METABOLIC BONE DISEASE AND VITAMIN D

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METABOLIC BONE DISEASE AND VITAMIN D

• M.DAVIES
• PHYSICIAN MANCHESTER ROYAL INFIRMARY

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Vitamin D The Sunshine Vitamin
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DISEASE AND LACK OF VITAMIN D

• RICKETS IN CHILDREN
• OSTEOMALACIA IN ADULTS

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PERCIVAL T. (1783) Observations on the
medicinal uses of the oleum jecoris aselli or cod
liver oil in chronic rheumatism and other painful
disorders. LONDON CLINICAL MEDICAL JOURNAL Vol.
3, 392-401
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About ten years since, an accidental
circumstance discovered to us a remedy, which
has been used with the greatest success, for
(chronic rheumatism), but it is very little
known, in any county, except Lancashire. It is
the cod or ling liver oil.
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A woman, who laboured under the most
excruciating rheumatism and was an out- patient
of this infirmary, being advised to rub her
joints with the oil, was induced to take it, at
the same time, internally. A few weeks restored
her to the use of her limbs and she was cured.
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RELATIONSHIP BETWEEN SUNLIGHT AND VITAMIN D

• MELLANBY 1921. Cured experimental rickets with
  cod liver oil and sometimes butter, ? vitamin A
• SHERMAN, PAPPENHEIMER in New York
• KORENSCHEVSKY in Oxford all produced rickets in
  rats cured with aerated hot cod liver oil which
  destroys vitamin A.
• HULDSCHINSKY 1919 (Deut. Med) cured four rachitic
  children with mercury arc lamp.
• HESS and UNGER 1921 cured rickets with sunshine
  on the roof of New York City Hospital.

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RELATIONSHIP BETWEEN SUNLIGHT AND VITAMIN D

• Hess and Weinstock, Steenbock and Black 1924
• Rats could be cured of rickets by
• 1) Irradiation
• 2) Irradiation of their food ergosterol
• converted to ergocalciferol (vitamin D2)
• 1932 Pure Vitamin D isolated.

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VITAMIN D THE SUNSHINE VITAMIN

• Vitamin D is NOT a vitamin as
• cholecalciferol is produced in the skin from
• u/v irradiation of 7-dehydrocholesterol
• cholecalciferol

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FORMS OF VITAMIN D

• VITAMIN D2 ergocalciferol
• VITAMIN D3 cholecalciferol

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VITAMIN D THE SUNSHINE VITAMIN

• UVB WAVELENGTH 290-320 nm
• Temperate climates May September
• BOSTON, Ma 42oN December February
• EDMONTON, Canada 52oN NOV MCH
• BERGEN, Norway 61oN OCT MCH
• CAPETOWN, SA 35oS NO PROBLEM
• SKIN TYPE AFFECTS THIS.

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VITAMIN D THE SUNSHINE VITAMIN

• Bad for cutaneous production
• Clothes
• Sun-block creams
• Glass
• Buildings
• Smog
• Old skin

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VITAMIN D - AS A VITAMIN

• Recommended requirement 400 iu
• (10?g) per day where diet is the only
• source.

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THE STING

• You cant get 10?g/day of vitamin D in a normal
  diet.

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THE SOLUTION

• Supplementation or Sunshine

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VITAMIN D THE HORMONE

• 1,25 (OH)2VITAMIN D Promotes Calcium
  absorption from the gut and aids bone health.
• Has antiproliferative effects on
  cells
• and turns on apoptotic genes.
• Analogues used in psoriasis.

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METABOLIC BONE DISEASE

• OSTEOMALACIA soft bones which bend
• OSTEOPOROSIS porous bones, thin bones which snap
• PAGETS DISEASE

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Normal bone remodelling
Osteoblast precursors
Osteoclasts
Resorption by osteoclasts
Reversal
Osteoblasts
Osteocyte
Formation
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Osteomalacia

• Impaired mineralisation phase of
• remodelling

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• VITAMIN D DEFICIENCY
• (i.e. 1,25-dihydroxyvitamin D deficiency)
• ?
• Failure to absorb dietary calcium
• ?
• Rickets in young osteomalacia in adult

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Vitamin D Deficiency Associations

• Intestinal Malabsorption
• Chronic Liver Disease
• Partial Gastrectomy
• Primary hyperparathyroidism
• Anticonvulsants
• Vegetarian Lifestyle
• Immigrants

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OSTEOMALACIA

• Causes
• Privational Vitamin D Deficiency
• Renal Disease
• Hypophosphataemia
• (XLH, Acquired Tumoral)
• Drugs Etidronate
• Toxins Cadmium, Aluminium

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Definition of Osteoporosis
A disease characterised by low bone mass and
microarchitectural deterioration of bone tissue
leading to enhanced bone fragility and a
consequent increase in fracture risk. World
Health Organisation (WHO), 1993
Normal bone Osteoporosis
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Normal bone remodelling
Osteoblast precursors
Osteoclasts
Resorption by osteoclasts
Reversal
Osteoblasts
Osteocyte
Formation
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Changes to bones with age

• Increased bone remodelling8
• Bone resorption outweighs bone formation6
• Increased porosity9
• Decreased BMD6
• Increased microdamage10
• Fragility fractures6

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Factors that determine bone strength

• Bone turnover 11-13
• Bone mineral density14
• Bone quality15
• Each one of these components can exert an effect
  on the risk of fracture

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Clinical Impact of Vertebral Fractures
Age 75
Age 66
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VITAMIN D THE HORMONE

• Other tissues can synthesise 1,25 (OH)2D
• Breast
• Colon
• Prostate
• Skin
• Macrophages

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VITAMIN D AND CANCER?

• The incidence of colon, breast and prostate
  cancer increase with latitude of residency.
• If 1,25(OH)2 vitamin D is produced locally for
  local use the less solar exposure the less
  substrate vitamin D is available for local
  production of 1,25(OH)2 vitamin D.

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HOW MUCH VITAMIN D DO WE NEED

• ?

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HOW MUCH VITAMIN D DO WE NEED

• 25OHD gt5 ng/ml
• 25OHD gt20 ng/ml

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HOW MUCH VITAMIN D DO WE NEED

• ?
• To protect where extra-renal and local 1,25D
  synthesis is required

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CONCLUSIONS

• Vitamin D is not a true vitamin.
• Most of us may have too little vitamin D.
• Especially a problem in the elderly.
• A sufficiency of vitamin D may protect against
  cancer, diabetes and autoimmune diseases