A Single-Dose, Open-Label, Prospective Clinical Study of Denosumab in Patients with Primary Hyperparathyroidism

Abstract

Background. The purpose of this study was to observe the effects of denosumab on bone mineral density (BMD), bone turnover markers and serum calcium in patients with primary hyperparathyroidism (PHPT) and osteoporosis.Methods. Seven consecutive patients with PHPT were administered a single subcutaneous injection of denosumab, 60 mg. The subjects were followed up to 6 months: serum calcium on days 1,3,7,14,30 and at 3 months and 6 months; serum intact parathyroid hormone (iPTH), C-telopeptide (CTX) and N-mid osteocalcin at baseline, 3 months and 6 months. BMD by DXA, at the femoral neck (FN) and lumbar spine (LS), were measured at baseline and at 6 months.Results. The patients (mean age= 69.8 yrs, range 62-81) had mild PHPT (mean total calcium = 10.8 mg/dL; mean PTH = 148.9 pg/mL); all had osteoporosis and four were currently treated with various bisphosphonates (BP). After 6 months mean LS BMD increased significantly by 4.5 % (p = 0.04) and mean FN BMD by 2.4% (p= 0.09 two-tailed; p = 0.047 one-tailed). Serum CTX decreased significantly by 90% at 3 months (p = 0.04), and by 48% at 6 months (p = 0.02); the similar changes for serum osteocalcin were 41% and 42% (p = 0.07, one-tailed), respectively. In the first two weeks, serum total Ca variably decreased vs. baseline (0.5 to 2.8 mg/dL) in six out of seven patients. After 6 months mean total serum Ca nonsignificantly increased vs. baseline (11.4 mg/dL vs. 10.8 mg/dL, p = 0.1). Serum iPTH levels did not significantly change at both 3 and 6 months; after 6 months there was a trend toward decreased values (p = 0.03 onetailed).Conclusion. Denosumab increased BMD at both lumbar spine and femoral neck, and significantly decreased bone resorption in patients with PHPT. The effects on hypercalcemia were mild and transient, with a numerical increase after 6 months.

Efficacy of antiresorptive agents bisphosphonates and denosumab in mitigating hypercalcemia and bone loss in primary hyperparathyroidism: A systematic review and meta-analysis

“…There were five studies in which denosumab was given to PHPT patients, of which two were excluded because data were not presented in the required format ( 31 , 32 ). The remaining three studies were included in the meta-analysis ( 21 , 25 , 26 ). There were two studies in which the effect of BPs was compared with PTX ( 15 , 20 ) and one study in which combination of BP and PTX was compared with PTX ( 22 ) in PHPT patients.…”

“…There was no effect on serum phosphate with ALN use. Only two denosumab studies measured serum calcium; in one, a decline in serum calcium was observed during the first month, after which it returned to baseline levels and continued until 50 weeks ( 21 ); and in the second, a decrease in serum calcium was observed in the first two weeks but then returned to the baseline levels and continued throughout the study (6 months) ( 26 ). PHPT is characterized by cortical bone loss with relative preservation of trabecular bone.…”

“…Unlike ALN, pooled analysis of the effect of denosumab on PTH levels after 12 months could not be done due to the paucity of data. Only one study examined the short-term effect of denosumab (3 and 6 months) on PTH levels in PHPT patients and found that the drug had no effect ( 26 ). Future studies are required to assess the effect of denosumab on PTH levels in PHPT patients.…”

Draft of clinical guidelines for the diagnosis and treatment of primary hyperparathyroidism in adult patients

“…Информация о влиянии деносумаба** на прирост МПК у пациентов с ПГПТ ограничена [283][284][285][286]. Однако по результатам рандомизированного плацебо-контроируемого двойного слепого исследования 3-ей фазы DENOCINA использование деносумаба** в дозе 60 мг 1 раз в 6 мес.…”

High Risk of Parathyroid Carcinoma and Genetic Screening in the First Diagnosed Romanian Family with Hyperparathyroidism-Jaw Tumor Syndrome and a Germline Mutation of the CDC73 Gene

“…Serum calcium varied between 10.65 and 12.4 mg/dL, PTH from 167 pg/mL to 567 pg/mL for four years. In the fifth year calcium rose to 13.5 mg/ dL and PTH to 1200 pg/mL and became refractory to iv bisphosphonates; denosumab was added as described (11,12). No OF or renal lesions were identified.…”