Welcome to Pharmacology by Lecturio.
I’m Dr. Shukle and today we are going to cover bone and calcium pharmacology.
Now when we talk about bone and calcium pharmacology
we have to understand some of the regulators of bone mineral homeostasis.
Homeostasis is essentially a big word that means keeping things the same.
Now the bone is constantly rebuilding itself and all of these modulators
can have an effect on the way that the bone rebuilds itself
because bone is mostly made out of calcium,
anything that happens that affects the way that the bones are metabolized
will affect your serum calcium levels.
Now, let’s focus on PTH which is parathyroid hormone and vitamin D.
Now remember that a drop in free calcium levels will stimulate parathyroid hormone
release from the parathyroid glands.
Any active metabolites of vitamin D play a secondary role in inhibiting the secretion of parathyroid hormone
so that’s important to remember when we’re giving drugs.
For example in different organs, you can have different activities of both parathyroid and vitamin D.
In the intestine, parathyroid hormone will indirectly increase calcium and phosphate absorption.
Now it will also increase, it do this by increasing vitamin D metabolites.
Now active vitamin D metabolites themselves increase calcium and phosphate absorption in the gut.
In the kidney, the parathyroid hormone will cause decrease calcium excretion,
now that makes sense because you want to maintain calcium levels in the body when you have parathyroid hormone,
however, your parathyroid hormone will also increase phosphate excretion.
Phosphate levels will go down because of kidney excretion with parathyroid hormone.
In terms of active vitamin D metabolites, you get an increased resorption of calcium and phosphate
but usually there’s a net increase in urinary calcium due to the effects in GI tract and bone.
The activity of parathyroid hormone in the bone is complicated.
First of all, there’s a difference between continuous high doses of parathyroid hormone
and intermittent dosing of parathyroid hormone.
So for example in the bone, calcium and phosphate resorption
is increased by continuous high concentrations of parathyroid hormone.
Meanwhile, intermittent dosing decreases resorption increases bone formation
so there’s a completely opposite effect depending on how the parathyroid is administered.
In terms of vitamin D metabolites there’s a direct effect on the bone -
it increases calcium and phosphate resorption from the bone and there’s indirect effect as well
that first promotes mineralization by increasing the availability of calcium and phosphate
so it’s a complicated mechanism in the bone.
The net effect on serum levels of these two hormones
is as such with parathyroid hormone serum calcium levels are increased
and serum phosphate levels are decreased.
With vitamin D metabolites, serum calcium and phosphate are both increased
so this is an important distinction between the two hormones
and you need to understand that both in clinical practice and on your exams.
I want reiterate a point.
At continuous high doses of parathyroid which are seen in hyperparathyroidism and tumors in the brain,
the net effect is increased bone resorption, hypercalcemia and hypophosphatemia.
At low intermittent doses of parathyroid hormone, there is a net increase in bone formation,
this is why teriparatide, which is recombinant truncated parathyroid hormone analogue is used in osteoporosis.
So completely different actions based on the way that the parathyroid hormone presents itself to the human body.
Let’s talk about vitamin D.
So vitamin D as you probably are well aware, it’s used in osteopenia and osteoporosis as a supplement.
It promotes calcium absorption from the gut, so you increase the amount of calcium being pulled out of food.
It also promotes bone resorption which means that it maintains serum calcium levels
and it also promotes bone remodeling.
It’s used in the treatment of rickets so you can see here an image of a poor child
who was deficient who ended up requiring vitamin D supplements
and she eventually improved and did well.
What are the non-medical uses of vitamin D?
It’s become a very popular supplement and part of that is based on real science.
So we know that D3 supplementation is associated with decreased elderly death,
but excess can increase death so one has to be careful with dosing.
Harm from vitamin D appears to occur at lower vitamin D levels in the Black population
than in the White population.
You have to be careful with the administration of your vitamin D in different racial groups.
There is no benefit to very high levels of high vitamin D or what we call supper normal levels
but correcting low levels reduce fracture risk so giving more vitamin D
in the person with normal vitamin D levels and normal bones will not make them super strong.
Now, cancer risk maybe worsened in patients who have low levels of vitamin D
but there’s no good research to support supplementation in patients with normal levels,
so you’re not going to reduce cancer risk in patients who have normal vitamin D levels.
And auto immune disease can be made worse with low levels, which isn’t surprising,
but it’s not prevented or treated with supplements if the patient has normal levels.
So if a patient has a normal vitamin D level using vitamin D supplements
really isn't going to benefit patients.
The following diseases are worsened by low levels but are not helped with supplements
in patients with normal vitamin D levels. Diabetes, depression, cognitive decline, pregnancy
and pre-eclampsia, patients who have weight loss, inflammatory and bowel disease,
multiple sclerosis, asthma, infections, HIV and stroke and cardiovascular disease and hypertension.
So this is something that occupies the internet but not the thoughtful minds of careful doctors.