Effects of denosumab treatment in chronic liver disease patients with osteoporosis

Saeki, Chisato; Saito, Mitsuru; Oikawa, Tsunekazu; Nakano, Masanori; Torisu, Yuichi; Saruta, Masayuki; Tsubota, Akihito

doi:10.3748/wjg.v26.i33.4960

Cited by 16 publications

(14 citation statements)

References 44 publications

(54 reference statements)

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“…Similarly, treatment with parathyroid hormone (1–34) induced enzymatic collagen cross-links, increased bone volume, and decreased pentosidine (non-enzymatic cross-links) levels in monkeys with ovariectomy, thereby improving bone strength [ 35 ]. We previously reported that administration of denosumab, a human monoclonal antibody against the receptor activator of nuclear factor kappa-B ligand, increased BMD, suppressed bone turnover, and decreased plasma pentosidine in CLD patients with osteoporosis [ 36 ]. The current clinical practice guidelines on CLD recommend supplementation with calcium and vitamin D for a T-score < −1.5 and administration of bisphosphonates to improve BMD in CLD patients with osteoporosis [ 37 ].…”

Section: Discussionmentioning

confidence: 99%

Plasma pentosidine levels are associated with prevalent fractures in patients with chronic liver disease

et al. 2021

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Aim Osteoporotic fractures negatively impact health-related quality of life and prognosis. Advanced glycation end products (AGEs) impair bone quality and reduce bone strength. The aim of this study was to determine the relationship between plasma levels of pentosidine, a surrogate marker for AGEs, and prevalent fractures in patients with chronic liver disease (CLD). Methods This cross-sectional study included 324 patients with CLD. Vertebral fractures were evaluated using lateral thoracolumbar spine radiographs. Information on prevalent fractures was obtained through a medical interview, medical records, and/or radiography. The patients were classified into low (L), intermediate (I), and high (H) pentosidine (Pen) groups based on baseline plasma pentosidine levels. Results Of the 324 patients, 105 (32.4%) had prevalent fractures. The prevalence of liver cirrhosis (LC) and prevalent fractures significantly increased stepwise with elevated pentosidine levels. The H-Pen group had the highest prevalence of LC (88.6%, p < 0.001) and prevalent fractures (44.3%, p = 0.007), whereas the L-Pen group had the lowest prevalence of LC (32.1%, p < 0.001) and prevalent fractures (21.0%, p = 0.007). Multiple logistic regression analysis identified pentosidine as a significant independent factor related to prevalent fractures (odds ratio = 1.069, p < 0.001). Pentosidine levels increased stepwise and correlated with liver disease severity. They were markedly high in patients with decompensated LC. In multiple regression analysis, liver functional reserve factors (total bilirubin, albumin, and prothrombin time-international normalized ratio) significantly and independently correlated with pentosidine levels. Conclusions Plasma pentosidine was significantly associated with prevalent fractures and liver functional reserve in patients with CLD. Pentosidine may be useful in predicting fracture risk and should be closely followed in CLD patients with advanced disease.

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Section: Discussionmentioning

confidence: 99%

Plasma pentosidine levels are associated with prevalent fractures in patients with chronic liver disease

et al. 2021

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“…Denosumab is a human monoclonal antibody for RANKL and mimics the endogenous effect of OPG, thereby inhibiting bone resorption and remodeling. Our study of CLD patients with osteoporosis revealed that denosumab increased BMD, suppressed bone turnover, and improved a bone quality marker after 12 months of treatment [ 155 ]. Meanwhile, RANK is expressed in skeletal muscle, and muscle-specific RANK deletion was protective against denervation-induced loss of muscle force in mice [ 156 ].…”

Section: Osteosarcopenia In Chronic Liver Diseasementioning

confidence: 99%

Influencing Factors and Molecular Pathogenesis of Sarcopenia and Osteosarcopenia in Chronic Liver Disease

Saeki

Tsubota

2021

Life

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The liver plays a pivotal role in nutrient/energy metabolism and storage, anabolic hormone regulation, ammonia detoxification, and cytokine production. Impaired liver function can cause malnutrition, hyperammonemia, and chronic inflammation, leading to an imbalance between muscle protein synthesis and proteolysis. Patients with chronic liver disease (CLD) have a high prevalence of sarcopenia, characterized by progressive loss of muscle mass and function, affecting health-related quality of life and prognosis. Recent reports have revealed that osteosarcopenia, defined as the concomitant occurrence of sarcopenia and osteoporosis, is also highly prevalent in patients with CLD. Since the differentiation and growth of muscles and bones are closely interrelated through mechanical and biochemical communication, sarcopenia and osteoporosis often progress concurrently and affect each other. Osteosarcopenia further exacerbates unfavorable health outcomes, such as vertebral fracture and frailty. Therefore, a comprehensive assessment of sarcopenia, osteoporosis, and osteosarcopenia, and an understanding of the pathogenic mechanisms involving the liver, bones, and muscles, are important for prevention and treatment. This review summarizes the molecular mechanisms of sarcopenia and osteosarcopenia elucidated to data in hopes of promoting advances in treating these musculoskeletal disorders in patients with CLD.

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“…У пацієнток із захворюваннями печінки запропоновано використання різних ліків від остеопорозу, але більшість досліджень включали невелику кількість пацієнток, що обумовлює відсутність консенсусу з цього питання [8,9].…”

Section: полтавський державний медичний університет українаunclassified

“…Бісфосфонати -антикатаболічні препарати, які збільшують кісткову масу та зменшують частоту переломів при постменопаузальному остеопорозі [10]. Їх вплив на перебіг захворювань печінки на сьогоднішній день не повністю визначений в осно-вному через невелику кількість досліджень та невелику кількість пролікованих пацієнток [5,6,8,9] Для включення в дослідження усім пацієнткам виключали наявність вірусних гепатитів В, С, у дослідження включали пацієнток із нормальними значеннями аланін та аспартатамінторансферази для виключення псевдопозитивної діагностики фіброзу печінки внаслідок ущільнення печінкової тканини на фоні запалення. Усі досліджені пацієнтки знаходились у менопаузі із середнім строком 7,8±3,5 років.…”

Section: полтавський державний медичний університет українаunclassified

Optimization of Antiosteoporotic Therapy in Patients with Liver Fibrosis

Ждан¹,

Ivanytsky²,

Бабаніна³

et al. 2021

Ukr. ž. med. bìol. sportu

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The purpose of the study: to investigate the effect of zolendronic acid on bone mineral density in patients with osteoporosis and fibrotic changes of the liver due to steatohepatitis. Materials and methods. We examined 28 female patients with a mean age of 55.3±4.7 years with decreased bone mineral density, nonalcoholic steatohepatosis and liver fibrosis. All studied patients were in menopause duration of 7.8±3.5 years. For inclusion in the study, all patients were excluded from the presence of comorbidities. The degree of liver fibrosis was determined on the basis of 2D shear wave elastometry by transcutaneous access by the method of shear wave in the SWE mode. The study included patients with liver fibrosis F1 - F3 on METAVIR. Determination of bone mineral density was performed using an X-ray densitometer DEXXUM T by dual energy absorption. Results and discussion. The initial level of liver tissue stiffness in the studied patients was 8.52±1.12 kPa, which corresponded to the stage of fibrosis F2 - F3 according to METAVIR. Isolated decrease in lumbar spine mineral density was diagnosed in 20 patients, 8 patients had a combination of decreased spinal mineral density with decreased femoral mineral density, mean T vertebral T-test was -2.25±0.2, mean femoral neck T-test was -1, 9±0.3. In order to maintain and restore bone mineral density, these patients were advised to minimize the factors that contribute to bone loss, mainly by stopping alcohol and smoking. Patients were advised to exercise as much as possible under the supervision of a rehabilitologist, especially to do exercises aimed at improving the mechanics of the spine. One year after administration of 5 mg zolendronic acid intravenously and daily intake of 1500 mg calcium and 800 IU vitamin D the level of liver tissue stiffness in the studied patients was 7.69±1.14 kPa, which corresponded to the stage of fibrosis F2 - F3 according to METAVIR and not due to a moderate decrease in indicators, there was no statistically significant difference. Isolated decrease in lumbar spine mineral density was diagnosed in 19 patients, in 9 patients there was a combination of decrease in spinal mineral density with decrease in femur mineral density, the average criterion of T vertebrae was 1.1±0.3 (p=0.032), the average criterion of T femoral neck -0.9±0.3 (p=0.029). The study of the level of alaline transaminase, aspartate transaminase, alkaline phosphatase, gamma-glutamyltranspeptidase did not reveal any abnormalities. After administration of zolendronic acid in 7 patients there was an increase in temperature to febrile levels within 2-3 days. None of the patients showed signs of bone fractures of any localization during the observation period. Conclusion. Thus, the administration of zolendronic acid to patients with decreased bone mineral density on the background of fibrous changes in liver tissue due to steatohepatitis is safe and highly effective

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Effects of denosumab treatment in chronic liver disease patients with osteoporosis

Cited by 16 publications

References 44 publications

Plasma pentosidine levels are associated with prevalent fractures in patients with chronic liver disease

Plasma pentosidine levels are associated with prevalent fractures in patients with chronic liver disease

Influencing Factors and Molecular Pathogenesis of Sarcopenia and Osteosarcopenia in Chronic Liver Disease

Optimization of Antiosteoporotic Therapy in Patients with Liver Fibrosis

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