Endocrine Abstracts

Context: Patients with primary hyperparathyroidism (PHPT) may be treated with denosumab due to coexisting osteoporosis. Few studies have been conducted in this population.

Case presentation: An 84-year-old woman was seen in the outpatient clinic in March 2018 due to calcium levels at the upper limit of reference range (10,2 mg/dl) associated with elevated levels of PTH (112 pg/ml) and sufficient 25(OH)Vit D (24 ng/ml) levels, findings consistent with mild PHPT. Her past medical history included: osteoporosis with vertebral fractures (T11 and T12 vertebral bodies) since 2009, hystero-annexectomy in 1973, quadrantectomy for breast carcinoma in 2009, bowel resection for adenocarcinoma in 2008, prior ischemic stroke, prior gastric ulcer treated with gastrectomy and current jejunum ulcer. The patient had been on Alendronate 70 mg weekly since 2008 and taking 1100 IU of vitamin D3, and furosemide 25 mg/day. Patient’s biochemistries were rechecked after three months: PTH was 61 pg/ml (12–88 pg/ml), serum Ca 11.3 mg/dl, serum phosphate 2.6 mg/dl, CTX 0.809 ng/ml. Due to age and comorbidities, the patient was not a good candidate for parathyroid surgery. Alendronate was stopped and denosumab 60 mg q6m was prescribed, the patient being evaluated every six months. In December 2020, a 2-cm area of active osteonecrosis appeared in the right mandibular region. Denosumab was promptly interrupted. To avoid potential rebound hypercalcemia the patient was immediately switched to cinacalcet at an initial dose of 30 mg per day, then increased at 60 mg per day after a few months, while checking serum calcium levels every 3 to 6 months, with safe control of serum calcium, PTH and overall symptoms.

Discussion: Denosumab is effective in improving BMD, lowering bone turnover and serum calcium in patients with PHPT, nonetheless, because of its mechanism of action, its discontinuation has been associated with rebound clinical fractures. Currently, limited data are available on the best management of patients discontinuing denosumab, although it is recommended to continue anti-osteoporotic treatment with oral or intravenous bisphosphonates. For our patient we could not consider these options due to coexisting active osteonecrosis. The patient had also two previous vertebral fractures. Hypercalcemia was managed with cinacalcet, and the patient has not sustained any fractures as of January 2022.

Conclusion: We suggest prompt cinacalcet use to manage potential rebound hypercalcemia following denosumab discontinuation in patients with PHPT, although these patients will remain at risk of rebound fractures.