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Osteoarthritis Targeted By New Disease-Modifying Drug
02 Aug 2007
As edited by Joint-Pain-Forum.com
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
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
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 adapted by www.Joint-Pain-Forum.com from original press release.
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).
Source: Amy Molnar
John Wiley & Sons, Inc.
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