Agreement

We appreciate Dr. Frost’s keen interest in our article. His comments are quite insightful. We believe the issues raised by Dr. Frost can be distilled down to one question: Does longitudinal growth increase under physiological levels of loading? Frost has proposed a longitudinal growth curve called the CGFR curve illustrated in Fig. 2 of his letter. The important feature of his theory is the upward sloping line on the right side of the curve. This region of the CGFR curve suggests that normal loading (i.e., everyday activities) increases longitudinal growth over that caused by trivial loading (i.e., disuse). To justify his theory, Frost cites “natural experiments,” namely, lower limb paralysis caused by myelomeningocele or poliomyelitis. Frost notes correctly that when one limb is affected by paralyzing disease, the longitudinal growth rate tends to be suppressed. We take some issue with Frost’s interpretation of these natural experiments. He assumes that the suppressed longitudinal growth in the paralyzed limb occurs solely because of disuse. We assert that it is also possible that the disease itself might affect limb growth. A better test of Frost’s theory would be an experiment that produces limb unloading without disease or paralysis. This experiment has been done. Growing rats subjected to hind limb unloading for 4 weeks did not exhibit reduced length of their affected limbs. The rats’ hind limbs were lifted off the ground by suspending their hind quarters. The limbs could be moved freely but did not support any weight. One might argue that the growth plates of the unloaded limbs sustained small loads because of the muscle contractions that caused the limbs to flail about, yet these loads would fall into the category that Frost called “trivial” and therefore, according the CGFR theory, longitudinal growth should be suppressed. This controlled experiment seems to contradict the CGFR theory. In an earlier experiment, Lanyon performed sciatic neurectomy followed by patellar tenotomy on very young (4-week-old) rats. Sixteen months later, the immobilized tibias were exactly the same length as the control tibias. This experiment shows that immobilization does not inhibit longitudinal growth over the long run. Nevertheless, a recent study reported reduced longitudinal growth rate in the tibias of young rats subjected to hind limb unloading for 3 weeks. This study used essentially the same protocol as the previously mentioned study that showed no influence of hind limb suspension on bone length. Unfortunately, the studies that reported longitudinal growth rate did not report total bone length and vice versa, therefore, it is difficult to resolve the disparate results. The results seem to suggest that longitudinal growth rate is suppressed by disuse, but that disuse does not affect the final length of the bone. Hence, it appears that the effect of unloading on skeletal growth is not quite as clear as Frost’s natural experiments might lead us to believe. Additional controlled experiments would be helpful. Our experiment tested the effects of compressive loading on longitudinal growth. We superimposed a short (10minute) application of dynamic compressive loading onto the normal daily activities of the rats. We applied three peak load magnitudes: 4 N, 8.5 N, and 17 N. The lowest of these loads was well within the normal loading range of rats (for discussion of normal loading in the rat ulna, please refer to the study by Ohashi et al. [p. 286]. Based on Frost’s CGFR theory, we anticipated that the 4-N load would enhance longitudinal growth and the 8.5-N and 17-N loads would suppress growth. Instead we found that all load magnitudes suppressed growth. Therefore, based on our experiments, we concluded that dynamic compressive loads superimposed on normal physiological loading suppress longitudinal growth. We conclude that the effect of mechanical compression on longitudinal growth follows a curve illustrated by the dashed line in Fig. 7 of our study (Fig. 1 of Frost’s letter). This is also consistent with the far right side of Frost’s CGFR curve.