Endocrine Abstracts

Background: Denosumab (DMAb) and zoledronic acid (ZA) are potent, anti-resorptive agents used to treat patients with osteoporosis. It has been suggested that they increase parathyroid hormone (PTH) levels in response to their antiresorptive effect, and that PTH elevation might be responsible for DMAb modeling actions on bone. The timeline and magnitude of PTH elevation post-DMAb and ZA has not been characterized in a large patient population.

Objective: To characterize PTH levels post-DMAb injection vs. baseline and vs. ZA injection.

Material and Methods: Female osteoporotic patients, ≥50 years, treated with DMAb or ZA, 2008–2020 were included if PTH was <1.5ULN before injection and if they had at least one PTH measurement 6 months after DMAb or 12 months after ZA injection. Exclusion criteria were creatinine >2mg/dl or diagnosis of hyperparathyroidism. Post-injection PTH levels were linked time-wise to previous injections.

Results: A total of 35,375 women, ≥50 years received DMAb or ZA for the first time in 2008–2020; 26,341 met the exclusion criteria. Of the remaining women, 5,640 received a first DMAb injection and 3,394 ZA. The DMAb group was older (73.2 vs. 69.8 years), was treated more frequently with osteoporosis medications before the injection (56.5% vs. 50.3%) and more had sustained a fracture (15.8% vs. 13.9%) compared to the ZA group. Vitamin D level was 80.9±21.9 nmol/l. Repeat PTH was available for 2,206 DMAb patients and 1,444 ZA. Among 772 PTH measurements in the first month post-DMAb, it was >1.5ULN in 156 (20.1%) and >2.5ULN in 74 (5.1%), whereas among 807 PTH measurements 5-months post-injection, it was >1.5ULN in 112 (13.9%) and >2.5ULN in 9 (1.1%). One-month post-ZA, PTH was >1.5ULN in 35/169 (20.7%) and >2.5ULN in 11 (6.5%), and decreased to >1.5ULN in 23/213 (10.7%) and to >2.5ULN in 2/213 (0.9%), 5 months after injection.

Discussion: This is the first study to examine PTH levels in a large population receiving DMAb or ZA injections, with precisely-timed PTH measurements post-injection. PTH levels increased by >1.5ULN in 20% of osteoporotic patients who received DMAb or ZA, while it increased to >2.5ULN in ~5% post-injection. PTH levels >2.5ULN declined gradually after treatment in both groups. It seems that PTH elevation is related to the antiresorptive effects of the drugs and is not a disease phenomenon. It is suggested to avoid checking PTH in the first few months post-DMAb and ZA therapy.