Diagnosis and Management of Cirrhosis-Related Osteoporosis

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Term Occurence Count Dictionary
testosterone 3 endocrinologydiseasesdrugs
zoledronic acid 4 endocrinologydiseasesdrugs
cholic acid 1 endocrinologydiseasesdrugs
hyperparathyroidism 2 endocrinologydiseases
raloxifene 1 endocrinologydiseasesdrugs
hyperthyroidism 1 endocrinologydiseases
hypogonadism 8 endocrinologydiseases
hypoparathyroidism 1 endocrinologydiseases
osteoporosis 55 endocrinologydiseases
prednisone 1 endocrinologydiseasesdrugs
calcitriol 2 endocrinologydiseasesdrugs
calcium carbonate 1 endocrinologydiseasesdrugs
cholecalciferol 1 endocrinologydiseasesdrugs

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Select Drug Character Offset Drug Term Instance
calcitriol 25357 drugs.Oral 25-hydroxyvitamin D supplementation can be prescribed at a dose of 260 μg every 2 weeks. Since calcitriol (1,25-dihydroxycholecalciferol) is the final active metabolite of vitamin D, it seems to be a better
calcitriol 25650 dose of 800 U but can also be taken at a weekly dose of 5000 U [[2]]. In a clinical trial in which calcitriol (0.5 mg twice per day) was given to 38 cirrhotic patients for 12 months, the authors showed that the
calcium carbonate 24804 not preclude the use of these supplements [[97]]. The supplement most widely consumed by patients is calcium carbonate , which must be ingested along with foods to increase absorption. Calcium citrate is more suitable for
cholecalciferol 25383 supplementation can be prescribed at a dose of 260 μg every 2 weeks. Since calcitriol (1,25-dihydroxy cholecalciferol ) is the final active metabolite of vitamin D, it seems to be a better treatment to these patients. Calcitriol
cholic acid 15967 and dose-dependent impact on osteoblastic activity [[22], [61], [62]]. Another study showed that litho cholic acid can impair the effects of vitamin D on osteoblasts [[63]]. Some clinical studies found a progressive
prednisone 5092 abuse, smoking, liver cirrhosis, neoplastic illness, malnutrition, prolonged glucocorticoid treatment ( prednisone 5 mg/day for >3 months), kidney disease, vitamin D deficiency, and some hormonal disturbances such
raloxifene 43532 the bone health of cirrhotic patients. The same can be said about calcitonin, sodium fluoride, and raloxifene .Notwithstanding the same problem regarding small samples, clinical trials with bisphosphonates combined
testosterone 12647 is a common finding in chronic liver disease. More than 90% of men with liver cirrhosis present low testosterone levels, which have an independent impact on mortality [[49], [50]]. There are many reasons for low levels
testosterone 13433 hypogonadism [[30]–[32]]. Some authors have hypothesized that low levels of sexual hormones (estrogen or testosterone ) increase the osteoclasts life spam and decrease it in osteoblasts, leading to higher bone resorption
testosterone 27735 cholestasis [[106]]. Moreover, the risk of developing hepatocellular carcinoma in patients receiving testosterone is another concern, although there are no clinical data to confirm this hypothesis [[21], [107]].Isoniemi
zoledronic acid 35945 the drug was changed to pamidronate 30 mg monthly [[127]].Crawford et al. evaluated the effect of zoledronic acid 4 mg on BMD of 32 patients submitted to OLT (18% of whom had osteoporosis). The drug infusion was
zoledronic acid 36397 osteoporosis) and reported that lumbar spine, femoral neck, and total hip BMD measurements favored zoledronic acid at the first 3 and 6 months after OLT. Fifteen patients did not complete the study, four of them because
zoledronic acid 37721 only in X-ray exams [[129]].Bodingbauer et al. recruited 96 patients after OLT to receive 4 mg of zoledronic acid monthly plus calcium and vitamin D or only calcium and vitamin D. The treatments were administered for
zoledronic acid 38433 [[130]]. Part of the study sample was reevaluated to reassess data from transiliac biopsies, showing that zoledronic acid reduced bone turnover in 21 patients [[131]].Monegal et al. performed a randomized controlled trial
Select Disease Character Offset Disease Term Instance
hyperparathyroidism 5249 vitamin D deficiency, and some hormonal disturbances such as diabetes, Cushing syndrome, hypogonadism, hyperparathyroidism , hyperthyroidism, and hypercalciuria [[22], [23]]. Prevalence in cirrhotic patients varies from 12 to
hyperparathyroidism 36675 group and 2 vertebral fractures in the placebo group). Despite the benefits in BMD, the drug induced hyperparathyroidism and postinfusion hypocalcemia [[128]].Atamaz et al. conducted a trial with 44 subjects receiving alendronate
hyperthyroidism 5270 and some hormonal disturbances such as diabetes, Cushing syndrome, hypogonadism, hyperparathyroidism, hyperthyroidism , and hypercalciuria [[22], [23]]. Prevalence in cirrhotic patients varies from 12 to 70% according to
hypogonadism 5235 kidney disease, vitamin D deficiency, and some hormonal disturbances such as diabetes, Cushing syndrome, hypogonadism , hyperparathyroidism, hyperthyroidism, and hypercalciuria [[22], [23]]. Prevalence in cirrhotic patients
hypogonadism 12893 patients, including hypothalamic-pituitary-gonadal axis dysfunction [[49]]. Some symptoms found in hypogonadism are similar to those seen in advanced liver disease, hampering the ability to recognize which of them
hypogonadism 13326 patients with hemochromatosis seem to be more prone to developing osteoporosis when they also have hypogonadism [[30]–[32]]. Some authors have hypothesized that low levels of sexual hormones (estrogen or testosterone)
hypogonadism 15098 consumption [[30]–[32], [58], [59]]. Moreover, these low osteocalcin levels can be added to malnutrition, hypogonadism , and other findings attributed to alcohol abuse.Similar to some of these effects, in vitro studies showed
hypogonadism 15429 accounts for osteoporosis in patients with hemochromatosis [[27], [30]–[32], [60]]. Thus, whereas hypogonadism has a dual effect on osteoclastic and osteoblastic cells, the toxic effects of alcohol and iron are
hypogonadism 27401 absorption [[27]].6.2. Hormonal ReplacementHormonal replacement can be a valuable approach for patients with hypogonadism , increasing BMD values in both genders and decreasing the risk of fractures in women [[102]–[105]].
hypogonadism 41743 patients who present any other risk factor for bone loss, such as cholestatic diseases, alcohol abuse, hypogonadism , or the other factors previously mentioned in this review. Furthermore, osteoporosis is the only cirrhosis
hypogonadism 43041 had a limited sample and a short follow-up. Studies on hormonal replacement therapy for patients with hypogonadism achieved interesting results in women, but concerns about hepatocellular carcinoma prevented similar
hypoparathyroidism 17331 increasing the risk of fractures [[8], [75]–[77]]. Calcium and vitamin D deficiency can lead to secondary hypoparathyroidism , which may increase bone turnover in cholestatic patients [[2], [78]]. Despite that, no clear association
osteoporosis 694 overlooked and scarcely treated, particularly those that are not related to the liver. This is the case of osteoporosis , the only cirrhosis complication that is not solved after liver transplantation, because bone loss often
osteoporosis 1118 on this population. Risk factors, physiopathology, diagnosis, screening strategies, and treatment of osteoporosis in cirrhotic patients are discussed, presenting the more striking data on this issue. Therapies used
osteoporosis 1663 longer survival of these patients has increased the risk of some extrahepatic manifestations such as osteoporosis . Regardless of the liver disease etiology, the presence of cirrhosis implies a risk of fractures two-fold
osteoporosis 2217 cirrhosis complication that persists for years after liver transplantation [[3]–[6]].Despite that, osteoporosis is often overlooked and few cirrhosis patients are submitted to exams to diagnose it. Even those who
osteoporosis 2506 few options that can be offered. Consequently, many patients with liver cirrhosis also suffer from osteoporosis , which can have a big impact on them. In particular, patients receiving glucocorticoids and/or those
osteoporosis 3040 suggested that bone status must be assessed in all cirrhotic patients [[8], [9]].The first studies of osteoporosis in liver diseases evaluated patients with alcoholic cirrhosis or chronic cholestatic diseases, such
osteoporosis 3307 Then, other studies assessed patients before and after OLT [[16], [17]]. Most of them have shown that osteoporosis is common among all cirrhotic patients regardless of the liver disease etiology or the degree of liver
osteoporosis 3573 of this review was to evaluate the physiopathology, the impact, the diagnosis, and the management of osteoporosis in patients with liver cirrhosis, in order to show the more recent data and establish some comparisons
osteoporosis 3860 PrevalenceAs the population has been reaching older ages, the prevalence of primary and idiopathic osteoporosis has been increasing worldwide, with a global prevalence estimated at around 200 million [[20]]. According
osteoporosis 4002 worldwide, with a global prevalence estimated at around 200 million [[20]]. According to the WHO definition, osteoporosis is diagnosed when bone density is less than 2.5 standard deviations below the peak value obtained from
osteoporosis 5607 the liver fibrosis is important in some particular conditions, such as cholestatic diseases, in which osteoporosis prevalence seems to be higher, varying from 20 to 44% even without an established diagnosis of cirrhosis
osteoporosis 5812 of cirrhosis and in proportion to the degree of liver insufficiency [[1], [23], [25]].Patients with osteoporosis are susceptible to fractures of different bones such as vertebrae, femoral neck, and distal radio. The
osteoporosis 6393 22% according to the degree of liver insufficiency [[1], [2], [4], [6], [25], [28], [29]].Although osteoporosis is asymptomatic in most cases, at five years after OLT it is related to symptoms associated with low
osteoporosis 8015 themselves.Prevention has been facilitated by BMD measurement, because it is the best predictor of fractures caused by osteoporosis . For each BMD reduction of one standard deviation, the risk of fractures is 2 to 3 times higher [[21],
osteoporosis 8351 fractures in all cirrhotic patients [[1]].3. PhysiopathologyAlthough the mechanisms of cirrhosis-related osteoporosis are not fully understood, it is well known that the association between liver and bone diseases occurs
osteoporosis 8656 activity [[22]]. Most studies point to a more significant impairment in bone formation, suggesting that osteoporosis in cirrhotic patients is a multifactorial disease in which different mechanisms act together to reduce
osteoporosis 11259 the degree of liver insufficiency and that it was higher in the subgroup of cirrhotic patients with osteoporosis and osteopenia. Of note, the sRANKL values were higher in patients with normal BMD in the lumbar spine.
osteoporosis 11759 attempt to maintain bone homeostasis in these patients [[45]].As the physiopathology of cirrhosis-related osteoporosis is not fully understood, other factors are briefly presented in this review in order to support a further
osteoporosis 11999 possible treatment options.3.1. Genetic FactorsUntil now, there is not a single known genetic marker of osteoporosis predisposition. Some genetic polymorphisms are linked to the development of chronic cholestatic diseases,
osteoporosis 12341 on bone loss than the collagen type Iα1 Sp1 polymorphism, which was previously evaluated in primary osteoporosis [[46], [47]]. Despite the reasonable knowledge on the possible role of these polymorphisms in PBC, more
osteoporosis 13293 Despite the iron overload effects, patients with hemochromatosis seem to be more prone to developing osteoporosis when they also have hypogonadism [[30]–[32]]. Some authors have hypothesized that low levels of sexual
osteoporosis 14432 even bone mineralization [[27], [54], [56], [57]]. IGF-1 levels are lower in cirrhotic patients with osteoporosis when compared to those without osteoporosis, and they are also associated with the degree of hepatic
osteoporosis 14476 [57]]. IGF-1 levels are lower in cirrhotic patients with osteoporosis when compared to those without osteoporosis , and they are also associated with the degree of hepatic insufficiency [[57]]. Of note, the IGF-1 replacement
osteoporosis 14677 the IGF-1 replacement in animals with cholestatic disease is able to mitigate and partially reverse osteoporosis [[1]].3.3. Toxic EffectsAlcohol is a well-known risk factor for osteoporosis in normal and cirrhotic
osteoporosis 14754 and partially reverse osteoporosis [[1]].3.3. Toxic EffectsAlcohol is a well-known risk factor for osteoporosis in normal and cirrhotic populations [[55]]. Bone biopsies from patients addicted to alcohol who presented
osteoporosis 15342 osteoblastic cells exposed to iron overload, another cause of decreased bone synthesis that accounts for osteoporosis in patients with hemochromatosis [[27], [30]–[32], [60]]. Thus, whereas hypogonadism has a dual effect
osteoporosis 16451 some liver diseases but are associated with bone loss [[67], [68]]. Of note, glucocorticoid-induced osteoporosis is a great concern in relation to the use of these drugs [[69]–[71]]. The bone side effects can be
osteoporosis 18307 patients, not all hepatic diseases lead to suppressed leptin levels, and clear data on its role in osteoporosis are still lacking [[1], [84]].Finally, smoking, lack of physical activity, malnutrition, and low body
osteoporosis 18514 low body mass index are common findings among cirrhotic patients. As all of them are associated with osteoporosis both in cirrhotic and noncirrhotic patients, their avoidance is suggested in order to preserve bone
osteoporosis 18704 order to preserve bone health [[85]–[88]]. Even though most factors involved in cirrhosis-related osteoporosis are more closely linked to bone formation, malnutrition and alcohol abuse have a widespread effect because
osteoporosis 19006 and vitamin deficiencies.Figure 1 presents some of these interactions observed in cirrhotic-related osteoporosis , focusing on its effects on osteoblastic and osteoclastic cells.5. Diagnosis and ScreeningScreening
osteoporosis 19123 focusing on its effects on osteoblastic and osteoclastic cells.5. Diagnosis and ScreeningScreening for osteoporosis is an important part of cirrhosis management, but it is not always performed [[89]]. Moreover, densitometry
osteoporosis 19710 absorptiometry (DXA) exam, emphasizing that a normal result should never be sufficient to discard the risk of osteoporosis and that any additional risk factor must lead to a higher level of awareness [[90]]. The exam allows
osteoporosis 22307 submitted to DXA [[9]].Since there are noninvasive measures that can be used as surrogate markers of osteoporosis , bone biopsies are rarely used in cirrhotic patients. In cases of bone loss, bone biopsies from cirrhotic
osteoporosis 22722 resorption surfaces, lowering the trabecular bone volume [[13], [94]].6. TreatmentMost recommendations for osteoporosis treatment in cirrhotic patients were based on results obtained from trials assessing postmenopausal
osteoporosis 23334 because nutritional deficits are common among cirrhotic patients.It is well known that patients with osteoporosis and/or fractures associated with skeletal fragility must be treated, and part of the treatment has been
osteoporosis 24012 deviation from normal values had a significant risk for vertebral fractures, showing that patients without osteoporosis also suffer fractures and should be considered for receiving prophylactic therapy [[25]].6.1. Calcium
osteoporosis 24274 amount of calcium ingestion has been debated for decades, calcium supplementation is still part of osteoporosis treatment. The total calcium intake should achieve a daily ingestion of 1.0 to 1.5 grams according to
osteoporosis 25988 widely used for osteoporotic patients, evidence confirming that these supplements could reverse or avoid osteoporosis is unclear [[27]].In a systematic review of calcium and vitamin supplementation to prevent or treat
osteoporosis 26101 is unclear [[27]].In a systematic review of calcium and vitamin supplementation to prevent or treat osteoporosis in the general population, Bolland et al. found small benefits in fracture avoidance from calcium and
osteoporosis 31204 selective estrogen-receptor modulator that shows estrogenic actions on bones. It has been used to treat osteoporosis in patients without liver diseases, but not yet in cirrhotic patients. A prior study was performed in
osteoporosis 31589 it for this population.6.5. BisphosphonatesAnticatabolic drugs seem to be a good option for treating osteoporosis in cirrhotic patients, because they are stricken by several metabolic alterations. Bisphosphonates appear
osteoporosis 31760 several metabolic alterations. Bisphosphonates appear to be helpful in the treatment of cirrhosis-related osteoporosis , because these drugs attach to the bone surface and prevent resorption (the so-called “antiresorptive”
osteoporosis 34987 administered to 43 patients after OLT, comparing BMD with 38 controls. Twenty-four patients (54% with osteoporosis ) and all the controls (23% with osteoporosis) presented a significant increase in lumbar spine but not
osteoporosis 35032 comparing BMD with 38 controls. Twenty-four patients (54% with osteoporosis) and all the controls (23% with osteoporosis ) presented a significant increase in lumbar spine but not in femoral neck BMD [[126]].Millonig et al.
osteoporosis 35295 weekly combined with calcium and vitamin D supplements for preventing bone loss in 98 patients who had osteoporosis or osteopenia and started receiving this drug after OLT. The authors assessed BMD before OLT and every
osteoporosis 36024 evaluated the effect of zoledronic acid 4 mg on BMD of 32 patients submitted to OLT (18% of whom had osteoporosis ). The drug infusion was given within seven days after OLT and repeated at one, three, six, and nine
osteoporosis 36298 administered. The authors compared the results with those of 30 patients receiving placebo (10% with osteoporosis ) and reported that lumbar spine, femoral neck, and total hip BMD measurements favored zoledronic acid
osteoporosis 40763 trial performed by Bansal et al., 215 cirrhotic patients were recruited to participate, of whom 47 had osteoporosis and received a monthly ibandronate dosage of 150 mg combined with calcium and vitamin D supplements
osteoporosis 41213 precision of BMD measures, as previously mentioned in this review and by other studies. Four patients with osteoporosis had fractures, 16 died, and 12 lost follow-up, so that only 19 completed the study. These 19 patients
osteoporosis 41586 cirrhotic patients have been submitted to many treatments to achieve better survival, cirrhosis-related osteoporosis has become more common, especially among patients who present any other risk factor for bone loss, such
osteoporosis 41828 alcohol abuse, hypogonadism, or the other factors previously mentioned in this review. Furthermore, osteoporosis is the only cirrhosis complication that worsens after liver transplantation. Thus, health professionals
osteoporosis 42198 should be submitted to specific exams, thereby reducing the budget of a whole population screening.Once osteoporosis is diagnosed in cirrhotic patients or in those who were already submitted to OLT, it is important to
osteoporosis 42894 to curb bone loss in this population, additional therapy must be prescribed.Most trials that assess osteoporosis treatment in cirrhotic subjects had a limited sample and a short follow-up. Studies on hormonal replacement
osteoporosis 44555 best options for this population [[133]].Figure 1Factors that can be involved in cirrhosis-related osteoporosis by modulating the activity of osteoblastic and osteoclastic cells. The factors most related to osteoblastic

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