Changes in serum vitamin D and PTH values using denosumab with or without bisphosphonate pre-treatment in osteoporotic patients: a short-term study

Yukio Nakamura, Mikio Kamimura, Shota Ikegami, Keijiro Mukaiyama, Shigeharu Uchiyama, Akira Taguchi, Hiroyuki Kato, Yukio Nakamura, Mikio Kamimura, Shota Ikegami, Keijiro Mukaiyama, Shigeharu Uchiyama, Akira Taguchi, Hiroyuki Kato

Abstract

Background: Denosumab is a fully human monoclonal antibody that inhibits receptor activator of nuclear factor kappa-β ligand (RANKL). Previous reports have shown that denosumab treatment of osteoporotic patients decreases bone resorption and fracture risk, but there have been no clinical studies on changes in bone turnover markers, 1,25(OH)2D3, or parathyroid hormone (PTH) in denosumab therapy with or without bisphosphonate (BP) pre-treatment in Japan.

Methods: Here, we report such findings in 22 patients (11 in the denosumab alone group and 11 in the BP pre-treated group) with osteoporosis following 4 months of treatment. Bone metabolism had been inhibited by prior BP administration in the BP pre-treated group.

Results: The bone resorption markers serum tartrate-resistant acid phosphatase type 5b and urinary type I collagen cross-linked N-telopeptide were significantly decreased from baseline values for the entire study period in both groups. The bone formation marker bone alkaline phosphatase was significantly decreased at 4 months in the denosumab alone group only, and N-terminal propeptide of type 1 procollagen was significantly decreased at 2 and 4 months in the denosumab alone group versus no remarkable change in the BP pre-treated group. In the denosumab alone group, 1,25(OH)2D3 and PTH were significantly increased at 1 week and decreased gradually thereafter, but these did not change notably in the BP pre-treated group.

Conclusions: Our results suggest that treatment with denosumab causes a strong inhibitory effect on bone resorption markers and mild inhibitory effect on bone formation markers. 1,25(OH)2D3 and PTH were significantly increased by denosumab but these did not change in the BP pre-treated group.

Trial registration: Current Controlled Trials NCT02156960. Registered 31 May 2014.

Figures

Fig. 1
Fig. 1
Low Ca stimulates PTH and 1,25(OH)2D3 expression. a Serum Ca in the denosumab alone group did not show any significant changes, but was decreased at 1 week and 1 month followed by a return to baseline levels at 4 months. In the BP pre-treated group, Ca was increased at 1 week and 1 month and gradually decreased thereafter. Group comparisons showed no significant differences at any time point. Straight line: Pre-treated BP group, dotted line: Denosumab alone group. b In the denosumab alone group, serum 1,25(OH)2D3 was significantly increased from 1 week to 2 months, and then gradually decreased thereafter. In the BP pre-treated group, serum 1,25(OH)2D3 did not significantly change during the study period. Group comparisons showed significant differences from 1 week to 4 months. Straight line: Pre-treated BP group, dotted line: Denosumab alone group. Asterisks indicate significant differences. c In the denosumab alone group, whole PTH was significantly increased at 1 week, and then gradually decreased thereafter. In the BP pre-treated group, PTH did not significantly change during the study period. Group comparisons showed significant differences at 1 week and 1 month. Straight line: Pre-treated BP group, dotted line: Denosumab alone group. Asterisks indicate significant differences
Fig. 2
Fig. 2
Bone absorption markers were significantly inhibited in the early stages of denosumab administration, whereas bone formation markers were gradually inhibited by denosumab. a In the denosumab alone group, serum TRACP-5b was significantly inhibited from 1 week to 4 months. TRACP-5b reached its minimum value at 1 month. In the BP pre-treated group, TRACP-5b was also significantly inhibited from 1 week to 4 months, albeit less than in the denosumab alone group. Group comparisons showed significant differences before administration and at 1 week of administration. Straight line: Pre-treated BP group, dotted line: Denosumab alone group. Asterisks indicate significant differences. b In the denosumab alone group, urinary NTX was significantly inhibited from 1 week to 4 months. Urinary NTX reached its minimum value at 2 months. In the BP pre-treated group, urinary NTX was also significantly inhibited from 1 week to 4 months, albeit less than in the denosumab alone group. Group comparisons showed a significant difference before administration. Straight line: Pre-treated BP group, dotted line: Denosumab alone group. Asterisks indicate significant differences. c In the denosumab alone group, BAP peaked at 1 month, but then decreased to a significant value at 4 months. In the BP pre-treated group, BAP did not change significantly during the observation period. Group comparisons showed a significant difference at 1 month. Straight line: Pre-treated BP group, dotted line: Denosumab alone group. Asterisks indicate significant differences. d In the denosumab alone group, P1NP was significantly decreased at 2 and 4 months. In the BP pre-treated group, P1NP did not change significantly during the observation period. Group comparisons showed significant differences from 1 week to 4 months. Straight line: Pre-treated BP group, dotted line: Denosumab alone group. Asterisks indicate significant differences

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