Selective oestrogen receptor modulators lasofoxifene and bazedoxifene inhibit joint inflammation and osteoporosis in ovariectomised mice with collagen-induced arthritis

Rheumatology (Oxford). 2016 Mar;55(3):553-63. doi: 10.1093/rheumatology/kev355. Epub 2015 Sep 30.

Abstract

Objective: RA predominantly affects post-menopausal women and is strongly associated with development of generalised osteoporosis. To find treatments that target both joint manifestations and osteoporosis in RA is desirable. The third generation of selective oestrogen receptor modulators (SERMs) [lasofoxifene (LAS) and bazedoxifene (BZA)] are new treatment options for post-menopausal osteoporosis. The aim of this study was to investigate the effects of LAS and BZA on arthritic disease and inflammation-associated bone loss using CIA in mice.

Methods: Female DBA/1 mice were ovariectomised and subjected to CIA as a model of post-menopausal RA. Mice received treatment with LAS, BZA, 17β-estradiol (E2) as reference or vehicle. Arthritis development was assessed and BMD was determined by peripheral quantitative CT of the femurs. Serologic markers of inflammation and cartilage destruction were analysed. Immune cells in lymph nodes were studied by flow cytometry.

Results: LAS and BZA reduced the clinical severity of arthritis as well as the grade of histologic synovitis and erosions on cartilage and bone. Moreover, SERMs protected against generalised bone loss in CIA by increasing trabecular BMD. Both SERMs decreased serum marker of cartilage destruction and LAS reduced serum IL-6 levels. SERMs did not alter Th17 cells in lymph nodes as E2 did.

Conclusion: The anti-osteoporotic drugs LAS and BZA were found to be potent inhibitors of joint inflammation and bone destruction in experimental arthritis. This study provides new important knowledge regarding the treatment regimen of post-menopausal women with RA who suffer from increased risk for osteoporosis.

Keywords: arthritis; oestrogen; osteoporosis; selective oestrogen receptor modulators.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Area Under Curve
  • Arthritis, Experimental / drug therapy*
  • Arthritis, Experimental / pathology
  • Biomarkers / blood
  • Collagen / pharmacology
  • Disease Models, Animal
  • Female
  • Flow Cytometry
  • Humans
  • Indoles / pharmacology*
  • Interleukin-6 / blood
  • Mice
  • Mice, Inbred DBA
  • Osteoarthritis / chemically induced
  • Osteoarthritis / drug therapy*
  • Osteoarthritis / physiopathology
  • Osteoporosis, Postmenopausal / drug therapy*
  • Osteoporosis, Postmenopausal / pathology
  • Ovariectomy / methods
  • Pyrrolidines / pharmacology*
  • Random Allocation
  • Selective Estrogen Receptor Modulators / pharmacology*
  • Tetrahydronaphthalenes / pharmacology*
  • Treatment Outcome

Substances

  • Biomarkers
  • Indoles
  • Interleukin-6
  • Pyrrolidines
  • Selective Estrogen Receptor Modulators
  • Tetrahydronaphthalenes
  • Lasofoxifene
  • Collagen
  • bazedoxifene