118 Rickets and Osteomalacia
Rickets and osteomalacia are diseases with multiple etiologies primarily related to abnormal metabolism of vitamin D and secondarily to calcium and phosphate metabolism. Of the many causes, by far the most important relate to dietary vitamin D deficiency and the activation of vitamin D precursors by the kidney and sunlight.
Rickets and osteomalacia are characterized pathophysiologically by a failure of normal mineralization of bone and epiphyseal cartilage and clinically by skeletal deformity. Rickets occurs in growing infants and children, and both bone and epiphyseal cartilage are affected. Osteomalacia occurs in adults after closure of the epiphyses, and its manifestations are often much less prominent.History
Historically, rickets was among the earliest diseases to be described. As early as 300 B.C., Lu-pu-wei described crooked legs and hunchback; however, these can occur with other disorders. More specifc references are found in the separate writings of three Chinese physicians of the seventh and eighth centuries A.D., including enlarged head, body wasting, pigeon breast, and delayed walking. By the tenth century, Chien-i, the Father of Chinese pediatrics, described many cases of rickets (Lee 1940).
In the second century A.D., Soranus of Ephesus mentioned characteristic deformities of the legs and spine in young children and remarked on the higher frequency in urban Rome compared to Greece. Slightly later, Galen’s work included a description of skeletal deformities in infants and young children, particularly the knock-knee, bow leg, and funnelshaped chest, and pigeon breast seen in rickets. Sporadic and somewhat ambiguous references to the disease were made until the mid-seventeenth century, when the classic descriptions of Daniel Whistler and Francis Glisson appeared.
In 1645 Whistler published his medical thesis in Latin, On the Disease of English Children which is Popularly Termed the Rickets.
Five years later, Glisson wrote the classic text on the subject, still unsurpassed as a clinical description of rickets. Both physicians considered the disorder of recent origin, and indeed the northern climate, crowded living conditions, and socioeconomic changes may have influenced its prevalence at that time. Glisson himself noted a number of cases affecting the “cradles of the rich,” perhaps related to the use of swaddling clothes and the vitamin D-deficient diet of pap and starch.The word “rickets” was first used in the London Bill of Mortality report for 1634. The derivation of the word has been a source of contention since that time. Possibilities include rucket in Dorset dialect, meaning “short of breath”; the verb rucken, meaning “to rock or reel”; the Middle English word wricken, denoting “to twist”; the Saxon word rick, meaning “heap” or “hump”; or the Norman word riquets, for hunchback. Glisson suggested the term “rachitis” derived from the Greek word for spine, and this term remains in use in many countries today.
Nearly 250 years passed before the specific role of vitamin D and its active metabolites was elucidated via biochemical studies. L. Findlay (1908) reproduced the disease in puppies raised in a confined, darkened space. A year later, Georg Schmorl (1909) demonstrated the striking seasonal variation of the disease by autopsy findings. In 1917 Alfred F. Hess and L. J. Unger described the prevention of rickets by use of cod liver oil or by ultraviolet irradiation. Shortly thereafter, a number of researchers, particularly the group of Elmer V. McCollum (1922), isolated vitamin D and related compounds. A better understanding of the exact mechanisms and conversion of vitamin D metabolism into more active forms was gained only since the mid-1960s and 1970s (Lund and DeLuca 1966; Fraser and Kodicek 1970).
Vitamin D is classified more accurately as a prohormone rather than a vitamin. It is formed by the interaction of ultraviolet light with a cholesterol derivative in the deeper layers of the skin, but small amounts of vitamin D may also be derived from dietary sources such as dairy product and fish liver oils.
Vitamin D is then hydroxylated once in the liver, and a second hydroxylation into the highly active hormone occurs in the kidney. It acts upon the target organs, intestine, and bone to regulate serum calcium and phosphate levels and the mineralization of bone.Paleopathology
As a disease producing characteristic skeletal deformities, rickets can be traced back to antiquity by direct examination of the skeletal evidence. As expected, the disease was extremely rare in ancient Egypt. Only one or two possible cases have been described in skeletal remains from North and South America. Most reported examples of ancient rickets come from Europe. A few date back to Neolithic times in Norway, Sweden, and Denmark. Examples become more plentiful during the Middle Ages in cities across northern and central Europe, again confirming the central role of inadequate sunlight in causing the disease (Steinbock 1976).
Epidemiology, Distribution, and Geography
As early as 1890, Theobald A. Palm gathered data via correspondence with medical missionaries worldwide and concluded that the main etiologic factor in rickets is the lack of sunlight. It was much later before scientists linked the variable pigmentation in the races of men with the regulation of vitamin D synthesis (Loomis 1967). The processes of pigmentation and keratinization of the outer layer of the skin (stratum corneum) directly affect the amount of solar ultraviolet radiation reaching the deeper stratum granulosum, where vitamin D is synthesized. White or depigmented skin of the northern latitudes allows maximum ultraviolet penetration. Black or heavily pigmented skin and Oriental or keratinized skin minimize UV penetration in southern latitudes to maintain vitamin D synthesis within physiological limits. The skin pigmentation or keratinization also plays a role in preventing sun-induced skin cancer, a greater problem among light-skinned groups who move to sunnier climates.
A cautionary note should be included when discussing the incidence or prevalence of rickets.
The diagnosis of rickets will vary, depending on the nature of the criteria utilized - clinical, radiographic, or biochemical. Moreover, the sensitivity of each of these methods varies considerably according to the stage of the disease or age of the individual.Historically, the incidence of rickets increased with the rise of sunless, crowded urban centers as part of the Industrial Revolution. Indeed, rickets may, among other things, be considered as an air pollution disease since factory-produced smog filters and decreases the available ultraviolet light (Loomis 1970). As Palm (1890) deduced from this worldwide correspondence: “It is in the narrow alleys, the haunts and playgrounds of the children of the poor, that this exclusion of sunlight is at its worst, and it is there that the victims of rickets are to be found in abundance.”
In 1899 Theodor Escherich reported that in Vienna 97 percent of infants between 9 and 15 months had clinical evidence of rickets. An autopsy analysis in Dresden, Germany, by Schmorl (1909) showed that 89 percent of all children between 2 months and 4 years of age exhibited evidence of active or healed rickets. Schmorl also noted a striking seasonal variation in the presence of rickets. Similar high numbers were reported near the turn of the century for Oslo, Bergen, Berlin, Glasgow, Dublin, Belfast, Edinburgh, Paris, Florence, and Moscow (cf. Owen 1889; Hess 1929). Some authorities noted a general decrease in rickets at higher altitudes in the Scottish Highlands and Swiss Alps, related to the increased ultraviolet component of solar radiation. However, cases became more numerous and severe at the highest altitudes, presumably related to the practice of keeping the infants heavily bundled or indoors nearly year round (see Feer 1916).
Large American cities also had a high prevalence of rickets. In 1900 John L. Morse estimated that 80 percent of all infants under 2 years of age in Boston had rickets. Hess reported in 1921 that 75 percent of New York City children had clinical evidence of rickets (see also Hess 1929).
Martha M. Eliot (1925) found that 83 percent of infants under 8 months of age in New Haven had radiographic findings of mild rickets. L. R. Du Buys (1924) noted that rickets was widespread in New Orleans, and the clinical manifestations were more marked in blacks than whites.As a deficiency disease involving sunlight and diet, cultural and socioeconomic factors interacting with climate are important in the epidemiology and geographic distribution of rickets and osteomalacia. In general, rickets is uncommon in sunny climates; however, even sun-rich areas may have rickets. For example, nearly 30 percent of children seen at an Ethiopian clinic had clinical evidence of rickets, primarily related to a shortened period of breast feeding and swaddling of infants to avoid the “evil eye” (Mariam and Sterky 1973). In many Moslem countries, the custom of purdah — the complete shielding of women and young children indoors or with veils — is a major factor in rickets and osteomalacia. A study of 1,482 Moslem girls in India, aged 5 to 17 years, showed that 40 percent had skeletal evidence of rickets (Wilson 1931).
Among many Asian groups the use of Chupatti flour as a dietary staple also contributes to the prevalence of rickets. The high phytate content in the wheat fiber binds calcium and zinc, resulting in decreased intestinal absorption of these minerals. In addition, the lignin component of wheat fiber binds to bile salts and ingested vitamin D, decreasing their absorption (Reinhold 1976). The use of raghif an unleavened bread rich in phytates, is also a factor in osteomalacia among Bedouin women of childbearing age (Shany et al. 1976).
An unfortunate synergistic effect of decreased sunlight and high cereal, rice, or maize diet has been reported in both epidemiological and experimental studies (Robertson et al. 1984; Sly et al. 1984). Indeed, the effects of phytates, lignin, and other components in these grains may be rachitogenic even in the presence of adequate sunlight (Wilson 1931; Pettifor et al.
1978).With the addition of synthetic vitamin D to dairy products and bread in the United States, there has been a dramatic decline in the incidence of rickets. Between 1956 and 1960, fewer than 0.4 cases per 100,000 pediatric admissions were for rickets. Vitamin D supplementation is not practiced in Britain, and 9 percent of young children in Glasgow had radiographic evidence of rickets (Richards et al. 1968). Osteomalacia among the elderly remains a significant public health problem related to decreased exposure to sunlight, intestinal malabsorption, poor diet, and decreased hydroxylation of vitamin D by the liver and kidneys. Osteomalacia in combination with osteoporosis is therefore an important factor in the occurrence of hip fracture among the elderly.
■ R. Ted Steinbock
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