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Query: UMLS:C0005940 (bone disease)
 7,459 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cystic fibrosis (CF) is the most common genetic disease that causes respiratory failure within the Caucasian population. The life span of patients with CF has gradually increased from a median of 2 years of age to >30 years. Concurrent with this increased lifespan, a variety of other nutritional, endocrine and bone issues have been recognised. Decreased absorption of fat-soluble vitamins (D and K in particular) because of pancreatic insufficiency, altered sex hormone production, chronic inflammation, a lack of physical activity, glucocorticoid treatment and an intrinsic hyper-resorptive bone physiology are some of the factors that contribute to the prominence of bone disease within the CF population. In some series, three-quarters of adult patients with CF have osteopenia or osteoporosis. Lung transplantation is one viable treatment for patients with end-stage CF, which requires a lifetime of antirejection medication. Immunosuppressant therapies have a detrimental effect on bone mineral density (BMD). To combat the multifactorial nature of CF-related bone disease, advances in nutritional and vitamin supplementation, and anti-resorptive and anabolic therapies have evolved. Chronic vitamin D depletion contributes to bone disease in the CF population. The isoform of vitamin D that is the best and safest supplement, with the lowest cost, has yet to be identified. However, it is clear that many patients with CF who receive the standard of care (i.e. two daily combination vitamin A, D, E and K tablets [ADEKs]) may still be vitamin D-deficient. More aggressive supplementation needs to be individualised, with close monitoring of serum 25-hydroxyvitamin D levels. Similarly, routine calcium supplementation may be important, and evidence is accumulating that vitamin K also plays an important role in maximising and maintaining BMD. Early recognition and treatment of delayed puberty in adolescents and hypogonadism in adults with hormone replacement therapy is recommended to maintain BMD in patients with CF. Bisphosphonates, including pamidronic acid, etidronic acid and alendronic acid, reduce bone resorption by inhibiting the recruitment and function of osteoclasts. Pamidronic acid is beneficial in improving BMD in CF patients before and after transplantation. Bisphosphonate therapy and minimisation of glucocorticoid dosage have been shown to be efficacious in glucocorticoid-induced osteoporosis. Teriparatide is the first US FDA-approved anabolic growth agent for bone, and has been shown to increase BMD and decrease fracture incidence in postmenopausal women. Teriparatide may offer a new avenue for treating bone disease in CF since many patients may have poor bone formation as well as accelerated bone breakdown. Numerous clinical trials are underway to optimise treatment of CF osteoporosis.
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PMID:Management of osteoporosis in adults with cystic fibrosis. 1471 16

Cystic fibrosis (CF) is the most common genetic disease within the Caucasian population and leads to premature respiratory failure. Approximately 60,000 individuals are currently living with CF in North America and Europe, 40% of whom are adults. The life span of these patients has increased from approximately 2 to 32 yr of age over the last three decades. Bone disease has emerged as a common complication in long-term survivors of CF. Some studies have observed that 50-75% of adults have low bone density and increased rates of fractures. Prevention and treatment of CF-related bone disease must address the myriad risk factors (decreased absorption of fat-soluble vitamins due to pancreatic insufficiency, altered sex hormone production, chronic lung infection with increased levels of bone-active cytokines, physical inactivity, and glucocorticoid therapy) for poor bone health. This review is a condensed and updated summary of the Guide to Bone Health and Disease in Cystic Fibrosis: A Consensus Conference, a statement that evolved from a meeting convened by the Cystic Fibrosis Foundation in May 2002 to address the pathogenesis, diagnosis, and treatment of bone disease in CF. The goal of this conference was to develop practice guidelines for optimizing bone health in patients with CF.
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PMID:Guide to bone health and disease in cystic fibrosis. 1561 15

The transport of anions across cellular membranes is crucial for various functions, including the control of electrical excitability of muscle and nerve, transport of salt and water across epithelia, and the regulation of cell volume or the acidification and ionic homeostasis of intracellular organelles. Given this broad range of functions, it is perhaps not surprising that mutations in Cl- channels lead to a large spectrum of diseases. These diverse pathologies include the muscle disorder myotonia, cystic fibrosis, renal salt loss in Bartter syndrome, kidney stones, deafness, and the bone disease osteopetrosis. This review will focus on diseases related to transepithelial transport and on disorders involving vesicular Cl- channels.
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PMID:Chloride channel diseases resulting from impaired transepithelial transport or vesicular function. 1607 45

Cystic fibrosis (CF) is a multisystem disease. Some of this is accounted for by CF transmembrane regulator (CFTR) dysfunction in individual organs but in some cases this is compounded by the effects of systemic inflammation. The inflammation is in response to the chronic infection in the airways and is particularly important as a contributor to CF-related bone disease, CF-related diabetes mellitus, CF-related arthropathy, and vasculitis. Preventing these multisystem complications is difficult. Aggressive specific therapies to treat complications is critically important to maintain nutrition, stop the damaging effects of diabetes, and improve bone mineral density. Aggressive treatment of lung disease to reduce systemic inflammation is likely to be of benefit in preventing the development of CF-related bone disease and may be beneficial in at least delaying the onset of CF-related diabetes. Aggressive treatment of pulmonary infection and inflammation in conjunction with holistic management plans to treat specific organ diseases is an important strategy in improving morbidity and reducing mortality in people with CF.
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PMID:How can we prevent multisystem complications of cystic fibrosis? 1756

As the incidence of cystic fibrosis (CF) bone disease is increasing, we analyzed CF transmembrane conductance regulator (CFTR) deficient mice (CF mice) to gain pathogenic insights. In these studies comparing adult (14 wk) CF and C57BL/6J mice, both bone length and total area were decreased in CF mice. Metaphyseal trabecular and cortical density were also decreased, as well as diaphyseal cortical and total density. Trabecular bone volume was diminished in CF mice. Female CF mice revealed decreased trabecular width and number compared with C57BL/6J, whereas males demonstrated no difference in trabecular number. Female CF mice had reduced mineralizing surface and bone formation rates. Conversely, male CF mice had increased mineralizing surface, mineral apposition, and bone formation rates compared with C57BL/6J males. Bone formation rate was greater in males compared with female CF mice. Smaller bones with decreased density in CF, despite absent differences in osteoblast and osteoclast surfaces, suggest CF transmembrane conductance regulator influences bone cell activity rather than number. Differences in bone formation rate in CF mice are suggestive of inadequate bone formation in females but increased bone formation in males. This proanabolic observation in male CF mice is consistent with other clinical sex differences in CF.
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PMID:Murine model for cystic fibrosis bone disease demonstrates osteopenia and sex-related differences in bone formation. 1904 17

Lung transplantation has become a viable option for those cystic fibrosis (CF) patients with end-stage lung disease. Despite the challenges that the CF patients present, the survival seen after lung transplantation is more favorable than seen in patients with chronic obstructive pulmonary disease and pulmonary fibrosis. Although the CF patients with severe respiratory disease usually are infected with organisms that display in vitro resistance to the commonly used antibiotics, these patients usually have successful outcomes with transplantation. The other challenges include the presence of nontuberculous mycobacteria, the significant incidence of liver involvement, the development of an ileus or the development of the distal intestinal obstruction syndrome, and the presence of gastroesophageal reflux. Most of the patients have metabolic bone disease, even preoperatively, that warrants treatment, especially with the significant loss of bone density seen in the first year after transplant, thought to be related, in part, to the high dose of corticosteroids. Diabetes mellitus and its consequences are not uncommon. The malabsorption of fat seen in the pancreatic-insufficient patients complicates the absorption kinetics of the anti-rejection drugs. In May 2005 the United Network of Organ Sharing instituted a lung-allocation score to better distribute the donated lungs to those patients who would achieve the most benefit. This score uses several variables to balance the likelihood of the patients living one year with a transplant versus one year without a transplant. With this change in the allocation of organs, the median waiting times have significantly decreased, the mortality on the waiting list has decreased, and the number of CF patients transplanted has not changed. With substantial experience, more programs are now transplanting patients who require constant mechanical ventilation or patients who have undergone previous pleural procedures, especially in the treatment of a pneumothorax. The limiting factor now in lung transplantation is the number of organs available. Efforts to increase the donor pool, such as alveolar recruitment strategies to improve gas exchange, have been effective in allowing more patients to be transplanted. Lung transplantation is now an accepted form of therapy in those patients who are developing progressive respiratory failure.
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PMID:Lung transplantation in cystic fibrosis. 1946 64

To study bone mineral density (BMD) of pre-pubertal cystic fibrosis (CF) children, and its relation with clinical and laboratory parameters, we enrolled 16 CF (8 girls) (4-8 years), and 16 control children (8 girls) (4-8 years). After anthropometric measurements, BMD, serum calcium, phosphorus, total alkaline phosphatase (ALP), 25-hydroxy vitamin D (25-OHD), parathyroid hormone, osteocalcin, tumor necrosis factor (TNF)-alpha, soluble TNF-alpha receptor 2 (sTNFR2), and soluble IL-2 receptor (sIL-2R) levels, and urinary calcium and hydroxyproline excretions were assessed. Disease severity of CF patients was determined with Shwachman-Kulczycki clinical and Brasfield radiological scoring systems.The mean Shwachman-Kulczycki and Brasfield scores of CF patients were indicating well-controlled disease. The anthropometric measurements, mean BMD values, and serum calcium, phosphorus and parathyroid hormone levels were within normal range and similar in both groups. Serum osteocalcin levels were lower, and ALP and 25-OHD levels were higher in CF. Although 24-hr urinary calcium excretions was higher in CF patients, hydroxyproline excretions were similar in both groups. There was no difference between two groups for the serum levels of sIL-2R, TNF-alpha and sTNFR2. Children with low vertebral z-scores had higher serum sIL-2R levels in both groups, but the same relation could not be shown for TNF-alpha and sTNFR2.We may speculate that younger, healthier and well-nourished patients with CF may have normal BMD, but the bone disease develop as patients get older because of the other contributing factors. Future well-designed longitudinal studies with large cohorts might show a relation with BMD and cytokines in CF.
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PMID:Relation of bone mineral density with clinical and laboratory parameters in pre-pubertal children with cystic fibrosis. 1950 63

A high prevalence of low bone mineralization is documented in adult patients with cystic fibrosis (CF). Osteopenia is present in up to 85% of adult patients and osteoporosis in 10% to 34%. In children, study results are discordant probably because of comparisons to different control populations and corrections for bone size in growing children. Malnutrition, inflammation, vitamin D and vitamin K deficiency, altered sex hormone production, glucocorticoid therapy, and physical inactivity are well known risk factors for poor bone health. Puberty is a critical period for bone mineralization and requires a careful follow-up to achieve optimal bone peak mass. Strategies for optimizing bone health, such as monitoring bone mineral density (BMD) and providing preventive care are necessary from childhood through adolescence to minimize CF-related bone disease in adult CF patients.
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PMID:Update on cystic fibrosis-related bone disease: a special focus on children. 1965 84

Dramatic changes in the life expectancy of cystic fibrosis (CF) patients are occurring, creating a cohort of aging individuals experiencing long-term complications of this chronic disease. The two most common of these complications include CF-related diabetes and CF bone disease. The clinical implications of each have become better understood, as have potential therapies. However, data obtained from the basic science studies of both diseases have not been widely recognized. In this review, we focus on the known and hypothesized pathogenesis of these two disorders. Additionally, the molecular underpinnings of CF will be explained along with the potential interactions with endocrine disease phenotypes.
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PMID:Endocrine parameters of cystic fibrosis: back to basics. 1967 Feb 66

Patients with cystic fibrosis are frequently affected with pancreatic insufficiency and are predisposed to the development of diabetes mellitus (DM) and bone demineralization. Cystic fibrosis-related diabetes mellitus is a clinical entity distinct from type 1 and type 2 diabetes, with important implications for the nutritional and pulmonary health of cystic fibrosis patients. This form of diabetes owes largely to insulin deficiency, but alterations in insulin sensitivity and hepatic glucose production have also been described. Therapy for cystic fibrosis-related diabetes differs substantially from type 2 DM, with careful attention to prandial glycemic excursions crucial to controlling its metabolic effects. Bone disease, including osteopenia and osteoporosis, also occurs with increased frequency in cystic fibrosis, owing to defects in intestinal absorption, chronic inflammation, lung disease, low body weight, and gonadal dysfunction. The pathogenesis, implications, diagnosis, and therapy of cystic fibrosis-related bone demineralization are discussed, with attention to recommended approaches to prevention of and treatment of established bone disease.
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PMID:Diabetes mellitus and bone disease in cystic fibrosis. 1976 May 39


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