines the impact of intermittent PTH on both cortical and cancellous bone. Given the principally catabolic actions of continuous PTH, this article reviews the skeletal actions of intermittent PTH 1-34 and the mechanisms underlying its effect.
Osteoporosis is a chronic disease. The aim of this study was to identify key genes in osteoporosis. 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.Objectives
Methods
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. 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.Objectives
Methods
This study presents the long-term survivorship, risk factors for prosthesis survival, and an assessment of the long-term effects of changes in surgical technique in a large series of patients treated by metal-on-metal (MoM) hip resurfacing arthroplasty (HRA). Between November 1996 and January 2012, 1074 patients (1321 hips) underwent HRA using the Conserve Plus Hip Resurfacing System. There were 787 men (73%) and 287 women (27%) with a mean age of 51 years (14 to 83). The underlying pathology was osteoarthritis (OA) in 1003 (75.9%), developmental dysplasia of the hip (DDH) in 136 (10.3%), avascular necrosis in 98 (7.4%), and other conditions, including inflammatory arthritis, in 84 (6.4%).Aims
Patients and Methods
Although we often encounter patients with an aortic aneurysm
who also have diffuse idiopathic skeletal hyperostosis (DISH), there
are no reports to date of an association between these two conditions
and the pathogenesis of DISH remains unknown. This study therefore
evaluated the prevalence of DISH in patients with a thoracic aortic
aneurysm (AA). The medical records of 298 patients who underwent CT scans for
a diagnosis of an AA or following high-energy trauma were retrospectively
examined. A total of 204 patients underwent surgery for an AA and
94 had a high-energy injury and formed the non-AA group. The prevalence
of DISH was assessed on CT scans of the chest and abdomen and the
relationship between DISH and AA by comparison between the AA and
non-AA groups.Aims
Patients and Methods
In order to address acetabular defects, porous metal revision acetabular components and augments have been developed, which require fixation to each other. The fixation technique that results in the smallest relative movement between the components, as well as its influence on the primary stability with the host bone, have not previously been determined. A total of 18 composite hemipelvises with a Paprosky IIB defect were implanted using a porous titanium 56 mm multihole acetabular component and 1 cm augment. Each acetabular component and augment was affixed to the bone using two screws, while the method of fixation between the acetabular component and augment varied for the three groups of six hemipelvises: group S, screw fixation only; group SC, screw plus cement fixation; group C, cement fixation only. The implanted hemipelvises were cyclically loaded to three different loading maxima (0.5 kN, 0.9 kN, and 1.8 kN).Objectives
Methods
The treatment of osteoporotic fractures is a major challenge, and the enhancement of healing is critical as a major goal in modern fracture management. Most osteoporotic fractures occur at the metaphyseal bone region but few models exist and the healing is still poorly understood. A systematic review was conducted to identify and analyse the appropriateness of current osteoporotic metaphyseal fracture animal models. A literature search was performed on the Pubmed, Embase, and Web of Science databases, and relevant articles were selected. A total of 19 studies were included. Information on the animal, induction of osteoporosis, fracture technique, site and fixation, healing results, and utility of the model were extracted.Objectives
Materials and Methods
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. 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.Aims
Materials and Methods
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. 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.Objectives
Methods
Oxidative stress plays a major role in the onset and progression of involutional osteoporosis. However, classical antioxidants fail to restore osteoblast function. Interestingly, the bone anabolism of parathyroid hormone (PTH) has been shown to be associated with its ability to counteract oxidative stress in osteoblasts. The PTH counterpart in bone, which is the PTH-related protein (PTHrP), displays osteogenic actions through both its N-terminal PTH-like region and the C-terminal domain. We examined and compared the antioxidant capacity of PTHrP (1-37) with the C-terminal PTHrP domain comprising the 107-111 epitope (osteostatin) in both murine osteoblastic MC3T3-E1 cells and primary human osteoblastic cells.Objectives
Methods
Treatment guidelines for atypical femoral fractures associated
with bisphosphonates have not been established. We conducted a systematic
review of the treatment of atypical femoral fractures first, to
evaluate the outcomes of surgical fixation of complete atypical fractures
and secondly, to assess whether prophylactic surgery is necessary
for incomplete atypical fractures. Case reports and series were identified from the PubMed database
and were included if they described the treatment of atypical femoral
fractures. In total, 77 publications met our inclusion criteria
and 733 patients with 834 atypical complete or incomplete femoral fractures
were identified.Aims
Materials and Methods
Microindentation has the potential to measure the stiffness of an individual patient’s bone. Bone stiffness plays a crucial role in the press-fit stability of orthopaedic implants. Arming surgeons with accurate bone stiffness information may reduce surgical complications including periprosthetic fractures. The question addressed with this systematic review is whether microindentation can accurately measure cortical bone stiffness. A systematic review of all English language articles using a keyword search was undertaken using Medline, Embase, PubMed, Scopus and Cochrane databases. Studies that only used nanoindentation, cancellous bone or animal tissue were excluded.Objectives
Methods
This study evaluated the mechanical performance, under low-load cyclic loading, of two different knotless suture anchor designs: sutures completely internal to the anchor body (SpeedScrew) and sutures external to the anchor body and adjacent to bone (MultiFIX P). Using standard suture loops pulled in-line with the rotator cuff (approximately 60°), anchors were tested in cadaveric bone and foam blocks representing normal to osteopenic bone. Mechanical testing included preloading to 10 N and cyclic loading for 500 cycles from 10 N to 60 N at 60 mm/min. The parameters evaluated were initial displacement, cyclic displacement and number of cycles and load at 3 mm displacement relative to preload. Video recording throughout testing documented the predominant source of suture displacement and the distance of ‘suture cutting through bone’.Objectives
Methods
We sought to determine whether specific characteristics
of vertebral fractures in elderly men are associated with low bone
mineral density (BMD) and osteoporosis. Mister osteoporosis Sweden is a population based cohort study
involving 3014 men aged 69 to 81 years. Of these, 1427 had readable
lateral radiographs of the thoracic and lumbar spine. Total body
(TB) BMD (g/cm²) and total right hip (TH) BMD were measured by dual
energy x-ray absorptiometry. The proportion of men with osteoporosis
was calculated from TH BMD. There were 215 men (15.1%) with a vertebral
fracture. Those with a fracture had lower TB BMD than those without
(p <
0.001). Among men with a fracture, TB BMD was lower in those
with more than three fractures (p = 0.02), those with biconcave
fractures (p = 0.02) and those with vertebral body compression of
>
42% (worst quartile) (p = 0.03). The mean odds ratio (OR) for
having osteoporosis when having any type of vertebral fracture was
6.1 (95% confidence interval (CI) 3.9 to 9.5) compared with those
without a fracture. A combination of more than three fractures and
compression in the worst quartile had a mean OR of 114.2 (95% CI
6.7 to 1938.3) of having osteoporosis compared with those without
a fracture. We recommend BMD studies to be undertaken in these subcohorts
of elderly men with a vertebral fracture. Cite this article: 2015;97-B:1106–10.
We aimed to investigate factors related to the technique of medial
opening wedge high tibial osteotomy which might predispose to the
development of a lateral hinge fracture. A total of 71 patients with 82 osteotomies were included in the
study. Their mean age was 62.9 years (37 to 80). The classification
of the type of osteotomy was based on whether it extended beyond
the fibular head. The level of the osteotomy was classified according
to the height of its endpoint.Aims
Patients and Methods
Osteoporosis has become an increasing concern for older people as it may potentially lead to osteoporotic fractures. This study is designed to assess the efficacy and safety of ten therapies for post-menopausal women using network meta-analysis. We conducted a systematic search in several databases, including PubMed and Embase. A random-effects model was employed and results were assessed by the odds ratio (OR) and corresponding 95% confidence intervals (CI). Furthermore, with respect to each outcome, each intervention was ranked according to the surface under the cumulative ranking curve (SUCRA) value.Objectives
Methods
The ageing population and an increase in both
the incidence and prevalence of cancer pose a healthcare challenge, some
of which is borne by the orthopaedic community in the form of osteoporotic
fractures and metastatic bone disease. In recent years there has
been an increasing understanding of the pathways involved in bone
metabolism relevant to osteoporosis and metastases in bone. Newer
therapies may aid the management of these problems. One group of
drugs, the antibody mediated anti-resorptive therapies (AMARTs)
use antibodies to block bone resorption pathways. This review seeks
to present a synopsis of the guidelines, pharmacology and potential pathophysiology
of AMARTs and other new anti-resorptive drugs. We evaluate the literature relating to AMARTs and new anti-resorptives
with special attention on those approved for use in clinical practice. Denosumab, a monoclonal antibody against Receptor Activator for
Nuclear Factor Kappa-B Ligand. It is the first AMART approved by
the National Institute for Health and Clinical Excellence and the
US Food and Drug Administration. Other novel anti-resorptives awaiting
approval for clinical use include Odanacatib. Denosumab is indicated for the treatment of osteoporosis and
prevention of the complications of bone metastases. Recent evidence
suggests, however, that denosumab may have an adverse event profile
similar to bisphosphonates, including atypical femoral fractures.
It is, therefore, essential that orthopaedic surgeons are conversant
with these medications and their safe usage. Take home message: Denosumab has important orthopaedic indications
and has been shown to significantly reduce patient morbidity in
osteoporosis and metastatic bone disease. Cite this article:
The aims of this study were to evaluate the clinical and radiological
outcomes of instrumented posterolateral fusion (PLF) performed in
patients with rheumatoid arthritis (RA). A total of 40 patients with RA and 134 patients without RA underwent
instrumented PLF for spinal stenosis between January 2003 and December
2011. The two groups were matched for age, gender, bone mineral
density, the history of smoking and diabetes, and number of fusion
segments. The clinical outcomes measures included the visual analogue scale
(VAS) and the Korean Oswestry Disability Index (KODI), scored before
surgery, one year and two years after surgery. Radiological outcomes
were evaluated for problems of fixation, nonunion, and adjacent
segment disease (ASD). The mean follow-up was 36.4 months in the RA
group and 39.1 months in the non-RA group.Aims
Methods
