Osteoporosis: Compston J

Compston J, Cooper A, Cooper C, Francis R, Kanis JA, Marsh D, McCloskey EV, Reid DM, Selby P, Wilkins M, Anonymous00031. · University of Cambridge School of Clinical Medicine, Department of Medicine, Cambridge, United Kingdom. · Maturitas. · Pubmed #19135323 No free full text.

Abstract: In 1999 and 2000 the Royal College of Physicians published guidelines for the prevention and treatment of osteoporosis [Royal College of Physicians. Osteoporosis: clinical guidelines for the prevention and treatment. London: Royal College of Physicians; 1999; Royal College of Physicians and Bone and Tooth Society of Great Britain. Update on pharmacological interventions and an algorithm for management. London, UK: Royal College of Physicians; 2000.; Royal College of Physicians. Glucocorticoid-induced osteoporosis. Guidelines on prevention and treatment; Bone and Tooth Society of Great Britain, National Osteoporosis Society and Royal College of Physicians. London, UK: Royal College of Physicians; 2002]. Since then, there have been significant advances in the field of osteoporosis including the development of new techniques for measuring bone mineral density, improved methods of assessing fracture risk and new treatments that have been shown to significantly reduce the risk of fractures. Against this background, the National Osteoporosis Guideline Group (NOGG), in collaboration with many Societies in the UK, have updated the original guidelines [Royal College of Physicians, National Osteoporosis Guideline Group on behalf of the Bone Research Society, British Geriatrics Society, British Orthopaedic Association, British Society of Rheumatology, National Osteoporosis Society, Osteoporosis 2000, Osteoporosis Dorset, Primary Care Rheumatology Society, Society for Endocrinology. Osteoporosis. Clinical guideline for prevention and treatment, Executive Summary. University of Sheffield Press; 2008], a practical summary of which is detailed below. The management algorithms are underpinned by a health economic analysis applied to the epidemiology of fracture in the UK.

Compston J. · Box 157, Department of Medicine, Addenbrooke's Hospital, Cambridge CB2 2QQ, UK. · Gut. · Pubmed #12477761 links to  free full text

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Compston J. · No affiliation provided · BMJ. · Pubmed #19549994 No free full text.

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Kanis JA, Adams J, Borgström F, Cooper C, Jönsson B, Preedy D, Selby P, Compston J. · No affiliation provided · Bone. · Pubmed #18156107 No free full text.

Abstract: The National Institute for Health and Clinical Excellence (NICE) in the UK has recently issued health economic appraisals for the primary and secondary prevention of osteoporotic fracture that are more restrictive than previous guidelines for the management of osteoporosis despite a marked reduction of the cost of intervention. The aim of the present study was to examine the cost-effectiveness of the bisphosphonate, alendronate for the prevention and treatment of fractures associated with osteoporosis. A second aim was to investigate reasons for any disparities in cost-effectiveness between our findings and the NICE appraisals. We compared the effects of alendronate 70 mg weekly by mouth for 5 years with no treatment in postmenopausal women with clinical risk factors for fracture and computed the incremental cost-effectiveness ratio (ICER) using a lifetime simulation model based on Markov cohort methodology. A sensitivity analysis examined other common interventions. Using a threshold of pound sterling 30,000 and pound sterling 20,000 per quality of life-year (QALY) gained to determine cost-effectiveness, alendronate was cost-effective for the primary prevention of fracture in women with osteoporosis irrespective of age as was treatment of women with a prior fragility fracture irrespective of BMD. Cost-effective scenarios were also found in women with strong risk factors for fracture with a bone mineral density value above the threshold for osteoporosis. The results were robust over reasonable assumptions in sensitivity analysis. We conclude that alendronate is a cost-effective agent for the prevention and treatment of fractures associated with osteoporosis. These findings, suitable for informing practice guidance, contrast with recent appraisals from NICE.

Compston J. · No affiliation provided · Menopause Int. · Pubmed #17540133 No free full text.

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Compston J. · No affiliation provided · N Engl J Med. · Pubmed #17476015 No free full text.

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Compston J. · No affiliation provided · Osteoporos Int. · Pubmed #14985947 No free full text.

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Compston J. · No affiliation provided · J R Coll Physicians Lond. · Pubmed #11191965 No free full text.

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Compston J. · No affiliation provided · Practitioner. · Pubmed #10790909 No free full text.

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Compston J. · Department of Medicine, Addenbrooke's Hospital, Cambridge, CB2 2QQ, UK. · Curr Osteoporos Rep. · Pubmed #18430393 No free full text.

Abstract: Bone-turnover suppression is central to the therapeutic benefit of many interventions used to prevent osteoporotic fractures. There are theoretical concerns that long-term suppression may have adverse effects on bone strength, although at present no direct evidence exists that this happens. Nevertheless, further research is required to establish the optimal duration of treatment with antiresorptive agents.

Seeman E, Compston J, Adachi J, Brandi ML, Cooper C, Dawson-Hughes B, Jönsson B, Pols H, Cramer JA. · Department of Medicine and Endocrinology, Austin Health, University of Melbourne, Melbourne, Australia. · Osteoporos Int. · Pubmed #17245547 No free full text.

Abstract: About 50% of patients fail to comply or persist with anti-osteoporosis treatment regimens within 1 year. Poor compliance is associated with higher fracture rates. Causes of poor compliance are unknown. As it is not possible to predict poor compliance, close monitoring of compliance is needed. Despite evidence supporting the anti-fracture efficacy of several pharmacological agents, approximately 50% of patients do not follow their prescribed treatment regimen and/or discontinue treatment within 1 year. Poor compliance is associated with higher fracture rates and increased morbidity, mortality and cost. However, as poor compliance, even to placebo, is associated with adverse outcomes, the higher morbidity appears to be only partly the result of lack of treatment: as yet, undefined characteristics place poor compliers at higher risk of morbidity and mortality. Only a small proportion (e.g., 6%) of the variability in compliance is explained by putative causal factors such as older age, co-morbidity or greater number of medications. Regimens with longer dosing intervals, such as weekly dosing, improve compliance, persistence and outcomes, but only modestly. As it is not possible to predict poor compliance, close monitoring of compliance should be an obligatory duty in clinical care. How this is best achieved has yet to be established, but poor persistence occurs as early as 3 months of starting treatment, indicating the need for early monitoring.

Compston J. · School of Clinical Medicine, University of Cambridge, Cambridge, UK. · Arq Bras Endocrinol Metabol. · Pubmed #17117283 links to  free full text

Abstract: Bone quality describes aspects of bone composition and structure that contribute to bone strength independently of bone mineral density. These include bone turnover, microarchitecture, mineralisation, microdamage and the composition of bone matrix and mineral. New techniques to assess these components of bone quality are being developed and should produce important insights into determinants of fracture risk in untreated and treated disease.

Geusens PP, Lems WF, Verhaar HJ, Leusink G, Goemaere S, Zmierczack H, Compston J. · Department of Rheumatology, University Hospital, Maastricht, the Netherlands. · J Eval Clin Pract. · Pubmed #16987116 No free full text.

Abstract: RATIONALE: At the request of a Dutch governmental organization, a multidisciplinary group of osteoporosis experts in the Netherlands published in 2002 a guideline on case finding, diagnosis, prevention and treatment of osteoporosis. These guidelines were evaluated for their validity and applicability. METHODS: Analysis by 5 external osteoporosis experts using the 'Appraisal of Guidelines for Research & Evaluation' ('AGREE') instrument. RESULTS: The score for the 6 domains of AGREE was 88% for the scope and purpose domain, 76% for stakeholder involvement, 81% for rigour of development, 84% for clarity and presentation, 77% for applicability and 73% for editorial independence. For single components of the domains of AGREE, highest scores were found for systematic methods used to search for evidence (100%), inclusion of individuals from all the relevant professional groups (95%) and ease of identifying key recommendations (95%). Lowest scores to single components of the several domains were given for piloting among target users (44%). All experts recommended the guidelines for use in practice. CONCLUSIONS: The AGREE instrument scored high for development, clarity and presentation but low for piloting among target users and implementation. Based on the guideline, algorithms from case finding to treatment were constructed that could be tested for piloting among target users and for implementation of the guideline.

Compston J. · University of Cambridge School of Clinical Medicine, Box 157, Addenbrooke's Hospital, Cambridge CB2 2QQ, UK. · Best Pract Res Clin Rheumatol. · Pubmed #16301194 No free full text.

Abstract: Many women seek advice about bone health at the time of the menopause. Although fracture probability is low in the majority, treatment may be cost-effective if targeted at those at highest risk. Optimal selection of individuals for intervention is based on a case-finding approach, fracture probability being estimated using a combination of bone mineral density and clinical risk factors. A variety of therapeutic interventions is available for the prevention of osteoporotic fractures in postmenopausal women. Hormone replacement therapy (HRT) is a second-line option in most, although it has a place in the management of perimenopausal women with menopausal symptoms who are at risk from fracture and in other postmenopausal women who express a preference for HRT over other options, after being fully informed about known risks and benefits.

Compston J. · Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital Hills Road, Box 157, CB2 2QQ, Cambridge, UK. · Calcif Tissue Int. · Pubmed #16059774 No free full text.

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Compston J. · Department of Medicine, University of Cambridge School of Medicine, Addenbrooke's Hospital, PO Box 157, Cambridge CB2 2QQ, UK. · Osteoporos Int. · Pubmed #15983729 No free full text.

Abstract: Evidence-based guidelines are increasingly used in the management of osteoporosis and have the potential to produce uniformly high standards of clinical care across different sectors of the health service. National guidelines for the prevention and treatment of osteoporosis are now available in a number of countries and, although sharing similarities, also differ in some respects. This review considers the challenges involved in the development and implementation of guidelines and proposes a paradigm for the unification of guidelines in the future.

Compston J. · Department of Medicine, Box 157, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 2QQ, UK. · Osteoporos Int. · Pubmed #15480571 No free full text.

Abstract: The antifracture efficacy of strontium ranelate, a compound with a novel mechanism of action on bone, has been assessed in two large, randomized, controlled trials conducted in postmenopausal women. Strontium ranelate was given at a daily dose of 2 g, and all women received calcium and vitamin D supplements. In women with established osteoporosis there was a 41% reduction in vertebral fractures over 3 years' treatment [relative risk (RR) 0.59; 95% confidence interval (CI) 0.48-0.73; P<0.001]; significant reductions were also seen after only 1 year of treatment. The beneficial effect was also seen for clinical vertebral fractures: over 3 years there was a significant reduction in new clinical vertebral fractures (RR 0.62; 95% CI 0.47-0.83; P<0.001); this reduction was also observed during the first year of treatment (RR 0.48; 95% CI 0.29-0.80; P=0.003). Over the 3-year treatment period significantly fewer patients had height loss and fewer patients reported new or worsening back pain in the treated group than in the control group. These results demonstrate that strontium ranelate is a new therapeutic option in the prevention of osteoporotic vertebral fractures in postmenopausal women.

Compston J. · Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Box 157, Cambridge, CB2 2QQ, UK. · Curr Rheumatol Rep. · Pubmed #14713404 No free full text.

Abstract: Osteoporosis is a common and serious complication of glucocorticoid therapy. Recent advances in the epidemiology, pathophysiology, and management of glucocorticoid-induced osteoporosis have stimulated the development of guidelines for the prevention and treatment of this condition. In this report, the updated recommendations of the American College of Rheumatology and guidelines recently produced by the Bone and Tooth Society, National Osteoporosis Society, and Royal College of Physicians in the UK are discussed with respect to their similarities and differences.

Compston J. · Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge, UK. · Horm Res. · Pubmed #14671402 No free full text.

Abstract: Osteoporosis is a common and serious complication of glucocorticoid therapy, resulting in increased risk of fragility fractures. Recent studies indicate that fracture risk is increased even at low doses of glucocorticoids and that this increased risk is seen soon after the commencement of glucocorticoid therapy. Both increased bone resorption and reduced bone formation contribute to bone loss, which affects cortical and cancellous sites. A number of interventions have been shown to prevent glucocorticoid-induced bone loss, although the strongest evidence exists for the bisphosphonates etidronate, alendronate and risedronate. Primary prevention of bone loss should be considered in all high-risk individuals taking oral glucocorticoids for 3 months or more, for example those aged 65 years or over or those with a previous fragility fracture. In other glucocorticoid-treated individuals, the decision to treat should be based on bone densitometry.

Compston J. · Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge, UK. · Eur J Gastroenterol Hepatol. · Pubmed #12867791 No free full text.

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Compston J. · Department of Medicine, University of Cambridge School of Clinical Medicine, UK. · Endocrine. · Pubmed #12014699 No free full text.

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Compston J. · Department of Medicine, University of Cambridge School of Clinical Medicine, UK. · Calcif Tissue Int. · Pubmed #11730248 No free full text.

Abstract: Important underlying causes of osteoporotic fracture in men include glucocorticoid therapy, low body weight, and reduced physical activity. Tobacco and alcohol use have been consistently identified as risk factors for vertebral fracture but there is less evidence that they contribute to hip fracture. Clinically overt hypogonadism is a strong risk factor for osteoporosis in men; however, the role of more subtle subclinical changes, as defined by biochemical criteria, remains to be established. The high comorbidity associated with osteoporosis, particularly in elderly men, contributes to fracture risk both through effects on bone mass and risk of falling. The management of osteoporosis in men includes diagnosis of and, where possible, correction of underlying contributory causes. Evidence from recent randomized controlled trials indicates that bisphosphonates are effective in the prevention of glucocorticoid-induced osteoporosis in men but the optimal criteria for selection of individuals for treatment requires further study.

Eastell R, Reid DM, Compston J, Cooper C, Fogelman I, Francis RM, Hay SM, Hosking DJ, Purdie DW, Ralston SH, Reeve J, Russell RG, Stevenson JC. · University of Sheffield Medical School, Sheffield, UK. · QJM. · Pubmed #11704688 links to  free full text

Abstract: The burden of non-vertebral fractures is enormous. Hip fractures account for nearly 10% of all fractures (and a much greater proportion in the elderly), while wrist fractures may account for up to 23% of all limb fractures. The best available predictors of non-vertebral fracture risk are low BMD and a tendency to fall. Hip, forearm, proximal humerus and rib fractures have all been associated with low BMD, though ankle fracture is not strongly related to osteoporosis. Although clinical risk factors identify only about one-third of postmenopausal women at increased risk of osteoporotic fracture, the occurrence of one fracture commonly predicts a second fracture. Guidelines are presented for identifying and treating patients at risk of non-vertebral osteoporotic fractures, especially those with a previous fracture, based on the algorithm recently published by the Royal College of Physicians and the Bone and Tooth Society. Prevention of falls and use of external hip protectors may reduce the occurrence of hip fracture. Treatment options for patients presenting with hip fracture include HRT, bisphosphonates, and calcium plus vitamin D, and for Colles' fracture include general measures, HRT, bisphosphonates, or calcitonin plus calcium.

Compston J. · Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Cambridge, CB2 2QQ, UK. · Baillieres Best Pract Res Clin Endocrinol Metab. · Pubmed #11035905 No free full text.

Abstract: A number of pharmacological interventions are now available for the prevention of osteoporotic fractures in post-menopausal women. These include hormone replacement therapy, bisphosphonates, raloxifene, calcitonin, calcitriol and combined calcium and vitamin D. Factors influencing the positioning of these agents in clinical practice include their efficacy in preventing fractures at both the spine and the hip, tolerability, side-effects, cost and, in the case of raloxifene and hormone replacement therapy, the extra-skeletal risks and benefits of long-term treatment. The rates of onset and offset of the treatment effect are also important considerations; the observations that relatively short-term intervention produces a significant reduction in fracture risk in women with established osteoporosis, that treatment benefits are greatest in those with low bone mineral density and that the beneficial skeletal effects are not maintained after the withdrawal of treatment have resulted in a shift from long-term preventive strategies towards the targeting of high-risk individuals for intervention.

Compston J. · Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, UK. · J Endocrinol Invest. · Pubmed #10532253 No free full text.

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