Julius Simoni Leere1, Jesper Karmisholt2, Maciej Robaczyk3, Simon Lykkeboe4, Aase Handberg5, Emilie Steinkohl6, Jens Brøndum Frøkjær6, Peter Vestergaard7. 1. Department of Clinical Medicine, Aalborg University, Aalborg, Denmark. Electronic address: j.leere@rn.dk. 2. Department of Clinical Medicine, Aalborg University, Aalborg, Denmark; Department of Endocrinology, Aalborg University, Aalborg, Denmark. 3. Department of Endocrinology, Aalborg University, Aalborg, Denmark. 4. Department of Clinical Biochemistry, Aalborg University, Aalborg, Denmark. 5. Department of Clinical Medicine, Aalborg University, Aalborg, Denmark; Department of Clinical Biochemistry, Aalborg University, Aalborg, Denmark. 6. Department of Clinical Medicine, Aalborg University, Aalborg, Denmark; Department of Radiology, Aalborg University, Aalborg, Denmark. 7. Department of Clinical Medicine, Aalborg University, Aalborg, Denmark; Department of Endocrinology, Aalborg University, Aalborg, Denmark; Steno Diabetes Center North Jutland, Aalborg, Denmark.
Abstract
BACKGROUND: Medical treatment options for primary hyperparathyroidism are scarce. We aimed to assess the efficacy of denosumab and combined with cinacalcet in patients with primary hyperparathyroidism. METHODS: In this randomised, single-centre, proof-of-concept, double-blind trial, patients aged at least 18 years with primary hyperparathyroidism were recruited from the Department of Endocrinology, Aalborg University Hospital, Aalborg, Denmark. Key eligibility criteria were a T-score between -1·0 and -3·5 at the lumbar spine, femoral neck, or total hip. Patients were assigned (1:1:1) via permuted block randomisation to receive 30 mg cinacalcet per day plus 60 mg denosumab subcutaneously every 6 months (n=14; combination group) for 1 year, denosumab plus placebo (n=16; denosumab group) for 1 year, or placebo plus placebo injection (n=15; placebo group) for 1 year. Primary outcomes were changes in bone mineral density (BMD) measured by dual x-ray absorptiometry at the lumbar spine, total hip, femoral neck, and distal forearm after 1 year. Additionally, effects on bone-metabolic biochemistry were explored. Patients and investigators were masked. All enrolled patients were included in efficacy analyses. The trial was done in an outpatient setting and is registered at ClinicalTrials.gov, NCT03027557, and has been completed. FINDINGS:Between March 14, 2017, and March 16, 2018 we recruited 285 participants. 16 patients were randomly allocated to the denosumab group, 15 to the combination group, and 15 to the placebo group. Dropout was limited to one patient in the combination group. Compared with placebo, BMD improved in groups receiving denosumab: lumbar spine (combination group 5·4% [95% CI 2·7-8·1], denosumab group 6·9% [95% CI 4·2-9·6]; p<0·0001), total hip (combination group 5·0% [3·0-6·9], denosumab group 4·1% [2·5-5·8]; p<0·0001), and femoral neck (combination group 4·5% [1·9-7·9]; p=0·0008, denosumab group 3·8% [1·4-6·3]; p=0·0022]). Changes in BMD at the third distal forearm were borderline significant. Six non-fatal serious adverse events occurred (combination group [n=2], denosumab group [n=1], placebo group [n=3]). The overall prevalence of adverse events did not differ between treatment groups, and no fatal adverse events occurred. INTERPRETATION: Evidence suggested denosumab was effective in improving BMD and lowering bone turnover in patients with primary hyperparathyroidism irrespective of cinacalcet treatment and might be a valid option for patients in which surgery is undesirable. FUNDING: Aalborg University Hospital and Aalborg University, Denmark.
RCT Entities:
BACKGROUND: Medical treatment options for primary hyperparathyroidism are scarce. We aimed to assess the efficacy of denosumab and combined with cinacalcet in patients with primary hyperparathyroidism. METHODS: In this randomised, single-centre, proof-of-concept, double-blind trial, patients aged at least 18 years with primary hyperparathyroidism were recruited from the Department of Endocrinology, Aalborg University Hospital, Aalborg, Denmark. Key eligibility criteria were a T-score between -1·0 and -3·5 at the lumbar spine, femoral neck, or total hip. Patients were assigned (1:1:1) via permuted block randomisation to receive 30 mg cinacalcet per day plus 60 mg denosumab subcutaneously every 6 months (n=14; combination group) for 1 year, denosumab plus placebo (n=16; denosumab group) for 1 year, or placebo plus placebo injection (n=15; placebo group) for 1 year. Primary outcomes were changes in bone mineral density (BMD) measured by dual x-ray absorptiometry at the lumbar spine, total hip, femoral neck, and distal forearm after 1 year. Additionally, effects on bone-metabolic biochemistry were explored. Patients and investigators were masked. All enrolled patients were included in efficacy analyses. The trial was done in an outpatient setting and is registered at ClinicalTrials.gov, NCT03027557, and has been completed. FINDINGS: Between March 14, 2017, and March 16, 2018 we recruited 285 participants. 16 patients were randomly allocated to the denosumab group, 15 to the combination group, and 15 to the placebo group. Dropout was limited to one patient in the combination group. Compared with placebo, BMD improved in groups receiving denosumab: lumbar spine (combination group 5·4% [95% CI 2·7-8·1], denosumab group 6·9% [95% CI 4·2-9·6]; p<0·0001), total hip (combination group 5·0% [3·0-6·9], denosumab group 4·1% [2·5-5·8]; p<0·0001), and femoral neck (combination group 4·5% [1·9-7·9]; p=0·0008, denosumab group 3·8% [1·4-6·3]; p=0·0022]). Changes in BMD at the third distal forearm were borderline significant. Six non-fatal serious adverse events occurred (combination group [n=2], denosumab group [n=1], placebo group [n=3]). The overall prevalence of adverse events did not differ between treatment groups, and no fatal adverse events occurred. INTERPRETATION: Evidence suggested denosumab was effective in improving BMD and lowering bone turnover in patients with primary hyperparathyroidism irrespective of cinacalcet treatment and might be a valid option for patients in which surgery is undesirable. FUNDING: Aalborg University Hospital and Aalborg University, Denmark.
Authors: Hun Jee Choe; Bo Kyung Koo; Ka Hee Yi; Sung Hye Kong; Jung Hee Kim; Chan Soo Shin; Jee Won Chai; Sang Wan Kim Journal: J Bone Miner Metab Date: 2021-11-10 Impact factor: 2.626
Authors: Paw Jensen; Lasse Hjort Jakobsen; Martin Bøgsted; Joachim Baech; Simon Lykkeboe; Marianne Tang Severinsen; Peter Vestergaard; Tarec Christoffer El-Galaly Journal: Blood Adv Date: 2022-04-26