Osteoporosis: Cooper C

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.

Kanis JA, Burlet N, Cooper C, Delmas PD, Reginster JY, Borgstrom F, Rizzoli R, Anonymous00089. · WHO Collaborating Centre for Metabolic Bone Diseases, University of Sheffield Medical School, Beech Hill Road, Sheffield S10 2RX, UK. · Osteoporos Int. · Pubmed #18266020 links to  free full text

Abstract: SUMMARY: Guidance is provided in a European setting on the assessment and treatment of postmenopausal women with or at risk from osteoporosis. INTRODUCTION: The European Foundation for Osteoporosis and Bone disease (subsequently the International Osteoporosis Foundation) published guidelines for the diagnosis and management of osteoporosis in 1997. This manuscript updates these in a European setting. METHODS: The following areas are reviewed: the role of bone mineral density measurement for the diagnosis of osteoporosis and assessment of fracture risk; general and pharmacological management of osteoporosis; monitoring of treatment; assessment of fracture risk; case finding strategies; investigation of patients; health economics of treatment. RESULTS AND CONCLUSIONS: A platform is provided on which specific guidelines can be developed for national use.

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.

Cooper C. · No affiliation provided · Bone. · Pubmed #16414319 No free full text.

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Delmas PD, Rizzoli R, Cooper C, Reginster JY. · No affiliation provided · Osteoporos Int. · Pubmed #15565349 No free full text.

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Cooper C, Walker-Bone K, Arden N, Dennison E. · No affiliation provided · Rheumatology (Oxford). · Pubmed #11136871 links to  free full text

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Cole ZA, Dennison EM, Cooper C. · MRC Epidemiology Resource Centre, University of Southampton, UK. · Salud Publica Mex. · Pubmed #19287891 links to  free full text

Abstract: Osteoporosis constitutes a major public health problem through its association with age related fractures. Fracture rates are generally higher in caucasian women than in other populations. Important determinants include estrogen deficiency in women, low body mass index, cigarette smoking, alcohol consumption, poor dietary calcium intake, physical inactivity, certain drugs and illnesses. Thus, modification of physical activity and dietary calcium/vitamin D nutrition should complement high risk approaches. In addition, the recently developed WHO algorithm for evaluation of 10-year absolute risk of fracture provides a means whereby various therapies can be targeted cost-effectively to those at risk. Risk factors, together with bone mineral density (BMD) and biochemical indices of bone turnover, can be utilised to derive absolute risks of fracture and cost-utility thresholds at which treatment is justified. These data will provide the basis for translation into coherent public health strategies aiming to prevent osteoporosis both in individuals and in the general population.

Cooper C, Westlake S, Harvey N, Dennison E. · MRC Epidemiology Resource Centre, University of Southampton, Southampton General Hospital, Southampton SO16 6YD. · Adv Exp Med Biol. · Pubmed #19227545 No free full text.

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Holroyd C, Cooper C, Dennison E. · MRC Epidemiology Resource Centre, University of Southampton, Southampton General Hospital, Southampton, UK. · Best Pract Res Clin Endocrinol Metab. · Pubmed #19028351 No free full text.

Abstract: Osteoporosis represents a major public health problem through its association with fragility fractures. All osteoporotic fractures increase patient morbidity; however, fractures of the hip and vertebrae are also linked with significant mortality. The public health burden of osteoporotic fracture is likely to rise in future generations, due in part to an increase in life expectancy. Understanding the epidemiology of this disease is therefore essential in trying to develop strategies to help reduce this load. This chapter will review the epidemiology of osteoporosis, including the relationship between low bone mass and fracture. It will review the epidemiology of fractures, concentrating on the sites where the majority of age-related fractures occur. Finally it will discuss new developments in the assessment of fracture risk.

Cole Z, Dennison E, Cooper C. · MRC Epidemiology Resource Centre, University of Southampton, Southampton General Hospital, Southampton SO16 6YD, UK. · Br Med Bull. · Pubmed #18477578 No free full text.

Abstract: BACKGROUND: Osteoporosis has a huge impact on public health, through the increased morbidity, mortality and economic costs associated with resultant fractures. The goal is to evaluate and identify those that are at risk of osteoporotic fracture in order to start preventative and therapeutic measures to reduce their risk of fracture. SOURCES OF DATA: This article reviews the data from randomized controlled trials for the current therapeutic agents available in the UK. It also reviews new trial data for promising osteoporosis therapies, in particular Denosumab, a monoclonal antibody against RANK ligand. AREAS OF AGREEMENT: Bisphosphonates are the current recommended first-line treatments for patients with osteoporosis. AREAS OF CONTROVERSY/GROWING POINTS: There are a number of patients where bisphosphonates are contraindicated. Under these circumstances, it is important that clinicians have access to alternative treatments. The long-awaited National Institute for Health and Clinical Excellence (NICE) technology appraisals for both primary and secondary prevention and the clinical guidelines will clarify this. Treatment decisions should be based on risk factors and pharmaceutical intervention given to those with the highest risks. AREAS TIMELY FOR DEVELOPING RESEARCH: Future studies are required to look at these agents in combination to see whether anti-fracture efficacy can be improved.

Cole ZA, Dennison EM, Cooper C. · Medical Research Council Epidemiology Resource Centre, Southampton General Hospital, Tremona Road, Southampton SO16 6YD, United Kingdom. · Curr Rheumatol Rep. · Pubmed #18460262 No free full text.

Abstract: Osteoporosis remains a major public health problem through its association with fragility fractures. Despite the availability of preventative therapeutic agents, the incidence and its associated costs continue to rise globally. Understanding osteoporosis epidemiology is essential to developing strategies to reduce the burden of osteoporotic fracture in the population. This article reviews the epidemiology of osteoporosis globally, highlighting recent advances. It describes the burden of common osteoporotic fractures, the associated morbidity and mortality, the clustering of fractures in individuals, and the identification of at-risk groups. It also highlights the development of new algorithms to identify individuals at high risk of fracture, enabling the implementation of appropriate treatment strategies.

Cooper C, Harvey N, Javaid K, Hanson M, Dennison E. · MRC Epidemiology Resource Centre and Centre for Developmental Origins of Health and Adult Disease, University of Southampton, Southampton General Hospital, Southampton, UK. · Nestle Nutr Workshop Ser Pediatr Program. · Pubmed #18196944 No free full text.

Abstract: Osteoporosis is a major cause of morbidity and mortality through its association with age-related fractures. Although most effort in fracture prevention has been directed at retarding the rate of age-related bone loss, and reducing the frequency and severity of trauma among elderly people, evidence is growing that peak bone mass is an important contributor to bone strength during later life. The normal patterns of skeletal growth have been well characterized in cross-sectional and longitudinal studies. It has been confirmed that boys have higher bone mineral content, but not volumetric bone density, than girls. Furthermore, there is a dissociation between the peak velocities for height gain and bone mineral accrual, in both genders. Puberty is the period during which volumetric density appears to increase in both axial and appendicular sites. Many factors influence the accumulation of bone mineral during childhood and adolescence, including heredity, gender, diet, physical activity, endocrine status, and sporadic risk factors such as cigarette smoking. In addition to these modifiable factors during childhood, evidence has also accrued that fracture risk might be programmed during intrauterine life. Epidemiological studies have demonstrated a relationship between birthweight, weight in infancy, and adult bone mass. This appears to be mediated through modulation of the set-point for basal activity of pituitary-dependent endocrine systems such as the hypothalamicpituitary-adrenal and growth hormone/insulin-like growth factor-1 axes. Maternal smoking, diet (particularly vitamin D deficiency), and physical activity also appear to modulate bone mineral acquisition during intrauterine life; furthermore, both low birth size and poor childhood growth are directly linked to the later risk of hip fracture. The optimization of maternal nutrition and intrauterine growth should also be included within preventive strategies against osteoporotic fracture, albeit for future generations.

Kanis JA, Oden A, Johnell O, Johansson H, De Laet C, Brown J, Burckhardt P, Cooper C, Christiansen C, Cummings S, Eisman JA, Fujiwara S, Glüer C, Goltzman D, Hans D, Krieg MA, La Croix A, McCloskey E, Mellstrom D, Melton LJ, Pols H, Reeve J, Sanders K, Schott AM, Silman A, Torgerson D, van Staa T, Watts NB, Yoshimura N. · WHO Collaborating Centre for Metabolic Bone Diseases, University of Sheffield Medical School, Beech Hill Road, Sheffield, S10 2RX, UK. · Osteoporos Int. · Pubmed #17323110 No free full text.

Abstract: SUMMARY: BMD and clinical risk factors predict hip and other osteoporotic fractures. The combination of clinical risk factors and BMD provide higher specificity and sensitivity than either alone. INTRODUCTION AND HYPOTHESES: To develop a risk assessment tool based on clinical risk factors (CRFs) with and without BMD. METHODS: Nine population-based studies were studied in which BMD and CRFs were documented at baseline. Poisson regression models were developed for hip fracture and other osteoporotic fractures, with and without hip BMD. Fracture risk was expressed as gradient of risk (GR, risk ratio/SD change in risk score). RESULTS: CRFs alone predicted hip fracture with a GR of 2.1/SD at the age of 50 years and decreased with age. The use of BMD alone provided a higher GR (3.7/SD), and was improved further with the combined use of CRFs and BMD (4.2/SD). For other osteoporotic fractures, the GRs were lower than for hip fracture. The GR with CRFs alone was 1.4/SD at the age of 50 years, similar to that provided by BMD (GR = 1.4/SD) and was not markedly increased by the combination (GR = 1.4/SD). The performance characteristics of clinical risk factors with and without BMD were validated in eleven independent population-based cohorts. CONCLUSIONS: The models developed provide the basis for the integrated use of validated clinical risk factors in men and women to aid in fracture risk prediction.

Dennison E, Mohamed MA, Cooper C. · MRC Epidemiology Resource Centre, Southampton General Hospital, Tremona Road, Southampton SO16 6YD, United Kingdom. · Rheum Dis Clin North Am. · Pubmed #17288968 No free full text.

Abstract: Osteoporotic fractures represent a significant public health burden, which is set to increase in future generations. Lifetime risk is high and lies within the range of 40% to 50% in women and 13% to 22% in men. Life expectancy is increasing worldwide, and it is estimated that the number of individuals aged 65 years and older will increase from the current figure of 323 million to 1555 million by the year 2050. These demographic changes alone can be expected to cause the number of hip fractures occurring worldwide to increase from 1.66 million in 1990 to 6.26 million in 2050. Based on current trends, hip fracture rates might increase in the United Kingdom from 46,000 in 1985 to 117,000 in 2016. The societal cost of these fractures is high; cost-effectiveness analyses showed cost-effectiveness in treating high-risk patients with antiresorptive drugs, particularly if administered as soon as possible after a first fragility fracture.

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.

Sambrook P, Cooper C. · Institute of Bone and Joint Research, University of Sydney, Sydney 2065, NSW, Australia. · Lancet. · Pubmed #16782492 No free full text.

Abstract: Osteoporosis is a serious public health issue. The past 10 years have seen great advances in our understanding of its epidemiology, pathophysiology, and treatment, and further advances are rapidly being made. Clinical assessment will probably evolve from decisions mainly being made on the basis of bone densitometry, to use of algorithms of absolute fracture risk. Biochemical markers of bone turnover are also likely to become more widely used. Bisphosphonates will probably remain the mainstay of therapy, but improved understanding of the optimum amount of remodelling suppression and duration of therapy will be important. At the same time, other diagnostic and therapeutic approaches, including biological agents, are likely to become more widespread.

Boonen S, Bischoff-Ferrari HA, Cooper C, Lips P, Ljunggren O, Meunier PJ, Reginster JY. · Leuven University Center for Metabolic Bone Diseases and Division of Geriatric Medicine, Katholieke Universiteit Leuven, Leuven, Belgium. · Calcif Tissue Int. · Pubmed #16622587 No free full text.

Abstract: Osteoporotic fractures are an extremely common and serious health problem in the elderly. This article presents the rationale for calcium and vitamin D supplementation in the prevention and treatment of osteoporotic fractures and reviews the literature evidence on the efficacy of this strategy. Two musculoskeletal risk factors are implicated in osteoporotic fractures in the elderly: the loss of bone mass due to secondary hyperparathyroidism and the increased propensity to falls. Calcium and vitamin D reverse secondary hyperparathyroidism with resultant beneficial effects on bone mineral density (BMD). Additionally, calcium and vitamin D supplementation significantly improves body sway and lower extremity strength, reducing the risk of falls. The effects of combined calcium and vitamin D on parathyroid function and BMD provide a strong rationale for the use of this therapy in the prevention and treatment of osteoporosis and osteoporotic fractures. There is general agreement that, in patients with documented osteoporosis, calcium and vitamin D supplementation should be an integral component of the management strategy, along with antiresorptive or anabolic treatment. Frail elderly individuals constitute another major target population for calcium and vitamin D because evidence from randomized studies in institutionalized elderly subjects demonstrates that these supplements reduce osteoporotic fracture risk, particularly in the presence of dietary deficiencies. However, the results of trials in community-dwelling subjects have been equivocal. Within the primary-care setting, further research is required to establish appropriate target subgroups for calcium and vitamin D supplementation; overall, the data are consistent with a benefit individuals with insufficient calcium and/or vitamin D, although patients with documented osteoporosis will derive further benefit in terms of fracture prevention from the addition of an antiresorptive agent.

Cooper C. · MRC Epidemiology Resource Centre, University of Southampton, Southampton General Hospital, Southampton SO16 6YD, UK. · Bone. · Pubmed #16520105 No free full text.

Abstract: Osteoporosis has had a significant public health impact, with many sufferers experiencing fractures. Such fractures lead to increased disability, mortality and reduced quality of life, all of which raise healthcare costs. Oral bisphosphonates are associated with significant antifracture efficacy and have therefore become the mainstay of treatment for postmenopausal osteoporosis. Poor therapeutic adherence with daily bisphosphonates has been improved by the introduction of weekly regimens, although adherence levels remain suboptimal. Bisphosphonate regimens with dosing intervals beyond a week have therefore been developed to address this issue. Oral ibandronate, a potent nitrogen-containing bisphosphonate, has been studied using daily and intermittent regimens (between-dose interval >2 months). The initial phase II 2-year study confirmed the feasibility of the intermittent regimen, providing increases in lumbar spine bone mineral density (BMD) superior to placebo (P < 0.01) and equivalent to the daily regimen (5.64% vs. 5.54%, respectively). BONE (Oral iBandronate Osteoporosis vertebral fracture trial in North America and Europe), a large phase III 3-year study was subsequently initiated, including 2946 women with postmenopausal osteoporosis and testing both a daily as well as an intermittent regimen with a dose-free interval of more than 2 months. Significant vertebral antifracture efficacy (the primary study endpoint) was demonstrated with daily (2.5 mg) and intermittent (20 mg every other day for 12 doses every 3 months) ibandronate in comparison with placebo (P < or = 0.0006). As a result of the study not being designed and powered to show an effect on non-vertebral fractures and the overall population being at low risk for osteoporotic fractures, differences in the incidence of non-vertebral fractures were similar between groups (8.2-9.1%) However, a post hoc analysis in a subgroup of patients with a femoral neck BMD T-score < -3.0 showed that daily ibandronate significantly reduced the risk of non-vertebral fractures (P = 0.012). Both regimens were associated with significant increases in lumbar spine and proximal femur BMD and normalization of bone turnover. As determined by adverse event incidence and laboratory evaluation, the safety profile for both ibandronate regimens was similar to that observed for placebo. The BONE study therefore confirmed that daily or intermittent ibandronate is an effective and well-tolerated treatment for postmenopausal women. Being the first study to demonstrate antifracture efficacy with an intermittent regimen, it provided "proof of concept" for beyond weekly dosing with ibandronate and prompted further development of a more convenient once-monthly regimen.

Cooper C, Westlake S, Harvey N, Javaid K, Dennison E, Hanson M. · MRC Epidemiology Resource Centre and Centre for Developmental Origins of Health and Adult Disease, University of Southampton, Southampton General Hospital, Southampton , SO16 6YD, UK. · Osteoporos Int. · Pubmed #16331359 No free full text.

Abstract: Osteoporosis is a major cause of morbidity and mortality through its association with age-related fractures. Although most effort in fracture prevention has been directed at retarding the rate of age-related bone loss and reducing the frequency and severity of trauma among elderly people, evidence is growing that peak bone mass is an important contributor to bone strength during later life. The normal patterns of skeletal growth have been well characterised in cross-sectional and longitudinal studies. It has been confirmed that boys have higher bone mineral content (BMC), but not volumetric bone density, than girls. Furthermore, there is a dissociation between the peak velocities for height gain and bone mineral accrual in both genders. Puberty is the period during which volumetric density appears to increase in both axial and appendicular sites. Many factors influence the accumulation of bone mineral during childhood and adolescence, including heredity, gender, diet, physical activity, endocrine status, and sporadic risk factors such as cigarette smoking. In addition to these modifiable factors during childhood, evidence has also accrued that fracture risk might be programmed during intrauterine life. Epidemiological studies have demonstrated a relationship between birth weight, weight in infancy, and adult bone mass. This appears to be mediated through modulation of the set-point for basal activity of pituitary-dependent endocrine systems such as the HPA and GH/IGF-1 axes. Maternal smoking, diet (particularly vitamin D deficiency), and physical activity also appear to modulate bone mineral acquisition during intrauterine life; furthermore, both low birth size and poor childhood growth are directly linked to the later risk of hip fracture. The optimisation of maternal nutrition and intrauterine growth should also be included within preventive strategies against osteoporotic fracture, albeit for future generations.

Sayer AA, Cooper C. · Geriatric Medicine, Southampton General Hospital, Southampton, SO16 6YD, UK. · Early Hum Dev. · Pubmed #16081228 No free full text.

Abstract: The prevalence of obesity, sarcopenia and osteoporosis is rising and there is increasing interest in determinants operating in early life. Fetal programming is the phenomenon whereby alterations in fetal growth and development in response to the prenatal environment have long term or permanent effects. Evidence for fetal programming of body composition and musculoskeletal development comes from epidemiological studies, investigation of the role of early undernutrition and preliminary findings on underlying mechanisms. Low birth weight and poor prenatal nutrition are associated with changes in adult body composition including altered fat distribution, reduced muscle mass and strength, and low bone mineral content. The mechanisms include a direct effect on cell number, altered stem cell function and resetting of regulatory hormonal axes. The next stage is translation of these findings into testable preventive strategies to maintain optimum body composition and minimize the risk of obesity, sarcopenia and osteoporosis in later life.

Reginster JY, Felsenberg D, Cooper C, Stakkestad JA, Miller PD, Kendler DL, Adami S, McClung MR, Bolognese MA, Civitelli R, Dumont E, Bonvoisin B, Recker RR, Delmas PD. · Unite d'Exploration du Metabolisme de l'Os et du Cartilage, CHU Centre Ville, Liége, Belgium. · Osteoporos Int. · Pubmed #15959614 No free full text.

Abstract: Oral daily and weekly bisphosphonates represent the current mainstay of treatment for postmenopausal osteoporosis (PMO). However, the inconvenience of frequent dosing is known to negatively affect adherence to therapy in the long term. This has prompted the development of convenient oral bisphosphonate regimens that feature simple, less frequent dosing schedules. Such regimens require high potency agents, which can be given at low effective doses and that also have good tolerability. Ibandronate is a potent, nitrogen-containing bisphosphonate with proven efficacy when given intermittently to estrogen-depleted beagle dogs, rats and cynomolgus monkeys. Clinically, a pivotal prospective study has established that oral ibandronate has significant vertebral fracture efficacy in PMO, whether given daily (2.5 mg) or intermittently (20 mg every other day for 12 doses every 3 months; extended between-dose interval>2 months). Both oral regimens were well tolerated, which is noteworthy as patients with a history of gastrointestinal (GI) disturbance were not specifically excluded. As a result of these findings, a large, multinational, randomized, double-blind study (Monthly Oral iBandronate In LadiEs: MOBILE) is currently exploring the non-inferiority of once-monthly oral ibandronate (100 or 150 mg) to the oral daily ibandronate (2.5 mg) regimen with proven anti-fracture efficacy, in terms of lumbar spine bone mineral density (BMD) change. As with the trials investigating the weekly administration of other bisphosphonates, vertebral fracture efficacy will be inferred if the study demonstrates the non-inferiority of once-monthly ibandronate to the proven oral daily regimen in terms of spinal BMD change. The availability of this once-monthly ibandronate regimen is expected to offer benefits in terms of convenience (by having to follow dosing recommendations once a month vs. once daily or weekly) and potentially tolerability (by reducing the potential for upper GI irritation that can result from frequent, repeated exposure). Greater convenience and tolerability may enhance the therapy adherence and, hence, improve long-term therapeutic outcomes in PMO.

Dennison E, Cole Z, Cooper C. · MRC Epidemiology Resource Centre, Southampton General Hospital, Southampton, UK. · Curr Opin Rheumatol. · Pubmed #15956843 No free full text.

Abstract: PURPOSE OF REVIEW: Osteoporosis remains a major public health problem through its association with fragility fractures. Recent data suggest that the annual cost in Europe is 13 billion euros, mainly accounted for by hospitalisation after fracture. Understanding the epidemiology of osteoporosis is an essential step in developing strategies to reduce the burden of osteoporotic fracture in the population. RECENT FINDINGS: This article will review recent advances surrounding the epidemiology of osteoporosis, the burden of fracture in children and adults in this country and abroad, morbidity associated with such fractures, associations of disease and medication with fragility fracture, and advances in diagnostic techniques and identification of at-risk groups. SUMMARY: The papers studied highlight the wealth of high-quality research in this field, and they help in the visualisation of strategies to identify individuals at high risk of fragility fracture and to quantify fracture risk by measurement of bone density, bone quality, and risk factor algorithms.

Harvey N, Cooper C. · MRC Environmental Epidemiology Unit, Southampton General Hospital, Southampton SO16 6YD, UK. · J Br Menopause Soc. · Pubmed #15107206 No free full text.

Abstract: Undernutrition and other adverse influences arising in fetal life or immediately after birth have a permanent effect on body structure, physiology and metabolism. Evidence is now accumulating from human studies that programming of bone growth might be an important contributor to the later risk of osteoporotic fracture. Body weight in infancy is a determinant of adult bone mineral content, as well as of the basal levels of activity of the GH/IGF-1 and HPA axes, and recent work has suggested a central role for vitamin D. Epidemiological studies have suggested that maternal smoking and nutrition during pregnancy influence intrauterine skeletal mineralization. Finally, childhood growth rates have been directly linked to the risk of hip fracture many decades later. Further work is needed to use this approach to develop novel therapeutic and preventative strategies to reduce the burden of osteoporotic fractures in the population.

Arden NK, Cooper C. · MRC Environmental Epidemiology Unit, Southampton General Hospital, Southampton SO 16 6YD, UK. · Eur J Gastroenterol Hepatol. · Pubmed #12867795 No free full text.

Abstract: Osteoporotic fractures are a common problem and associated with significant morbidity, mortality and costs. There is now increasing evidence that patients with coeliac disease are at an increased risk of osteoporotic fracture. With the advent of new therapeutic agents to reduce the risk of fracture, it is important to identify people at highest risk. The best predictors of future fracture include a previous osteoporotic fracture, low bone density, active inflammatory bowel disease, the use of oral corticosteroids and an increased risk of falling.

Christodoulou C, Cooper C. · MRC Environmental Epidemiology Unit, University of Southampton, Southampton General Hospital, Southampton. · Postgrad Med J. · Pubmed #12697910 links to  free full text

Abstract: Osteoporosis is a very common disorder, which results in an increase in fracture risk. The annual cost attributable to hip, vertebral, and wrist fractures in England and Wales is pound 1.7 billion. Significant mortality and morbidity are associated with osteoporotic fractures. The method that is most widely used for the diagnosis of osteoporosis is dual energy x-ray absorptiometry. The aim of prevention and treatment of osteoporosis is to prevent the occurrence of future fractures. Lifestyle changes should be encouraged in high risk patients. Pharmacological treatments include the bisphosphonates, hormone replacement therapy, selective oestrogen receptor modulators, calcitonin, the 1-34 fragment of parathyroid hormone, calcium and vitamin D supplements, and calcitriol.