Osteoporosis by drdoc on-line  

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.
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more detailed and complex update can go to the osteoporosis updates page -Osteoporosis update page

a) Define it.
b) Explain bone anatomy and influences.
c) Classify the disease types
d) Look at risk factors
d) Explain the seriousness of the problem and explain peak density.
e) Explain how we measure it.
f) What we look for in examinations.
g) Prevention
h) Treatment
i)
What is on the horizon.

Definition
A systemic disease characterised by low bone mass and micro-architectural
deterioration of bone tissue with a consequent increase in fragility and susceptibility
to fracture risk.
Note - the amount of bone is less but the mineral organic matrix is normal.
It is important to realise that there are other important determinants of fracture such
as age, and extraskeletal factors such as environmental hazards and neuromuscular
function which might increase the tendency to trauma in the first place.


BONE ANATOMY AND FUNCTION

It is important to realise that bone is alive and in a constant state of turnover.
There are two main types of bone:-

  • Trabecular Bone(or spongy) such as in the spine and which is like a
    lattice structure with interconnecting bridges and marrow between. This
    provides a large surface area of the bone surface and turnover is
    8X more rapid in this than .....
  • Cortical Bone / compact - such as the long bones with a “shell” and
    marrow in the middle.

The bone itself consists of a matrix of protein and then the mineral component laid
onto this - Calcium Salts and other minerals including Sodium, Magnesium and
Fluoride.
The process of turnover is called
remodelling. There are two cells that are
involved - the
osteoclast
that eats up old bone and the osteoblast which
follows to lay down new bone.

In osteoporosis - the process of absorption is greater than the process of laying down
new bone. The resorption occurs at the surface. As noted - the trabecular bone has the
greatest surface area and is most at risk. It is important again to realise that the bone
itself is normal - but there is not enough of it and the bone mass is then reduced and the
lattice or network is weakened and may therefore fracture. This process is an ongoing
one and occurs over years.

The major determinant of whether one is going to fracture is the
peak bone mineral density.
There is an exponential increase in fracture risk with
reduction in the bone mass. There is an ongoing reduction of bone mass once one
reaches the age of 28 - 30, but this accelerates after the menopause in females.
In healthy men, the loss is 3 - 5% per decade.
In women, the loss before menopause is 3 - 5%, but at menopause increases to 1% - 5%
per year for the first 10 years and then levels off after age 75 to 3% per decade.
The fracture risk starts at <20% of that of the mean young
premenopausal value.
There are different types of osteoporosis which I will mention to make you understand
that the problem is wider than simply related to hormones and age or sex.


We can classify the disease into several types


CLASSIFICATION

Generalized and Regional

Of the generalized variety, the majority are associated with post-menopausal or the ageing
process, but many medical conditions also can cause it, including
Thyroid disease,
Adrenal gland disease,
Anorexia and over exercising which may induce amenorrhoea and also other....
Arthritis or medical diseases - such as Emphysema and Rheumatoid Arthritis.
Other environmental problems can aggravate it - including calcium deficiency and
alcoholism or drugs - especially high dose Cortisone.

The likelihood of developing osteoporosis is determined by the magnitude of the
peak bone mass and the rate of loss.


Certain people have higher risk factors

1. Genetic - Especially family history Caucasian and Asian Absence of generalized
osteoarthritis.
2. Anthropometric - Physical stature - ie., thin / small / fair people
3. Hormonal - Early menopause or late menarche. Exercise induced or anorexia.
Nulliparity.
4. Dietary - Low or inadequate calcium intake or high protein diets.
5. Lifestyle - Sedentary / immobilized people who do not do weight bearing exercises.
Alcohol or smoking in excess. Excess caffeine.
6. Concurrent illnesses Glandular problems. Thyroid / adrenal / parathyroid.
Rheumatoid Arthritis Stroke Parkinson’s Disease.


Lets look at the Risk:- What does it mean?
This basically is
fracture risk
.
There is an enormous impact
- morbidity
- illness and mortality
- death
- huge costs.
Fractures will occur at the spine, wrist and hips.
Estimated costs in the
USA:- $20 billion / year = 1.5 million fractures.
UK:- 614 million pounds /year.
47 000 hip fractures in England / Wales in 1985.


SPINAL FRACTURES.
In the spine minimal trauma can cause fracture. Usually its in the
Thoracic / Chest and Lumbar Area. 12% of males over 60 will have fractures.
33% of females over 65 will develop fractures.

They can be extremely painful or absolutely painless.
Once they occur - further fractures will occur and 85% will refracture by 10 years.
The patient will progressively become “bent”.
The incidence of general sickness and mortality rises due to the greater infirmity of the
patient.


HIP FRACTURES.
The hip fracture is the most severe and again trauma may be insignificant.
Here hospitalisation is on average 20 - 30 days.
Surgical fixation or joint replacement is required and there is a high mortality and
morbidity.
Only 25% regain former mobility and there is a 12 - 40% mortality by 1 year.
8% will refracture.
5% of males fracture in their lifetime.
16% of Caucasian females fracture in there lifetime.


THE WRIST FRACTURE.
The other common fracture is at the wrist with a fall with the arm outstretched -
The Colles Fracture.
20% of females will fracture by age 70 and require 4 - 6 weeks in plaster.


Therefore, as age increases, there is an exponential rise in fracture rate which is
related to the bone mineral density. In fact, the strength is proportional to the
density of bone squared.


Can this density be measured?
The answer is yes - by several methods:-

1. Xrays - this only detects after 30 - 50% reduction in density.
2. Radiogrammetry
3. Single Photon Absorptiometry - Radio Nuclide source of energy.
4. Single Energy Xray absorptiometry using Xrays.
5. Dual Photon Absorptiometry - using a Dual Energy Radio Nuclide source and a
detector.
6.
Dual Energy Xray Absorptiometry - DEXA. Using 2
Xray energy sources - improving accuracy.
7.
Quantitative CT Scanning -QCT...where a selected slice is
measured and the actual sample selected. This eliminates false negative artefact from
other structures.
8. Forearm and wrist scanners.

The interpretation of the Dexa is done by comparing the score versus the
premenopausal measure - the T-score.
Fracture threshold is when the T-score is 80%.
The Lower the measure, the greater the fracture risk.
Site specific measurements improve the prediction for fractures at a particular site.
The presence of osteopenia is when T-score is 90% - at which time, there is a 2 x
increased risk of fracture in the future.
At 25% loss, there is a 4 - 6 x increased risk - ie.. T-score - 75%.

Looking at Lifetime Risk vs Current Fracture Risk

Standard deviation (SD)
from the mean

T -score

Lifetime hip
fracture risk

Current hip
fracture risk

1 SD

T-score 90%

30%

4%

2 SD

T-score 75%

60%

12%

3 SD

T-score 60%

 

18%

Osteopenia is at 1 - 2 SD
Osteoporosis is at >2.5 SD
Severe Osteoporosis is >2.5 SD + 1 fracture.


Note however the diagnosis is made by evaluation of the patient / bone mineral
density and use of other medical tests to exclude other illnesses including malignancies
and other bone conditions which may imitate osteoporosis.
These tests may include blood tests, bone scanning and even possibly bone biopsy, if
clinically indicated.

A low bone mineral density is the most important predictor of fragility fracture risk.

On everyone’s mind will be who do we scan - “or do I need a scan?”-
So who needs to be scanned and when?

The answer to this is more or less as follows:-

1. Firstly; high risk factor - genetic risk / anthropometric risk / normal risk /
concurrent diseases or high risk medications.
2. Xray Abnormality suspecting low bone mass
3. Patient demand / request

Follow up bone scan is recommended at 18 months to assess progress of therapy or
if there is a borderline result - this will identify a segment of the population who lose
bone at a rapid rate - “fast losers”.
Since the bone density represents 80% of the fracture risk it makes sense that
maximizing the peak bone mass will prevent osteoporosis.


To do this we recommend - Preventative Methods.

1. Physical weight bearing activity. This builds up muscles and strengthens the bone
architecture. ie., walking / light jogging / impact aerobic.
2. Adequate diet ---- Average diet is 0.5g of calcium / day.
3. Calcium supplement ----1g post menopausal and osteoporosis ---- 1.5g
if no oestrogen.
4. Vitamin D----- RDA 400 iu.
5. Adequate fluoride in water - 1ppm .
6. Restriction of alcohol or caffeine and smoking.
7. Avoidance of medications that aggravate the situation or limitation of dose -
ie., steroids.


Therapy


Hormones
At the menopause hormonal replacement therapy becomes the most important factor.
This requires 0.625mg of conjugated estrogen’s or 1 - 2mg of estradial or 10mg of
estriol. The estrogen patches are protective as well.
I would aim for 10 - 15 years of treatment and at least 5 years - unfortunately, only a
small percentage of females take these.

The indications I feel outweigh the potential risk of the therapy.

The oestrogen supplementation has come under question since publication of the woman's health initiative study, which showed an increase in cardiovascular events, equivalent to eight in 10,000 woman years.

Contra indications include:-

Established breast / endometrial cancer Active liver disease and melanoma.
Undiagnosed abnormal vaginal bleeding.
The risk of breast cancer is 1.1 - 1.7
The benefit in reducing stroke or heart attack is 50%
Progesterone is required if the uterus is in situ to avoid uterine cancer.
When the therapy is withdrawn - bone loss resumes at the former rate
and there is no acceleration or catch up.
The Progesterone’s are used in the last 10 - 13 days of each cycle.
These may aggravate fluid retention or bloating and also aggravate headaches, mood
changes and acne. Breast tenderness is also seen.
The main effect is to reduce the osteoclast activity and increase calcium absorption
and reduce loss in the kidney.


Calcium :- Calcium itself should be given at night and it is important to
realise that not all are equal. The important part is called elemental calcium.
Only a percentage of Calcium by weight is elemental calcium and therefore effective. NOT ALL CALCIUM TABLETS ARE THE SAME.
The best Calcium is that with the higher elemental component:-

Type of Calcium

Percentage of elemental component

Carbonate

40%

Phosphate

31%

Lactate

13%

Gluconate

9%

By giving Calcium, there is a slight reduction in risk of fracture and reduced bone
turnover.


Vitamin D - Increases the absorption of Calcium from the bowel and is given in
several different forms. The body converts the basic form of Calciferol to the active
form by steps in the liver and kidney. These active forms can be obtained
therapeutically, but are more expensive.
One form called
Calcitriol has been shown to reduce fractures in the
vertebral spine.
.However no other studies have supported this literature.

Nevertheless, we now know that vitamin D. deficiency is endemic, due to lack of sun exposure and supplementation of 400 to 800 units a day are recommended. In the case of deficiency, we recommend 50,000 units, weekly for one month and then every second week for six months.  Vitamin D levels and calcium levels should be monitored.

Fluoride - Increase bone fluoroappatite formation which fewer lattices in
pharmacological doses promotes production of bone and is especially anabolic
to trabecular bone.
This effect is fairly dramatic, but there is concern regarding the quality of the bone
and in fact the reduction in spinal fractures is controversial and there is an
increased risk of hip fracture.
The dose is 15 - 25mg/day.
It is not my personal practice to use it.
Most rheumatologists would definitely not endorse this product.

It frequently causes nausea and excess doses cause limb pain - thought to be from
micro-fractures.


Thiazides - are diuretics used for hypertension and are noted to have a benefit
in the elderly with up to 30% reduction in fractures. Therefore, are useful in elderly
hypertensives.


Anabolic Steroids - These have been used for several years since the 1940’s
for established osteoporosis and increase the osteoblasts activity and therefore,
increase bone mass. They act especially on cortical bone.
They are most useful in elderly low turnover status.
They are masculinizing and have toxic effects on the liver, but benefits outweigh the
risks.
Those used are Stanozolol (PO) and Nandrolone (imi), as well as testosterone and
oxymethalone. They also increase muscle bulk and self confidence, but side effects
have reduced their use.
I personally find newer better therapies available today.
These refer to newer groups of anti-osteoporosis therapies, especially that of Bisphosphonates - the most recently marketed.


The Bisphosphonates have a potent action on the bone inhibiting the
resorption and mineralization of bone and cartilage. The latter effect potentially
causes osteomalacia and is an undesirable effect. Therefore, early generation
products were cyclical. Etidronate given for two weeks every 3 months at
400mg / day. The second generation products, ie.,
Pamidronate (Aredia) and
Alendronate (Fosamax) and newer drugs such as Boniva and Aclasta,
do not impair mineralization to the same
degree and have a more potent effect on the resorption of bone. They bind
strongly to the bone and inhibit the osteoclast precursors stopping trabecular
bone loss.
They decrease vertebral failures by a factor of 10 and increase bone mass by 5%
over 2 years. They maintain the overall quantity of the bone. They reduce bone
pain and have low toxicity with virtually no side effects. They can cause some
esophageal inflammation if not swallowed properly. They are potentially
expensive however. They cannot be swallowed at the same time as Calcium or
Calcium containing food or beverages - as they bind to the calcium and absorption
is reduced. The product should therefore be used first thing on waking and with a
full glass of water after which the patient should sit up and walk around.
No other food should be taken for at least 30 minutes.

The most recent bisphosphonate available is called Aclasta-Zoledronic acid. This is given as a yearly infusion of 5 mg.  It is given over 15 minutes to 20 minutes.  Caution is required in cases of renal impairment and in the case of bad dental hygiene.

Results show a 70% reduction in vertebral fracture and a 40% reduction in hip fracture. There are also some concerns about avascular necrosis of bone, but these are predominantly at the higher doses commonly used in cancer therapy. Avascular necrosis of the jaw is seen occasionally in the higher more frequent dosing schedules used for breast cancer and myeloma. Reports in osteoporosis dosing is VERY rare.

Bisphosphonates are now being questioned regarding long-term use and safety after 10 years.  There are reports of midshaft bone fracture occurring associated with pain and cortical thickening of the bone.  But these are very rare.  Risk of fracture should be assessed with a bone density test and therapy can be continued in those patients thought to be at risk of common fracture. If bone density shows good improvement, drug holidays may be recommended, or consideration for a drug switch to a different class, may be made.  Research is being continued, and this problem is being monitored to see if it is a significant issue.

Protos -- sodium ranelate .  This is given as a daily dose of 2 g.  It must be given away from food because of absorption problems. This forms under the category of anabolic therapy.  It is not licensed in America yet. Daily dosing means compliance issues and tolerability of the drug because of nausea is an issue.


Calcitonin (miacalcic) is a hormone that acts on the osteoclast to reduce
bone resorption. They are extremely useful in fracture and prevention. However,
the use is limited by cost. There is now a nasal form given as 200 Units 3 times per
week and this is now available in the USA and Europe at affordable cost. We have a
injectable form. The cost is R100/amp in this country (South Africa) and therefore,
I only use it in established fractures. It is very useful as it has an analgesic effect as
well. Long-term use has been shown to improve densities by 2 - 3% by 2 years and
reduce the fracture incidence.
However the research studies of this drug poor and most rheumatologists no longer use this medication except short-term after fracture for some pain relief.


The Horizon
What other therapies are on the Horizon?
the future is going to bring a series of biologic therapy for the treatment of osteoporosis.  The first of these is currently being assessed by the Food and Drug Administration in the USA and is known
as Denosumab. This is an anabolic type of treatment with good increase in bone density and better structure of bone is noted on biopsy. It works by opposing binding of receptor activator to the receptor of the osteoclast cell lineage.


Therefore, in Summary:-
Osteoporosis is a disease of bone remodelling. The amount of bone formed reduces
with age and is accelerated by females after menopause.
Prevention can be achieved by:-

Encouraging calcium consumption and exercise and hormones to increase peak
bone mass. Early recognition through risk factor assessment is vital to target
those most in need of early intervention and protection.
Treatment is available and the therapeutic interventions now
available are opening up hope for people not only in prevention, but also in therapy.
Fractures are no longer necessarily meaning a death sentence or a confinement to a
wheel chair.
My recommendation is that the problem should be treated aggressively and
monitored effectively. Education in forums like this are a start in propagating
information and knowledge that a common condition is now treatable and that
the days of painkillers alone have passed.


The microarchitecture


Bone structure with fracture of the microstructural bone bridges



Vertebral fracture

Dr David Gotlieb
Original Article : copyright
Cape Town
South Africa
December1996

Revised 2011


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