Dr. A. Michael Parfitt brought to the attention of the Editorial Board his article published in a journal not often reviewed by Growth, Genetics & Hormones.  I have summarized some of the highlights of this very interesting article and recommend that the readership review the full paper, as it is of great interest.

 

Parfitt AM. Misconceptions: Epiphyseal Fusion Causes Cessation of Growth. Bone 2002;30:337-339.

 

This paper brings to light the fact that when the bone reaches its appointed genetically determined length, the following takes place: the longitudinal growth ceases, the epiphysis fuses with the metaphysis, and the growth plate disappears. Pediatric endocrinologists have always believed that growth stops because the epiphysis fuses, and that short adult stature could result from early fusion of the epiphyseal growth plate. The reverse is also true - a sustained linear growth through puberty could be a consequence of failure of epiphyseal fusion.  However, Dr. Parfitt suggests that the epiphysis fuses because growth stops.  In other words, fusion is the marker of growth cessation, not a determinant of it.

 

Epiphyseal fusion is an active process that might not necessarily be preceded by, nor automatically follow, the cessation of growth.  Endochondral ossification represents the culmination of a sequence of changes in the cartilage cells and their associated matrix. These events must always occur in the same order, requiring a minimum period of time. It has been shown that the growth plate narrows, not because cartilage replacement occurs earlier, but because cartilage addition occurs more slowly as the rate of chondroblast proliferation declines. The growth plate does not begin to disappear until proliferation has stopped altogether.  Collectively, the data demonstrate that epiphyseal fusion does not precede, but rather follows the cessation of growth.  Nevertheless, fusion is not simply the result of continued cartilage replacement with no further cartilage addition; this is an active process with its own hormonal controls, cellular mechanisms and structural features. For example, if there is estrogen deficiency, the epiphyses may remain unfused long after growth has stopped, with resumption of the normal timetable of fusion after replacement of the missing hormone.  However the complexity of estrogen action at the growth plate has contributed to the current confusion.  Estrogen has separate and independent effects on chondroblast proliferation and on active epiphyseal fusion. It has a biphasic effect on proliferation, which is stimulated by low levels and inhibited by high levels.  The latter predominate in late adolescence in both sexes, leading initially to growth cessation and subsequently to active fusion.  Dr. Parfitt concludes that recognizing the correct temporal relationship between growth cessation and fusion is an essential first step to understanding the complexities of growth plate function, but evidently a great deal more work is needed to clarify all the sequences. 

 

Editor’s Comment: The effects of the high levels of estrogens found in sexual precocity may account for the early fusion of the epiphyses and the reduced height of the patients. The biphasic effect of estrogen on chondroblast proliferation as stated by Dr. Parfitt would account for these findings.

 

Fima Lifshitz, MD

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