Management of Adynamic Bone Disease in Chronic Kidney Disease
Adynamic bone disease (ABD) in chronic kidney disease should be treated by allowing plasma levels of intact PTH to rise in order to increase bone turnover, primarily by decreasing or eliminating calcium-based phosphate binders and vitamin D therapy. 1
Diagnosis of Adynamic Bone Disease
ABD is characterized by:
- Low bone turnover
- Low bone volume
- Normal mineralization
- Markedly decreased cellularity with minimal or no fibrosis 2
Diagnostic criteria:
- Gold standard: Bone biopsy showing decreased bone formation rate, low cellularity, and normal or decreased osteoid thickness 3
- Laboratory indicators:
Management Algorithm
Step 1: Reduce or Eliminate Calcium Load
- Decrease doses of calcium-based phosphate binders 1
- Consider switching to non-calcium containing phosphate binders, especially in patients with hypercalcemia 5
- Monitor calcium-phosphorus product closely (goal: <55 mg²/dL²) 5
Step 2: Adjust Vitamin D Therapy
- Reduce or eliminate vitamin D therapy to allow PTH levels to rise 1
- Discontinue vitamin D therapy if corrected total calcium exceeds 10.2 mg/dL 5
Step 3: Consider Dialysate Calcium Adjustment
- Lowering dialysate calcium (1.0 to 2.0 mEq/L) may be considered to stimulate PTH secretion 1
- Note: This approach should be considered experimental and used with caution 1
Step 4: Monitor PTH and Bone Markers
- Target intact PTH levels: Allow to rise above 100 pg/mL 1
- For optimal bone formation rate, maintain PTH between one and three times the upper limit of normal 3
- Monitor bone alkaline phosphatase as a marker of treatment response 1, 4
- Continue treatment until clinical indicators of ABD normalize 1
Step 5: Consider Advanced Therapies for Refractory Cases
- For patients with persistently low BMD despite conventional management, teriparatide (PTH1-34) may be considered as an experimental approach 6
- Small pilot studies have shown improvement in lumbar spine BMD with teriparatide 20 μg/day subcutaneously 6
Clinical Implications and Complications
ABD is associated with significant complications:
- Increased risk of fractures (4-fold increase in hip fracture risk compared to general population) 1
- Hypercalcemia due to impaired bone buffering capacity 1
- Increased risk of vascular calcification 2
- Potentially increased mortality 2
Monitoring Parameters
- Serum calcium and phosphorus: Every 3 months 5
- Intact PTH: Regular monitoring to ensure levels rise appropriately 1
- Bone alkaline phosphatase: To assess treatment response 1, 4
- Bone mineral density: Consider in patients with high fracture risk 5
Pitfalls and Caveats
Cinacalcet Warning: Avoid calcimimetics like cinacalcet in ABD as they can worsen the condition by further suppressing PTH. The FDA label specifically warns that adynamic bone disease may develop if iPTH levels are suppressed below 100 pg/mL 7
Aluminum Exposure: Ensure patients are not exposed to aluminum-containing phosphate binders, as aluminum overload can cause or worsen ABD 1, 3
PTH Resistance: In uremia, bone tissue may be resistant to PTH, requiring relatively higher PTH levels to maintain normal bone turnover 8
Diagnostic Challenges: While low PTH strongly suggests ABD, some histological studies have found adynamic bone despite PTH values well above 400 pg/mL, possibly due to PTH assay limitations 1
Risk Factors: Be vigilant in patients with diabetes, advanced age, and those on peritoneal dialysis, as these factors increase ABD risk 2
By following this management approach, clinicians can effectively address adynamic bone disease, potentially reducing fracture risk and improving bone health in patients with chronic kidney disease.