Parathyroid hormone changes following denosumab treatment in postmenopausal osteoporosis

Abstract

Introduction: Denosumab is a fully human monoclonal antibody to RANKL and represents a distinct class of antiresorptives in osteoporosis treatment, since it inhibits osteoclast maturation in the early stages of development and osteoclast activity, rather than impairing viability of osteoclasts. In both preclinical and clinical studies denosumab induced a dose-dependent increase in parathyroid hormone (PTH) levels. This increase in PTH is considered compensatory against the transient dose-dependent decrease in serum calcium levels, while hypocalcemic events seem infrequent even among subjects not receiving calcium and/or vitamin D (Ca/D) supplements.In this study we monitored PTH changes following a single injection of denosumab. The primary end point was the alteration of PTH 1 month after the injection while receiving a commonly used (1 gr/800 IU) or double-dose (2 gr/1,600 IU) supplementation with calcium and vitamin D. The secondary end point was the alteration of PTH 6 months after denosumab injection.

Comparative effects of denosumab or bisphosphonate treatment on bone mineral density and calcium metabolism in postmenopausal women

“…This finding is consistent with the results of two previous clinical studies, according to which the increase in circulating PTH occurs early, within the first 15 to 30 days following denosumab administration and persists, albeit attenuated, for six months 23,24 . In the present study, however, the effect of denosumab on PTH was evident after 12 months of treatment.…”

Efficacy of Denosumab Therapy Following Treatment with Bisphosphonates in Women with Osteoporosis: A Cohort Study

“…Interestingly, the measurement of bone biochemical markers after the first infusion of denosumab, showed a significant increase of serum PTH and VitD levels after 6 months of denosumab treatment ( p < 0.001), confirming previous observation by Makras and colleagues [ 41 ]. But, unlike described in a more recent manuscript, PTH levels did not further change after the first six months of treatment [ 42 ].…”

Effects of denosumab as compared with parathyroidectomy regarding calcium, renal, and bone involvement in osteoporotic patients with primary hyperparathyroidism

“…In the patients who received Dmb, the present results showed a transient decrease in cCa, with the minimum reached on day 7 following the first injection and then remained stable at 1 year after treatment. On the other hand, those who underwent Dmb treatment showed a compensatory increase in serum wPTH, not only transiently following the first injection [20], but that was sustained at 1 year after treatment. The effects of this compensatory consequence on bone metabolism and tumor growth warrant further investigation.…”