Background/Purpose: Denosumab and Zoledronic acid are antiresorptive drugs commonly used in the treatment of osteoporosis (OP). Zoledronic acid is a third-generation bisphosphonate that inhibits osteoclastic bone resorption through the mevalonate pathway. Denosumab is a humanized monoclonal antibody that binds to RANK-L preventing osteoclastic activation. Both can cause hypocalcemia and parathormone (PTH) elevations have been described during their use. Its prevalence, the mechanism by which it occurs, and the clinical repercussions are unknown.

The aim of our study was to analyze the prevalence of PTH elevation above the reference value in patients receiving zoledronic acid or denosumab and its relationship with other clinical-analytical parameters.

Methods: Retrospective observational study in patients with OP who have received treatment with denosumab or zoledronic at least two years. Patients were successively recruited from our service’s osteoporosis database.

Patients diagnosed with primary hyperparathyroidism or with glomerular filtration rate < 30ml/min at the baseline visit were excluded from the study. Clinical and demographic data were obtained from the electronic health record. Statistical analysis was performed using R software.

Results: 91 patients with a mean age (Standard Deviation-SD) of 68 (11.3) years at the start of treatment were included.

49 (81.6% women) patients started treatment with zoledronic and 42 (61.9% women) with Denosumab.

Table 1 shows the analytical parameters throughout the follow-up.

18.4% of the patients treated with zoledronic had elevated PTH levels on some occasion compared to 35.7% of the patients treated with Denosumab (p=0.055).

Patients with persistently elevated PTH during the two visits were 3 (6%) with zoledronic and 9 (21.4%) with Denosumab (p< 0.02).

Using a logistic regression model, we analyzed the possible relationship between the elevated value of PTH (≥65pg/mL) and other clinical-analytical variables (Table 2).

We found an inverse statistically significant association between corrected calcium and glomerular filtration rate compared to elevated PTH.

We calculated the progression of the T. Score between the baseline visit and the second visit in the lumbar spine, femoral neck, and total hip. We call this parameter “delta T Score”.

Using a linear regression model, we analyzed the lumbar Delta T-Score against the variables listed in table 3.

Normal PTH values and female gender are associated in a statistically significant way with a worse evolution of bone mineral density at the lumbar region.

We did not find these associations in femoral neck or total hip.

Conclusion: We found a high prevalence of hyperparathyroidism in our patients, higher in those treated with Denosumab.

The elevation of PTH seems to be associated, inversely, with serum levels of ionic calcium and glomerular filtration rate. Elevated PTH levels are associated with a better evolution of bone mineral density. In this context, we believe that the elevation of PTH could act as a marker of treatment effectiveness. Other studies would be necessary to corroborate these findings.

ACR Meeting Abstracts - https://acrabstracts.org/abstract/incidence-of-hyperparathyroidism-in-patients-with-osteoporosis-treated-with-zoledronic-acid-or-denosumab/