Although nowhere nearly as robustly (or obviously) as muscles, bones also develop in response to exercise. Because this effect is largely hidden from view, however, most athletes are not aware of its importance to athletic performance. In truth, bones must increase in strength in parallel to muscle mass in order to support the higher levels of mechanical stress being placed upon them by stronger, larger muscles. As we will learn today both these processes are reliant on creatine…

In my last post (see Creatine builds strong bones… part 1) I made the case that creatine supplementation, by way of maximizing muscular force generation, promotes bone formation (osteogenesis). Although muscular activity surely contributes to the bone formation observed with creatine, this cannot be the entire story. Situations have been described where creatine treatment promotes osteogenesis outside the animal. That is, creatine supplementation, in the absence of mechanical stimulation imposed by skeletal muscle, also appears to promote bone formation.

Osteogenesis: Delicate Balance Between Bone Loss and Gain
Osteogenesis is an ongoing battle between two types of bone progenitor cells, osteoclasts that destroy existing bone and osteoblasts that lay down new bone matrix. Mechanical stimulation activates osteoblasts, whereas it inhibits the destructive behavior of osteoclasts. Via the selective activation of osteoblasts exercise stimulates bone development.

Creatine Supports Bone and Cartilage Development
Areas of active bone and cartilage growth have been shown to possess high levels of phosphocreatine (the biologically active form of creatine). The incidence of creatine transporters (that deliver creatine to the inside of cells) is also elevated in areas of bone and cartilage growth. These two findings provide strong evidence for the importance of creatine to the developmental programs of bone and shock-absorbing cartilage. The study we discuss today demonstrates just how sensitive one is to the presence of creatine.

The Study:
“Stimulatory effects if creatine on metabolic activity, differentiation and mineralization of primary osteoblast-like cells in monolayer and micromass cell cultures.” Gerber et al., (2005) European Cells and Materials Volume 10, pages 8-22.
This study was conducted under auspices of a respected colleague at the Swiss Federal Institute of Technology, the ETH. The investigator’s name is Dr. Theo Wallimann one of the leading experts on creatine transport mechanisms.

Dr. Walliman and colleagues conducted their analysis on osteoblastic progenitor cells in tissue culture and hence, outside the animal. Briefly, osteoblasts were isolated from the bones of rats and transferred into sterile containers where they were allowed to organize themselves into either three-dimensional or two-dimensional systems of cells; the three-dimensional configuration is a closer approximation to the natural state. That is, bones are more like solid posts, than flat sheets. The advantage of conducting studies in tissue culture is the cells reside in a minimized environment that is completely under the control of the experimenter and not influenced by other tissue types, or hormones released by the animal into the blood stream. In essence, the scientist can then be assured that they are only examining the effects of creatine on bone development - osteogenesis.

The authors of the study found that creatine treatment significantly improved the ability of osteoblasts to produce nascent bone matrix. Moreover, the “osteogenic” effect of creatine was greater in the three-dimension cultures, providing even greater physiological relevance to the effect of creatine.

Interestingly, lower doses (10 mM; 1.3 grams per liter of cell medium) of creatine appeared to be more effective, than larger doses (20 mM; 2.6 grams per liter of cell medium) at permitting osteoblasts to multiply in number. Larger doses of creatine monohydrate, while still promoting the excretion of bone matrix, reduced the number of surviving cells. That is, although both concentrations of creatine promoted bone development, the larger dose seemed to slow cell growth. This is not the first study to demonstrate an adverse of effect of high doses of creatine monohydrate on cells grown outside the animal. Another study also demonstrated that larger doses of creatine (greater than 0.1%; 1 gram per liter of cell medium) also slowed the growth of muscle cells when maintained in tissue culture. This second study will be discussed at a later date in this blog. Nevertheless, the reason for this growth retarding effect of higher doses of creatine is still unclear. Therefore, at least in tissue culture, high doses of creatine monohydrate appear to exert a negative effect, whereas more moderate doses exert a clear benefit on cell duplication.

This creatine guide gives a dosing protocol to be used with moderate doses of creatine:
http://www.creatinemonohydrate.net/creatine_guide.html

Remaining to be Shown
More studies need to be conducted in intact animals to corroborate this preliminary, yet provocative, finding – that creatine directly enhances the osteogenic potential of osteoblasts. Studies examining the effect of creatine on cartilage formation from progenitors cells (chondrocytes) also needs to be undertaken.

Take home
In brief, creatine supports development of muscle, bone as well as cartilage. On the one level, creatine increases force production by muscle, which serves as an anabolic stimulus for bones and cartilage. On the other level, creatine appears to directly stimulate the production of muscle, bones and most likely cartilage – independently of mechanical stimulation. The combination of creatine and exercise will thus have an even more potent effect on the developmental programs of these important support tissues.

Although for a young person it is hard to image what a loss of these tissues means to one’s quality of life, most elderly endure reduced mobility daily. Creatine supplementation would thus help improve the quality of life of the elderly by helping maintain more youthful levels of muscle, bone and cartilage.

Learn about other benefits of creatine supplementation for the elderly at the following links:
http://www.creatinemonohydrate.net/creatine_elderly.html
http://www.creatinemonohydrate.net/creatine_sarcopenia.html

Stay tuned to part three of this series of posts discussing the positive effects of creatine supplementation over bone development.