Following the description in 1937 by Albright, Butler, and Bloomberg (1) of "rickets
resistant to vitamin D," a number of observations were published, particularly
by Van Crefeld and Arons (2), Fraser and Salter (3), and by Royer (4) which indicated
that there was a variant of resistant rickets which differed from classical hereditary
hypophosphatemic vitamin D-resistant rickets by its clinical and biological symptoms,
and response to therapy.
Rickets was primarily a disease of temperate countries but after a long period of
eradication it has reappeared among the immigrants in these countries (1-5).
India is the seventh largest country in the world with great diversity in its topography,
climate, ecology, and demographic characteristics. Its land mass falls between
7° and 37° of latitude South.
China is a developing country located in the temperate zone. Its mainland extends
approximately from 20° to 53° northern latitude. In 1988 China had a large population
of 1.08 billion, with almost 300 million children under the age of 14. About 20 million
infants are born each year.
Vitamin D is a most interesting seco-sterol that has its origin dating back at least
0.5 billion years ago when it was produced in ocean-dwelling plankton (1).
In the past 20 years a voluminous literature has been written on the role of vitamin
D in calcium homeostasis. This outpouring of experimental findings stemmed from
the discovery that vitamin D was the precursor of a steroid hormone, 1,25-dihydroxyvitamin
D [1,25(OH)2D], which affects calcium transport across cell membranes
In most mammalian species, 80% to 90% of body phosphate is present in bone
mineral as a major component of hydroxyapatite. The rest is in soft tissue, blood
cells, and in the extracellular fluid.
Parathyroid hormone (PTH), an 84 amino acid, linear polypeptide with a molecular
weight of 9500, is the principal regulator of the concentration of ionic calcium in
A sound knowledge of the basic mechanism of endochondral ossification is paramount
for understanding normal and disturbed growth.
Bone matrix formation and mineralization is a complex process which is under
the control of the osteoblasts and nearby osteoid osteocytes.
In many countries the "common" denomination given to vitamin D-deficient rickets
only has an historical meaning as the affection has become rare.
There has been until recently a general consensus among experts in the field of
metabolic bone disease, that a dietary lack of calcium produces few pathological
consequences in man.
Metabolic bone disease is a well recognized problem in premature infants. It has
been called "osteopenia, osteoporosis, hypomineralization, undermineralization, demineralization,
or rickets of prematurity."
The quality of the mature skeleton reflects a long series of uninterrupted biological
events that have their beginning early in gestation.
Rickets or osteomalacia may arise from a defect anywhere in the bone mineralization
pathway, which begins with the process of vitamin D activation, includes
input of minerals to the bloodstream, and ends with accumulation of mineral crystals
Chronic hypophosphatemia is one major cause of rickets and osteomalacia in growing
children (see Preface of this volume).
Rickets has probably been a common disease entity since ancient history (1). Data
regarding prevalence of the condition are only available, however, since the latter
half of the nineteenth century when epidemic proportions were noted in industrialized
countries, including Norway.
Introduction of vitamin D to dried or evaporated milk, administration of cod-liver
oil supplements, and health education at school, in maternity hospitals and by general
practitioners, greatly reduced the prevalence of vitamin D-deficiency rickets in the
United States after 1938 (1) and in Great Britain after 1945 (2).
The prevalence of nutritional rickets in different populations depends on their
geographical situation, skin pigmentation, and socioeconomic level.
Although it has been known for over 40 years that vitamin D is essential for maintenance
of normal calcium and phosphorus metabolism in human beings, the daily
amount of vitamin D needed by an infant for protection from rickets is still far from
being precisely established.