Oral Calcitonin May Delay Onset of Joint Disease and Relieve Pain of OA
January 04, 2006Oral calcitonin may have a chondroprotective role in osteoarthritis (OA), according to data in rats presented last month at the 10th World Congress of the Osteoarthritis Research Society International (OARSI) in Boston, Massachusetts.1
Although calcitonin is an established antiresorptive agent, its disease-modifying effects on chondrocytes and cartilage metabolisms have not been well established until now.
This new study, however, may help to explain how calcitonin affects osteoarthritis. "Calcitonin acts both directly on osteoclasts, resulting in inhibition of bone resorption and following attenuation of subchondral bone turnover, and directly on chondrocytes, attenuating cartilage degradation and stimulating cartilage formation," says researcher Morten Karsdal, MSC, PhD, of the department of pharmacology at Nordic Bioscience in Herlev, Denmark. "Therefore, calcitonin may be a future efficacious drug for OA."
As a result of the findings, the researchers conclude that "clinical assessment of calcitonin for chondroprotection seems warranted."
In vivo effects of calcitonin on bone remodeling and cartilage degradation shown
In the study, 50 rats were randomly assigned to five groups: ovarectomies (OVX) alone; OVX plus estrogen; OVX plus 2 mg/kg calcitonin plus 50 mg/kg 5-CNAC; OVX plus 50 mg/kg 5-CNAC; and placebo. Treatments were administered for 6 weeks after surgery and blood samples for biomarker analysis were taken at baseline, day 3, and weeks 1, 2, 4, and 6.
The rats underwent bilateral OVX, which resulted in a marked increase in bone turnover and cartilage degradation, as expected from previous studies. Treatment with calcitonin decreased cartilage degradation, which was quantified by measuring the changes in the concentration of C-telopeptides of collagen type II (CTX-II). Changes in the severity scores of articular cartilage erosion were visualized in histological sections of the knee.
Researchers also measured the direct effects of calcitonin on the activity of chondrocytes in articular cartilage cultures grown in the presence of oncostatin M and tumor necrosis factor-alpha (TNF-α), either with or without 100 nM calcitonin. The articular cartilage explants that were exposed to oncostatin M and TNF-α showed a 50-fold increase in CTX-II release, which was reduced by 50% in the presence of 100 nM calcitonin.
"Calcitonin acts directly on articular chondrocytes; [it] upregulates cyclic AMP (cAMP) levels in chondrocytes, resulting in inhibition of MMP expression and the related collagen type II degradation, thereby providing direct chondroprotective effects," the research team explains.
Pain relief plus chondroprotection
Unlike several other potential disease-modifying OA drugs, calcitonin also has a "unique analgesic effect on bone pain, which might relieve at least in part symptoms accompanying joint disease," says Dr. Karsdal, adding that this may be an important factor influencing future drug compliance.
Exactly how calcitonin impacts pain is not yet fully understood. However, "preclinical evidence tends to support a direct, receptor-mediated action that is independent of opioid action," Dr. Karsdal explains. "Some evidence, however, has suggested a calcitonin interaction with opioid receptors."
Reference
- Sondergaard BC, Østergaard S, Qvist P, et al. Oral calcitonin protects against experimentally induced osteoarthritis. Presented at: 10th World Congress of the Osteoarthritis Research Society International; December 8–11, 2005; Boston, Mass. Abstract P133.