How to diagnose and treat Chronic Kidney Disease (CKD) with Bone Mineral Density (BMD) issues?

Diagnosis and Treatment of CKD-MBD (Chronic Kidney Disease-Mineral and Bone Disorder)

For patients with CKD G3a-G5D with bone mineral density issues, diagnosis should include biochemical assessment, imaging studies, and possibly bone biopsy, while treatment should be based on serial assessments of phosphate, calcium, and PTH levels considered together, with medication choices accounting for the magnitude and reversibility of biochemical abnormalities. 1

Diagnostic Approach

Biochemical Assessment

• Monitor serum levels of calcium, phosphate, PTH, and alkaline phosphatase activity beginning in CKD G3a 1
• Frequency of monitoring should be based on CKD stage:
  • CKD G3a-G3b: calcium and phosphate every 6-12 months; PTH based on baseline level and CKD progression 1
  • CKD G4: calcium and phosphate every 3-6 months; PTH every 6-12 months 1
  • CKD G5/G5D: calcium and phosphate every 1-3 months; PTH every 3-6 months 1
• Alkaline phosphatase activity should be monitored every 12 months in CKD G4-G5D, or more frequently with elevated PTH 1
• Treatment decisions should be based on trends in PTH levels rather than single values 1

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
• DXA BMD predicts fractures across the spectrum of CKD severity, including CKD G3a to G5D 1
• Lateral abdominal radiograph can detect vascular calcification, and echocardiogram can detect valvular calcification 1
• Thoracic/lumbar spine films may be used to assess for fractures 1

Bone Biopsy

• Bone biopsy remains the gold standard for diagnosis and classification of renal osteodystrophy 1
• Consider bone biopsy if knowledge of the type of renal osteodystrophy will impact treatment decisions 1
• No longer a prerequisite for initiation of antiresorptive therapies in patients with CKD G3a-G4 1

Treatment Approach

General Principles

• Base treatment on serial assessments of phosphate, calcium, and PTH levels, considered together 1
• Consider the magnitude and reversibility of biochemical abnormalities when selecting treatments 1
• Treatment choices should take into account potential adverse effects (e.g., antiresorptives may exacerbate low bone turnover, denosumab may cause hypocalcemia) 1

Management of Mineral Metabolism

Phosphate Management

• Suggest lowering elevated phosphate levels toward the normal range 1
• Focus treatment on patients with overt hyperphosphatemia rather than maintaining normal phosphate levels in non-dialysis patients 1
• Consider dietary phosphate restriction, phosphate binders, and intensified dialysis (for G5D patients) 1
• Limit use of calcium-based phosphate binders in patients with hyperphosphatemia 1, 2
• Avoid long-term use of aluminum-containing phosphate binders 1

Calcium Management

• Avoid hypercalcemia in all GFR categories of CKD 1
• Avoid inappropriate calcium loading whenever possible 1, 2
• Personalize calcium recommendations based on the patient's mineral metabolism status and overall calcium balance 2

PTH Management

• Treat patients with PTH values that are progressively increasing or persistently above the upper limit of normal 1
• Do not base treatment on a single elevated value 1
• For patients not on dialysis: avoid routine use of calcitriol or vitamin D analogues due to increased risk of hypercalcemia 1
• For patients on dialysis: calcimimetics, calcitriol, and vitamin D analogues are acceptable first-line options 1

Treatment of CKD-Associated Osteoporosis

Antiresorptive Therapy

• Consider antiresorptive agents (bisphosphonates, denosumab) for patients with CKD G3a-G4 with low BMD 3
• Post-hoc analyses of clinical trials found comparable efficacy of these drugs in improving BMD and reducing fracture risk in individuals with moderate reductions of GFR 3
• For patients at high risk for fracture, facilities lacking ability to perform bone biopsy should not withhold antiresorptive therapy 1

Vitamin D Supplementation

• Consider low-dose active vitamin D supplementation to help control PTH 2
• Monitor for hypercalcemia when using vitamin D supplementation 2

Acidosis Correction

• Treat metabolic acidosis (e.g., with sodium bicarbonate) to improve bone health by reducing bone resorption 2

Monitoring and Follow-up

• Regularly assess response to therapy with laboratory monitoring of mineral metabolism parameters 2
• Continue monitoring BMD in patients receiving treatment for CKD-associated osteoporosis 1
• Assess for fracture risk regularly, as patients with CKD have elevated risk of fractures 4

Important Considerations and Pitfalls

• Avoid overtreatment of secondary hyperparathyroidism, as low bone turnover can result from excessive PTH suppression 2
• Recognize that therapeutic interventions aimed at improving one parameter often have unintended effects on others 1
• Low BMD in CKD patients is associated with poor renal outcomes, highlighting the importance of proper management 4
• Physical activity may be beneficial, as low physical activity is associated with low BMD in CKD patients 4
• Bone disease in CKD is complex with overlapping features of renal osteodystrophy and other forms of osteoporosis 1