Weight Loss Affects Bone
Yet another delegate cautioned on the potential effects of significant weight loss on bone and cartilage. There is evidence, he said, that weight loss of 5-10 kg can significantly affect bone turnover, increasing bone resorption and thus putting patients at a risk of becoming osteopenic. “Are we looking at a new population of osteoporosis patients who may then also be at risk for fractures?” he asked.
Separately at OARSI 2024, Anne C. Bay-Jensen, PhD, chief technology officer at Nordic Bioscience in Herlev, Denmark, and colleagues reported data showing that weight loss was associated with an increase in bone and cartilage degradation.
Although Dr. Bay-Jensen and colleagues found that losing weight was associated with improved patient outcomes, there was a 1.58-fold increase in the bone resorption marker CTX-I in people who had lost weight vs a 1.37-fold gain in those whose weight remained stable and 1.11-fold increase in those who gained weight.
Moreover, there was a 1.15-fold increase in the cartilage degradation marker C2M in the weight loss group and 0.84-fold decrease in the interstitial matrix degradation marker C3M.
GLP-1 and Bone Effects
Another question is whether GLP-1 receptor agonists might be having direct effects on the bone that may be beneficial in OA. They might, postdoctoral researcher Eda Çiftci, PhD, of AO Research Institute Davos in Switzerland, and collaborators, said during the poster sessions at OARSI 2024.
Dr. Çiftci and researchers reported the findings of an in vitro study that looked at whether liraglutide might have anti-inflammatory and anabolic effects on a human chondrocytes model that had been treated with interleukin (IL)-1-beta to “mimic an inflammatory OA condition.”
The release of the proinflammatory cytokines IL-6 and IL-8 was reduced by treatment with liraglutide when compared with control chondrocytes. Furthermore, the expression of the proteoglycan aggrecan — important for articular cartilage function — also was preserved.
These results suggest that liraglutide does indeed have anabolic and anti-inflammatory effects, Dr. Çiftci and fellow researchers concluded.
New Role for Dipeptidyl Transferase Inhibitors?
Researchers are also looking at the potential role for other diabetes medications in OA management, including the dipeptidyl peptidase (DPP) 4 inhibitors.
Although these drugs are considered “weight neutral,” in vitro studies have suggested that the DPP4 enzyme may have a role to play in chondrocyte survival and inflammation, Yu-Hsiu Chen, MD, of the Tri-Service General Hospital and the National Defense Medical Center in Taipei, Taiwan, told this news organization. The DPP4 enzyme inactivates GLP-1, so there is rationale there.
“Last year, we published a paper where we found the concentration of DPP4 in the synovial fluid was correlated with radiographic change in knee OA,” Dr. Chen said. This time, “we’re trying to see if a DPP4 inhibitor can be used as a treatment.”
For their analysis, they used data on people newly diagnosed with type 2 diabetes who were and were not using DPP4 inhibitors obtained from Taiwan’s National Health Insurance Research Database. This database contains information on 99% of the Taiwanese population, Dr. Chen said.
Matching 165,333 DPP4 inhibitor users with an equal number of nonusers showed that there was a significant 58% risk reduction for developing OA with DPP4 inhibitor use (hazard ratio, 0.42; 95% CI, 0.41-0.44).
DPP4 inhibitor use was also associated with a 58% risk lower risk for total knee replacement (TKR) and a 62% lower risk for total hip replacement.
Dr. Chen and colleagues concluded: “These results strongly indicate that DPP4 inhibitors could be considered as a viable treatment approach for individuals with type 2 [diabetes mellitus] who are at risk for developing OA or [who] already have OA.”