title: PTH [1-34]-induced alterations of the subchondral bone provoke early osteoarthritis.
abstract: OBJECTIVE
  To test the hypothesis that changes in the subchondral bone induced by parathyroid hormone (PTH [1-34]) reciprocally affect the integrity of the articular cartilage within a naïve osteochondral unit in vivo.
  
  
  METHODS
  Daily subcutaneous injections of 10 μg PTH [1-34]/kg were given to adult rabbits for 6 weeks, controls received saline. Blood samples were continuously collected to monitor renal function. The subchondral bone plate and subarticular spongiosa of the femoral heads were separately assessed by micro-computed tomography. Articular cartilage was evaluated by macroscopic and histological osteoarthritis scoring, polarized light microscopy, and immunohistochemical determination of type-I, type-II, type-X collagen contents, PTH [1-34] receptor and caspase-3 expression. Absolute and relative extents of hyaline and calcified articular cartilage layers were measured histomorphometrically. The correlation between PTH-induced changes in subchondral bone and articular cartilage was determined.
  
  
  RESULTS
  PTH [1-34] enhanced volume, mineral density, and trabecular thickness within the subarticular spongiosa, and increased thickness of the calcified cartilage layer (all P < 0.05). Moreover, PTH [1-34] led to cartilage surface irregularities and reduced matrix staining (both P < 0.03). These early osteoarthritic changes correlated with and were ascribed to the increased thickness of the calcified cartilage layer (P = 0.026) and enhanced mineral density of the subarticular spongiosa (P = 0.001).
  
  
  CONCLUSIONS
  Modifications of the subarticular spongiosa by PTH [1-34] cause broadening of the calcified cartilage layer, resulting in osteoarthritic cartilage degeneration. These findings identify a mechanism by which PTH-induced alterations of the normal subchondral bone microarchitecture may provoke early osteoarthritis.
authors.affiliation: Center of Experimental Orthopaedics, Saarland University, Homburg/Saar, Germany; Department of Orthopaedic Surgery, Saarland University Medical Center, Homburg/Saar, Germany. Electronic address: patrick.orth@uks.eu.
authors.forename: P
authors.initials: P
authors.lastname: Orth
authors.affiliation: Center of Experimental Orthopaedics, Saarland University, Homburg/Saar, Germany. Electronic address: mmcucchiarini@hotmail.com.
authors.forename: M
authors.initials: M
authors.lastname: Cucchiarini
authors.affiliation: Institute of Medical Biometry, Epidemiology and Medical Informatics, Saarland University Medical Center, Homburg/Saar, Germany. Electronic address: imbei@med-imbei.uni-saarland.de.
authors.forename: S
authors.initials: S
authors.lastname: Wagenpfeil
authors.affiliation: Institute for Clinical and Experimental Surgery, Saarland University Medical Center, Saarland University, Homburg/Saar, Germany. Electronic address: michael.menger@uks.eu.
authors.forename: M D
authors.initials: MD
authors.lastname: Menger
authors.affiliation: Center of Experimental Orthopaedics, Saarland University, Homburg/Saar, Germany; Department of Orthopaedic Surgery, Saarland University Medical Center, Homburg/Saar, Germany. Electronic address: henning.madry@uks.eu.
authors.forename: H
authors.initials: H
authors.lastname: Madry
mesh_terms: D000818:Animals; D001707:Biopsy, Needle; D002358:Cartilage, Articular / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005270:Femur Head / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000473:pathology; D007150:Immunohistochemistry; D007279:Injections, Subcutaneous; D010003:Osteoarthritis / Q000139:chemically induced* / Q000000981:diagnostic imaging / Q000473:pathology; D010281:Parathyroid Hormone / Q000008:administration & dosage / Q000009:adverse effects*; D011817:Rabbits; D011897:Random Allocation; D012016:Reference Values; D012680:Sensitivity and Specificity; D055114:X-Ray Microtomography / Q000379:methods
chemical_list: D010281:Parathyroid Hormone
keywords: Articular cartilage; Early osteoarthritis; Femoral head; Osteochondral unit; PTH [1-34]; Subchondral bone