From the Guidelines
The underlying mechanism of immobilization-associated hypercalcemia is increased bone resorption due to lack of mechanical stress on the skeleton, as supported by the most recent guidelines from the National Comprehensive Cancer Network (NCCN) 1. When a person is immobilized for an extended period, the absence of weight-bearing and muscle activity leads to accelerated bone breakdown. Osteoclasts, the cells responsible for bone resorption, become more active, while osteoblasts, which form new bone, decrease their activity. This imbalance results in a net release of calcium from the bones into the bloodstream, causing hypercalcemia. Key points to understand:
- Onset: Hypercalcemia typically develops within weeks to months of immobilization.
- Risk factors: Individuals with pre-existing high bone turnover (e.g., adolescents, patients with Paget's disease) are at higher risk.
- Prevention and management:
- Early mobilization when possible
- Adequate hydration
- Bisphosphonates (e.g., zoledronic acid 4 mg IV) may be used in severe cases to inhibit bone resorption, as recommended by the NCCN Panel members 1
- Calcitonin can provide rapid but short-term reduction in serum calcium
- Monitoring: Regular serum calcium checks are important for immobilized patients, especially those at high risk. Understanding this mechanism is crucial for healthcare providers to anticipate, prevent, and manage hypercalcemia in immobilized patients, particularly in settings such as intensive care units or long-term care facilities. The NCCN guidelines also emphasize the importance of treating hypercalcemia with hydration, bisphosphonates, denosumab, steroids, and/or calcitonin 1.
From the Research
Underlying Mechanism of Hypercalcemia Associated with Immobilization
The underlying mechanism causing hypercalcemia associated with immobilization is attributed to an increase in bone resorption and diminished bone formation, characterized clinically by elevated serum calcium levels, hypercalciuria, increased risk of urinary lithiasis, and renal failure 2.
Key Factors Contributing to Hypercalcemia
- Decreased mechanical loading from prolonged bedrest tends to increase osteoclast-induced bone resorption while promoting osteocytes to secrete proteins such as sclerostin to reduce osteoblast-mediated bone formation 3.
- A dysregulation between bone resorption and formation is central to the pathogenesis of this disease 3.
- Increased rates of bone resorption, as shown by elevated urinary hydroxyproline/creatinine ratios and elevated calcium/creatinine ratios, contribute to the development of hypercalcemia 4.
- Sepsis may also contribute to the development of hypercalcemia by leading to cytokine release, which in turn affects bone resorption and formation 4.
Pathophysiology
The pathophysiology of immobilization hypercalcemia indicates that increased bone resorption is primarily responsible for the disorder 5. Normal levels of PTH acting with increased activity in the abnormal environment of immobilized bone may also contribute to the development of hypercalcemia 6.
Clinical Implications
Understanding the underlying mechanism of hypercalcemia associated with immobilization is crucial for the development of effective treatment strategies, which may include the use of calcitonin, glucocorticoids, pamidronate, and denosumab to inhibit bone resorption and prevent further complications 2, 3, 4, 5.