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ShareAug. 1, 2007 — The world's most common joint disease, osteoarthritis (OA) affects more than 10 percent of American adults, nearly 80 percent of people past age 55, and about three times as many women as men. Treatment has been targeted at controlling the pain that tends to come with the progressive loss of articular cartilage cushioning the joints, disintegration of the underlying bone, and the formation of bone spurs or osteophytes. No drug has been proven to block OA's specific joint-destroying processes.
A new study indicates promise of bone-building calcitonin for protecting post-menopausal women against cartilage degradation and joint destruction. Calcitonin, an amino acid hormone produced by the thyroid gland, has been shown to decrease bone breakdown and increase bone density. Typically prescribed as a nasal spray, it is widely used in the treatment of Paget's disease and osteoporosis.
Whether this drug can also counteract the cartilage damage characteristic of OA remains unknown. Yet, based on the results of a recent study on female rats, featured in the August 2007 issue of Arthritis & Rheumatism (http://www.interscience.wiley.com/journal/arthritis), oral calcitonin may effectively protect postmenopausal women from the ongoing pain and ultimate disability of joint destruction.
Conducted by a team of researchers in Denmark, this study focused on ovariectomized rats, a model that closely resembles the changes in the human skeletal system during menopause. Key among them is loss of estrogen, which has been associated with accelerated cartilage degradation. Fifty female Sprague-Dawley rats were divided, randomly and equally, into 5 study groups: ovariectomy; ovariectomy, plus 60-day release estrogen pellet inserted; ovariectomy, plus 2.0 mg/kg of salmon calcitonin and 50 mg/kg of 5CNAC, a carrier; ovariectomy, plus 50 mg/kg of 5CNAC; and sham operation. Blood samples were collected from every rat at baseline, on day 3, and after 1, 2, 4, 6, and 9 weeks.
Each rat's body weight was recorded at regular intervals. After 9 weeks, the rats were euthanized. Then, researchers assessed each blood sample for increases in C-telopeptide type II collagen (CTX-II), shown to correlate with degradation of articular cartilage in rats; microscopically examined and blindly scored a section of every rat's knee joint for surface erosions of cartilage; and performed statistical analyses of the data.
Compared with the sham-operated group, all the ovariectomized rats experienced a marked increase in levels of CTX-II for the first 6 weeks, indicating accelerated articular cartilage degradation. During the 9-week trial, estrogen therapy effectively worked to counteract this increase to levels lower than the carrier and non-treated groups, whose levels were not significantly different. However, calcitonin worked better, bringing levels to below those even in the sham-operated group.
Similarly, estrogen and calcitonin both provided significant protection against surface erosions of knee joint cartilage. Again, calcitonin worked better, preventing erosions completely. Of note, the rats that had estrogen therapy gained the least weight of all the ovariectomized rats, effectively easing the erosive toll on the weight-bearing knee joints. Interestingly, calcitonin had no positive impact on body weight, yet protected against the erosions linked to joint destruction in OA.
"Calcitonin treatment may counter the acceleration of cartilage degradation and the related rise of surface erosions," concludes the study's lead author, Bodil-Cecilie Sondergaard, "indicating important chondroprotective properties of this drug which need to be explored in upcoming clinical trials."
Reflecting on the implications of these findings for human OA, Steven B. Abramson, MD, and Stephen Honig, MD, New York University School of Medicine and Hospital for Joint Diseases, raise the question of whether calcitonin's impact on cartilage is strictly preventative, rather than therapeutic, and of potential benefit only in the early stages of the disease.
"However, despite this caveat, the study remains an intriguing one," Dr. Abramson notes, "since it reinforces the possibility that currently available antiresorptive drugs may have DMOAD (disease-modifying osteoarthritis drug) properties." Dr. Honig adds: "The recognition, enhanced by the report of Sondergaard and colleagues, that antiresorptive agents may target abnormalities of both cartilage and bone represents a significant advance in our understanding of the OA disease process and could lead to new disease-modifying treatments in the near future."
Article: "The Effect of Oral Calcitonin on Cartilage Turnover and Surface Erosion in an Ovariectomized Rat Model," Bodil-Cecilie Sondergaard, Svetlana Oestergaard, Claus Christiansen, Laszló B. Tankó, and Morten Asser Karsdal, Arthritis & Rheumatism, August 2007; (DOI: 10.1002/art.22797).
Editorial: "Antiresorptive Agents and Osteoarthritis: More Than a Bone to Pick"," Steven B. Abramson and Stephen Honig, Arthritis & Rheumatism, August 2007; (DOI: 10.1002/art.22796).
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