Each minute, within the skeleton, more than a million sites of old worn-out bone are being eaten away by osteoclast cells, while new fresh bone is laid down by other specialized build-up cells known as osteoblasts. Just how this process of bone recycling and rebuilding is controlled has long been a question of scientific speculation.
Here is where RANK, RANK-L, and OPG enter the picture. Scientific breakthroughs have identified these three strange-sounding proteins and how they participate in the bone turnover process — and thereby identified a new place where science and pharmacology can intervene to prevent bone breakdown.
This insight into the nature of bone breakdown has led to the development of a different kind of osteoporosis drug — Prolia, a monoclonal antibody that was approved for postmenopausal osteoporosis by the FDA on June 1st. Prolia works on the RANK, RANK-L, and OPG proteins, but its mechanisms are unfamiliar to most people. So I thought I would familiarize you with what these acronyms mean:
• RANK is short for “receptor activator of NF-kB” — a receptor sitting on bone breakdown osteoclast cells waiting to be activated. Once activated, RANK signals osteoclasts to mature, get active, and to begin breaking down bone.
• RANK-L is a molecule that binds to RANK, activating it, and initiating the bone-recycling process. In essence, it turns RANK on.
• OPG, short for osteoprotegerin, is a competitor of RANK-L. OPG binds to RANK and does not activate the bone breakdown cells. OPG keeps RANK-L from locking on to osteoclasts, and thus limits the bone breakdown activity of the osteoclasts.
So for someone in good health, the RANK/RANK-L/OPG system is a key regulator of bone breakdown, allowing the body to refresh and renew bone without excessive bone breakdown or excessive bone build-up.
Now for the quiz . . . if you want to reduce bone breakdown what would you do? Well, you could either:
1. Increase OPG so that it would bind to the RANK receptor on the bone breakdown cells and thus deactivate them; or
2. You could inhibit the ability of RANKL to bind to RANK, thus avoiding the activation of the bone breakdown cells.
The new bone drug Prolia takes the second route, inhibiting RANK-L. Sound good? Well it sure can be in some cases, but there is always a price to pay when you interfere with a mechanism of disease instead of addressing the causes of the disease. Two logical questions arise: What other role(s) does activated RANK play in the rest of the body — roles that taking Prolia might interfere with? And is it good for overall health to inhibit RANK-L? In an upcoming article, I will talk more about this new osteoporosis medication. For now, you can be ahead of the crowd — you know about RANK, RANK-L, and OPG.
Be well and enjoy the summer!
We created the Osteo Blast blog as our forum to express opinions and educate the public about natural means of supporting and improving bone health and overall wellness. As part of this forum, we sometimes discuss medical issues and medications, and their effects on bone health in general. However, we cannot advise readers about specific medical issues in this forum. If you wish to obtain advice from Susan E. Brown, PhD, about your specific bone health and nutritional concerns, please visit our Consultations page. Other specific medical questions should be referred to your healthcare provider.