What is the management of adynamic bone disease?

From the Guidelines

The management of adynamic bone disease primarily focuses on reducing oversuppression of parathyroid hormone (PTH) and stimulating bone turnover. First, reduce or discontinue vitamin D analogs and calcimimetics that suppress PTH, as suggested by the K/DOQI clinical practice guidelines for bone metabolism and disease in chronic kidney disease 1. Lower the calcium concentration in dialysate to 2.5 mEq/L for hemodialysis patients to stimulate PTH secretion, as recommended by the guidelines 1. Decrease or stop calcium-based phosphate binders and switch to non-calcium binders like sevelamer or lanthanum. Target a higher PTH level (150-300 pg/mL) to promote bone turnover, as suggested by the guidelines 1. Some key points to consider in the management of adynamic bone disease include:

• Limit aluminum exposure by avoiding aluminum-containing medications and ensuring proper water purification for dialysis, as aluminum toxicity can worsen bone disease 1.
• Consider reducing the dose of or discontinuing bisphosphonates if they're being used, as they can suppress bone turnover.
• Monitor serum calcium, phosphorus, and PTH levels regularly to guide therapy adjustments.
• For severe cases with fractures, teriparatide (recombinant PTH 1-34) may be considered to stimulate bone formation, though evidence in dialysis patients is limited 1.
• Physical activity should be encouraged to improve bone strength. This approach aims to restore the balance of bone formation and resorption by allowing appropriate PTH activity, which is essential for normal bone remodeling in patients with chronic kidney disease. It is also important to note that bone biopsy may be necessary in some cases to diagnose adynamic bone disease, especially when serum PTH levels are between 100 and 500 pg/mL (11.0 to 55.0 pmol/L) and there are symptoms such as hypercalcemia, bone pain, or increased bone alkaline phosphatase activity 1.

From the FDA Drug Label

Adynamic bone disease may develop if iPTH levels are suppressed below 100 pg/mL. One clinical study evaluated bone histomorphometry in patients treated with cinacalcet for 1 year. Three patients with mild hyperparathyroid bone disease at the beginning of the study developed adynamic bone disease during treatment with cinacalcet Two of these patients had iPTH levels below 100 pg/mL at multiple time points during the study. In three 6-month, phase 3 studies conducted in patients with CKD on dialysis, 11% of patients treated with cinacalcet had mean iPTH values below 100 pg/mL during the efficacy-assessment phase If iPTH levels decrease below 150 pg/mL in patients treated with cinacalcet, the dose of cinacalcet and/or vitamin D sterols should be reduced or therapy discontinued.

The management of adynamic bone disease involves reducing or discontinuing cinacalcet and/or vitamin D sterols if iPTH levels decrease below 150 pg/mL to prevent further suppression of iPTH levels below 100 pg/mL 2.

• Key steps in managing adynamic bone disease include:
  • Monitoring iPTH levels closely
  • Adjusting the dose of cinacalcet and/or vitamin D sterols as needed
  • Discontinuing therapy if necessary to prevent adynamic bone disease.

From the Research

Management of Adynamic Bone Disease

The management of adynamic bone disease (ABD) is crucial to prevent its complications, such as increased risk of fracture and vascular calcification. The following are some key points to consider:

• Overcoming the insufficient osteoanabolic stimulation in ABD is the ultimate treatment goal 3
• The relationship between low PTH level, ABD, increased risk fracture, and vascular calcifications may at least partially explain the association of ABD with increased mortality rates 3
• Reducing calcium and vitamin D load to restore parathyroid activity is a potential therapeutic approach for patients with ABD 4
• Anabolic treatment has been suggested to improve turnover and bone mass in patients with advanced CKD and low bone turnover, although uncertainty about safety remains 5

Risk Factors and Prevention

Several risk factors have been linked to ABD, including:

• Calcium loading 3, 6, 4
• Ageing 3, 6
• Diabetes 3, 6
• Hypogonadism 3
• Parathyroidectomy 3
• Peritoneal dialysis 3, 6
• Antiresorptive therapies 3, 5 Prevention of ABD is essential, especially in patients with diabetic, white, and elderly populations 3

Diagnosis and Treatment

The gold standard for precise diagnosis of ABD is histomorphometric analysis of tetracycline double-labeled bone biopsies 3

• ABD is characterized by low bone turnover, low bone volume, normal mineralization, and markedly decreased cellularity with minimal or no fibrosis 3
• Differentiating the causes of adynamic bone in advanced chronic kidney disease informs osteoporosis treatment 5
• The use of antiresorptive agents in advanced CKD has been limited by the lack of large clinical trials and fear of causing kidney dysfunction and adynamic bone disease 5