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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.


Bone & Joint Research
Vol. 5, Issue 7 | Pages 301 - 306
1 Jul 2016
Madhuri V Santhanam M Rajagopal K Sugumar LK Balaji V

Objectives

To determine the pattern of mutations of the WISP3 gene in clinically identified progressive pseudorheumatoid dysplasia (PPD) in an Indian population.

Patients and Methods

A total of 15 patients with clinical features of PPD were enrolled in this study. Genomic DNA was isolated and polymerase chain reaction performed to amplify the WISP3 gene. Screening for mutations was done by conformation-sensitive gel electrophoresis, beginning with the fifth exon and subsequently proceeding to the remaining exons. Sanger sequencing was performed for both forward and reverse strands to confirm the mutations.


The Bone & Joint Journal
Vol. 98-B, Issue 2 | Pages 160 - 165
1 Feb 2016
Farrier AJ C. Sanchez Franco L Shoaib A Gulati V Johnson N Uzoigwe CE Choudhury MZ

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: Bone Joint J 2016;98-B:160–5.


Bone & Joint 360
Vol. 4, Issue 4 | Pages 27 - 29
1 Aug 2015

The August 2015 Trauma Roundup360 looks at: Thromboprophylaxis not required in lower limb fractures; Subclinical thyroid dysfunction and fracture risk: moving the boundaries in fracture; Posterior wall fractures refined; Neurological injury and acetabular fracture surgery; Posterior tibial plateau fixation; Tibial plateau fractures in the longer term; Comprehensive orthogeriatric care and hip fracture; Compartment syndrome: in the eye of the beholder?


The Journal of Bone & Joint Surgery British Volume
Vol. 90-B, Issue 10 | Pages 1261 - 1270
1 Oct 2008
Hadjipavlou AG Tzermiadianos MN Bogduk N Zindrick MR

The pathophysiology of intervertebral disc degeneration has been extensively studied. Various factors have been suggested as influencing its aetiology, including mechanical factors, such as compressive loading, shear stress and vibration, as well as ageing, genetic, systemic and toxic factors, which can lead to degeneration of the disc through biochemical reactions. How are these factors linked? What is their individual importance? There is no clear evidence indicating whether ageing in the presence of repetitive injury or repetitive injury in the absence of ageing plays a greater role in the degenerative process. Mechanical factors can trigger biochemical reactions which, in turn, may promote the normal biological changes of ageing, which can also be accelerated by genetic factors. Degradation of the molecular structure of the disc during ageing renders it more susceptible to superimposed mechanical injuries.

This review supports the theory that degeneration of the disc has a complex multifactorial aetiology. Which factors initiate the events in the degenerative cascade is a question that remains unanswered, but most evidence points to an age-related process influenced primarily by mechanical and genetic factors.


Bone & Joint Research
Vol. 5, Issue 4 | Pages 106 - 115
1 Apr 2016
Gruber HE Ode G Hoelscher G Ingram J Bethea S Bosse MJ

Objectives

The biomembrane (induced membrane) formed around polymethylmethacrylate (PMMA) spacers has value in clinical applications for bone defect reconstruction. Few studies have evaluated its cellular, molecular or stem cell features. Our objective was to characterise induced membrane morphology, molecular features and osteogenic stem cell characteristics.

Methods

Following Institutional Review Board approval, biomembrane specimens were obtained from 12 patient surgeries for management of segmental bony defects (mean patient age 40.7 years, standard deviation 14.4). Biomembranes from nine tibias and three femurs were processed for morphologic, molecular or stem cell analyses. Gene expression was determined using the Affymetrix GeneChip Operating Software (GCOS). Molecular analyses compared biomembrane gene expression patterns with a mineralising osteoblast culture, and gene expression in specimens with longer spacer duration (> 12 weeks) with specimens with shorter durations. Statistical analyses used the unpaired student t-test (two tailed; p < 0.05 was considered significant).


Bone & Joint 360
Vol. 3, Issue 6 | Pages 29 - 31
1 Dec 2014

The December 2014 Children’s orthopaedics Roundup360 looks at: predicting drift in supracondylar fractures; do normal hips dislocate?; the burden of trampoline fractures; muscle eversion activity is strongly predictive of outcome in CTEV; the modified Dunn osteotomy; plaster and moulded casts; and psychology and fractures.


Bone & Joint 360
Vol. 3, Issue 6 | Pages 31 - 34
1 Dec 2014

The December 2014 Research Roundup360 looks at: demineralised bone matrix not as good as we thought?; trunk control following ACL reconstruction; subclinical thyroid dysfunction: not quite subclinical?; establishing musculoskeletal function in mucopolysaccharidosis; starting out: a first year in consultant practice under the spotlight; stroke and elective surgery; sepsis and clots; hip geometry and arthritis incidence; and theatre discipline and infection.


Bone & Joint 360
Vol. 3, Issue 3 | Pages 37 - 39
1 Jun 2014

The June 2014 Research Roundup360 looks at:Intraoperative irrigation a balance of toxicities; Ibandronate effective in bone marrow oedema; Risk stratification in damage control surgery; Osteoblast like cells potentially safe; Better wear and antibacterial?; Assessing outcomes in hip fracture.


Bone & Joint 360
Vol. 2, Issue 5 | Pages 43 - 44
1 Oct 2013
Grimer RJ


The Bone & Joint Journal
Vol. 96-B, Issue 10 | Pages 1349 - 1354
1 Oct 2014
Conway J Mansour J Kotze K Specht S Shabtai L

The treatment of infected nonunions is difficult. Antibiotic cement-coated (ACC) rods provide stability as well as delivering antibiotics. We conducted a review of 110 infected nonunions treated with ACC rods. Patients were divided into two groups: group A (67 patients) with an infected arthrodesis, and group B (43 patients) with an infected nonunion in a long bone. In group A, infected arthrodesis, the success rate after the first procedure was 38/67 (57%), 29/67 (43%) required further surgery for either control of infection or non-union. At last follow-up, five patients required amputation, representing a limb salvage rate of 62/67 (93%) overall. In all, 29/67 (43%) presented with a bone defect with a mean size of 6.78 cm (2 to 25). Of those with a bone defect, 13/29 (45%) required further surgery and had a mean size of defect of 7.2 cm (3.5 to 25). The cultures were negative in 17/67 (26%) and the most common organism cultured was methicillin-resistant staphylococcus aureus (MRSA) (23/67, (35%)). In group B, long bones nonunion, the success rate after the first procedure was 26/43 (60%), 17/43 (40%) required further surgery for either control of infection or nonunion. The limb salvage rate at last follow-up was 43/43 (100%). A total of 22/43 (51%) had bone defect with a mean size of 4.7 cm (1.5 to 11.5). Of those patients with a bone defect, 93% required further surgery with a mean size of defect of 5.4 cm (3 to 8.5). The cultures were negative in 10/43 (24%) and the most common organism cultured was MRSA, 15/43 (35%). ACC rods are an effective form of treatment for an infected nonunion, with an acceptable rate of complications.

Cite this article: Bone Joint J 2014; 96-B:1349–54


Bone & Joint 360
Vol. 3, Issue 3 | Pages 34 - 37
1 Jun 2014

The June 2014 Children’s orthopaedics Roundup360 looks at: plaster wedging in paediatric forearm fractures; the medial approach for DDH; Ponseti – but not as he knew it?; Salter osteotomy more accurate than Pemberton in DDH; is the open paediatric fracture an emergency?; bang up-to-date with femoral external fixation; indomethacin, heterotopic ossification and cerebral palsy hips; lengthening nails for congenital femoral deformities, and is MRI the answer to imaging of the physis?


The Journal of Bone & Joint Surgery British Volume
Vol. 89-B, Issue 12 | Pages 1553 - 1560
1 Dec 2007
Gaston MS Simpson AHRW

This paper reviews the current literature concerning the main clinical factors which can impair the healing of fractures and makes recommendations on avoiding or minimising these in order to optimise the outcome for patients. The clinical implications are described.


The Journal of Bone & Joint Surgery British Volume
Vol. 94-B, Issue 10 | Pages 1313 - 1320
1 Oct 2012
Middleton RG Shabani F Uzoigwe CE AS Moqsith M Venkatesan M

Osteoporosis is common and the health and financial cost of fragility fractures is considerable. The burden of cardiovascular disease has been reduced dramatically by identifying and targeting those most at risk. A similar approach is potentially possible in the context of fragility fractures. The World Health Organization created and endorsed the use of FRAX, a fracture risk assessment tool, which uses selected risk factors to calculate a quantitative, patient-specific, ten-year risk of sustaining a fragility fracture. Treatment can thus be based on this as well as on measured bone mineral density. It may also be used to determine at-risk individuals, who should undergo bone densitometry. FRAX has been incorporated into the national osteoporosis guidelines of countries in the Americas, Europe, the Far East and Australasia. The United Kingdom National Institute for Health and Clinical Excellence also advocates its use in their guidance on the assessment of the risk of fragility fracture, and it may become an important tool to combat the health challenges posed by fragility fractures.


The Journal of Bone & Joint Surgery British Volume
Vol. 93-B, Issue 10 | Pages 1289 - 1295
1 Oct 2011
Yoon RS Hwang JS Beebe KS

For over a decade, bisphosphonate administration has evolved and become the cornerstone of the prevention and treatment of fragility fractures. Millions of post-menopausal women have relied on, and continue to depend on, the long-acting, bone density-maintaining pharmaceutical drug to prevent low-energy fractures. In return, we have seen the number of fragility fractures decrease, along with associated costs and emotional benefits. However, with any drug, there are often concerns with side effects and complications, and this unique drug class is seeing one such complication in atypical subtrochanteric femoral fracture, counterproductive to that which it was designed to prevent. This has created concern over long-term bisphosphonate administration and its potential link to these atypical fractures. There is controversial evidence surrounding such a definitive link, and no protocol for managing these fractures.

This review offers the latest information regarding this rare but increasingly controversial adverse effect and its potential connection to one of the most successful forms of treatment that is available for the management of fragility fractures.


Bone & Joint Research
Vol. 1, Issue 2 | Pages 13 - 19
1 Feb 2012
Smith MD Baldassarri S Anez-Bustillos L Tseng A Entezari V Zurakowski D Snyder BD Nazarian A

Objectives

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.

Methods

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.


The Journal of Bone & Joint Surgery British Volume
Vol. 92-B, Issue 5 | Pages 679 - 686
1 May 2010
Das De S Setiobudi T Shen L Das De S

There have been recent reports linking alendronate and a specific pattern of subtrochanteric insufficiency fracture. We performed a retrospective review of all subtrochanteric fractures admitted to our institution between 2001 and 2007. There were 20 patients who met the inclusion criteria, 12 of whom were on long-term alendronate. Alendronate-associated fractures tend to be bilateral (Fisher’s exact test, p = 0.018), have unique radiological features (p < 0.0005), be associated radiologically with a pre-existing ellipsoid thickening of the lateral femoral cortex and are likely to be preceded by prodromal pain. Biomechanical investigations did not suggest overt metabolic bone disease. Only one patient on alendronate had osteoporosis prior to the start of therapy. We used these findings to develop a management protocol to optimise fracture healing. We also advocate careful surveillance in individuals at-risk, and present our experience with screening and prophylactic fixation in selected patients.


The Journal of Bone & Joint Surgery British Volume
Vol. 91-B, Issue 2 | Pages 259 - 263
1 Feb 2009
Dimmen S Nordsletten L Engebretsen L Steen H Madsen JE

Conventional non-steroidal anti-inflammatory drugs (NSAIDs) and newer specific cyclo-oxygenase-2 (cox-2) inhibitors are commonly used in musculoskeletal trauma and orthopaedic surgery to reduce the inflammatory response and pain. These drugs have been reported to impair bone metabolism. In reconstruction of the anterior cruciate ligament the hamstring tendons are mainly used as the graft of choice, and a prerequisite for good results is healing of the tendons in the bone tunnel. Many of these patients are routinely given NSAIDs or cox-2 inhibitors, although no studies have elucidated the effects of these drugs on tendon healing in the bone tunnel.

In our study 60 female Wistar rats were randomly allocated into three groups of 20. One received parecoxib, one indometacin and one acted as a control. In all the rats the tendo-Achillis was released proximally from the calf muscles. It was then pulled through a drill hole in the distal tibia and sutured anteriorly. The rats were given parecoxib, indometacin or saline intraperitoneally twice daily for seven days. After 14 days the tendon/bone-tunnel interface was subjected to mechanical testing.

Significantly lower maximum pull-out strength (p < 0.001), energy absorption (p < 0.001) and stiffness (p = 0.035) were found in rats given parecoxib and indometacin compared with the control group, most pronounced with parecoxib.


The Journal of Bone & Joint Surgery British Volume
Vol. 91-B, Issue 2 | Pages 264 - 270
1 Feb 2009
Hasegawa T Miwa M Sakai Y Niikura T Kurosaka M Komori T

The haematoma occurring at the site of a fracture is known to play an important role in bone healing. We have recently shown the presence of progenitor cells in human fracture haematoma and demonstrated that they have the capacity for multilineage mesenchymal differentiation. There have been many studies which have shown that low-intensity pulsed ultrasound (LIPUS) stimulates the differentiation of a variety of cells, but none has investigated the effects of LIPUS on cells derived from human fracture tissue including human fracture haematoma-derived progenitor cells (HCs). In this in vitro study, we investigated the effects of LIPUS on the osteogenic activity of HCs. Alkaline phosphatase activity, osteocalcin secretion, the expression of osteoblast-related genes and the mineralisation of HCs were shown to be significantly higher when LIPUS had been applied but without a change in the proliferation of the HCs. These findings provide evidence in favour of the use of LIPUS in the treatment of fractures.


The Journal of Bone & Joint Surgery British Volume
Vol. 91-B, Issue 8 | Pages 1013 - 1018
1 Aug 2009
Agarwala S Shah S Joshi VR

The use of bisphosphonates in the treatment of avascular necrosis of the femoral head is an encouraging but relatively new option with most published data being derived from small trials with limited follow-up. We present a clinicoradiological analysis of 395 hips with avascular necrosis which were treated with oral alendronate for three years with a mean follow-up of four years (1 to 8).

Our results show an improvement in the clinical function, a reduction in the rate of collapse and a decrease in the requirement for total hip replacement, compared with the findings of other studies in which no treatment was given. This improvement is particularly marked if the treatment is begun in the pre-collapse stages of the disease. Even in Ficat stage-III hips some benefit was obtained from treatment with alendronate by at least a delay in the need for total hip replacement.