教育演講9:副甲狀腺功能亢進的診斷與治療
       Hyperparathyroidism, Diagnosis and Treatment

程 序 表

E9-4
慢性腎臟病骨病變
Renal Osteodystrophy
盧國城
台北慈濟腎臟科

  Patients with chronic kidney disease (CKD) often develop “chronic kidney disease-mineral and bone disorder” (CKD-MBD). This systemic CKD-related syndrome is manifested by complex abnormalities in bone and mineral metabolism—including bone lesions referred to as renal osteodystrophy (ROD)—and/or extraskeletal calcification. Disruptions in mineral metabolism and bone microarchitecture occur early in the course of CKD, typically beginning with a high bone turnover rate resulting from secondary hyperparathyroidism (SHPT). The condition worsens with the progressive decline in kidney function, as the high bone turnover leads to reduced bone mineral density (BMD) during chronic renal failure. Patients with SHPT exhibit preferential loss of cortical bone (e.g., the distal radius and the femoral neck), often with preserved or slightly increased cancellous bone (e.g., the lumbar spine). Several factors impact the progression of CKD-MBD. In CKD stages 3 and 4, patients with diabetes have lower cortical bone BMD when compared with nondiabetic patients. Calcium load also has a negative impact on the progression of vascular calcification in dialysis patients with adynamic bone disease. Low bone volume is associated with increased coronary calcifications in patients on dialysis, with the degree of risk depending on the patient’s age and dialysis duration. Regular treatments with heparin or anti-platelet drugs also impact BMD in hemodialysis (HD) patients. Low BMD is a major risk factor for hip fracture, and this risk is exacerbated in patients undergoing peritoneal dialysis (PD), who show a significant reduction in cortical BMD. Following kidney transplantation, the greatest rates of bone loss and increased fracture rates are observed in the first 6-18 months, caused by both pre-transplantation bone disease and immunosuppressive therapy. Various medical treatments for SHPT can improve bone mass. Patients with refractory SHPT may require a parathyroidectomy (PTX), which provides marked, sustained improvements in BMD. Markers of bone turnover can predict how PTX will change BMD. Renal osteodystrophy can’t be assessed by BMD measurements alone; the gold standard for ROD diagnosis is based on histomorphological changes revealed by bone biopsy. However, because of technical difficulties and a lack of testing facilities, it is often more convenient to use several serum bone markers to measure changes in bone turnover. The combined use of BMD and marker measurements may be a valuable approach in clinical practice.
  Low 25(OH)D levels are common in chronic kidney disease (CKD) patients and are implicated in all-cause mortality and morbidity risks. Furthermore, the progression of CKD is accompanied by a gradual decline in 25(OH)D production. Vitamin D deficiency in CKD causes skeletal disorders, such as osteoblast or osteoclast cell defects, bone turnover imbalance, and deterioration of bone quality, and nonskeletal disorders, such as metabolic syndrome, hypertension, immune dysfunction, hyperlipidemia, diabetes, and anemia. Extra-renal organs possess the enzymatic machinery for converting 25(OH)D to 1,25(OH)2D, which may play considerable biological roles beyond the traditional roles of vitamin D. Pharmacological 1,25(OH)2D dose causes hypercalcemia and hyperphosphatemia as well as adynamic bone disorder, which intensifies vascular calcification. Conversely, native vitamin D supplementation reduces the risk of hypercalcemia and hyperphosphatemia, which may play a role in managing bone and cardio–renal health and ultimately reducing mortality in CKD patients. Nevertheless, the combination of native vitamin D and active vitamin D can enhance therapy benefits of secondary hyperparathyroidism because of extra-renal 1α-hydroxylase activity in parathyroid gland.
  The underlying mechanisms of bone loss and fractures in CKD patients are complex and remain unresolved. In contrast to bone biopsy, recently available noninvasive investigative measures for detecting both bone quantity and quality losses are still clinically unavailable as screening or diagnosing techniques. Bone-targeted pharmacotherapy was revealed to minimally affect the incidence of fractures and is associated with adverse effects in this specific population. Individualized therapy, including vitamin D supplementation, phosphate control, anti-resorptive agent use, dialysis, and medical and surgical PTX, might benefit these patients. Researchers should investigate the mechanisms of and targeted therapy for both qualities- and quantity-related bone loss in CKD patients.