title: Systemic but no local effects of combined zoledronate and parathyroid hormone treatment in experimental autoimmune arthritis.
abstract: BACKGROUND
  Local bone erosions and osteoporosis in rheumatoid arthritis (RA) are the result of a more pronounced bone resorption than bone formation. Present treatment strategies for RA inhibit inflammation, but do not directly target bone erosions. The aim of the study was in experimental arthritis to investigate the juxtaarticular and systemic effects of simultaneous osteoclast inhibition with zoledronate (ZLN) and osteoblast stimulation with parathyroid hormone (PTH).
  
  
  METHODS
  Arthritis was induced in 36 SKG mice. The mice were randomized to three treatment groups and an untreated group: ZLN, PTH, PTH+ZLN, and untreated. Arthritis score and ankle width measurements were performed. Histological sections were cut from the right hind paw, and design-based stereological estimators were used to quantify histological variables of bone volume and bone formation and resorption. The femora were DXA- and μCT-scanned, and the bone strength was determined at the femoral neck and mid-diaphysis.
  
  
  RESULTS
  Locally, we found no differences in arthritis score or ankle width throughout the study. Similarly, none of the treatments inhibited bone erosions or stimulated bone formation in the paw. Systemically, all treatments improved bone mineral density, strength of the femoral neck and mid-diaphysis, and μCT parameters of both cortical and trabecular bone. In addition, there was an additive effect of combination treatment compared with single treatments for most trabecular parameters including bone mineral density and bone volume fraction.
  
  
  CONCLUSIONS
  No local effect on bone was found by the combined action of inhibiting bone resorption and stimulating bone formation. However, a clear systemic effect of the combination treatment was demonstrated.
authors.affiliation: Department of Rheumatology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Kresten Krarup
authors.initials: KK
authors.lastname: Keller
authors.affiliation: Department of Biomedicine - Anatomy, Aarhus University, Aarhus, Denmark.
authors.forename: Jesper Skovhus
authors.initials: JS
authors.lastname: Thomsen
authors.affiliation: Department of Rheumatology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Kristian
authors.initials: K
authors.lastname: Stengaard-Pedersen
authors.affiliation: Department of Rheumatology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Ellen-Margrethe
authors.initials: EM
authors.lastname: Hauge
mesh_terms: D015502:Absorptiometry, Photon; D000818:Animals; D001169:Arthritis, Experimental / Q000150:complications* / Q000188:drug therapy*; D001327:Autoimmune Diseases / Q000150:complications* / Q000188:drug therapy*; D001696:Biomechanical Phenomena / Q000187:drug effects; D015519:Bone Density / Q000187:drug effects; D004164:Diphosphonates / Q000494:pharmacology / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005121:Extremities / Q000473:pathology; D005260:Female; D005269:Femur / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D007093:Imidazoles / Q000494:pharmacology / Q000627:therapeutic use*; D051379:Mice; D010281:Parathyroid Hormone / Q000494:pharmacology / Q000627:therapeutic use*; D055114:X-Ray Microtomography; D000077211:Zoledronic Acid
chemical_list: D004164:Diphosphonates; D007093:Imidazoles; D010281:Parathyroid Hormone; D000077211:Zoledronic Acid