A new study has shown promise for the development of a disease-modifying drug for osteoarthritis.
The study has raised hopes for developing bone-building calcitonin for protecting post-menopausal women against cartilage degradation and joint destruction.
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 so far.
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, oral calcitonin may successfully protect postmenopausal women from the ongoing pain and eventual 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. 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.
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 noticeable boost 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 offset 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 indicating important chondroprotective properties of this drug which need to be explored in upcoming clinical trials," concludes the study's lead author, Bodil-Cecilie Sondergaard.
Stephen Honig, MD, New York University School of Medicine and Hospital for Joint Diseases says, "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."