@rjd Agreed - "fully suppressing bone turnover" doesn't make sense. The bone remodeling process includes breakdown and rebuilding. You want good turnover, and you don't want the breakdown process to be greater than the rebuilding process.

@rjd

That’s an excellent point. The foundation of healthy adult bone lies in balanced remodeling - the removal of old or damaged bone and the formation of new bone, as you mentioned.

However, bisphosphonates act selectively on osteoclasts to reduce bone resorption. Because bone formation is coupled to resorption, osteoblast activity also decreases secondarily, leading to an overall reduction of bone turnover. The end result, unfortunately, isn’t a perfectly balanced turnover - far from it. I’d also like to add that a CTX of 361 in an untreated person would probably be considered appropriate, provided there is adequate osteoblast activity.

At present, there’s no precise way to fine-tune these agents to maintain an ideal level of bone turnover, or balanced resorption and formation. The therapeutical goal is to suppress remodeling enough to reduce fracture risk and preserve bone mass, without over-suppression (which might necessitate drug holidays or dosing adjustments). In hindsight, my earlier wording “fully suppressed” would have been better expressed as “sufficiently suppressed.”

That’s my understanding, and I’d love to hear your or anyone else’s thoughts on it.