The aim of treatment is to improve symptoms and reduce corrected calcium level to within the normal range and, if possible, treating the underlying disease. Effective treatments reduce serum calcium by inhibiting bone resorption, increasing urinary calcium excretion, or decreasing intestinal calcium absorption.r The timing and type of treatment are dependent on the severity of the hypercalcaemia and associated symptoms.
It is also important to review the patient’s other medications and consider discontinuing or dose reducing (if appropriate) any medications that may be contributing to hypercalcaemia (e.g., thiazide diuretics, calcitriol, calcium supplementation, antacids, lithium).
Symptomatic hypercalcaemia requires prompt and often inpatient management with intravenous rehydration and administration of a bisphosphonate.
Patients with HCM are volume depleted as a result of impaired renal concentrating ability and decreased oral intake. The dehydration leads to a reduction in the glomerular filtration rate that further reduces the ability of the kidney to excrete the excess serum calcium. Rehydration reverses this situation and is a critical component of therapy.
Intravenous sodium chloride 0.9% is recommended, with the rate and duration dependent on the patient’s volume, cardiovascular and renal status.r Volumes and times should be determined by the treating clinician, and local institutional policy should be followed. For acute severe hypercalcaemia a reasonable infusion rate for an adult is:
- sodium chloride 0.9% 4 to 6 litres by intravenous infusion over 24 hours.r
- Monitor for fluid overload if renal impairment or elderly.
- Loop diuretics rarely used and only if fluid overload develops; not effective for reducing serum calcium.r If loop diuretics are used, other electrolytes e.g. potassium and phosphate need to be monitored and replaced.
- Monitor serum calcium response – with nadir reached at 2 to 4 days.
- May need to consider dialysis if severe renal failure.
Intravenous bisphosphonates are used because they have a faster onset of action and the burden of treatment is more favourable than with oral bisphosphonates. The choice of bisphosphonate may be determined by local policy i.e. either zoledronic acid or pamidronate. However, zoledronic acid may be more favourable as it is more potent than pamidronate and can be administered over a shorter time period (15 minutes compared with two hours).
- Bisphosphonates can cause nephrotoxicity, adequate hydration can enhance renal protection.
- In patients with renal impairment, bisphosphonates may be contraindicated or dose adjustments may be required. Refer to product information for detail.
- Monitor serum calcium response – maximum effect occurs at 2 to 4 days. For pamidronate, if plasma calcium does not decrease within 48 hours, further treatments may be given.r For zoledronic acid, dose may be repeated after at least 7 days in patients who are refractory to initial treatment or who subsequently relapse.r
- Can cause hypocalcaemia if vitamin D deficiency or suppressed PTH.
Denosumab is a RANKL monoclonal antibody which inhibits osteoclast activation and function. It may be an option for patients with hypercalcemia that is refractory to zoledronic acid or in whom bisphosphonates are contraindicated due to severe renal impairment. Regular monitoring of calcium is important as the risk of hypocalcaemia is high, particularly in patients with reduced renal function.
Calcitonin blocks osteoclast activity and also renal tubular reabsorption of calcium. Calcitonin effect is rapid, usually within a few hours of first administration. Clinical use is limited by the transient effect and development of tolerance within days of use. Because of its limited duration of effect, calcitonin is most beneficial in symptomatic patients with severe hypercalcemia i.e. serum calcium > 3.5 mmol/L, when combined with hydration and bisphosphonates. Calcitonin and hydration provide a rapid reduction in serum calcium concentration, while a bisphosphonate provides a more sustained effect.
No dose adjustments are required in patients with renal insufficiency. In Australia, calcitonin is available as salcatonin.
Corticosteroids can be given, but may only be useful where hypercalcaemia is due to sarcoidosis, lymphoma or vitamin D intoxication or multiple myeloma. Additionally they often take several days (~ 2-4 days) to achieve the desired effect.