Case: Vitamin D: Prevention of Rickets and Osteoporosis.
Principals: Elmer McCollum
Vitamin D is an essential micronutrient. It has a major role in the fixation of Calcium in
our body and therefore plays an important role in the growth and maintenance of a
healthy skeleton. However, further roles of vitamin D have been discovered over the
last decades and are still explored today, such as immuno-modulatory and anti-
Lack of vitamin D is divided into two levels of severity-deficiency and insufficiency.
These are defined according to the concentration of 25(OH)D in the serum, the
circulating, more stable form of the vitamin. Deficiency status is defined as 0 to 40
nmol/L while insufficiency includes the range of 40 to 80 nmol/L.
Deficiency, which defines an extreme lack of the micronutrient is directly related to
Rickets, a sever childhood disease that causes bone deformities, and to Osteomalacia, a
painful adulthood disease where the deficient calcium fixation leads to softening of the
bones, affecting mainly women following pregnancy.
Vitamin D insufficiency was found to be related to different long latency diseases,
including those related to Calcium such as Osteoporosis, Muscle pain and fatigue and
Hypertension/Cardiovascular diseases. Due to its antiproliferative and
immunomodulatory functions, vitamin D deficiency is also related to Cancer (breast,
colon, prostate), to Diabetes, Multiple sclerosis and Lupus. (Whiting & Calvo, 2005)
Vitamin D is produced in the human body from Pre-vitamin D3, depending on the
exposure to sun-light, more specifically to Ultraviolet-B radiation. Seasonal variations
of exposure, use of sun screen, melanin pigmentation and ageing, all affect the
cutaneous production of the vitamin. Vitamin D is also obtained by dietary intake of
eggs, liver and fatty fish as well as supplementation and fortified foods. The need for
dietary intake is closely related to UVB exposure. In the absence of exposure to
sunlight, the dietary requirement for vitamin D becomes much higher than in its
presence, resulting in the complexity of recommendations establishment for dietary
intake and fortification. (Holick, 2004; Whiting & Calvo, 2005)
History and Investigation of Rickets
Rickets is one of the most important diseases of infancy because of its serious
complications, including disorders of long bone growth, bowing of legs, pelvic deformity
and, in extreme forms in infants, tetany and convulsions.
The early history of rickets seems to begin with ancient medical writings from the 1st and
2nd century AD, describing bone deformities among infants, by Soranus, a Roman
physician and Galen, of the same era. In 1650 Francis Glisson, a Cambridge physician,
published a treatise on Rickets, describing the clinical features and suggesting treatments.
At the turn of the 20th century, Rickets was rampant among infants living in
industrialized, polluted cities of north-America and Europe. The disease had a very
common occurrence, and yet- nor its exact etiology neither effective treatment were
elusive. Anti-rachitic properties of Cod-liver oil were known and used and together with
dietary animal experiments and epidemiologic understanding of the correlation between
sun-light exposure and Rickets, led to solving the riddle of Rickets. Edward Mellanby, an
English physician, was the first to clearly establish the role of diet in the cause of rickets,
via animal experiments led in 1919, and to determine the existence of an "antirachitic
factor". However, it was Elmer McCollum, a nutritional biochemist, who developed a
method of biological analysis of nutritive value of foods and eventually discovered
vitamin D, thereby discerning the exact nature of the "antirachitic" dietary factor.
(Rajakumar, 2003). In 1919, investigators in Germany showed that exposure to sunlight
cured rickets, and that it acted by altering fats to produce vitamin D.
Rickets, a childhood nutritional deficiency disease, was widespread in industrialized
countries. In 1870, for example, it was believed that as many as one third of the poor
children of such cities as London and Manchester suffered from obvious rickets. As late
as 1921, McCollum claimed that probably half of the children in the United States had
rickets (Rosen p 387).
Rickets remained widespread until fortification of milk was introduced in the 1940s
during World War II in Britain and North America. Rickets prevalence in the United
Kingdom, especially in the industrial cities in northern England and Scotland, declined
dramatically. In Canada, although antirachitic procedures (cod liver oil and adding
vitamin D to milk) were routine during the 1940s, the practice waned in the 1950 and
1960s. The 1971 Canadian national nutrition survey found significant vitamin D
deficiencies in certain age, sex, ethnic and geographic population groups. Addition of
vitamin D was made mandatory in Canada in 1979, and rickets disappeared. During the
years, hospitalizations for rickets in Montreal followed the abandonment of vitamin D
Vitamin D content of human milk is extremely low and the exclusively breast-fed infant
not adequately exposed to sunlight may develop clinical rickets. In adults, malabsorption
or poor dietary intake of vitamin D can result in osteomalacia with fragile bones and
frequent fractures. Among the elderly, who are closed-in especially during winter months
or among homebound or institutionalized patients, vitamin D deficiency is common.
Reemergence of Rickets has been noted in the United States and affected mostly black
infants who were exclusively breastfed over 6 months. Rickets cases reported in the US
between 1996 and 2003 numbered 166, among mostly black breast fed children
In Israel, during the late 1970s, clinical signs of rickets were reported among 1.5% of
children 0-2 attending mother and child health stations. During the 1980s, admissions
to hospital in several parts of the country reported dozens of cases per year among
hospitalized children. In 1995, a Canadian report noted that despite the knowledge of
sunlight and enrichment of milk with vitamin D, rickets had not completely
disappeared, and that 17 cases of nutritional rickets were diagnosed at the Toronto Sick
Children's Hospital from 1990 to 1995.
Another burning issue related to lack of vitamin D is Osteoporosis. Osteoporosis has its
highest occurrence among post-menopausal women and result in the lost of bone-mass,
often leading to fractures, including those of the hip and spine. Those fractures are
related to significantly higher morbidity and mortality.
In 1998, a study that showed the prevalence of vitamin D deficiency was common
among hospitalized patients was reported in the New England Journal of Medicine
(Thomas, 1998). An editorial in the same edition noted that residents of latitudes of 40
degrees north of the equator make little vitamin D in winter. The editorial goes onto
state "Administration of vitamin D to older subjects with or without low serum 25-
hydroxyvitamin D concentrations slow bone turnover and increases bone density. Most
important of all, vitamin D and (calcium) supplementation in older subjects can reduce
the rates of hip and other fractures." (Utiger, 1998)
Vitamin D is attracting much attention from researchers for a role in immune system
maintenance and in cancer prevention, and while this is still in the hypothesis
generation stage, the evidence for such roles is mounting (Cantorna , Zhu, Froicu , and
Wittke, 2004). The immense spread of those diseases in the world makes the issue of
adequate vitamin D supply a global concern, affecting people of all ages and socio-
economic classes and stressing the need for supplementation and fortification.
Global high prevalence of vitamin D insufficiency and re-emergence of rickets and the
growing scientific evidence linking low circulating 25-hydroxyvitmain D to increased
risk of osteoporosis, diabetes, cancer and autoimmune disorders have stimulated
recommendations to increase sunlight (UVB) exposure as a source of vitamin D.
However, concern over increased risk of melanoma with unprotected UVB exposure
has led to the alternative recommendation that sufficient vitamin D should be supplied
through dietary sources alone.
Vitamin D intake is often too low to sustain healthy circulating levels of 25-
hydroxyvitmain D in countries without mandatory staple food fortification, such as
with milk and margarine. Even in countries that do fortify, vitamin D intakes are low in
some groups due to their unique dietary patterns, such as low milk consumption,
vegetarian diet, limited use of dietary supplements, or loss of traditional high fish
The solution, therefore, lies in a multiple strategy approach, considering both
supplementation, targeted to higher risk groups, and food fortification in order to reach
the general population. However, the effect of fortification of food with vitamin D in
reducing the risk of fracture or other chronic disease risk has not been appropriately
evaluated in any country to date. (Calvo, Whiting and Barton, 2005)
Public Health Importance
Hypovitaminosis D and related abnormalities in bone chemistry are most common in
elderly residents in Europe but are reported in all elderly populations. Adequate
exposure to summer sunlight is the essential means to ample supply, but oral intake
augmented by both fortification and supplementation is necessary to maintain baseline
stores (McKenna, 1992). Although hypovitaminosis D has been detected frequently in
elderly and housebound people, widespread preventive action has been slow to develop.
In 1995 the number of hip fractures in 15 countries of EC has been 382,000 and the
estimated total care cost of about 9 billion of ECUs. (Gennari,2003) In the United
Kingdom, hip fractures were found to place the greatest demand on resources and
have the greatest impact on patients because of increased mortality, long term
disability, and loss of independence. (Woolf and Akesson, 2003)
Given the public health implications of osteoporotic fractures, the primary goal of
osteoporosis therapy is to prevent fractures by slowing or preventing bone loss,
maintaining bone strength, and minimizing or eliminating factors that may
contribute to falls (North American Menopause Society, 2002). It goes on to
recommend that steps be taken to increase vitamin D intake, by nutritional advice to
patients, planning institutional meals and alerting physicians to the nearly universal
need for more vitamin D. A widespread increase in vitamin D intake is likely to
have a greater effect on osteoporosis than many other interventions. (Utiger, 1998)
Concern with Vitamin D deficiency among elderly women with a high risk of
fracture particularly in winter months has raised the issue of routine vitamin D
supplementation, which is cheap and effective and should be considered in people
over 70 years of age who have a high risk of fracture and who live in temperate
climates or northern.
To conclude, vitamin D deficiency not only causes rickets among children but also
precipitates and exacerbates osteoporosis among adults and causes the painful bone
disease osteomalacia. Vitamin D deficiency has been associated with increased risks of
deadly cancers, cardiovascular disease, multiple sclerosis, rheumatoid arthritis, and type
1 diabetes mellitus. Maintaining blood concentrations of 25-hydroxyvitamin D above
80 nmol/L ( approximately 30 ng/mL) not only is important for maximizing intestinal
calcium absorption but also may be important for providing the extrarenal 1alpha-
hydroxylase that is present in most tissues to produce 1,25-dihydroxyvitamin D(3).
Although chronic excessive exposure to sunlight increases the risk of nonmelanoma
skin cancer, the avoidance of all direct sun exposure increases the risk of vitamin D
deficiency, which can have serious consequences. Sensible sun exposure (usually 5-10
min of exposure of the arms and legs or the hands, arms, and face, 2 or 3 times per
week) and increased dietary and supplemental vitamin D intakes are reasonable
approaches to guarantee vitamin D sufficiency. (Holick, 2004)
Where Do We Go from Here?
Prevention of vitamin D deficiency conditions should include routine supplements of
vitamin A and D for infants from 1-12 months. Standard textbooks of pediatrics and of
public health should take the same position in respect to vitamin D deficiency. It is a
problem in childhood and the elderly that cannot be addressed by providing vitamins to
high risk groups, and milk fortification is justified. The use of milk as the vehicle for
supplementation is logical, since vitamin D is fat-soluble, acid labile substance that
requires buffering against the acid milieu of the stomach; the high calcium content of
milk is a bonus. (Haddad, 1992) Fortification of baby formulas, infant cereals and milk
products is one of the most important public health nutrition measures used. Failure to
promote its application internationally has been an important lapse of the international
In addition, the recommended adequate intake should be further increased. . To increase
intake, the amount of vitamin D in milk or cereal could be increased, but because that is
not likely to be effective for adults, fortification of other foods should be considered.
The amount of vitamin D in supplemental multivitamins or calcium supplements should
be increased substantially, and all adults should be advised to take them. (Utiger, 2003)
For older persons, supplemental oral intakes of approximately 1300 IU/d are needed to
reach the low end of the optimal range of vitamin D levels. This cannot be monitored
clinically because of difficulty in routine clinical measurement of serum 25(OH)D(3)
concentrations among patients, so that a population risk group approach is needed,
along with standardization and improved reproducibility and sensitivity of
measurements of serum 25(OH)D(3) levels.
The American Academy of Pediatrics in 2003 published new guidelines for vitamin D
”Rickets in infants attributable to inadequate vitamin D intake and decreased exposure
to sunlight continues to be reported in the United States. It is recommended that all
infants, including those who are exclusively breastfed, have a minimum intake of 200
IU of vitamin D per day beginning during the first 2 months of life. In addition, it is
recommended that an intake of 200 IU of vitamin D per day be continued throughout
childhood and adolescence, because adequate sunlight exposure is not easily
determined for a given individual.” (Gartner and Greer AAP, 2003)
All countries should adopt a fortification policy for vitamin D for the benefit of all age
groups including the extremes of life but also the adolescent and middle ages. It seems
likely that the elderly would benefit additionally from a daily supplement of 10
micrograms of vitamin D.
Major international organizations including the World Health Organization, UNICEF
and the Food and Agriculture Organization have failed to address the problem of
vitamin D deficiency. This is possibly explainable on the grounds that there are more
acute micronutrient deficiency problems such as Iodine, Vitamin A and iron deficiency
internationally, but this does not justify ignoring the problem, especially in northern
climate countries where sun exposure is limited seasonally and where no other source
of vitamin D is available such as in fortified milk. Preventing fractures in elderly people
is a priority, especially with the increase in the elderly possibly to a quarter of
population in the industrialized countries over the next 2 decades.
The population approach in nutrition has a well-established track record in preventing
important micronutrient deficiency conditions and related chronic diseases. Food
fortification is essential to reach many who either do not or cannot respond to the
individual approach of health education and a healthy diet, due lack of knowledge or
access, or to its higher cost, and supplementation is essential for specific high-risk
The ramifications of all this are many: fortification of milk products with vitamin D;
routine supplements to infants and children up to adolescents, routine supplements to
adult and elderly; measures to prevent falls among the elderly; education about the need
for regular sun exposure for the adult and elderly population (avoiding excess for fear
of skin cancers), regulation and education among food manufacturers of good
fortification and manufacturing practices; education for good nutrition and increased
awareness of nutrition among primary care givers and the public generally.
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