title: Selective oestrogen receptor modulators lasofoxifene and bazedoxifene inhibit joint inflammation and osteoporosis in ovariectomised mice with collagen-induced arthritis.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Centre for Bone and Arthritis Research, Department of Rheumatology and Inflammation Research and annica.andersson@rheuma.gu.se.
authors.forename: Annica
authors.initials: A
authors.lastname: Andersson
authors.affiliation: Centre for Bone and Arthritis Research, Department of Rheumatology and Inflammation Research and.
authors.forename: Angelina I
authors.initials: AI
authors.lastname: Bernardi
authors.affiliation: Centre for Bone and Arthritis Research, Department of Rheumatology and Inflammation Research and.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Stubelius
authors.affiliation: Centre for Bone and Arthritis Research, Department of Rheumatology and Inflammation Research and.
authors.forename: Merja
authors.initials: M
authors.lastname: Nurkkala-Karlsson
authors.affiliation: Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Claes
authors.initials: C
authors.lastname: Ohlsson
authors.affiliation: Centre for Bone and Arthritis Research, Department of Rheumatology and Inflammation Research and.
authors.forename: Hans
authors.initials: H
authors.lastname: Carlsten
authors.affiliation: Centre for Bone and Arthritis Research, Department of Rheumatology and Inflammation Research and.
authors.forename: Ulrika
authors.initials: U
authors.lastname: Islander
mesh_terms: D000818:Animals; D019540:Area Under Curve; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000473:pathology; D015415:Biomarkers / Q000097:blood; D003094:Collagen / Q000494:pharmacology; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D015850:Interleukin-6 / Q000097:blood; D051379:Mice; D008811:Mice, Inbred DBA; D010003:Osteoarthritis / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy* / Q000473:pathology; D010052:Ovariectomy / Q000379:methods; D011759:Pyrrolidines / Q000494:pharmacology*; D011897:Random Allocation; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D007211:Indoles; D015850:Interleukin-6; D011759:Pyrrolidines; D020845:Selective Estrogen Receptor Modulators; D013764:Tetrahydronaphthalenes; C111332:Lasofoxifene; D003094:Collagen; C447119:bazedoxifene
keywords: arthritis; oestrogen; osteoporosis; selective oestrogen receptor modulators