Bone Mineral Density vs. Bone Fractures
Bone mineral density is used to
diagnose osteoporosis. Normal bone
mineral density is considered less than or equal to 1 standard deviation below
the mean bone mineral density of 30 year old men and women. Osteopenia is diagnosed when between 1 to 2.5
standard deviations below the mean and osteoporosis is diagnosed when greater
than or equal to 2.5 standard deviations below the mean.
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Normal Bone
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Discussions about osteoporosis
are largely concerned with bone mineral density, but the actual end-point we
want to avoid are the bone fractures. Normally
bone mineral density is related to fractures, but sometimes bone mineral
density is affected strongly without having much impact on fracture rates and
vice versa. Ironically, having excessive
bone mineral density due to osteopetrosis
(a rare inherited disorder and an uncommon side effect of bisphosphonates (a class
of drugs used to treat osteoporosis)) can actually increase the risk of bone
fractures. For these reasons I’ll use
fracture rates over bone mineral density wherever possible
Bone Formation and Resorption
Bones are much more than calcium,
it is living tissue. It’s important to
know a little about bones to understand osteoporosis.
Osteoblasts are like bone
stem cells that are responsible for bone formation. They produce a matrix of osteoid, which is the
unmineralised, organic part of bone, made mostly of collagen, and produce osteocalcin, which is a
mineral binding protein to help mineralise osteoids. When osteoids are mineralised they become osteocytes, the most common
cell in bone. I’ll refer to this process
as bone formation.
Osteoclasts break down bone
tissue and release the bound minerals in a process called bone resorption. Bones have a natural turnover rate – osteoclasts
break down damaged bone cells and osteoblasts form fresh bone cells. Osteoclasts are important as this process is
necessary to adapt to exercise, recover from damage, remove old cells and
maintain calcium homeostasis [1].
Like adipocytes (fat cells) and
myocytes (muscle cells), osteocytes also regulate their growth by using a
negative feedback system. Osteocytes
produce a protein called sclerostin,
which inhibits further bone formation.
Cell
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Negative Regulator
of Growth
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Adipocytes
|
Leptin
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Myocytes
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Myostatin
|
Osteocytes
|
Sclerostin
|
One function of bone turnover is
to maintain calcium homeostasis. Calcium is necessary for neurotransmitter release, muscle contraction, etc. Serum calcium levels is tightly regulated by
two main hormones: parathyroid hormone and calcitonin. Parathyroid hormone
is released in response to low serum calcium to increase it by stimulating
osteoclasts to break down bone and release calcium, activating vitamin D (to
1,25-hydroxyvitamin D) to increase calcium absorption in the intestine and
increase reabsorption in the kidneys. Calcitonin is released in
response to high serum calcium to decrease it by decreasing osteoblast
activity, calcium absorption and reabsorption (essentially the opposite of
parathyroid hormone).
This may lead one to think that
osteoclasts and parathyroid hormone are ‘bad’ while osteoblasts and calcitonin
are ‘good’. Remember that both bone
remodelling and calcium homeostasis is important – all four are ‘good’ in the
right amount. Osteoporosis is likely due
to too little osteoblast activity (bone formation) and/or too much osteoclast
activity (bone resorption). Hyperparathyroidism,
which may be caused by cancer, vitamin D deficiency and kidney failure, can lead
to osteoporosis. But intermittent pulses
of parathyroid hormone (the normal physiological condition) actually improve
bone mineral density and bone quality by increasing IGF-1, preventing
osteoblast apoptosis and inhibiting sclerostin [1].
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