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.

We present the prevalence of multiple fractures in the elderly in a single catchment population of 780 000 treated over a 12-month period and describe the mechanisms of injury, common patterns of occurrence, management, and the associated mortality rate. A total of 2335 patients, aged ≥ 65 years of age, were prospectively assessed and of these 119 patients (5.1%) presented with multiple fractures. Distal radial (odds ratio (OR) 5.1, p <  0.0001), proximal humeral (OR 2.2, p < 0.0001) and pelvic (OR 4.9, p < 0.0001) fractures were associated with an increased risk of sustaining associated fractures. Only 4.5% of patients sustained multiple fractures after a simple fall, but due to the frequency of falls in the elderly this mechanism resulted in 80.7% of all multiple fractures. Most patients required admission (> 80%), of whom 42% did not need an operation but more than half needed an increased level of care before discharge (54%). The standardised mortality rate at one year was significantly greater after sustaining multiple fractures that included fractures of the pelvis, proximal humerus or proximal femur (p < 0.001). This mortality risk increased further if patients were < 80 years of age, indicating that the existence of multiple fractures after low-energy trauma is a marker of mortality.

We analysed which pre-operative factors could be used to predict the length of in-patient stay following unilateral primary total hip replacement undertaken for osteoarthritis. Data were collected prospectively from 2302 patients undergoing primary total hip replacement over a nine-year period. The relationships between the various pre-operative factors and length of stay were studied separately using either Student’s t-test or Pearson’s correlation, and then subjected to multiple linear regression analysis.

The mean length of stay was 8.1 days (median 7; 3 to 58). After adjusting for the effects of other pre-operative factors, younger age, male gender, higher combined Harris hip function and activity score, higher general health perception dimension of the Short-Form 36 score, and non-steroidal anti-inflammatory drug use were all found to be significantly associated with a reduced length of stay.

Fractures in patients aged ≥ 65 years constitute an increasing burden on health and social care and are associated with a high morbidity and mortality. There is little accurate information about the epidemiology of fractures in the elderly. We have analysed prospectively collected data on 4786 in- and out-patients who presented with a fracture over two one-year periods. Analysis shows that there are six patterns of the incidence of fractures in patients aged ≥ 65 years. In males six types of fracture increase in incidence after the age of 65 years and 11 types increase in females aged over 65 years. Five types of fracture decrease in incidence after the age of 65 years. Multiple fractures increase in incidence in both males and females aged ≥ 65 years, as do fractures related to falls.

Analysis of the incidence of fractures, together with life expectancy, shows that the probability of males and females aged ≥ 65 years having a fracture during the rest of their life is 18.5% and 52.0%, respectively. The equivalent figures for males and females aged ≥ 80 years are 13.3% and 34.8%, respectively.

Cite this article: Bone Joint J 2014;96-B:366–72.

The October 2012 Oncology Roundup³⁶⁰ looks at: the causes of primary bone tumours; adjuvant chemotherapy in the longer term; vascularised fibular grafts to salvage massive femoral allografts; a new look at old risks; reconstruction with excised irradiated bone; predicting chemosensitivity in osteosarcoma ; and chemotherapy, osteoporosis and the risk of fracture.

Diabetes mellitus is recognised as a risk factor for carpal tunnel syndrome. The response to treatment is unclear, and may be poorer than in non-diabetic patients. Previous randomised studies of interventions for carpal tunnel syndrome have specifically excluded diabetic patients. The aim of this study was to investigate the epidemiology of carpal tunnel syndrome in diabetic patients, and compare the outcome of carpal tunnel decompression with non-diabetic patients. The primary endpoint was improvement in the QuickDASH score. The prevalence of diabetes mellitus was 11.3% (176 of 1564). Diabetic patients were more likely to have severe neurophysiological findings at presentation. Patients with diabetes had poorer QuickDASH scores at one year post-operatively (p = 0.028), although the mean difference was lower than the minimal clinically important difference for this score. After controlling for underlying differences in age and gender, there was no difference between groups in the magnitude of improvement after decompression (p = 0.481). Patients with diabetes mellitus can therefore be expected to enjoy a similar improvement in function.

The December 2014 Shoulder & Elbow Roundup³⁶⁰ looks at: cuff tears and plexus injury;

corticosteroids and physiotherapy in SAI; diabetes and elbow arthroplasty; distal biceps tendon repairs; shockwave therapy in frozen shoulder; hydrodilation and steroids for adhesive capsulitis; just what do our patients read?; and what happens to that stable radial head fracture?

There is little evidence on the cost effectiveness of different brands of hip prostheses. We compared lifetime cost effectiveness of frequently used brands within types of prosthesis including cemented (Exeter V40 Contemporary, Exeter V40 Duration and Exeter V40 Elite Plus Ogee), cementless (Corail Pinnacle, Accolade Trident, and Taperloc Exceed) and hybrid (Exeter V40 Trilogy, Exeter V40 Trident, and CPT Trilogy). We used data from three linked English national databases to estimate the lifetime risk of revision, quality-adjusted life years (QALYs) and cost.

For women with osteoarthritis aged 70 years, the Exeter V40 Elite Plus Ogee had the lowest risk of revision (5.9% revision risk, 9.0 QALYs) and the CPT Trilogy had the highest QALYs (10.9% revision risk, 9.3 QALYs). Compared with the Corail Pinnacle (9.3% revision risk, 9.22 QALYs), the most commonly used brand, and assuming a willingness-to-pay of £20 000 per QALY gain, the CPT Trilogy is most cost effective, with an incremental net monetary benefit of £876. Differences in cost effectiveness between the hybrid CPT Trilogy and Exeter V40 Trident and the cementless Corail Pinnacle and Taperloc Exceed were small, and a cautious interpretation is required, given the limitations of the available information.

However, it is unlikely that cemented brands are among the most cost effective. Similar patterns of results were observed for men and other ages. The gain in quality of life after total hip arthroplasty, rather than the risk of revision, was the main driver of cost effectiveness.

Cite this article: Bone Joint J 2015;97-B:762–70.

The routine use of patient reported outcome measures (PROMs) in evaluating the outcome after arthroplasty by healthcare organisations reflects a growing recognition of the importance of patients’ perspectives in improving treatment. Although widely embraced in the NHS, there are concerns that PROMs are being used beyond their means due to a poor understanding of their limitations.

This paper reviews some of the current challenges in using PROMs to evaluate total knee arthroplasty. It highlights alternative methods that have been used to improve the assessment of outcome.

Cite this article: Bone Joint J 2015;97-B:3–9.

The aim of this study was to define return to theatre (RTT) rates for elective hip and knee replacement (HR and KR), to describe the predictors and to show the variations in risk-adjusted rates by surgical team and hospital using national English hospital administrative data.

We examined information on 260 206 HRs and 315 249 KRs undertaken between April 2007 and March 2012. The 90-day RTT rates were 2.1% for HR and 1.8% for KR. Male gender, obesity, diabetes and several other comorbidities were associated with higher odds for both index procedures. For HR, hip resurfacing had half the odds of cement fixation (OR = 0.58, 95% confidence intervals (CI) 0.47 to 0.71). For KR, unicondylar KR had half the odds of total replacement (OR = 0.49, 95% CI 0.42 to 0.56), and younger ages had higher odds (OR = 2.23, 95% CI 1.65 to 3.01) for ages < 40 years compared with ages 60 to 69 years). There were more funnel plot outliers at three standard deviations than would be expected if variation occurred on a random basis.

Hierarchical modelling showed that three-quarters of the variation between surgeons for HR and over half the variation between surgeons for KR are not explained by the hospital they operated at or by available patient factors. We conclude that 90-day RTT rate may be a useful quality indicator for orthopaedics.

Cite this article: Bone Joint J 2014; 96-B:1663–8.

We aimed to determine quality of life and burnout among Dutch orthopaedic trainees following a modern orthopaedic curriculum, with strict compliance to a 48-hour working week. We also evaluated the effect of the clinical climate of learning on their emotional well-being.

We assessed burnout, quality of life and the clinical climate of learning in 105 orthopaedic trainees using the Maslach Burnout Inventory, linear analogue scale self-assessments, and Dutch Residency Educational Climate Test (D-RECT), respectively.

A total of 19 trainees (18%) had poor quality of life and 49 (47%) were dissatisfied with the balance between their personal and professional life. Some symptoms of burnout were found in 29 trainees (28%). Higher D-RECT scores (indicating a better climate of learning) were associated with a better quality of life (r = 0.31, p = 0.001), more work-life balance satisfaction (r = 0.31, p = 0.002), fewer symptoms of emotional exhaustion (r = -0.21, p = 0.028) and depersonalisation (r = -0,28, p = 0.04).

A reduced quality of life with evidence of burnout were still seen in a significant proportion of orthopaedic trainees despite following a modern curriculum with strict compliance to a 48-hour working week. It is vital that further work is undertaken to improve the quality of life and reduce burnout in this cohort.

Cite this article: Bone Joint J 2014;96-B:1133–8.

The Oxford hip and knee scores (OHS and OKS) are validated patient-reported outcome measures used in patients undergoing total hip replacement (THR), hip resurfacing (HR), total knee replacement (TKR) and unicompartmental knee replacement (UKR). We analysed the absolute OHS and OKS and change in scores following THR, HR, TKR, and UKR performed at one specialist centre. All patients undergoing and completing at least one Oxford score were eligible for inclusion in the study which included 27 950 OHS and 19 750 OKS in 13 682 patients. Data were analysed using non-linear quantile regression. The median absolute Oxford scores for THR, HR, TKR and UKR were pre-operative 68.8% (15.0/48), 58.3% (20.0/48), 66.7% (16.0/48), 60.4% (19.0/48) respectively: and post-operative asymptote was 14.6% (41.0/48), 5.8% (45.2/48), 31.2% (33.0/48), 29.2% (34.0/48). The median asymptotic change from the pre-operative score for THR, HR, TKR and UKR were 47.9% (23.0/48), 47.9% (23.0/48), 33.3% (16.0/48) and 32.4% (15.5/48), respectively. The median time at which no further appreciable change in score was achieved post-operatively was 0.7 years for THR, 1.1 years for HR, 0.9 years for TKR and 1.1 years for UKR.

The curves produced from this analysis could be used to educate patients, and to audit the performance of a surgeon and an institution. The time to achieve a stable improvement in outcome varied between different types of joint replacement, which may have implications for the timing of post-operative review.

Cite this article: Bone Joint J 2014; 96-B:928–35.

Total hip replacement causes a short-term increase in the risk of mortality. It is important to quantify this and to identify modifiable risk factors so that the risk of post-operative mortality can be minimised. We performed a systematic review and critical evaluation of the current literature on the topic. We identified 32 studies published over the last 10 years which provide either 30-day or 90-day mortality data. We estimate the pooled incidence of mortality during the first 30 and 90 days following hip replacement to be 0.30% (95% CI 0.22 to 0.38) and 0.65% (95% CI 0.50 to 0.81), respectively. We found strong evidence of a temporal trend towards reducing mortality rates despite increasingly co-morbid patients. The risk factors for early mortality most commonly identified are increasing age, male gender and co-morbid conditions, particularly cardiovascular disease. Cardiovascular complications appear to have overtaken fatal pulmonary emboli as the leading cause of death after hip replacement.

Cite this article: Bone Joint Res 2014;3:175–82

The February 2013 Children’s orthopaedics Roundup³⁶⁰ looks at: the human genome; new RNA; cells, matrix and gene enhancement; the histology of x-rays; THR and VTE in the Danish population; potential therapeutic targets for GCT; optimising vancomycin elution from cement; and how much sleep is enough.

An understanding of the remodelling of tendon is crucial for the development of scientific methods of treatment and rehabilitation. This study tested the hypothesis that tendon adapts structurally in response to changes in functional loading. A novel model allowed manipulation of the mechanical environment of the patellar tendon in the presence of normal joint movement via the application of an adjustable external fixator mechanism between the patella and the tibia in sheep, while avoiding exposure of the patellar tendon itself. Stress shielding caused a significant reduction in the structural and material properties of stiffness (79%), ultimate load (69%), energy absorbed (61%), elastic modulus (76%) and ultimate stress (72%) of the tendon compared with controls. Compared with the material properties the structural properties exhibited better recovery after re-stressing with stiffness 97%, ultimate load 92%, energy absorbed 96%, elastic modulus 79% and ultimate stress 80%. The cross-sectional area of the re-stressed tendons was significantly greater than that of stress-shielded tendons.

The remodelling phenomena exhibited in this study are consistent with a putative feedback mechanism under strain control. This study provides a basis from which to explore the interactions of tendon remodelling and mechanical environment.

Objectives

This study aimed to investigate time-dependent gene expression of injured human anterior cruciate ligament (ACL), and to evaluate the histological changes of the ACL remnant in terms of cellular characterisation.

Between September 2004 and December 2005 we carried out a prospective study of all cases of sepsis of the hip in childhood at a South African regional hospital with a large local population, and which also took referrals from nine rural hospitals. The clinical, radiological, ultrasound and bacteriological features were assessed. All the hips were drained by arthrotomy and the diagnosis was confirmed microbiologically and histologically. Hips with tuberculosis were excluded. The children were reviewed in a dedicated clinic at a mean follow-up of 8.1 months (3 to 18).

There were 40 hips with sepsis in 38 patients. Two patients were lost to follow-up. Nine (24%) had multi-focal sepsis. Overall, 13 hips (34%) had a full and uncomplicated clinical and radiological recovery and 25 (66%) had complications. All patients treated by arthrotomy and appropriate antibiotics within five days of the onset of symptoms had an uncomplicated recovery. Initial misdiagnosis was associated with a delay to arthrotomy. However, ‘deprivation’, consultation with a traditional healer, maternal educational attainment and distance to a primary health-care facility were not associated with delay to arthrotomy. The early correct diagnosis of this condition, common in the developing world, remains a significant factor in improving the clinical outcome.

We report the effects of local administration of osteogenic protein-1 on the biomechanical properties of the overstretched anterior cruciate ligament in an animal model. An injury in the anterior cruciate ligament was created in 45 rabbits. They were divided into three equal groups. In group 1, no treatment was applied, in group II, phosphate-buffered saline was applied around the injured ligament, and in group III, 12.5 μg of osteogenic protein-1 mixed with phosphate-buffered saline was applied around the injured ligament. A control group of 15 rabbits was assembled from randomly-selected injured knees from among the first three groups. Each rabbit was killed at 12 weeks.

The maximum load and stiffness of the anterior cruciate ligament was found to be significantly greater in group III than either group 1 (p = 0.002, p = 0.014) or group II (p = 0.032, p = 0.025). The tensile strength and the tangent modulus of fascicles from the ligament were also significantly greater in group III than either group I (p = 0.002, p = 0.0174) or II (p = 0.005, p = 0.022).

The application of osteogenic protein-1 enhanced the healing in the injured anterior cruciate ligament, but compared with the control group the treated ligament remained lengthened. The administration of osteogenic protein-1 may have a therapeutic role in treating the overstretched anterior cruciate ligament.