What is renal osteodystrophy?

Renal Osteodystrophy: A Comprehensive Overview

Renal osteodystrophy is a complex bone disorder characterized by abnormal bone metabolism that occurs as a result of chronic kidney disease, manifesting as various patterns of skeletal abnormalities including high-turnover and low-turnover bone disease, which significantly impacts morbidity, mortality, and quality of life. 1, 2

Definition and Classification

• Renal osteodystrophy refers specifically to the bone pathology component of the broader Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD) syndrome 3
• It encompasses several bone disorders that develop as kidney function deteriorates, typically beginning when GFR falls below 60 mL/min/1.73 m² (CKD Stage 3) 4
• Bone biopsy remains the gold standard for diagnosis and classification of renal osteodystrophy 1, 4

Types of Renal Osteodystrophy

Renal osteodystrophy includes several distinct bone conditions:

• High-turnover bone disease (osteitis fibrosa): Characterized by increased osteoclastic and osteoblastic activity and elevated PTH levels 2, 5
• Low-turnover bone disease (adynamic bone disease): Characterized by suppressed bone formation with various degrees of bone resorption and low or nearly normal PTH levels 2, 6
• Osteomalacia: Characterized by defective mineralization of osteoid tissue, often associated with vitamin D deficiency, hypophosphatemia, or aluminum toxicity 2, 6
• Mixed uremic osteodystrophy: Characterized by various degrees of mineralization defect and hyperparathyroid bone changes 6, 7

Pathophysiology

The development of renal osteodystrophy involves several key mechanisms:

• Phosphate retention due to decreased renal clearance 5, 8
• Decreased production of active vitamin D (calcitriol) by the kidneys 9, 8
• Hypocalcemia resulting from decreased intestinal calcium absorption 9, 8
• Secondary hyperparathyroidism due to the above factors 5, 10
• Reduced numbers of vitamin D receptors and calcium sensors in the parathyroid gland 5
• Skeletal resistance to the calcemic action of PTH 5
• Altered bone microarchitecture with trabecular and cortical deterioration 2

Clinical Manifestations

• Increased risk of fractures compared to the general population 2, 4
• Bone pain and skeletal deformities 10
• Extraskeletal calcification, particularly vascular calcification 3
• Increased cardiovascular morbidity and mortality 8, 3

Diagnostic Approach

Laboratory Assessment

• Monitor serum levels of calcium, phosphate, PTH, and alkaline phosphatase beginning in CKD G3a 4
• Frequency of monitoring should be based on CKD stage 4
• Treatment decisions should be based on trends in laboratory values rather than single abnormal results 1, 4

Imaging Studies

• Dual-energy X-ray absorptiometry (DXA) BMD testing is recommended for patients with CKD G3a-G5D if results will impact treatment decisions 1, 4
• Lateral abdominal radiograph can detect vascular calcification 4

Bone Biopsy

• Remains the gold standard for diagnosis and classification of renal osteodystrophy 1, 7
• Should be considered if knowledge of the type of renal osteodystrophy will impact treatment decisions 1
• Quantitative bone histomorphometry with double tetracycline labeling is used for evaluation 6, 7

Management Approach

Treatment of renal osteodystrophy should be based on serial assessments of phosphate, calcium, and PTH levels, considered together 1, 4:

Phosphate Management

• Lower elevated phosphate levels toward the normal range 1, 4
• Consider dietary phosphate restriction, phosphate binders, and intensified dialysis for G5D patients 4
• Limit use of calcium-based phosphate binders in patients with hyperphosphatemia 4

Calcium Management

• Maintain serum calcium levels within the normal range 1
• Avoid hypercalcemia in all GFR categories of CKD 4

PTH Management

• Treat patients with PTH values that are progressively increasing or persistently above the upper limit of normal 4
• For patients not on dialysis, avoid routine use of calcitriol or vitamin D analogues due to increased risk of hypercalcemia 4
• For patients on dialysis, calcimimetics, calcitriol, and vitamin D analogues are acceptable first-line options 4, 9

Acidosis Management

• Treat metabolic acidosis to improve bone health by reducing bone resorption 4
• Maintain serum levels of total CO2 >22 mEq/L (22 mmol/L) 6

Monitoring and Follow-up

• Regularly assess response to therapy with laboratory monitoring of mineral metabolism parameters 4
• Continue monitoring BMD in patients receiving treatment for CKD-associated osteoporosis 4
• Base treatment on trends in laboratory values rather than single abnormal results 1, 4

Modern Perspective

The approach to renal osteodystrophy has evolved to recognize it as part of the broader CKD-MBD syndrome 2, 3:

• Current terminology includes "CKD-associated osteoporosis" to acknowledge the global impact of kidney disease on bone strength 2
• Management strategies must be tailored to the specific bone quality impairments in each individual 2
• Treatment should focus on improving morbidity, mortality, and quality of life outcomes 2, 8