肝性骨营养不良的治疗

Hepatic osteodystrophy (HOD) is a metabolically associated bone disease mainly manifested as osteoporosis with the characteristic of bone loss induced by chronic liver disease (CLD). Due to its high incidence in CLD patients and increased risk of fracture, the research on HOD has received considerable interest. The specific pathogenesis of HOD has not been fully revealed. While it is widely believed that disturbance of hormone level, abnormal secretion of cytokines and damage of intestinal barrier caused by CLD might jointly affect the bone metabolic balance of bone formation and bone absorption. At present, the treatment of HOD is mainly to alleviate the bone loss by drug treatment, but the efficacy and safety are not satisfactory. Mesenchymal stromal cells (MSCs) are cells with multidirectional differentiation potential, cell transplantation therapy based on MSCs is an emerging therapeutic approach. This review mainly summarized the pathogenesis and treatment of HOD, reviewed the research progress of MSCs therapy and the combination of MSCs and scaffolds in the application of osteoporotic bone defects, and discussed the potential and limitations of MSCs therapy, providing theoretical basis for subsequent studies.

… hepatic osteodystrophy. Herein, we identify liver fibrosis with osteoporotic phenotypes in hepatic osteodystrophy … Furthermore, for the treatment of hepatic osteodystrophy, since the liver …

INTRODUCTION This study aimed to evaluate the effects of denosumab and alendronate on bone mineral density (BMD) and liver fibrosis markers in patients with both primary osteoporosis (OP) and metabolic dysfunction-associated steatotic liver disease (MASLD). METHODS This was a single-center, retrospective observational study. A total of 60 patients diagnosed with both OP and MASLD were identified from Zhejiang Hospital and categorized into two groups based on their actual treatment received: denosumab (n=30) or alendronate (n=30). Baseline data, including demographic information, clinical characteristics, BMD, and liver fibrosis markers, were obtained from medical records. These measures were again obtained from records after approximately one year of treatment to evaluate changes in BMD and liver fibrosis markers. RESULTS In the denosumab group, marked improvements in BMD were observed at the lumbar spine (L1-4), femoral neck, and total hip (all P < 0.01). Additionally, there were notable reductions in liver fibrosis markers, such as FIB-4 and NFS (P < 0.01 and P < 0.05, respectively). In the alendronate group, only an increase in lumbar spine (L1-4) BMD was noted (P < 0.05), with no statistically significant changes observed in femoral neck or total hip BMD (P > 0.05), nor in liver fibrosis markers. CONCLUSION Denosumab use was associated with improvements in BMD and reductions in liver fibrosis in patients with OP and MASLD, suggesting it may be a promising therapeutic option.

The nephrotoxicity of adefovir dipivoxil (ADV) can induce Fanconi syndrome, which causes hypophosphatemic osteomalacia. We report a case of a 67-year-old postmenopausal woman who had been receiving long-term adefovir dipivoxil therapy for chronic hepatitis B. She presented with severe bone pain and multiple pseudofractures, and was diagnosed with drug-induced hypophosphatemic osteomalacia. Following discontinuation of adefovir and supplementation with vitamin D and phosphate, her biochemical parameters normalized and bone pain significantly improved, indicating that osteomalacia had been essentially corrected. However, although follow-up bone mineral density (BMD) showed significant improvement compared to pretreatment values, it remained markedly below the reference range for age-matched women. Postmenopausal osteoporosis was therefore suspected, and anti-osteoporotic pharmacotherapy was initiated after correction of osteomalacia. This case suggests that BMD can improve substantially after removal of the causative factor in drug-induced osteomalacia; however, if patients have underlying risk factors for osteoporosis, low BMD may persist even after osteomalacia resolution, necessitating further evaluation and intervention.

Background & objectives: Vitamin D plays an important role in bone metabolism, and liver is the intermediary site of vitamin D metabolism. The purpose of this study was to study the prevalence of vitamin D deficiency and bone health in patients with cirrhosis. Methods: Prospectively, serum 25-hydroxy vitamin D [25(OH)D] level were assessed in cirrhotics by chemiluminescence method. Endocrine Society Clinical practice guideline was used to define deficiency and insufficiency of vitamin D. Bone mineral density (BMD) was assessed using dual-energy X-ray absorptiometry and the World Health Organization criteria was used to define osteoporosis and osteopenia. The lowest T score at the left hip neck or lumbar spine was taken as osteoporosis or osteopenia. The Child-Turcotte-Pugh score was used to assess the severity of cirrhosis. Results: Cirrhotics (n=350, male: 278, compensated: 210) were included. Mean serum 25(OH)D level was 8.75 ng/ml. The prevalence of vitamin D deficiency (VDD) and low-BMD (osteopenia and osteoporosis) was 89.4 and 86 per cent, respectively. VDD, insufficiency and osteoporosis was found in 86.7, 11.9 and 33.8 per cent, respectively, in patients with compensated cirrhosis; and 93.6, 3.6 and 40 per cent, respectively, in patients with decompensated cirrhosis. Body mass index of >25 kg/m2 was protective for bone health. Interpretation & conclusions: VDD and low-BMD is prevalent in Indian patients with cirrhosis and should be looked for in patients with cirrhosis for its prevention.

… Introduction: Vitamin D supplementation is recommended for osteoporosis with chronic liver disease, … Despite widespread use of Vitamin D supplementation, its clinical efficacy in …

… denosumab and bisphosphonates for osteoporosis in tenofovir-exposed chronic hepatitis B … increased BMD in patients with autoimmune liver disease [23]. Although a few case reports …

Background: Osteoporosis is a common complication in patients with primary biliary cholangitis (PBC). This study aimed to compare the efficacy and safety of denosumab and zoledronic acid (ZOL) in treating osteoporosis in PBC patients. Methods: This multicenter, randomized, open-label trial enrolled Japanese patients with PBC and osteoporosis. Patients were randomized to receive either subcutaneous denosumab 60 mg every 6 months (denosumab group) or i.v. zoledronic acid 5 mg yearly (ZOL group). The primary endpoint was the mean percent change in bone mineral density (BMD) at the lumbar spine and total hip from baseline to 12 months. Results: Of 47 enrolled patients, 41 (87.2%) completed the study (denosumab: n=21; ZOL: n=20). At 12 months, lumbar spine BMD increased by 7.5% in the denosumab group and 6.4% in the ZOL group, demonstrating the non-inferiority of denosumab (95% CI: −1.6% to 3.8%). Although the total hip BMD increased more in the denosumab group than in the ZOL group (5.0% vs. 2.6%, p<0.01), the difference did not meet the predefined non-inferiority margin (95% CI: −1.3% to 6.2%). Serum ALP to upper limit of normal ratio and bone turnover markers significantly decreased in both groups; however, the rates of change were not significantly different between them. The incidence of adverse events was significantly lower in the denosumab group compared with the ZOL group (14.3% vs. 50.0%, p=0.013). Conclusions: Denosumab is a safe and effective treatment option for osteoporosis in patients with PBC.