PTH [1-34]-induced alterations of the subchondral bone provoke early osteoarthritis

• Published in: Osteoarthritis and cartilage Vol. 22; no. 6; pp. 813 - 821
• Main Authors: Orth, P, Cucchiarini, M, Wagenpfeil, S, Menger, M.D, Madry, H
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-06-2014
• Subjects: Animals; Articular cartilage; Biopsy, Needle; Cartilage, Articular - diagnostic imaging; Cartilage, Articular - drug effects; Cartilage, Articular - pathology; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Administration Schedule; Early osteoarthritis; Femoral head; Femur Head - diagnostic imaging; Femur Head - drug effects; Femur Head - pathology; Immunohistochemistry; Injections, Subcutaneous; Osteoarthritis - chemically induced; Osteoarthritis - diagnostic imaging; Osteoarthritis - pathology; Osteochondral unit; Parathyroid Hormone - administration & dosage; Parathyroid Hormone - adverse effects; PTH [1-34]; Rabbits; Random Allocation; Reference Values; Rheumatology; Sensitivity and Specificity; Subchondral bone; X-Ray Microtomography - methods; Early osteoarthritis; Osteochondral unit; Articular cartilage; Femoral head; PTH [1-34]; Subchondral bone
• ISSN: 1063-4584; 1522-9653
• DOI: 10.1016/j.joca.2014.03.010

Summary 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. Design 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.