What is the best approach for an 86-year-old patient with hyperthyroidism, hypercalcemia, osteopenia of the forearm, congestive heart failure (CHF), and chronic kidney disease (CKD): Denosumab or Cinacalcet (Cinacalcet hydrochloride)?

From the Guidelines

For an 86-year-old patient with hyperthyroidism, hypercalcemia, osteopenia of the forearm, congestive heart failure (CHF), and chronic kidney disease (CKD), denosumab would generally be the preferred approach over cinacalcet. Denosumab (Prolia) is administered as a 60mg subcutaneous injection every 6 months and does not require dose adjustment for kidney function, making it particularly suitable for patients with CKD 1. This medication works by inhibiting RANK ligand, which reduces bone resorption and helps address both the osteopenia and hypercalcemia. In contrast, cinacalcet primarily targets hypercalcemia associated with parathyroid disorders but doesn't directly address the bone loss. Additionally, cinacalcet requires careful dose titration, may cause gastrointestinal side effects, and could potentially worsen heart failure symptoms through electrolyte disturbances. Before starting denosumab, ensure the patient has adequate vitamin D levels and consider calcium supplementation if dietary intake is insufficient, while monitoring for hypocalcemia which can occur after administration 1. The underlying hyperthyroidism should also be addressed simultaneously, as treating this condition may help improve both the hypercalcemia and cardiac status. Key considerations in this decision include the patient's advanced age, the presence of CKD, and the need to balance the treatment of hypercalcemia with the potential for adverse effects on bone health and cardiovascular status. The choice between denosumab and cinacalcet should be guided by the individual patient's clinical profile, including the severity of hyperparathyroidism, the presence of bone disease, and the risk of cardiovascular events. Given the potential for cinacalcet to have limited benefits and significant side effects in patients with CKD, as noted in studies such as the EVOLVE trial 1, denosumab may offer a more favorable risk-benefit profile for this patient. Ultimately, the decision should be made in consultation with a healthcare provider, taking into account the latest clinical guidelines and the patient's unique needs and circumstances.

From the FDA Drug Label

Cinacalcet tablet is a positive modulator of the calcium sensing receptor indicated for: • Secondary Hyperparathyroidism (HPT) in adult patients with chronic kidney disease (CKD) on dialysis. • Hypercalcemia in adult patients with Parathyroid Carcinoma (PC). • Hypercalcemia in adult patients with primary HPT for whom parathyroidectomy would be indicated on the basis of serum calcium levels, but who are unable to undergo parathyroidectomy.

The patient has hypercalcemia, hyperthyroidism, osteopenia, CHF, and CKD.

• Cinacalcet is indicated for hypercalcemia in patients with Parathyroid Carcinoma or primary HPT.
• However, the patient's hyperthyroidism and osteopenia are not directly addressed by cinacalcet.
• Denosumab is not mentioned in the provided drug labels, so its use cannot be directly evaluated based on this information.
• Given the patient's complex medical conditions, including CKD and CHF, caution should be exercised when considering any new medication, especially one that can lower serum calcium levels, such as cinacalcet.
• The patient's CKD is not specified as being on dialysis, which is a crucial factor for cinacalcet use, as it is not indicated for patients with CKD not on dialysis due to an increased risk of hypocalcemia 2. The FDA drug label does not answer the question.

From the Research

Treatment Options for Hyperthyroidism and Hypercalcemia

• The patient's condition involves hyperthyroidism, hypercalcemia, osteopenia, congestive heart failure (CHF), and chronic kidney disease (CKD), making treatment challenging.
• Two potential treatment options are denosumab and cinacalcet, both of which have been studied in the context of hypercalcemia and bone disease.

Cinacalcet as a Treatment Option

• Cinacalcet has been shown to be effective in reducing serum calcium levels in patients with primary hyperparathyroidism 3, 4.
• It works by increasing the sensitivity of parathyroid calcium-sensing receptors to extracellular calcium, thereby reducing parathyroid hormone (PTH) secretion.
• Studies have demonstrated that cinacalcet can normalize serum calcium levels in most patients, although it may only modestly reduce PTH levels 3.
• Additionally, cinacalcet has been shown to reduce the size of parathyroid adenomas in patients with primary hyperparathyroidism 5.

Denosumab as a Treatment Option

• There is limited information available on the use of denosumab in the context of hyperthyroidism and hypercalcemia.
• However, denosumab is a monoclonal antibody that inhibits RANKL, a protein involved in bone resorption, and is used to treat osteoporosis and other bone diseases.

Comparison of Treatment Options

• Cinacalcet may be a more suitable option for this patient, given its ability to reduce serum calcium levels and PTH secretion, as well as its potential to reduce the size of parathyroid adenomas.
• However, the patient's CKD and CHF may affect the efficacy and safety of cinacalcet, and careful monitoring of renal function and calcium levels would be necessary.
• Denosumab may also be considered, but its use in this context would be off-label, and more research would be needed to determine its safety and efficacy in patients with hyperthyroidism and hypercalcemia.

Additional Considerations

• The patient's hyperthyroidism would need to be managed concurrently with treatment for hypercalcemia and osteopenia.
• The use of cinacalcet or denosumab would require careful monitoring of the patient's condition, including regular measurements of serum calcium, PTH, and renal function 6, 7.