Bone loss in Crohn's disease: exercise as a potential countermeasure

Crohn's disease (CD) is associated with a number of secondary conditions including osteoporosis, which increases the risk of bone fracture. The cause of metabolic bone disease in this population is believed to be multifactorial and may include the disease itself and associated inflammation, high-dose corticosteroid use, weight loss and malabsorption, a lack of exercise and physical activity, and an underlying genetic predisposition to bone loss. Reduced bone mineral density has been reported in between 5% to 80% of CD sufferers, although it is generally believed that approximately 40% of patients suffer from osteopenia and 15% from osteoporosis. Recent studies suggest a small but significantly increased risk of fracture compared with healthy controls and, perhaps, sufferers of other gastrointestinal disorders such as ulcerative colitis. The role of physical activity and exercise in the prevention and treatment of CD-related bone loss has received little attention, despite the benefits of specific exercises being well documented in healthy populations. This article reviews the prevalence of and risk factors for low bone mass in CD patients and examines various treatments for osteoporosis in these patients, with a particular focus on physical activity.     

Bisphosphonate therapy for secondary osteoporosis: adult perspective

BACKGROUND: A number of disease states and drugs can upset the balance between bone formation and resorption resulting in increased fracture risk. Glucocorticoids are the most recognized cause of secondary osteoporosis. Hypogonadism, weight loss, and chronic inflammation are other contributors to bone loss in a variety of disease states. Bisphosphonates are potent inhibitors of bone resorption, and there is a variety of secondary osteoporosis where they produce substantial increases in bone density and reduce fracture risk by about 50%. Upper gastrointestinal tract intolerance with oral agents and a flu-like syndrome with intravenous bisphosphonates are the principal adverse effects associated with their use. CONCLUSIONS: Numerous disease states and medications can adversely affect the skeleton. Additional effects of aging and menopause can substantially increase an individual's fracture risk. It is important that physicians assess fracture risk in susceptible patients and initiate treatment when indicated.     

Bone Homeostasis in Intestinal Disorders

Diagnosis and therapy of osteoporosis associated with gastrointestinal diseases is a remarkable problem. Osteoporosis is most common in celiac disease, Crohn’s disease, chronic liver disease, and in postgastrectomy patients. Protocols regarding prevention, diagnosis and therapy are based on results gained from patients with osteoporosis in the general population. This review aims to summarize the special aspects and most important clinical data regarding the bone loss associated with gastrointestinal diseases.     

Perspectives on osteoporosis in pediatric inflammatory bowel disease

Osteoporosis is now recognized as a problem in children with chronic illness. Decreased bone mineral density and increased risk of fracture have been reported in children with inflammatory bowel disease (IBD). Recent studies have led to a better understanding of the pathogenesis of bone loss. There are many risk factors for osteopenia and osteoporosis in children with IBD. Dual-energy x-ray absorptiometry remains the diagnostic procedure of choice for assessment of bone mineral density, but other modalities are being explored. Guidelines for diagnosis and treatment of osteoporosis in children have not been established. This article reviews the current understanding of osteopenia and osteoporosis in children with IBD.     

Where is bone science taking us?

Bone science has over the last decades unraveled many important pathways in bone and mineral metabolism and the interplay between genetic factors and the environment. Some of these discoveries have led to the development of pharmacological treatments of osteoporosis and rare bone diseases. Other scientific avenues have uncovered a role for the gut microbiome in regulating bone mass, which have led to investigations on the possible therapeutic role of probiotics in the prevention of osteoporosis. Huge advances have been made in identifying the genes that cause rare bone diseases, which in some cases have led to therapeutic interventions. Advances have also been made in understanding the genetic basis of the more common polygenic bone diseases, including osteoporosis and Paget's disease of bone (PDB). Polygenic profiles are used for establishing genetic risk scores aiming at early diagnosis and intervention, but also in Mendelian randomization (MR) studies to investigate both desired and undesired effects of targets for drug design.     

Risk factors for osteoporosis in inflammatory bowel disease patients

Inflammatory bowel disease (IBD) patients exhibit higher risk for bone loss than the general population. The chronic inflammation causes a reduction in bone mineral density (BMD), which leads to osteopenia and osteoporosis. This article reviewed each risk factor for osteoporosis in IBD patients. Inflammation is one of the factors that contribute to osteoporosis in IBD patients, and the main system that is involved in bone loss is likely RANK/RANKL/osteoprotegerin. Smoking is a risk factor for bone loss and fractures, and many mechanisms have been proposed to explain this loss. Body composition also interferes in bone metabolism and increasing muscle mass may positively affect BMD. IBD patients frequently use corticosteroids, which stimulates osteoclastogenesis. IBD patients are also associated with vitamin D deficiency, which contributes to bone loss. However, infliximab therapy is associated with improvements in bone metabolism, but it is not clear whether the effects are because of inflammation improvement or infliximab use. Ulcerative colitis patients with proctocolectomy and ileal pouches and Crohn’s disease patients with ostomy are also at risk for bone loss, and these patients should be closely monitored.     

Chronic glucocorticoid therapy-induced osteoporosis in patients with obstructive lung disease

Long-term glucocorticoid (GC) therapy has been instrumental in decreasing morbidity and mortality in a variety of chronic inflammatory diseases, including persistent asthma. Long-term GC therapy is also widely prescribed for COPD. One of the important and often unrecognized side effects of chronic GC therapy is secondary osteoporosis. The risk of GC-induced bone loss is roughly correlated with daily dose, duration, and total cumulative lifetime dose of GC treatment. Oral prednisone increases the risk of bone loss and fracture. High doses of inhaled GCs may also increase the risk of osteopenia/osteoporosis, but the risk appears to be less than that associated with oral GCs. Hormone replacement therapy, oral and parenteral bisphosphonates, supplemental calcium and vitamin D, calcitonin, and fluoride compounds have been used, experimentally, in the management of GC-induced bone loss. Asthma and COPD specialists are key prescribers of oral and inhaled steroids and are likely to encounter patients with significant bone loss. Despite known risk factors and the availability of reliable diagnostic tools to recognize bone loss, the opportunity to slow, reverse, and treat bone loss is often missed. We present a review of the current literature regarding the incidence, treatment, and prevention of osteopenia/osteoporosis secondary to chronic GC therapy in adult asthma and COPD patients. Guidelines are presented regarding the identification of patients at risk for developing GC-induced secondary bone loss, and therapeutic alternatives are discussed.     

Pharmacological treatment of osteoporosis for people over 70

Osteoporosis has been defined as "a systemic disease characterized by low bone mass and microarchitectural deterioration of bone tissue, with consequent increase in bone fragility and susceptibility to fracture". The impact of osteoporosis is most pronounced in elderly populations who run the greatest risk of fractures. The probability of developing mainly hip, vertebral and other non-vertebral fractures (for example, a Colles fracture) not only depends on bone mineral density (BMD) but also on age. Older patients are more susceptible to fracture than younger patients with the same BMD T-score. As the older population increases, the incidence of osteoporotic fractures is expected to rise dramatically over the next few decades. Although hip fractures are considered to be the most severe and economically important osteoporotic fracture, vertebral fractures also lead to adverse health outcomes, including back pain, height loss and kyphosis. These changes may result in significant declines in physical performance, function and, ultimately, loss of independence. The challenge for physicians is to prevent bone loss, to diagnose and treat osteoporosis before fractures occur, and to treat patients who have already experienced a fracture to prevent recurrent fractures. The objective of this review is to analyze the capacity to reduce fractures as the key element to evaluate the effectiveness of available medications: calcium and Vitamin D, bone formation drugs, antiresortive drugs, and dual-effect drugs. In view of the paucity of information about treatment of osteoporosis in the elderly population, available studies were not designed with this objective, so that this article reviews data mostly deriving from post-hoc analysis or sub-analysis of the main phase III clinical trials of each of the tested medications.     

Osteoporosis and cardiovascular disease: brittle bones and boned arteries, is there a link?

Both osteoporosis and cardiovascular disease (CVD) are major public health problems leading to increased morbidity and mortality. Although traditionally viewed as separate disease entities that increase in prevalence with aging, accumulating evidence indicates that there are similar pathophysiological mechanisms underlying both diseases. In addition to menopause and advanced age, other risk factors for CVD such as dyslipidemia, oxidative stress, inflammation, hyperhomocystinemia, hypertension, and diabetes have also been associated with increased risk of low bone mineral density (LBMD). Elevated LDL and low HDL cholesterol are associated with LBMD, altered lipid metabolism is associated with both bone remodeling and the atherosclerotic process, which might explain, in part, the co-existence of osteoporosis and atherosclerosis in patients with dyslipidemia. Similarly, inflammation plays a pivotal role in both atherosclerosis and osteoporosis. Elevated plasma homocysteine levels are associated with both CVD and osteoporosis. Nitric oxide (NO), in addition to its known atheroprotective effects, appears to also play a role in osteoblast function and bone turnover. Supporting this notion, in a small randomized controlled trial, nitroglycerine (an NO donor) was found to be as effective as estrogen in preventing bone loss in women with surgical menopause. Statins, agents that reduce atherogenesis, also stimulate bone formation. Furthermore, bisphosphonates, used in the treatment of osteoporosis, have been shown to inhibit atherogenesis. Intravenous bisphosphonate therapy significantly decreases serum LDL and increases HDL in postmenopausal women. The exciting possibilities of newer pharmacological agents that effectively treat both osteoporosis and CVD hold considerable promise. However, it is important to emphasize that the current evidence linking both of these diseases is far from conclusive. Therefore, additional research is necessary to further characterize the relationship between these two common illnesses.     

Management of osteoporosis in liver disease

Osteoporosis resulting in a high risk for fracture is a common complication in patients with liver disease, particularly in those with chronic cholestasis and with end-stage cirrhosis. The pathogenesis of bone loss in liver patients is poorly understood but it mainly results from low bone formation as a consequence of cholestasis or the harmful effects of alcohol or iron on osteoblasts. Increased bone resorption has also been described in cholestatic women with advanced disease. The management of bone disease in liver patients is addressed to reduce or avoid the risk factors for osteoporosis and fracture. Bisphosphonates associated with supplements of calcium and vitamin D are safe and effective for increasing bone mass in patients with chronic cholestasis and after liver transplantation, though no clear achievements in descreasing the incidence of fractures have been described, probably because of the low number of patients included in the therapeutic trials. Randomized studies assessing bisphosphonates in larger series of patients, the development of new drugs for osteoporosis and the improvement in the management of liver transplant recipients may change the future.     

Bisphosphonates for osteoporosis prevention and treatment

As potent inhibitors of bone resorption, bisphosphonates (BPs) have been used to treat a variety of disorders of calcium and bone metabolism, including osteoporosis. Paget's disease, and metastatic bone disease. Numerous clinical studies have shown BPs to be useful and cost-effective options for the prevention and treatment of fractures and bone loss associated with postmenopausal osteoporosis, senile osteoporosis in men, and glucocorticoid-induced osteoporosis. With proper self-administration in patients without underlying gastrointestinal (GI) disorders, oral bisphosphonates are usually safe, however, they can cause upper GI irritation. The most common side effects are nausea, diarrhea, gastritis, and esophageal irritation Newer, longer-acting BPs and parenteral administration have lead to options for patients who cannot tolerate oral BPs.     

低氧环境下帕金森病与骨质疏松的相关性研究进展

帕金森病是多见于老年人的神经退行性疾病,严重影响患者的生活质量。骨质疏松亦是老年人的一种常见疾病,以易发生骨折为特征的一种全身代谢性骨骼疾病。有研究证明,帕金森病患者更易患骨质疏松,两者具有高度相关性。而低氧环境可能加重帕金森病患者的病情及并发症,其可能机制为缺氧阻断成骨细胞的生长与分化、促进破骨细胞的形成,增加骨质疏...     

The pathophysiology of bone disease in gastrointestinal disease

Reduced bone mass and the increased risk of fracture in gastrointestinal diseases have a multifactorial pathogenesis. Undoubtedly, genetics play an important role, but other factors such as systemic inflammation, malnutrition, hypogonadism, glucocorticoid therapy in inflammatory bowel disease (IBD) and other lifestyle factors, such as smoking or being sedentary, may contribute to reduced bone mass. At a molecular level the proinflammatory cytokines that contribute to the intestinal immune response in IBD and probably also in coeliac disease are also known to enhance bone resorption. The discovery of the role of the receptor to activated NFkappaB (RANK) interaction with its ligand RANKL in orchestrating the balance between bone resorption and formation may link mucosal and systemic inflammation with bone remodelling, since RANK-RANKL are also involved in lymphopoiesis and T-cell apoptosis. Low circulating leptin in response to weight loss in any gastrointestinal disease may be an important factor in reducing bone mass. This report will summarize current concepts regarding gastrointestinal diseases (primarily IBD, coeliac disease and postgastrectomy states) and low bone mass and fracture.     

Oral antiresorptive therapy

Oral antiresorptive agents play a pivotal role in the management of osteoporosis. This paper discusses the effects and potential future role of newer agents such as ibandronate. Alternative dosing schedules and routes of administration have become available and may improve fracture protection, compliance, and tolerability for the long term treatment of a chronic condition such as osteoporosis. Increasingly these agents are being used to reduce bone loss in other diseases associated with high risk for osteoporosis such as organ transplantation and cystic fibrosis. Such studies may act as prototypes for the extended use of this class of drugs in other chronic inflammatory disease states. The innovative, yet disappointing results from combining an antiresorptive agent (alendronate) with the anabolic effects of teriparatide is also discussed. The major problem that remains is the lack of direct comparison between the agents in terms of fracture endpoints.     

Osteoporosis in men: Pathophysiology and treatment

Osteoporosis has long been long considered a disease of the aging female skeleton. However, it is now clear that men are also at risk for this disorder. Epidemiologic studies have confirmed that osteoporotic fractures in men are an increasing public health problem, in part due to increased longevity and increased public awareness. Recent large-scale population studies in men have led to advances in our understanding of bone fragility and its treatment in men. This article reviews what is known about the factors in men that lead to acquisition, maintenance, and loss of bone, as well as new insights into causes, pathogenesis, and treatment of osteoporosis in men.     

Epidemiology of osteoporosis in rheumatic diseases

Much work has been directed at establishing the impact of osteoporosis and related fragility fractures in rheumatic diseases. Several cross-sectional studies reported that disability and reduced motility that are due to functional impairment are among the most important determinants of bone loss in different rheumatic diseases. At the same time, longitudinal studies have confirmed the detrimental effect of uncontrolled disease activity on bone density. In this perspective, the suppression of inflammation probably remains the main concern when considering treatment options. Besides these variables, pharmacologic agents that are used commonly in the treatment of these conditions probably have an adjunctive effect on bone loss in rheumatic patients. Large epidemiologic studies have demonstrated clearly that patients who have RA, SLE, or AS are at an increased risk for fragility fractures. Further studies are required to investigate the effective impact of osteoporosis and fragility fractures in other rheumatic diseases, and to define the relationship between OA and osteoporosis. A better appreciation of the impact and mechanisms of osteoporosis in rheumatic diseases by rheumatologists represents a clinical challenge; however, a greater understanding of this frequent complication will improve the quality of health care and the lives of patients who have rheumatic diseases.     

Transplantation osteoporosis

In the past two decades, there has been a rapid increase in the number of organ transplanted worldwide, including Brazil, along with an improvement in survival and quality of life of the transplant recipients. Osteoporosis and a high incidence of fragility fractures have emerged as a complication of organ transplantation. Many factors contribute to the pathogenesis of osteoporosis following organ transplantation. In addition, most patients have some form of bone disease prior to transplantation, which is usually related to adverse effects of end-stage organ failure on the skeleton. This chapter reviews the mechanisms of bone loss that occur both in the early and late post-transplant periods, as well as the features specific to bone loss after kidney, lung, liver, cardiac and bone marrow transplantation. Prevention and treatment for osteoporosis should be instituted prior and in the early and late phase after transplantation, and will also be addressed in this article.     

Serum and urinary markers of bone remodeling: assessment of bone turnover

It appears that at present, serum BGP is the one bone protein that has the most promise for assisting in the diagnosis and management of high turnover metabolic bone disease states. If further studies confirm its usefulness in osteoporosis as a predictor of rapid bone loss without the need for bone biopsy, this serum marker will then not only allow early detection but also an appropriate choice of therapy in osteoporosis, i.e. the use of specific inhibitors of high turnover states such as estrogen, calcitonin, or bisphosphonates. In addition, it may also permit more accurate follow-up of patients suffering from diseases such as primary hyperparathyroidism after surgery. In low turnover osteoporosis, it may also serve a useful function to observe whether the osteoblast can be stimulated to enhance bone formation with therapies such as fluoride, anabolic steroids, PTH, etc. As yet, additional measurements, such as bone histomorphometry and other bone mineral markers, are required for definitive diagnosis. Hopefully, the availability of specific well-characterized antibodies against BGP may define its role more accurately. Recently, several other new bone proteins have been identified but at present they have very limited clinical application. Future studies into the structure-function relationship of these bone proteins may identify those markers which will be most relevant to the diagnosis and treatment of metabolic bone disease.     

Gut, inflammation and osteoporosis: basic and clinical concepts

Chronic inflammatory disorders such as inflammatory bowel diseases (IBD) affect bone metabolism and are frequently associated with the presence of osteoporosis. Bone loss is regulated by various mediators of the immune system such as the pro-inflammatory cytokines tumour necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), IL-6, or interferon-gamma. TNF-alpha, a master cytokine in human IBD, causes bone erosions in experimental models and these effects are exerted by osteoclasts. Other TNF-related cytokines such as receptor activator of nuclear factor kappa B (RANK), its ligand, RANKL, and osteoprotegerin are important mediators in inflammatory processes in the gut and are critically involved in the pathophysiology of bone loss. The awareness and early diagnosis of osteoporosis in states of chronic inflammation, together with applied therapies such as bisphosphonates, may be beneficial in inflammation-associated osteoporosis. Although several mechanisms may contribute to osteoporosis in patients with IBD and coeliac disease, inflammation as an important factor has so far been neglected. As key inflammatory mediators in IBD such as TNF-alpha are involved in the disease process both in gut and bone, we hypothesise that neutralisation of TNF-alpha could prove an efficient strategy in the treatment of inflammation-related osteoporosis in the future.     

Determinants of skeletal fragility

Strategies to reduce fracture risk must be based on a sound understanding of the mechanisms that underline the increased incidence of fractures with age and with certain diseases. There is evidence that in addition to bone minerals density, other factors influence bone strength. The chapter reviews the biomechanical aspects of age-related fractures, including the interacting roles of traumatic loading and bone strength, and the factors that determine a bones resistances to fracture. Also discussed are the mechanisms by which anti-catabolic and anabolic therapies for osteoporosis may affect bone strength. Finally, several current and future methodologies for improving assessment of bone strength in patients are evaluated.