Bone Health in Patients With Liver Diseases

Osteoporosis is the most common bone disease in chronic liver disease (CLD) resulting in frequent fractures and leading to significant morbidity in this population. In addition to patients with cirrhosis and chronic cholestasis, patients with CLD from other etiologies may be affected in the absence of cirrhosis. The mechanism of osteoporosis in CLD varies according to etiology, but in cirrhosis and cholestatic liver disease it is driven primarily by decreased bone formation, which differs from the increased bone resorption seen in postmenopausal osteoporosis. Direct toxic effects from iron and alcohol play a role in hemochromatosis and alcoholic liver disease, respectively. Chronic inflammation also has been proposed to mediate bone disease in viral hepatitis and nonalcoholic fatty liver disease. Treatment trials specific to osteoporosis in CLD are small, confined to primary biliary cholangitis and post-transplant patients, and have not consistently demonstrated a benefit in this population. As it stands, prevention of osteoporosis in CLD relies on the mitigation of risk factors such as smoking and alcohol use, treatment of underlying hypogonadism, and encouraging a healthy diet and weight-bearing exercise. The primary medical intervention for the treatment of osteoporosis in CLD remains bisphosphonates though a benefit in terms of fracture reduction has never been shown. This review outlines what is known regarding the pathogenesis of bone disease in CLD and summarizes current and emerging therapies.     

Bone Density, Vitamin D Status, and Disordered Bone Remodeling in End-Stage Chronic Liver Disease

Hepatic osteodystrophy occurs in up to 50% of patients with chronic liver disease (CLD). The aim of this study was to determine the relative contribution of increased resorption and decreased formation to hepatic osteodystrophy by measuring biochemical markers. Twenty-seven patients with advanced CLD (14 female, 13 male) were enrolled. Bone mineral density (BMD), measured at the lumbar spine, and femoral neck, were measured by dual energy X-ray absorptiometry (DXA); bone turnover was assessed using biochemical markers of bone formation and resorption. Based on WHO criteria, osteoporosis and osteopenia were present in 41% and 18% of patients, respectively. All three markers of bone resorption (free deoxypyridinoline, pyridinoline, and hydroxyproline) were increased significantly in patients with CLD. There was a less marked change in the markers of bone formation (osteocalcin, procollagen type 1 peptide, and bone alkaline phosphatase), resulting in a negative uncoupling index in 23/27 (85%) of the patients. Only two (7%) patients had biochemical changes consistent with osteomalacia. The results suggest that increased bone resorption is the predominant cause of hepatic osteodystrophy and therapeutic strategies should be designed to suppress bone resorption, especially in preparation for liver transplantation. Bone biomarkers may be useful alternatives to bone biopsy in evaluating hepatic osteodystrophy. Received: 11 September 1997 / Accepted: 22 September 1998     

Bone Disease and Liver Transplantation: A Review

Liver transplantation is currently the most effective and almost routine treatment for chronic and acute liver diseases. The survival of transplanted patients has increased exponentially, which has led to more knowledge of the long-term complications secondary to the underlying pathology or the various treatments that must be followed. Bone metabolic disease is a chronic complication of liver transplantation that inhibits quality of life. The factors that contribute to the development of bone disease are different according to the various etiologies of liver damage. All patients should be examined for osteoporosis risk factors because the incidence of new fractures in transplant patients is higher during the first year after transplantation, reflecting the greater bone loss during this time. This article outlines a proposal for a treatment algorithm; we propose that pharmacologic therapy in patients post liver transplant should first consider the diagnosis of osteoporosis by bone mineral density, the patient's personal and family history of spine and femoral neck fractures, and the use glucocorticoids (dose and time) until a tool is available that allows the best estimation of the fracture risk in this population of patients.     

关注系统性红斑狼疮继发性骨质疏松

系统性红斑狼疮（systemic lupus erythematosus,SLE)是多系统损害的自身免疫性疾病,糖皮质激素和免疫抑制剂是治疗的主要药物。SLE的骨损害包括骨量减少、骨质疏松(osteoporosis. OP)、无菌性骨坏死和骨折,随着SLE生存期的延长,心血管并发症和OP成为影响患者生活质量和生存的主要因素,同时OP对于心血管的发病也有促进作用,是目前备受关注的并发症。OP是一种以骨量减少和骨组织的细微结构破坏为特征的全身性疾病。关于SLE的骨质疏松也存在不少争议,主要集中在OP的发病率和骨质疏松与激素治疗关系两个方面。就OP发病率来讲,不同的研究得出的结论不同。SLE的骨质疏松涉及多种机制包括炎性因素、免疫介导的因素、固有因素、代谢因素、药物因素和疾病本身的因素。SLE相关的骨质疏松的治疗首先是治疗原发病,此外健康的生活方式包括钙剂和维生素D的补充也非常重要,对诊断骨质疏松的SLE患者应及时给予双膦酸盐治疗。     

Transplantation osteoporosis

Transplantation is an established therapy for end-stage diseases of the kidney, endocrine pancreas, heart, liver, and lung, and for many hematologic disorders. Improved survival rates have been accompanied by increased recognition of previously neglected long-term complications of transplantation such as fractures and osteoporosis. Pretransplantation bone disease and immunosuppressive therapy result in rapid bone loss and increased fracture rates early after transplantation. Patients should be assessed and pretransplantation bone disease should be treated. Preventive therapy initiated in the immediate posttransplantation period is indicated in patients with osteopenia or osteoporosis, as further bone loss will occur in the first several months after transplantation. Long-term organ transplant recipients should also have bone mass measurement and treatment of osteoporosis. Bisphosphonates are the most promising approach for the management of transplantation osteoporosis. Active vitamin D metabolites may have additional benefits in reducing hyperparathyroidism, particularly after kidney transplantation. Large, multicenter treatment trials with oral or parenteral bisphosphonates and calcitriol are recommended.     

Osteoporosis in end-state renal disease

Maintaining the intricate bone mineral homeostasis in patients with chronic renal failure and renal osteodystrophy is a complex and challenging process. In addition to the well described high-turnover bone disease caused by secondary hyperparathyroidism and low-turnover disease in the form of osteomalacia (either from aluminum or a dynamic bone disease) osteopenia also is present in end-stage renal disease patients. In contrast to abnormalities in the ability of bone to remodel, osteopenia is a deficiency in bone mass or volume. The prevalence of fractures in dialysis patients, regardless of histomorphometry appears to exceed that observed in elderly women. This osteopenia that occurs in chronic renal failure patients secondary to multiple factors that include hypogonadism, medications (such as corticosteroids), immobilization, and the typical osteopenia associated with aging. All of these factors amplify the risk of fracture in dialysis patients.     

Atraumatic diplaced bilateral femoral neck fracture in a patient with hypophosphatemic rickets in postpartum period: A missed diagnosis

IntroductionSimultaneous bilateral femoral neck fracture is an uncommon condition. There are very few cases reported in the literature and most of these cases have underlying bone pathologies such as renal osteodystrophy and osteomalacia. In some cases bilateral femoral neck fractures occur due to generalized seizures or high-energy trauma.Presentation of caseIn this case report “atraumatic bilateral femoral neck fracture in a 26 year old woman in postpartum period with hypophosphatemic rickets disease” is presented.DiscussionFemoral neck fractures are more frequently seen in elderly because of the reduction of bone quality and developing osteoporosis. In the literature generalized epilepsy, osteomalacia, hypovitaminosis D and chronic renal failure are shown as facilitating causes of bilateral femoral neck fractures. In patients without any additional pathology electric shock, electroconvulsive therapy, and high-energy trauma can lead to femoral neck fractures. In our patient there was also an underlying pathology, she has been followed due to autosomal recessive hypophosphatemic rickets disease since she was one year old. In the treatment of bilateral femoral neck fractures open/closed reduction internal fixation or hip arthroplasty are applied.ConclusionFor patients with bone metabolic diseases and/or the patients in pregnancy and postpartum period, preventive measures should be increased to reduce the risk of pathologic fracture. Admitting to the hospital physicians must be more careful about detecting fractures in these patients.     

Association between vascular calcification and osteoporosis in men with type 2 diabetes

Atherosclerotic vascular disease is common in diabetes, and some data support a link with bone loss. This study evaluates the association between osteoporosis and clinical and metabolic factors and chronic complications of diabetes. We studied 59 diabetic men aged 50-80 yr who were assessed with bone densitometry (dual-energy X-ray absorptiometry). Of them, 10.2% of the patients were found to have osteoporosis in the lumbar spine and 45.8% osteopenia, whereas in the femoral neck, 11.8% had osteoporosis and 49% had osteopenia. There was a significant association of osteoporosis in the lumbar spine L1-L4 (p=0.004) and in the femoral neck (p=0.036) with iliac artery calcification. In addition, there was no association with any other metabolic factors, clinical factors, or chronic complications of diabetes evaluated, except for an association between a previous personal history of fractures (p=0.016) and low bone mineral density in the femoral neck. In conclusion, we found a positive association between the iliac artery calcification and osteoporosis in type 2 diabetic male patients.     

Bone Disorders in Patients With Chronic Liver Disease Awaiting Liver Transplantation

Background

An important complication of chronic liver disease is osteodystrophy, which includes osteoporosis and the much rarer osteomalacia. Both conditions are associated with significant morbidity through fractures resulting in pain, deformity, and immobility. Liver transplantation may further deteriorate bone metabolism. The aim of the present study was to investigate the frequency and severity of hepatic osteodystrophy among patients with liver cirrhosis who were referred for liver transplantation. We also evaluated modifications in bone metabolism after liver transplantation.

Materials and methods

We recruited 35 consecutive patients with chronic liver disease who were undergoing assessment for transplantation over a 1-year period. Bone mass in the total skeleton and proximal hip was evaluated using a dual-energy X-ray absorptiometry device (Lunar Prodigy Advance, GE Healthcare, USA). According to World Health Organization recommendations, osteoporosis was defined as a T score < −2.5 and osteopenia as T score between −1 and −2.5.

Results

We enrolled in the study 35 patients, including 8 females and 27 males of overall mean age of 57 ± 7, who showed a viral etiology (57%) or alcohol etiology (28%), Child-Pugh 8.7 ± 2.3. The overall prevalence of osteodystrophy was 40% (26% osteopenia and 14% osteoporosis). No difference was evident according to gender, severity of liver disease (Child-Pugh, Model for End-stage Liver Disease), or origin of liver disease. A subgroup of 10 transplanted patients reached 3-month follow-up, showing total body T score with a significant decrease after 3 months while femoral T scores tended to decrease insignificantly.

Conclusions

This study revealed a high prevalence of low bone mineral density among cirrhotic patients before liver transplantation. We suggest that both bone mineral density and biochemical examinations should be considered to be routine tests to identify the status of bone mass and bone metabolism among recipients prior to liver transplantation.     

肝源性骨质疏松的发病机制研究

在我国,骨质疏松的患病率越来越高。临床实践中发现,肝病患者更容易发生骨质疏松,甚至进一步发展为骨质疏松性骨折,患者的生活质量大大地降低。研究显示,约30%慢性肝病患者可发生骨折。肝源性骨质疏松的发病机制与很多因素有关,包括了糖代谢紊乱、纤维连接蛋白、胰岛素样生长因子1、各种细胞因子、维生素D的减少以及性激素的失衡等等。本文就肝病患者中发生骨量丢失的机制进行综述。     

肝移植术后的骨质疏松诊断和治疗

肝移植是目前较为成熟的器官移植技术,随着肝移植和术后免疫抑制技术的不断发展,肝移植患者的术后生存率得到很大提升。总体而言,肝移植手术后患者生存质量良好,但近来研究发现肝移植患者术后骨质疏松症和骨折发生率显著增加。术后患者骨质疏松的发生主要与肝移植前存在的骨量减少和术后的骨量的大量丢失有关。所有肝移植患者均应进行骨质量评估,优选在移植前期或移植后早期进行,建议所有患者进行骨密度测量,并应包括可能导致骨病的代谢因素,评估骨折风险,并据此进行肝移植的骨病管理。本综述讨论了肝移植后的骨密度变化和骨折发生率,肝移植前后导致骨质疏松的因素以及对骨质疏松的管理。     

Osteoporosis in Rett syndrome: a case study presenting a novel management intervention for severe osteoporosis

The present article describes a successful novel therapeutic intervention with Aredia with one child with Rett syndrome, after suffering from six pathological fractures within less than 3 years due to severe osteoporosis. Since the initiation of the treatment (3 years ago), the child has not suffered any fractures. Patients with chronic diseases and those with disabilities or on anticonvulsant medications are at risk for low bone density and possibly for the resultant pathologic fractures that define osteoporosis in children. Individuals with Rett syndrome (RS) have been shown to have low bone mineral density (or osteopenia) at a young age. If osteoporosis occurs in a girl with RS, it can inflict pain and seriously impair the child’s mobility and quality of life. The present article describes a case study of a child with RS (showing an average of 1.75 fractures annually for the 4 years preceding the treatment) before and after a treatment with Aredia. Patient received 30 mg/day for 3 days on a once every 3-month cycle. There was a 45 % improvement in bone mass density (BMD) values from pre–post-intervention. The child had no fractures in the 3 years posttreatment. This finding is significant (p?<?0.03). The BMD Z-scores of the child showed severe osteoporosis (Z-score of ?3.8) at pre-intervention and are elevated to osteopenia levels (Z-score of ?1.3) at post-intervention measurements. All measurements suggest that the treatment successfully reversed the osteoporotic process and prevented further fractures. This change caused great relief to the child and her family and an improvement in their quality of life. The findings support the ability (in one case) to reverse the progression of osteoporosis in individuals with Rett syndrome showing severe osteoporosis with multiple fractures.     

Bilateral femoral insuffiency fractures treated with inflatable intramedullary nails: a case report

Stress fractures could be classified as fatigue fractures and insufficiency fractures (IF). Fatigue fractures occur when abnormal mechanical stress is applied to a normal bone, on the other hand insufficiency fractures occur when normal to moderate pressure is applied to a bone that has decreased resistance (Daffner and Pavlov in Am J Radiol 159:242-245, 1992). IF have been observed mainly in patients with postmenopausal osteoporosis, and are becoming more common with the increase of elderly population (Daffner and Pavlov in Am J Radiol 159:242-245, 1992). Other systemic and metabolic conditions that can result in osteopenia and IF include osteomalacia, hyperparathyroidism, hyperthyroidism, rheumatoid arthritis, fluoride treatment, diabetes mellitus, fibrous dysplasia, Paget's disease, irradiation and mechanical factors (Daffner and Pavlov in Am J Radiol 159:242-245, 1992; Soubrier et al. in Joint Bone Spine 70:209-218, 2003; Epps et al. in Am J Orthop 33:457-460, 2004; Austin and Chrissos in Orthopedics 28:795-797, 2005). In this case report, the authors present an osteoporotic woman who developed bilateral insufficiency fracture of the femoral shaft after longstanding steroid, thyroxine replacement and alendronate therapy due to partial empty sella syndrome and osteoporosis, resulting in the treatment of the fracture by inflatable intramedullary nailing.     

2型糖尿病性骨质疏松症发病机制研究进展

2型糖尿病属于临床常见病,可引发骨骼、血管、神经等多系统并发症,骨质疏松症是其常见并发症之一。2型糖尿病性骨质疏松症患者主要表现为骨代谢异常、骨脆性增加,易发生骨折。当前关于2型糖尿病性骨质疏松症发病机制的研究众多,其中涉及高血糖状态、氧化应激、糖尿病慢性并发症、细胞因子及激素水平变化等多个方面。笔者就国内外关于2型糖尿病性骨质疏松症发病机制的最新研究进行综述,旨在为下一步研究及临床工作提供参考。     

Chronic complications of spinal cord injury

Spinal cord injury (SCI) is a serious medical condition that causes functional, psychological and socioeconomic disorder. Therefore, patients with SCI experience significant impairments in various aspects of their life. The goals of rehabilitation and other treatment approaches in SCI are to improve functional level, decrease secondary morbidity and enhance health-related quality of life. Acute and long-term secondary medical complications are common in patients with SCI. However, chronic complications especially further negatively impact on patients’ functional independence and quality of life. Therefore, prevention, early diagnosis and treatment of chronic secondary complications in patients with SCI is critical for limiting these complications, improving survival, community participation and health-related quality of life. The management of secondary chronic complications of SCI is also important for SCI specialists, families and caregivers as well as patients. In this paper, we review data about common secondary long-term complications after SCI, including respiratory complications, cardiovascular complications, urinary and bowel complications, spasticity, pain syndromes, pressure ulcers, osteoporosis and bone fractures. The purpose of this review is to provide an overview of risk factors, signs, symptoms, prevention and treatment approaches for secondary long-term complications in patients with SCI.     

Quantitative computed tomography reflects vertebral fracture morbidity in osteopenic patients

We studied the relationship between spontaneous vertebral compression fractures and lumbar vertebral trabecular bone density in 69 consecutive patients with suspected osteopenia. Seven had biopsy-confirmed osteomalacia. The remaining 62 were divided into three groups: group 1--asymptomatic patients suspected of having osteopenia on plain films, but with no vertebral compression fractures (N = 24); group II--those with one to five vertebral compression fractures (N = 16); and group III--those with six or more vertebral compression fractures (N = 22). A quantitative computed tomographic (QCT) scan of the lumbar spine was performed on all patients. Patients in group I had QCT values of 94 +/- 23 mg/cm3 (mean +/- SE); those in group II had QCT values of 66 +/- 28 mg/cm3; and those in group III had values of 34 +/- 28 mg/cm3. There were significant differences among all groups (P less than .001), although there was considerable overlap of individuals among the groups. There was no significant difference between the mean QCT value of patients with one compression fracture and the value of those with between two and five compression fractures. Patients with biopsy-proven osteomalacia had higher vertebral trabecular bone density than patients with osteoporosis and compression fractures. Our study provides evidence suggesting a strong inverse relationship between QCT-measured vertebral bone density and the presence of vertebral compression fractures in a group of osteopenic patients.     

Anti-epileptic medication and bone health

Background Epilepsy is a common chronic neurological disorder, usually requiring long-term treatment with anti-epileptic drugs (AED). Many studies have reported that AED therapy is associated with metabolic bone disease and is a major iatrogenic risk factor for fractures. There remains uncertainty about the type(s) of bone disease due to AED treatment, and the pathogenesis of AED-associated fractures. Rationale Deficits in bone mineral density (BMD) are widely reported in AED-treated patient populations. However, much of the research conducted to date has been limited by factors such as small sample size, potentially biased subject selection, a lack of selection of appropriate control data, and failure to take account of important confounding influences. The pathogenesis of AED-associated fractures is likely to be multifactorial, due to factors including reduced BMD, impaired bone quality (due to osteoporosis and/or osteomalacia), increased propensity to fall, and fractures associated with seizures or loss of consciousness. Recommendations Patients receiving long-term AED should be monitored for indices of bone health, including BMD and vitamin D status. Lifestyle factors should be optimized, vitamin D status maintained, and fall prevention strategies introduced as appropriate. Good seizure control is important. The use of additional, specific osteoporosis therapy is not evidence-based in this setting, but would appear reasonable in patients with clinically significant decreases in BMD, applying current treatment guidelines for osteoporosis. Conclusion There is a pressing need for improved understanding of the pathogenesis of AED-associated bone disease, for better definition of the risk associated with specific AED regimens, and for the development of evidence-based preventive and treatment approaches in this common but neglected disorder.     

Impact of long-term immunosuppressive therapy on psychosocial and physical well being in liver transplant recipients

To achieve the fullest potential of transplantation, continuing concern for the recipients' quality of life must be a part of the process. Database records of patients who are currently alive and received transplants between 1982 and 1991 were retrospectively analyzed. Recipients were contacted and asked to answer a quality-of-life questionnaire. Of 105 liver transplant recipients, 51 died within 10 years after transplantation; 47 were contacted. Posttransplant complications included hypertension (64%), posttransplant diabetes mellitus (17%), osteopenia (40%), osteoporosis (26%), and heart disease (17%). Most recipients reported all aspects of their life to be average, if not better than their age-matched peers. Although most recipients complained about side effects of immunosuppressive agents, they were all happy to be alive and agreed that their quality of life showed an impressive favorable change to a level exceeding that of the general population. These results suggest that liver transplantation not only improved survival but also quality of life.     

Survey of spine surgeons on attitudes regarding osteoporosis and osteomalacia screening and treatment for fractures,fusion surgery,and pseudoarthrosis

Background contextOsteoporosis and osteomalacia are significant risk factors for fracture and spine instrumentation failure. Low-energy fractures are becoming increasingly more common because of an increase in life expectancy and age of the population. Decreased bone density is an independent risk factor for instrumentation failure in spinal fusion operations.PurposeTo assess the awareness and practice patterns of spine surgeons regarding metabolic bone disorders and osteoporosis with emphasis on fracture care and arthrodesis.Study design/settingQuestionnaire study.Patient sampleSpine surgeons attending the “Disorders of the Spine” conference (January 2007, Whistler, British Columbia, Canada).Outcome measuresRespondent reported frequencies of diagnostics, screening, and treatment methods for patients with low-energy spine fractures, pseudoarthrosis, and those undergoing spinal arthrodesis.MethodsA ten-question survey was administered to orthopedic surgeons and neurosurgeons who treated spine fractures and degenerative spine conditions in their practice. The survey was given to those who were attending a continuing medical education spinal disorders conference. The survey asked about treatment patterns with respect to osteoporosis and osteomalacia workup and treatment for patients with low-energy spine fractures, pseudoarthrosis, and those undergoing spinal arthrodesis.ResultsOf the 133 surgeons to whom the questionnaire was distributed at this meeting, 114 questionnaires were returned that corresponds to a response rate of 86%. Twenty-one surveys were excluded because of incomplete biographical information, resulting in a total of 93 completed questionnaires that were available for analysis. When treating patients with low-energy spine fractures, 60% checked dual-energy X-ray absorptiometry (DEXA) and 39% checked metabolic laboratories (of those who did not order laboratories and DEXA about 63% refer for treatment). Before instrumented fusion, 44% of those queried checked DEXA and 12% checked metabolic laboratories (vitamin D, parathyroid hormone [PTH], and calcium [Ca]). Before noninstrumented fusion, 22% checked DEXA and 11% checked metabolic laboratories. Before addressing pseudoarthrosis, 19% checked DEXA and 20% checked metabolic laboratories.ConclusionsDespite of the large number of elderly patients undergoing spine care and the high incidence of osteoporosis and/or osteomalacia in this population, a large portion of the spine surgeons who responded to the survey reported that they do not perform routine osteoporosis/osteomalacia workups. Of those who do perform workups, some commented that it will change their surgical plan or preoperative treatment. It appears that there is a need for increased awareness among spine specialists regarding osteoporosis screening and treatment. Osteoporosis practice patterns may also be affected with newly evolving government quality reporting regulations.     

Lack of osteomalacia in chronic cholestatic liver disease

Assessment of osteomalacia using rigorous histologic definition was carried out in 36 unselected patients with chronic cholestatic liver disease, 33 with primary biliary cirrhosis, and 3 with primary sclerosing cholangitis. Disease duration varied from 1 to 11 years. The mean values for total trabecular bone volume, osteoid volume, osteoid surface, and mineralization appositional rate were all decreased when compared to age-matched and sex-matched controls. There was a highly significant decrease in the mean osteoid seam width in both females (P = 0.001) and males (P = 0.02), and a significant prolongation of the mineralization lag time was found in females (P = 0.05), but failed to reach significance in males. These results excluded osteomalacia but were more indicative of osteoporosis. Biochemical evidence of osteomalacia was also absent, with serum calcium, serum phosphorus, and mean 25-hydroxyvitamin D levels not significantly different from control values, although there was a nonsignificant decrease in the mean value of 25-hydroxyvitamin D in patients with elevated serum bilirubin levels, and all patients with levels below 20 nmol/L had avoided sunlight exposure. The present results suggest that osteoporosis is the major type of metabolic bone disease in patients with chronic cholestatic liver disease.