Musculoskeletal System

Bone, Joint - Degeneration

Narrative

Comment:

Degeneration of the joint (osteoarthritis arthrosis, osteoarthrosis, osteoarthropathy, degenerative joint disease) is a noninflammatory, progressive disease of cartilage characterized by loss of articular cartilage, subchondral bone thickening (Figure 1) and cyst formation, and formation of osteophytes within the affected joint space. Early lesions of osteoarthritis consist of tinctorial alterations of the cartilage characterized by loss of basophilia and fibrillar consistency (resulting from loss of mucopolysaccharides) of the cartilaginous matrix, fissure formation, and hypertrophy and hyperplasia of cartilage, evidenced by irregularly arranged clusters of enlarged chondrocytes. Severe lesions may be associated with cartilaginous clefts (Figure 2), leading to erosion and loss, thickening of the joint capsule and synovium (Figure 3), and osteophytosis and subchondral bone cyst formation. Synovial tissue may become thickened, with villous projections emanating from the synovium and protruding into the joint space. With chronicity, the synovium may undergo cartilaginous or bony metaplasia. In severe cases, ankylosis (fusion) of the joint may occur. Ultrastructurally, degenerative changes are characterized by abnormal Golgi, increased intracellular microfilaments, decreased numbers of proteoglycan granules, and disruption of collagen within the cartilaginous matrix.

Degenerative joint disease occurs in nearly all strains of rats and mice as a component of the aging process. In the B6C3F1 mouse, the disease occurs more commonly in males than females and has an incidence in the stifle joint of up to 2% for males and 4% for females. The disease is known to preferentially affect the stifle and elbow joints in the mouse but also occurs in the distal thoracic vertebrae and joints of the sternum. In the F344 rat, spontaneous lesions have been reported as early as 13 months. Although a normal age-related change, the disease is multifactorial and influenced by diet, strain, sex hormones, and weight, in addition to exposure to various toxicants, which can cause alterations in the cartilaginous matrix. Chondromucinous/cystic degeneration (aseptic necrosis) of articular cartilage or growth plates in the rat should not be confused with degenerative joint disease. This is a common spontaneous lesion in aged rats that may lead to spontaneous fractures of bony trabeculae of the physis and epiphysis but does not cause degenerative lesions of the articular cartilage.

Recommendations:

Degenerative joint disease/osteoarthritis should be diagnosed as "Bone, Joint – Degeneration" and given a severity grade. It is not necessary to record all of the individual components, but they should be described in the narrative if the disease appears correlated with chemical exposure. In the narrative, the terms "degenerative joint disease" or "osteoarthritis" may be used to connote the disease associated with the morphology, if appropriate.

Related Links:

Bone - Joint - Inflammation

References:

Leininger JR, Riley MGI. 1990. Bones, joints, and synovia. In: Pathology of the Fischer Rat: Reference and Atlas (Boorman G, Eustis SL, Elwell MR, Montgomery CA, MacKenzie WF, eds). Academic Press, San Diego, 209-226.

Long PH, Leininger JR. 1999. Bones, joints, and synovia. In: Pathology of the Mouse (Maronpot R, Boorman G, Gaul BW, eds). Cache River Press, St Louis, 645-678.

Schunke M, Tillmann B, Bruck M, Muller-Ruchholtz W. 1988. Morphologic characteristics of developing osteoarthritic lesions in the knee cartilage of STR/IN mice. Arthritis Rheum 31:898-905.

Abstract: http://www.ncbi.nlm.nih.gov/pubmed/3395383

Sheldon WG, Bucci TJ, Turturro A. 1996. Thoracic apophyseal osteoarthiritis in feed-restricted and ad libitum-fed B6C3F1 mice. In: Pathobiology of the Aging Mouse, Vol 2 (Mohr U, Dungworth DL, Capen CC, Carlton WW, Sundberg JP, Ward JM, eds). ILSI Press, Washington, DC, 445-453.

Silberberg M, Silberberg R. 1970. Age-linked modification of the effect of estrogen on joints and cortical bone of female mice. Gerontologica 16:201-211.

Sokoloff L. 1956. Natural history of degenerative joint disease in small laboratory animals. 1. Pathologic anatomy of degenerative joint disease in mice. AMA Arch Pathol 62:118-128.

Stanescu R, Knyszynski A, Muriel M, Stanescu V. 1993. Early lesions of the articular surface in a strain of mice with very high incidence of spontaneous osteoarthritic-like lesions. J Rheumatol 20:102-110.

Abstract: http://www.ncbi.nlm.nih.gov/pubmed/8441138

Yamamoto H, Iwase N, Kohno M. 1999. Histopathological characterization of spontaneously developing osteoarthropathy in the BCBC/Y mouse established newly from B6C3F1 mice. Exp Toxicol Pathol 51:15-20

Abstract: http://www.ncbi.nlm.nih.gov/pubmed/10048708

Yamamoto K, Shishido T, Masaoka T, Imakiire A. 2005. Morphological studies on the ageing and osteoarthritis of the articular cartilage in C57 black mice. J Orthop Surg (Hong Kong) 13:8-18.

Abstract: http://www.ncbi.nlm.nih.gov/pubmed/15872395

Yamasaki K. 1993. Morphological studies on the bone and cartilage of laboratory animals. Exp Anim 42:11-21.

All Images

Bone, Joint - Degeneration in a female F344/N rat from a chronic study. The articular surface of the femorotibial joint is roughened and contains clefts (arrow).

Bone, Joint - Degeneration in a female F344/N rat from a chronic study (higher magnification of Figure 1). There is roughening and cleft formation of the articular surface and thickening of the subchondral bone.

Bone, Joint - Degeneration in a male B6C3F1/N mouse from a chronic study. The synovial lining of the femorotibial joint is hyperplastic.

Authors and Reviewers

Authors

Mark J. Hoenerhoff, DVM, PhD, DACVP
Associate Professor
In Vivo Animal Core,Unit for Laboratory Animal Medicine
University of Michigan
Ann Arbor, MI

Amy Brix, DVM, PhD, DACVP
Senior Pathologist
Experimental Pathology Laboratories, Inc.
Research Triangle Park, NC

Reviewers

Philip H. Long, DVM, PhD, DACVP
Presiden and Senior Pathologist
Vet Path Services, Inc.
Mason, OH

Joel R. Leininger, DVM, PhD, DACVP
JRL Consulting, LLC
Chapel Hill, NC