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"Tuck, Stephen"
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The clinical utility of bone marker measurements in osteoporosis
Osteoporosis is characterised by low bone mass and structural deterioration of bone tissue, resulting in increased fragility and susceptibility to fracture. Osteoporotic fractures are a significant cause of morbidity and mortality. Direct medical costs from such fractures in the UK are currently estimated at over two billion pounds per year, resulting in a substantial healthcare burden that is expected to rise exponentially due to increasing life expectancy. Currently bone mineral density is the WHO standard for diagnosis of osteoporosis, but poor sensitivity means that potential fractures will be missed if it is used alone. During the past decade considerable progress has been made in the identification and characterisation of specific biomarkers to aid the management of metabolic bone disease. Technological developments have greatly enhanced assay performance producing reliable, rapid, non-invasive cost effective assays with improved sensitivity and specificity. We now have a greater understanding of the need to regulate pre-analytical sample collection to minimise the effects of biological variation. However, bone turnover markers (BTMs) still have limited clinical utility. It is not routinely recommended to use BTMs to select those at risk of fractures, but baseline measurements of resorption markers are useful before commencement of anti-resorptive treatment and can be checked 3–6 months later to monitor response and adherence to treatment. Similarly, formation markers can be used to monitor bone forming agents. BTMs may also be useful when monitoring patients during treatment holidays and aid in the decision as to when therapy should be recommenced. Recent recommendations by the Bone Marker Standards Working Group propose to standardise research and include a specific marker of bone resorption (CTX) and bone formation (P1NP) in all future studies. It is hoped that improved research in turn will lead to optimised markers for the clinical management of osteoporosis and other bone diseases.
Journal Article
Changes in bone density and bone turnover in patients with rheumatoid arthritis treated with rituximab, results from an exploratory, prospective study
Data describing the effect of in vivo B cell depletion on general bone loss in patients with rheumatoid arthritis (RA) are limited. Given the pathogenetic role of B cells in RA, it is tempting to speculate that B cell depletion might have a beneficial effect on bone loss. We prospectively investigated the changes in bone mineral density (BMD), bone turnover, inflammation and disease activity before and after rituximab in 45 RA patients over a 12 month period, 36 patients of whom completed the study and were included in the analysis. There was no significant change in our primary endpoint; lumbar spine BMD after 12 months. However, we found a significant decrease in neck of femur (mean -0.017 g/cm2, 95% CI -0.030, -0.004 p = 0.011) and total femur BMD (mean -0.016 g/cm2, 95% CI -0.025, -0.007 p = 0.001). Additionally, there was a significant increase in procollagen type 1 amino-terminal propeptide (P1NP) and bone specific alkaline phosphatase (BAP); biomarkers of bone formation (median change from baseline to 12 months; P1NP 11.3 μg/L, 95% CI -1.1, 24.8 p = 0.025; BAP 2.5 μg/L, 95% CI 1.2, 3.6 p = 0.002), but no significant change in bone resorption or osteocyte markers. The fall in BMD occurred despite improvement in disease control. Post-menopausal women had the lowest mean lumbar spine, femoral and forearm BMD at baseline and after 12 months, additionally they had a higher level of bone turnover throughout the study. In conclusion, BMD was maintained at the lumbar spine and forearm, but fell at the femur sites. A high prevalence of vitamin D deficiency was observed and these patients had lower BMD and evidence of higher bone turnover.
Journal Article
Striking first : preemption and prevention in international conflict
Taking a close look at the Iraq war, the 1998 attack against Al Qaeda in Afghanistan, and the Cuban Missile Crisis, among other conflicts, this text argues that neither the Bush Doctrine nor customary international law is capable of adequately responding to the pressing security threats of our times.
Book
The Night Malcolm X Spoke at the Oxford Union
Less than two months before he was assassinated, Malcolm X spoke at the Oxford Union—the most prestigious student debating organization in the United Kingdom. The Oxford Union regularly welcomed heads of state and stars of screen and served as the training ground for the politically ambitious offspring of Britain’s better classes. Malcolm X, by contrast, was the global icon of race militancy. For many, he personified revolution and danger. Marking the fiftieth anniversary of the debate, this book brings to life the dramatic events surrounding the visit, showing why Oxford invited Malcolm X, why he accepted, and the effect of the visit on Malcolm X and British students. Stephen Tuck tells the human story behind the debate and also uses it as a starting point to discuss larger issues of Black Power, the end of empire, British race relations, immigration, and student rights. Coinciding with a student-led campaign against segregated housing, the visit enabled Malcolm X to make connections with radical students from the Caribbean, Africa, and South Asia, giving him a new perspective on the global struggle for racial equality, and in turn, radicalizing a new generation of British activists. Masterfully tracing the reverberations on both sides of the Atlantic, Tuck chronicles how the personal transformation of the dynamic American leader played out on the international stage.
eBook
Adult Paget's disease of bone
Adult Paget’s disease of bone is the second commonest metabolic bone condition after osteoporosis. The condition is characterised by increased bone cell activity, with bone-resorbing osteoclasts often larger and containing more nuclei than normal and osteoblasts producing increased amounts of disorganised bone. This leads to expanded bone of poor quality possessing both sclerotic and lytic areas. Paget’s disease of bone has a strong genetic element, with a family history being noted in 10–20% of cases. A number of genetic defects have been found to be associated with the condition. The most common disease-associated variants identified affect the SQSTM1 gene, providing insights into disease aetiology, with the clinical value of knowledge of SQSTM1 mutation status currently under active investigation. The diagnosis may be suggested by an isolated raised total alkaline phosphatase (ALP) without other identifiable causes. This can be confirmed on plain X-ray and the extent determined by isotope bone scan. The mainstay of treatment are the bisphosphonates, especially intravenous zoledronate which results in long-term suppression of bone turnover. ALP is the usual means of monitoring the condition, although more specific bone turnover markers can be helpful, especially in coincident liver disease. Patients should be followed up to monitor for biochemical relapse or development of complications, which may require medical or surgical intervention.
Journal Article
Prospective comparative study of quantitative X-ray (QXR) versus dual energy X-ray absorptiometry to determine the performance of QXR as a predictor of bone health for adult patients in secondary care
ObjectivesTo evaluate a method of quantitative X-ray (QXR) for obtaining bone health information from standard radiographs aimed at identifying early signs of osteoporosis to enable improved referral and treatment. This QXR measurement is performed by postexposure analysis of standard radiographs, meaning bone health data can be acquired opportunistically, alongside routine imaging.DesignThe relationship between QXR and dual energy X-ray absorptiometry (DEXA) was demonstrated with a phantom study. A prospective clinical study was conducted to establish areal bone mineral density (aBMD) prediction model and a risk prediction model of a non-normal DEXA outcome. This was then extrapolated to a larger patient group with DEXA referral data.SettingSecondary care National Health Service Hospital.Participants126 consenting adult patients from a DEXA clinic.InterventionsAll participants underwent a DEXA scan to determine BMD at the lumbar spine (L2–L4) and both hips. An additional Antero-Posterior pelvis X-ray on a Siemens Ysio, fixed digital radiograph system was performed for the study.OutcomePerformance of QXR as a risk predictor for non-normal (osteoporotic) BMD.ResultsInterim clinical study data from 78 patients confirmed a receiver operator curve (area under the ROC curve) of 0.893 (95% CI 0.843 to 0.942) for a risk prediction model of non-normal DEXA outcome. Extrapolation of these results to a larger patient group of 11 029 patients indicated a positive predictive value of 0.98 (sensitivity of 0.8) for a population of patients referred to DEXA under current clinical referral criteria.ConclusionsThis study confirms that the novel QXR method provides accurate prediction of a DEXA outcome.Trial registration numberISRCTN98160454; Pre-results.
Journal Article
Osteoprotegerin, RANKL and bone turnover in postmenopausal osteoporosis
BackgroundOsteoprotegerin (OPG) and receptor activator of nuclear factor κ B ligand (RANKL) play a critical role in the regulation of bone turnover, but the relative importance of these two cytokines in the pathogenesis of postmenopausal osteoporosis is controversial.AimTo investigate the relationship between circulating levels of OPG, RANKL, bone turnover and bone mineral density (BMD) in postmenopausal women.MethodsA cross-sectional study of 185 women with osteoporosis and 185 age- and sex-matched control subjects was undertaken. Measurements were made of plasma OPG, RANKL, interleukin-6 (IL-6), sex steroids, calciotropic hormones, biochemical markers of bone turnover, BMD and anthropometry. Health questionnaires were administered.ResultsPlasma RANKL was significantly higher (p<0.0001) in women with osteoporosis (0.66±0.67 pmol/l) than in control subjects (0.37±0.38 pmol/l), as was plasma OPG (18.70±9.70 pmol/l in women with osteoporosis, 10.44±5.85 pmol/l in control subjects; p<0.0001). OPG/RANKL ratio was higher in women with osteoporosis (51.3) than in control subjects (36.6). The women with osteoporosis also had significantly higher biochemical markers of bone turnover, IL-6 and parathyroid hormone and lower 25-hydroxyvitamin D and oestradiol than the control subjects. Multiple regression analysis showed that lumbar spine and femoral neck BMD in postmenopausal women were best predicted by OPG and RANKL, giving an R2 value of 15.5% and 14.9%, respectively.ConclusionsThis study indicates that the circulating levels of OPG and RANKL are inversely related to BMD and contribute to the development of osteoporosis in postmenopausal women.
Journal Article