OSTEOPOROSIS: Part 1 Flashcards
Definition of Osteoporosis
“Osteoporosis is defined as a skeletal disorder characterized by
compromised bone strength predisposing to an increased risk of
fracture.”
Incidence of Osteoporosis
n 1 in 3 women and 1 in 5 men over the age of 50 have
osteoporosis.
n Over 70% of all fractures in people over the age of 45 believed due
to osteoporosis.
n Average 50 year old woman has a lifetime fracture risk of 40%.
n The overall cost of osteoporosis (direct and indirect) estimated to
be $4.6 billion.
Care Gap in Osteoporosis
n There remains a substantial care gap in the management of
osteoporosis.
n Only 5-25% with fragility fractures are assessed for osteoporosis
– and only half of those will be treated
Addressing care gap:
How can you help?
Bone Strength
Bone Quality (Micro-architecture
Microfracture
Turnover
Mineralization)
+ bone quantity (bone mineral density)
Bone quantity is what we can measure that bone marrow density. Only about 30 to 40% of the whole picture of bone strength is from that bone quantity.
The rest of it is own quality. It’s that micro-architecture that we talked about, the development of those. If there’s any micro fractures in between, that’s going to make that bone quality not as good. The turnover, how fast that bone turnover is happening can also affect it. And then just how well that the bone is mineralizing.
males often have a bigger bone diameter than, than females
Bone Loss During Adult Life
Men -20 to -30%
Women
-35 to -50%
Peak bone mass
Menopause
develop our peak bone mass between around 25 to 35 is when we have our peak bone mass.
if you can have a higher peak bone mass, we have a bigger bone bank
What’s also important is how much we lose and how fast we lose as well.
This increase bone loss and females can lose up to two to 3% of their bone density every single year for the next ten years. After their final menstrual period. Then after that, once that ten years is gone, then they still lose bone density, but it’s more gradual.
it’s probably more due to aging than the effects of the low estrogen. Women can lose anywhere 35-50% of their bone density, bone mass over their lifetime.
We also see they men get to a little higher peak bone mass, maybe because bone diameter or other factors, they do lose bone density as well, but it’s much more gradual.
the slope in the women after that ten years post-menopausal is very similar to the men, and that’s because it’s due to aging more than anything else.
Peak Bone Mass
- Peak bone mass is a major determinant of fracture risk later in life
- Determinants of peak bone mass not well understood
n genetics is primary factor
n nutritional status
n physical activity
n hormones
It’s believed that 60 to 80 per cent of our variability in peak bone mass is probably due to genetics. And that’s why asking about family history super important when you’re assessing somebody. Nutritional status is also important. Calcium and vitamin D,
weight-bearing is anything that is just gravity on the bones because that increases bone remodeling. It makes it stronger with that, so not increases, but it helps with that bone remodeling process.
Then hormones, so estrogen, testosterone are all important. Parathyroid hormone all have effects during that time.
Pathophysiology of Bone Loss
n Bone loss from
§ Increased bone remodeling (high
turnover)
§ Net loss of bone in each bone
remodeling unit/incomplete filing
of unit (remodeling imbalance)
n Loss in trabecular bone is greater
than cortical bone.
Menopause – high turnover
Elderly – remodeling
imbalance (low turnover)
Fractures are Multifactorial
Low BMD
Impaired bone quality
Falls
very ten years we go through our whole skeleton gets remodeled, so it’s always going through bone remodeling. Bone remodeling includes bone resorption with the osteoclastic, bone resorption and bone formation. And bone formation with is with our osteoblasts.
bone formation with is with our osteoblasts. In this process takes the whole process of bone remodeling, takes about three months
What can happen with osteoporosis is that there could be an increase in bone resorption much faster. And this can exceed the bone formation.
you can see these pits developing here that aren’t formed and those, those are not good structure. There’s less dense and they can not have as good micro architecture
increased bone remodeling called high turnover, so especially increased bone resorption, that high turnover where bone formation can happen.
loss of estrogen is you see an increase activity of those osteoclasts
Aging:remodeling imbalance called low turnover, where bone formation can’t keep up at all. And so there’s some effect on those osteoblasts
rabecular bone is found highly in our spine. cortical bone high amounts in other parts of the body. So you think of the hips, you think of the even the wrist. Those are all throughout the rest of the body
trabecular bone. It was it had all those struts and it was a little spongy. There’s a lot of surface area in there. It has a high high bone remodeling rate. It it goes through bone remodeling much more than cortical bone. It’s going faster. It’s about five times faster. Expect to see more factures with trabeculary bone?
Common Sites for Fracture
Incidence of
osteoporotic fractures
Vertebral/Spine Hip Wrist
Non-vertebral fractures – includes wrist, ribs etc
non vertebral fractures, we’re often referring to fractures of the wrist, of ribs, any other fracture then a spine and often a hip fracture.
the primary outcome for a lot of drug therapy studies is looking at vertebral fracture reduction. Then they look at hip fracture reduction. And then they could talk about non vertebral fracture reduction. There’s some reasons why is because it’s easier to show vertebral fracture reduction. Why is that? Why? Because you’re gonna do a study for three to five years. You’re going to see effects there quicker with the vertebral fractures because it’s a higher bone remodeling, you’re going to see the outcomes.
, a little bit similar in men, but it happens a little quicker in women because of the loss of the estrogens so much in that first ten years.
start seeing initially as those vertebral fractures because of that high bone remodeling, high, higher rate.
Start seeing wrist fractures, then it starts to balance out
only a third of vertebral fractures are ever clinically diagnosed. And the reason for that is only a third associated with pain.
as somebody gets older, that then you start seeing those hip fractures happening, right.
Wrist fractures plateau: younger, you fall and reach out with your hands. When you’re older, you tend to have a slower gait. You may be more careful and then you’re going to fall. You tend to fall more to your side. And that’s how hip fractures can happen. T
Impact of Fractures
n Fracture cascade: Fractures predict future fractures
n Pain
n Cosmetic Deformities
n Dowagers hump, kyphosis
n Loss of height
n Physical symptoms
n restrict lung function, GI
n Reduced Mobility:
n 2/3 of hip fractures
n Decreased mood, loss of self esteem
n Loss of independence (50% of hip fractures)
Fractures are associated with decreased survival.
28% of women and 37% of men will die within the first year after hip fracture, and within 5 years after vertebral fracture
Someone’s had no fracture, this is their relative risks so increases slightly.
. One fracture, look at that. Relative risk goes up quite a bit to fractures. It starts going up and then multiple fractures or he’s got severe osteoporosis and it’s a really, really increased risk of fracturing. Again.
imminent fracture, is a fracture that’s happened within the last one to two years. And the reason it’s imminent fracture is that it seems to trigger off possibly of the risk of another fracture quickly.
here’s some movement for those fractures was imminent fractures to be more aggressive with treatment early on with things like anabolic agents.
kyphosis:The spine can’t support shouldrs, stooped over
you can become their body gets shorter, like you’ll see, they’re shorter to that. And so if you lose that, that height in your spine, what happens is your pelvis gets closer to your diaphragm, your home, and your lungs. And that can restrict lung function. So they can have issues with lung function and can have issues with GI movement as well. If
up to almost 30% of females and up to 37% of males will die within the first year after a hip fracture. And most people don’t realize that. I don’t know why it’s more in males than in females, but that’s been the reports.
Risk factors for osteoporosis/fractures
n Age
n Genetics
§ family history (especially
parental hip fracture)
n Fragility fracture after 40 years
n Low BMI <20 kg/m2
Anybody who’s had a low trauma fracture, so we call that fragility fracture after the age of 40 is usually where we think okay, that might be their risk.
So what the way we ask the question to see if they have a fragility fracture, is that tell me about your fracture. How did it happen? What happened? How did you fall? If they fell from standing height or less than That’s a fragility fracture.
Oh, I was walking along and then I felt then that’s a fragility fracture if they fell down five flights of stairs, we consider that more of a trauma fracture.
low BMI, low muscle mass, especially is a big risk factor.
Lifestyle, calcium intake, vitamin D. If they’re a smoker smoking. It will increases metabolism investigations for one thing, but it also has direct effects on osteoclast as well somehow.
4 more more cups of coffee FYI t caffeine can result in increased secretion of calcium diuretic.
n Lifestyle
§ low calcium intake
§ low vitamin D
§ current smoker
§ physical inactivity
§ alcohol excess (3 or more
glasses daily)
§ high caffeine
Hypogonadal states
n Early menopause (<45years)
n Premature ovarian insufficiency
n Previous amenorrhea (e.g. eating
disorders)
n Hypogonadism in men
n Endocrine conditions
n Hyperthyroidism
n Hyperparathyroidism
n Cushing’s syndrome
n Diabetes Type I and II
Risk factors for osteoporosis/fractures
n Rheumatologic conditions
n Rheumatoid arthritis
n Systemic Lupus
n GI conditions
n Inflammatory bowel disease
n Celiac
n Other
n Chronic kidney disease
n HIV
n COPD
n Malignancy
Medications that lead to bone loss and/or fractures
risk factors con’t
Strong evidence
* Glucocorticoids
* Aromatase Inhibitors
* Anticonvulsants
* Chemotherapy
* Anti-androgen therapy
* Excess thyroid replacement
* Long term heparin therapy
anticonvulsants can possibly increase as well. It’s probably from the increase in vitamin, especially the inducers of vitamin D metabolism.
Not as clear with ssris
long-term heparin therapy heparin has also been shown to affect the bones as well.
What I consider those strongest on here really is the glucocorticoids, aromatase inhibitors, and the anti-androgens therapy, where often we may need to use preventative medications with those
Moderate evidence
* SSRIs
* Proton pump inhibitors (PPIs)
* Thiazolidinediones
* Depot medroxyprogesterone
acetate (DMPA)
* Antiretrovirals (tenofovir, ?certain
protease inhibitors)
* Vitamin A (preformed, retinol)
>10,000 IU/day
Glucocorticoid Induced Osteoporosis (GIOP)
n Use of systemic steroid for cumulative dose of 3 months or
longer is risk factor.
n Mechanism of action:
§ increase bone resorption
§ decrease bone formation
§ decrease calcium absorption
n Consider patients at risk if:
§ >7.5 mg prednisone daily for over 3 months (cumulative
dose)
cumulative doses over three months or longer. And that’s cumulative in the last year. So it doesn’t mean all at one time. It could be at different times and that last year would be a risk factor. And we also consider it if they’re on 7.5 mg of prednisone daily or more.
Patient Assessment
Identifying patients at risk of fractures:
n Patient History:
n Assessment of risk factors
n Fracture history: prior fragility fracture
n Loss of height
n height loss: historical loss > 6 cm
prospective loss > 2 cm
n BMI
n Fall history
how much height are you now compared to? What were you in your 20s,
what is considered significance is over 6 cm and that’s about 2.5 “
. So progressive loss is more than 2 cm, which is almost 1 “. So if they are losing 1 “ each year, which could be significant if you look at a number of years. That prospective loss
We ask, how many times have you fallen in the last year?
rib-pelvis and occiput to wall distances
Monitoring height
Timed Up and Go (TUG) test
n Use a wall mounted
stadiometer
n Bare feet
n Heels, buttocks back
against board
n Monitor annually for
height change
The rib two pelvis. It should be greater than more than 2 cm part which is like two fingers. And if you go in, it should be more than two. Should be often like three. Probably three. Right. But if it’s less than two, then it means that there has been possibly fracutre that has happened
So you should be able to go to the wall and you just say go against the wall, against there. And it should be there should be no for the most part, should be nothing there. But if I have some kyphosis, then this part gets distance there. We measure that distance between that and that. If it’s more than, like 5 cm is kinda the risks of more than 5 cm. And don’t worry about knowing the exact numbers, just know that that we would measure that, then it’s considered significant
look at their gait and frailty. We get them to sit, then they from a chair, then they stand. They walk about 10 ft.
And then we have then turn around and walk back and turn and sit down. And so if they take a long time, usually more than 12 s or more, maybe they have a higher risk of falls,
Patient Assessment in Osteoporosis
Laboratory tests:
n Check for secondary causes:
§ serum 25 OH vitamin D (based on guidelines)
§ calcium, corrected for albumin
§ PTH
§ TSH
§ creatinine
§ phosphorous
§ testosterone in male
Note: Bone resorption marker may be used clinically in some centers – Ntelopeptide (NTX), C-telopeptide (CTX)
There are chemicals that are released by bone resorption and there are chemicals that are released by bone formation. You can actually get for both bone resorption and bone formation markers. But for clinically significant ones, we may get a bone resorption marker. And you can see we can get something called N tele peptide or C tail peptide and TX or CTX for short. We can get them at HHS and we can monitor how fast bone resorption is happening.
