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

Giovanni Adami1, Giovanni Orsolini2, Maurizio Rossini2

  • 1Rheumatology Unit, University of Verona, Pz Scuro 10, Verona, 37134, +0458124049, Italy. giovanni.adami@univr.it.

BMC Rheumatology
|September 10, 2024
PubMed
Abstract

Insights

Tofacitinib treatment in rheumatoid arthritis (RA) increased sclerostin but decreased bone formation markers. Importantly, this JAK inhibitor did not cause significant bone loss, suggesting a complex effect on bone metabolism in RA patients.

Area of Science:

  • Rheumatology
  • Immunology
  • Bone Metabolism

Background:

  • Rheumatoid arthritis (RA) is associated with significant bone loss.
  • The impact of Janus kinase (JAK) inhibitors on bone metabolism in RA is not fully understood.
  • Investigating tofacitinib's effects on bone turnover markers and density is crucial for RA management.

Purpose of the Study:

  • To evaluate the effects of tofacitinib on serum bone turnover markers and modulators in RA patients.
  • To assess changes in bone mineral density (BMD) and radiographic parameters during tofacitinib treatment.
  • To explore the relationship between tofacitinib, bone metabolism, and bone loss in RA.

Main Methods:

  • Prospective observational study of active RA patients initiating tofacitinib after failure of other disease-modifying antirheumatic drugs (DMARDs).
  • Serum levels of bone turnover markers (CTX, P1nP, B-ALP) and modulators (sclerostin, Dkk-1, etc.) were measured serially over 12 months.
  • Bone mineral density (BMD), metacarpal index (MCI), and radiographic scores (SvdH, BHI) were assessed.

Main Results:

  • Tofacitinib effectively suppressed disease activity (DAS28-CRP) and reduced glucocorticoid dosage.
  • Serum sclerostin levels significantly increased, while bone formation markers (P1nP, B-ALP) significantly decreased.
  • No significant changes in BMD, BHI, MCI, or SvdH score were observed, indicating no net bone loss.

Conclusions:

  • Tofacitinib treatment in RA is linked to increased sclerostin and reduced bone formation markers.
  • Despite biochemical changes, tofacitinib did not lead to significant bone loss or worsening of radiographic damage.
  • These findings highlight a complex modulation of bone metabolism by JAK inhibition in RA.
Keywords:
Bone Mineral density (BMD)Bone metabolism inflammationBone turnover markers (BTMs)Tofacitinib

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