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When crystals of hydroxyapatite (a complex of calcium, hydroxyl and phosphate
ions) are laid down between collagen fibers, bone calcification occurs. These
ions in bone are in dynamic equilibrium with ions present in the bloodstream, an equilibrium
which is regulated by Vitamin D and by two peptide hormones, Parathyroid hormone
(PTH) and calcitonin. As late as the 1930’s and 1940’s, when the role of dietary
Vitamin D in normal bone growth and development was not recognized, rickets was
an all too common feature of community life, particularly in areas with the sun exposure.
The role of Vitamin D is largely played at the site of the mucosal cells
of the intestine, where it stimulates calcium absorption and retrieval to the blood stream
from food passing through the gut, as well as in the proximal tubgles of the
kidney, where it promotes re-absorption of phosphate which would otherwise be excreted
in urine. The constant turnover (dynamic equilibrium) of the ions of bone crystal
between those in the bloodstream and those stored in bone itself, is a important feature
both in formation and in repair of bone.
Three types of cells work together in this process:
osteoblasts, osteocytes, osteoclasts. The osteoblasts synthesis the matrix upon
which bone crystals are laid down; the osteocytes interlink this matrix with long filaments;
the osteoclasts, which sit on the surface of bone crystals, are important in maintaining
calcium and phosphate ion equilibrium with the blood stream. How these cells actually
interact in the calcification of bone is an area of intense research and many theories
abound. It is known that PTH acts directly on osteoblasts, facilitating their interaction
via other chemical activators with osteoclasts.
In particular, the role of bone-specific alkaline
phosphatase, which
releases free phosphate for combination with calcium in hydroxyapatite crystals,
is still unclear. What is clear, however, is that individuals who present with Vitamin D -
resistant rickets have abnormally high levels of alkaline phosphatase in their bloodstream,
but little phosphate, presumable because their natural ‘active’ Vitamin D as well as calcium
in these individuals usually indicate normal or only sightly lower than normal
concentrations. Research into these questions, as reported for example, at the 2nd
European Kidney Research Forum, continues apace. It should be clear that the typical therapy for individuals suffering
from Familiar Hypophoshatemia is a combination of the active form of Vitamin D (called
dihydrocalciferol, ergocalciferol or just calciferol, this drug also
goes under the proprietary name of Rocatrol) and supplements of phosphate and/or calcium.
Under this sort of therapy, measured phosphate and alkaline phosphatase levels
in the bloodstream return to normal levels; there is now enough free phosphate (either
as supplied as free ions, or as correctly re-absorbed in the kidneys) to inhibit further
production of the bone-specific alkaline phosphatase). Furthermore, calcium is absorbed and retrieved
correctly by the intestinal cells under the influence of good, active Vitamin
D (or is also supplied as free ions). Bone growth then proceeds, with the appropriate laying
down of bone crystal as can be seen by a chronological series of X-rays. The dramatic role of the dynamic equilibrium of progressive bone growth
under theraph is illustrated in real cases of Vitamin D - resistant rickets, where
the bowed legs of growing children can be observed to straighten, over the course of
several years, against the influence of gravity.
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