The relationship between prior cinacalcet therapy and the course of hungry bone syndrome in patients who underwent surgery for secondary hyperparathyroidism

Introduction. Hypocalcaemia, including hungry bone syndrome (HBS) after parathyroidectomy (PTE), is associated with adverse outcomes, yet its prevention is often inadequate. We evaluated whether preoperative cinacalcet therapy reduces the risk severe postoperative hypocalcemia.

Methods. A retrospective, single-center study (2011-2019) included 713 patients. The primary endpoint was of hypocalcemia, defined as an ionized calcium (Ca²⁺) level below 0.9 mmol/L on day 2 or 3 after PTE. Secondary endpoints included the need for intravenous calcium supplementation and length of hospital stay (<7 days vs. ≥7 days).

Results. Preoperative median parathyroid hormone (PTH) was 1.247 pg/L [910-1.871], mean total serum calcium was 2.47 mmol/L (±0.22), ionized calcium was 1.23 mmol/l (±0.13), and alkaline phosphatase was IU/L 188 [128-491]. HBS was detected in 68.4% [95% CI 64.6-71.9] of patients. The median minimum Ca²⁺ level on postoperative days 2-3 was 0.73 mmol [0.64-0.82] in patients with HBS versus 1.02 mmol [0.95-1.1] in those without HBS (p<0.001). ROC analysis using total calcium to detect HBS showed a sensitivity of 85.7% [95CI 80%-88%] and specificity of 97.6 [93-99%] at a cutoff of <1.78 mmol, with an AUC of 0.96 [95%CI 093-0.99]. Cinacalcet was used preoperatively in 32% of patients at doses of 30 mg/day (n=101), 60 mg/d (n=66), 90 mg (n=22) or more (n=2). In a multivariable logistic analysis, HBS development was not associated with cinacalcet use but it was associated with baseline PTH (24% higher HBS risk of per 100 pg/ml increase) and with Ca²⁺ (43% lower risk per 0.1 mmol/l increase). In the multivariable regression, cinacalcet use was independently associated with shorter hospital stay (36% risk reduction). Patients receiving ≥60 mg/day of cinacalcet were more likely to require intravenous more than 10 grams of intravenous calcium (p=0.005).

Conclusion: Preoperative cinacalcet therapy was not associated with the frequency of biochemical HBS, as defined by the minimum Ca2+ level. However, prior cinacalcet risk use was associated with shorter hospital stay, which may serve as a surrogate marker of lower HBS severity.

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