Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.
Department of Clinical Medicine, Aalborg University, Aalborg, Denmark; Department of Endocrinology, Aalborg University, Aalborg, Denmark.
Lancet Diabetes Endocrinol. 2020 May;8(5):407-417. doi: 10.1016/S2213-8587(20)30063-2.
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.
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.
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.
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.
Aalborg University Hospital and Aalborg University, Denmark.
原发性甲状旁腺功能亢进症的治疗选择有限。我们旨在评估 denosumab 联合 cinacalcet 在原发性甲状旁腺功能亢进症患者中的疗效。
在这项随机、单中心、概念验证、双盲试验中，我们从丹麦奥尔堡大学医院内分泌科招募了年龄至少 18 岁的原发性甲状旁腺功能亢进症患者。主要入选标准为腰椎、股骨颈或全髋关节的 T 评分在-1.0 到-3.5 之间。患者通过区组随机化（1:1:1）分配接受每日 30mg cinacalcet 联合每 6 个月皮下注射 60mg denosumab（n=14；联合组）治疗 1 年，denosumab 联合安慰剂（n=16；denosumab 组）治疗 1 年，或安慰剂联合安慰剂注射（n=15；安慰剂组）治疗 1 年。主要结局为 1 年后腰椎、全髋关节、股骨颈和远端前臂的双能 X 线吸收法骨密度（BMD）变化。此外，还探讨了对骨代谢生化的影响。患者和研究人员均设盲。所有入组患者均纳入疗效分析。该试验在门诊环境中进行，在 ClinicalTrials.gov 上注册，NCT03027557，现已完成。
在 2017 年 3 月 14 日至 2018 年 3 月 16 日期间，我们招募了 285 名参与者。16 名患者被随机分配至 denosumab 组，15 名至联合组，15 名至安慰剂组。仅 1 名联合组患者脱落。与安慰剂相比，接受 denosumab 治疗的患者 BMD 改善：腰椎（联合组 5.4%[95%CI 2.7-8.1]，denosumab 组 6.9%[95%CI 4.2-9.6]；p<0.0001），全髋关节（联合组 5.0%[3.0-6.9]，denosumab 组 4.1%[2.5-5.8]；p<0.0001）和股骨颈（联合组 4.5%[1.9-7.9]；p=0.0008，denosumab 组 3.8%[1.4-6.3]；p=0.0022）。第三远端前臂的 BMD 变化有显著意义。发生 6 例非致死性严重不良事件（联合组[n=2]，denosumab 组[n=1]，安慰剂组[n=3]）。治疗组之间不良事件的总体发生率无差异，且无致死性不良事件发生。
有证据表明，denosumab 可有效提高原发性甲状旁腺功能亢进症患者的 BMD 并降低骨转换，无论是否联合 cinacalcet 治疗，均可作为手术不可取的患者的有效选择。
奥尔堡大学医院和奥尔堡大学，丹麦。
