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Traditional Chinese Medicine Opens New Path to Treatment of Bone Loss

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Ten million Americans over the age of 50 suffer from osteoporosis. In addition, 34 million are at a serious risk for developing this debilitating bone disease. The severe loss of bone mass and breakdown of the architecture of the bone, osteoporosis thins the bones to a point where a mere cough can cause a fracture. 20% of those suffering with osteoporosis will die within a year after sustaining a broken hip. Within 15 years, half of all Americans over age 50 will be at risk for osteoporosis-related fractures, according to the Surgeon General.

University of British Columbia scientists believe a compound found in red sage, which is used in traditional Chinese medicine, could help prevent bone loss without causing severe side effects. The team was able to block cathepsin K (CatK), which plays a key role in the breakdown of collagen in bones during osteoporosis.

The study (“Ectosteric Inhibitor of Cathepsin K Inhibits Bone Resorption in Ovariectomized Mice”) is published in the Journal of Bone and Mineral Research.

“The potent cathepsin K (CatK) inhibitor, Tanshinone IIA sulfonic sodium (T06), was tested for its in vitro and in vivo antiresorptive activities. T06 binds in an ectosteric site of CatK remote from its active site and selectively inhibits collagen degradation with an IC50 value of 2.7 ± 0.2 μM (CatK:T06 molar ratio of 1:5). …T06 suppresses bone resorption in both human and mouse osteoclasts equally well (IC50 value for human and mouse osteoclasts: 237 ± 60 nM and 245 ± 55 nM, respectively) and its antiresorptive activity is fully reversible in both cell types,” write the investigators.

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“This study indicates that the ectosteric inhibitor, T06, is a selective antiresorptive CatK inhibitor that may overcome the shortcomings of side effect–prone active site-directed drugs, which all failed in clinical trials.”

“The development of osteoporosis drugs by pharmaceutical companies has focused heavily on blocking CatK in recent years,” said Dieter Brömme, D.Sc., professor in the faculty of dentistry and a Canada Research Chair in Proteases and Disease. “All clinical trials to date have failed due to side effects ranging from stroke, skin fibrosis, and cardiovascular issues. We’ve found a way to block CatK only in bone tissue that we think will prevent these other negative effects.”

T06 was tested in human and mouse bone cells and a mouse model and it prevented bone loss and increased the bone mineral density of the mice by 35%, when compared with the control group. Dr. Brömme and colleagues had previously carried out work on red sage (known as Danshen in Chinese and used to treat bone problems) in stopping the activity of CatK in limited ways.

Most drugs in development are active site-directed inhibitors, which act like master keys and lock the entire enzyme, blocking both its disease-relevant functions such as collagen degradation and its other normal functions, according to Preety Panwar, Ph.D., a research associate in the Brömme lab.

“CatK is a multifunctional enzyme with important roles in other parts of the body, and we think completely blocking it is what causes unexpected side effects in other drugs,” said Dr. Panwar. “Our compound only locks the collagen-degrading CatK activity, preventing the unregulated breakdown of collagen in bones without any other negative impacts.”


The treatment could also potentially be used to treat a variety of other bone and cartilage diseases such as arthritis and certain bone cancers, note the researchers.

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