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. 2024 Sep 10;8(1):40.
doi: 10.1186/s41927-024-00414-6.

Effects of tofacitinib on bone turnover markers and bone modulators in patients with rheumatoid arthritis

Giovanni Adami  1 , Giovanni Orsolini  2 , Maurizio Rossini  2 , Anna Fratucello  3 , Angelo Fassio  2 , Ombretta Viapiana  2 , Elena Fracassi  2 , Riccardo Bixio  2 , Davide Gatti  2
Affiliations

Effects of tofacitinib on bone turnover markers and bone modulators in patients with rheumatoid arthritis

Giovanni Adami et al. BMC Rheumatol. .

Abstract

Background: Rheumatoid arthritis (RA) is characterized by bone loss. It is unclear whether JAK inhibitors can attenuate bone loss in RA by modulating bone metabolism. The main objective of our study is to investigate the effects of tofacitinib on serum levels of bone turnover markers and modulators. Secondary objectives were to assess changes in bone mineral density (BMD), metacarpal index, bone erosions.

Methods: We conducted a prospective observational study on patients with active RA failure to bDMARDs or tsDMARDs initiating treatment with tofacitinib. We measured at baseline and after 1, 2, 3, 6, 9 and 12 months: serum bone turnover markers (CTX, P1nP, B-ALP), bone modulators (Dkk-1, sclerostin, vitamin D, PTH, OPG and RANKL), BMD and radiographic parameters (Sharp van der Heijde score [SvdH], bone health index [BHI] and metacarpal index [MCI]).

Results: 30 patients were enrolled in the study of whom 21 completed the study through month 12. Tofacitinib was clinically effective by suppressing DAS28-CRP. Glucocorticoids daily dose significantly decreased from baseline. We found a negative correlation between pre-study cumulative and daily dose of glucocorticoids and baseline B-ALP serum levels (r -0.592, p 0.012). Sclerostin serum levels increased significantly during the study period, while P1nP and B-ALP (markers of bone formation) decreased significantly. BMD levels, BHI, MCI and SvdH score did not change.

Conclusion: Treatment with tofacitinib was associated with a significant increase in sclerostin serum levels and a parallel decrease in markers of bone formation. However, no significant bone loss was observed.

Keywords: Bone Mineral density (BMD); Bone metabolism inflammation; Bone turnover markers (BTMs); Tofacitinib.

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Conflict of interest statement

Giovanni Adami has received advisory board honoraria, consultancy fees and/or speaker fees from Theramex, UCB, Lilly, Galapagos, Fresenius Kabi, Amgen, BMS, Abiogen and Pfizer. Davide Gatti has received advisory board honoraria, consultancy fees and/or speaker fees from Abiogen, Celgene, Eli-Lilly, Neopharmed-Gentili, Pfizer, UCB. Maurizio Rossini reports advisory board honoraria, consultancy fees and/or speaker fees from AbbVie, Amgen, BMS, Eli-Lilly, Galapagos, Menarini, Sandoz, Theramex, UCB, outside the submitted work. Ombretta Viapiana has received advisory board honoraria and speaker fees from Gilead, Fresenius Kabi, Biogen, Eli-Lilly, UCB, Abbvie, MSD, BMS. Angelo Fassio reports personal fees from Abiogen, Novartis, Neopharmed. The other authors have disclosed no conflicts of interest.

Figures

Fig. 1
Fig. 1
Changes in Sharp van der Heijde (SvdH) score, metacarpal index (MCI) and bone health index (BHI) in the upper panel. Changes in bone mineral density (BMD) at lumbar spine, total hip and femoral neck in the lower panel. BMD changes were tested with mixed-effect model analysis for repeated measures (MMRM), p-values are adjusted for multiple comparisons using the Tukey’s procedure. SvdH score, BHI and MCI changes were tested with Wilcoxon signed-ranks test. Error bars represent 95% CI
Fig. 2
Fig. 2
Changes in bone turnover markers (BTMs) in the study period. Changes were tested with mixed-effect model analysis for repeated measures (MMRM), p-values are adjusted for multiple comparisons using the Tukey’s procedure. Error bars represent 95% CI
Fig. 3
Fig. 3
Changes in serum bone modulators in the study period. Changes were tested with mixed-effect model analysis for repeated measures (MMRM), p-values are adjusted for multiple comparisons using the Tukey’s procedure. Error bars represent 95% CI
Fig. 4
Fig. 4
Correlation matrix of baseline characteristics and bone parameters of the study population. Asterisks shows p-value < 0.05 adjusted for multiplicity using the two-stage step-up procedure by Benjamini, Krieger, and Yekutieli (with an FDR Q value of 5%)
See this image and copyright information in PMC

References

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