History of Vitamin D from 500 million years ago to orthopaedic practice today – 2019

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Vitamin D: part I; from plankton and calcified skeletons (500 million years ago) to rickets - Sept 2018

Int Orthop. 2018 Sep;42(9):2273-2285. doi: 10.1007/s00264-018-3857-3. Epub 2018 Mar 5.
Hernigou P1, Auregan JC2, Dubory A2.

The vitamin D history started early in the evolution of life (billion years ago) as a photochemical reaction producing an inert molecule. During the early evolution of vertebrates, this molecule became essential for calcium and bone homeostasis of terrestrial animals and arrived to the status of hormone. Phytoplankton, zooplankton, and most plants and animals that are exposed to sunlight have the capacity to make vitamin D. Vitamin D is critically important for the development, growth, and maintenance of a healthy skeleton from birth until death. The major function of vitamin D is to maintain calcium homeostasis. It accomplishes this by increasing the efficiency of the intestine to absorb dietary calcium. When there is inadequate calcium in the diet to satisfy the body's calcium requirement, vitamin D communicates to the osteoblasts that signal osteoclast precursors to mature and dissolve the calcium stored in the bone. The typical "vitamin D-deficiency" disorder was observed for growing children in the west and south of England in the early 1600s. This disease was described by Glisson and named "rickets" (known also as "the English disease") and was observed with epidemic proportions in northern Europe and North America. The corrections of deformities of rickets were at the origin of the name "orthopedia" and of the technique of osteotomies.

In VitaminDWiki Vitamin D: part I - from plankton and calcified skeletons (500 million years ago) to rickets – March 2018
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Vitamin D: part II; cod liver oil, ultraviolet radiation, and eradication of rickets - March 2019

Int Orthop. 2019 Mar;43(3):735-749. doi: 10.1007/s00264-019-04288-z. Epub 2019 Jan 9.
Hernigou P1, Auregan JC2, Dubory A3.

PURPOSE:
After Glisson's description of rickets, it took two centuries to realize that rickets was due to the absence of antirachitic nutrients in the diet or lack exposure of the skin to ultraviolet rays. This bone disease caused by vitamin D deficiency was one of the most common diseases of children 100 years ago. This paper explores how the definition, diagnosis, and treatment of rickets shifted in the first decades of the twentieth century.

MATERIAL AND METHODS:
Although benefits of cod liver oil as food were known as early as the seventh century, cod liver oil was only proposed as medicinal for rickets in Northern Europe at the end of the eighteenth century. The relationship between rickets and nutritional deficiency was suspected and demonstrated between 1880 and 1915, at the same time of the discovery of other vital substances (vitamins) needed to prevent beriberi, scurvy, and pellagra. Understanding that the lack of photosynthesized vitamin D or the lack of dietary vitamin D was a similar risk of rickets was an important turn in the comprehension of the disease. We look at the sequence and turn of events related to the discovery of vitamin D.

RESULTS:
Rickets has been recognized first as a disease of urban living people. Cod liver oil had been used since 1700 as a nonspecific treatment for a range of diseases. Generations of children in cities of the north of Europe had learned to hate the taste and smell of the black oily liquid and then grown up to be parents who, in turn, hated to force it down their children's throats. Occasional papers before 1900 pointed to its efficacy for rickets, and most textbooks of the early 1900s mentioned it only as a treatment option. The discovery in the early 1900s that artificial and natural ultraviolet rays had both antirachitic activity allowed to produce antirachitic foods just by food irradiation with artificial ultraviolet irradiation. Clinical guidelines were adopted to propose exposure to sunlight or to artificial ultraviolet radiation to prevent rickets in children. By the mid-1920s, rickets was promoted as universal, at times invisible to non-experts, but present to some degree in nearly every young child regardless of race or class. It was thus used to promote the young disciplines of preventive medicine, pediatrics, and public health. Innovative advances were made in the understanding of vitamin D synthesis from 1915 to 1935. A public health campaign of the 1930s was a success to eradicate rickets, using irradiated ergosterol from yeast to enrich milk and other foods with vitamin D, ensuring that the general population was consuming sufficient vitamin D.

CONCLUSION:
Rickets therefore provides an excellent window into the early politics of preventive health and the promotion of targeted interventions in the world. It is also a relevant historical counterpoint for current debates over the role of risk factors (absence of light or sun) for disease (today's so-called "lifestyle" diseases).
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Vitamin D history part III: the "modern times"-new questions for orthopaedic practice: deficiency, cell therapy, osteomalacia, fractures, supplementation, infections - April 2019

Int Orthop. 2019 Apr 29. doi: 10.1007/s00264-019-04334-w
Hernigou P1, Sitbon J2, Dubory A2, Auregan JC3.

PURPOSE:
The nutritional basis for rickets was described between 1880 and 1915, at the same period of discovery of other "vital substances" or vitamins. In contrast, rickets could also be prevented or cured by sunshine. But as the capacity to produce vitamin D depends on exposure to ultraviolet B rays (UVB) from sunlight or artificial sources, vitamin D became one of the most frequently used "drugs" in the twentieth century to compensate for insufficient exposure to UVB of humans. Furthermore, as the understanding of vitamin D metabolism grew during the twentieth century, other concerns than rickets occurred for the orthopaedic surgeon: In recent history, deficiency is explored as being an associated factor of different bone pathologies as fracture or prosthetic infection. The aim of this review is to analyze these new data on vitamin D.

MATERIALS AND METHODS:
During the twentieth century, there were many concerns for the orthopaedic surgeon: sources and synthesis of vitamin D, regulation of the calcium deposition process for both children and adults, when vitamin D deficiency is observed, and what the best method of vitamin D supplementation is. As target genes regulated by vitamin D are not limited to those involved in mineral homeostasis, orthopedists recently discovered that vitamin D might prevent periprosthetic infection.

RESULTS:
The primary source (80%) of vitamin D is dermal synthesis related to the sun. Dietary sources (20%) of vitamin D are fat fishe, beef, liver, and eggs. Vitamin D is produced industrially to be used in fortified foods and supplements. Maintenance of skeletal calcium balance is mediated through vitamin D receptors. Progenitor cells, chondrocytes, osteoblasts, and osteoclasts contain these receptors which explains the role of vitamin D in cell therapy, in the prevention of rickets and osteomalacia. Despite fortified foods, the prevalence of deficiency remains endemic in north latitudes. However, the definition of vitamin D insufficiency or deficiency remains controversial. Vitamin D has been evaluated in patients undergoing fractures and elective orthopaedic procedures Although supplementation may not be able to prevent or cure all the orthopaedic pathologies, oral supplementation is able to improve the vitamin D levels of deficient patients. These vitamin D level improvements might be associated with better functional and clinical outcomes after some surgical procedures and improvement of immunity to decrease the risk of infection in arthroplasties.

CONCLUSION:
Vitamin D deficiency is frequent and concerns millions of people in the world. It is therefore normal to find hypovitaminosis in various orthopaedic populations including trauma and arthroplasties. However, we do not know exactly if this phenomenon only reflects the general prevalence of vitamin D deficiency or has an influence on the outcome of some pathologies on specific populations at risk. After the success of treatment of rickets, it is disappointing that we are still wondering in the twenty-first century whether supplementation of a substance synthetized millions of years ago by plankton and necessary for growth of all the animals may improve (or not) clinical and functional outcomes of a simple fracture in humans.

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Vitamin D and evolution: Pharmacologic implications - July 2019

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