OSTEOPOROSIS

Are you at risk?
The biggest osteoporotic risk factor is simply being a woman. You are ten times more prone to suffer from osteoporosis at an earlier age than your male counterpart.

Osteoporosis means, fragile bones, these bones break easily by slightest trauma. One in four women suffer from osteoporosis with increasing age after menopause 

Women suffer more

1) They have an initial lower bone mass

2) Have a higher bone loss with age particularly at menopause when oestrogen is decreased, as they are the most important hormones in keeping the bone mass.

3) Women live longer.

It is estimated that about 56% of women suffer from a fracture after the age of 60.These fractures include spine, hip, wrist, ribs and upper arm. This makes life difficult and painful.

Osteoporosis is somewhat difficult to treat but easy to prevent. This prevention should start early in childhood with good nutrition, plenty of milk and calcium as this is required for bone formation, sports activities, and sunshine as this gives us vitamin D. This should continue in adolescence. The maximum bone mass is achieved in our late 20s to early 30s, after which it begins to decline. Fractures are the main side effect of osteoporosis and they should be prevented. However besides osteoporosis there are many other risk factors which can cause fractures.

These include:-

1) Being a female

2) Age

3) Weight and height

4) Parental hip fracture at a young age

5) Smoking

6) Alcohol

7) Glucocorticoid drugs

8) Antidepressants called serotonin uptake inhibitors

    For example- Prozac

 9) Drugs for acidity called proton pump inhibitors

10) Vitamin D and K deficiency

11) Personal history of soft trauma fracture

12) Rheumatoid arthritis

13) Ethnicity-(Caucasians have the highest risk for fractures.)

14) Premature menopause

15) Lactose intolerance and bowel problems

When we talk about osteoporosis we always wonder how to make this diagnosis. There are many tests to make this diagnosis, which I will talk about in the next few lines. However it is clear from the above list that assessing the fracture risk is even more important than making the diagnosis of osteoporosis. Many women have fractures without osteoporosis.  There are several tools by which fracture risk assessments are done .The tools WHO: uses are called FRAX, WHO does not always include BMD in their risk assessment. These tools depend on local factors, such as facility for bone density, local economic factors, reimbursement by insurance and people willing to pay for health issues. There is no unified strategy to use. Basically if fracture risk is high, the individual is treated pronto, if intermediate do BMD and reassess, if low follow the normal protocol. Bone is a living tissue it is constantly being made and destroyed this keeps a balance. It is under the control of many chemicals and hormones. It consist of a mesh if proteins called collagen in which minerals are deposited mainly calcium. The tough outer wall of the bone is called cortical bone; the inner tissue is called trabecular bone or spongy bone or cancellous bone it is, porous and contains bone marrow, produces blood cells.

Normal Bone                          Osteoporotic Bone

It is this part of the bone that loses its minerals; it is mainly calcium and becomes thin, thus causing osteoporosis.  99% of our body calcium is stored in our bones. There are two types of cells involved in our constant bone remodelling. They are called osteoblasts which form the bones and osteoclasts which destroy the bone. A fine balance is maintained in this activity to keep the bones well tuned, maintain body calcium levels, as this is very important for the activity of the heart and muscles. As already mentioned this is controlled by various hormones and chemicals in the body. Bone modelling and remodelling is done at the same time. The bones are also sculpted. The maximum bone mass is achieved at around the age of 30, after which it slowly starts to decrease. The adult skeleton is replaced about every 10 years. The oestrogens keep the bone destroying cells osteoclasts under control, and maintain the beneficial role of vitamin D.

So why does osteoporosis happen?

Many of these reasons overlap with fracture risks:

1) Oestrogen deficiency in women which happens at menopause, testosterone deficiency in men which happens with aging.

2) Under activity of adrenal glands (a hormone producing gland in our body).

3) Under activity of a hormone Calcitonin (produced by the Thyroid Gland)

4) Over activity of another hormone called Parathyroid.This drains the calcium from the bones.

5) Under activity of the pituitary gland. This is the most important hormone producing gland in our body. It is often called the band master of the body orchestra.

6) Prolonged absence of periods which results in oestrogen deficiency caused by: anorexia nervosa, excessive exercise ,high Prolactin level, a hormone which comes from the Pituitary gland, surgical removal of ovaries or prolonged suppression of ovaries for medical treatment). All these cause oestrogen deficiency

6) Hypogonadism (poor functioning sex glands or may come from the poor activity of the Pituitary ) again Oestrogen is depleted in women and likewise Testosterone in men.

7) Brittle bone disease (Osteogenesis imperfecta) .

This is a genetic disorder where the bones are fragile due to defective collagen, and break easily. It can be mild to severe. 

8) Malabsorption syndrome, chronic inflammatory bowel disease

9) Drugs, corticosteroids, heparin, antidepressant and proton pump inhibitors (used for acidity of the oesophagus and stomach)

10) Chronic diseases, diabetes, renal, arthritis, liver, multiple myeloma, Systemic lupus Erythematosus (these two are complex diseases) and HIV.

11) Prolonged immobilization.

DIAGNOSIS OF OSTEOPOROSIS AND FRACTURE RISK

The thoughts on diagnosis of osteoporosis should start with a woman’s personal history and risk factors which have been enumerated in the previous few lines for example long term use of corticosteroids, smoking weight below BMI of 21. However X-rays play a most important role in the gold diagnosis of osteoporosis. The best of these tests is called DEXA; in simple words we can call it bone densitometry. The test measures what is called BONE MINERAL DENSITY (BMD), it measures a certain amount of minerals and tissues in a certain volume of bone (W/G/CM2). This tells us if the bone is normal or a certain amount of bone is lost. This is expressed on 2 measurements, T score, which compares it to a young white young woman 30 years of age. The other is called Z score, which compares it to the bone density in the same age group. 

A T score of -1 is considered osteopenia, a T score of      -2.5 or below is considered osteoporosis. This is an expensive test costing approximately $125 American dollars, and also it is not available in many parts of the world, nor is it advocated routinely.  At the time of bone density assessment you do not need any preparation you just lay on a machine with your clothes on, the machine then scans your body, it takes about 15 minutes and reports are calculated.

The fracture risk is expressed at the same time. Different fracture risk tools are used in different countries. Bone density is not always used to assess fracture risk.

Besides DEXA scan, different types of x-ray studies are used, QCT, (quantitative computerised axial tomography), ultrasound of the heel, plain lateral x-ray of the thoracolumbar region of the spine, this is often useful when we cannot do BMD.

Several basic blood tests are required to exclude many other problems:-

1) Normal Full Blood Examination.

2) Hormones, Thyroid, Parathyroid, Oestrogens, Pituitary and Testosterone in men.

3) Alkaline phosphatase, Homocysteine a congenital problem in causation of osteoporosis.

4) Serum calcium and vitamin D

5) Bone turnover markers, are a recent tool which measure the end products of osteoblastic and osteoclastic activity of bone in serum, blood or urine, which gives us what is happening to the bones. These are rapid, reliable and cost effective tests. One has to understand its biological analytical and standardization process. At this stage these are very useful for fracture risk assessment independent of B.M.D. In clinical practice it is useful to assess the progress of people on osteoporosis treatment particularly those who are on a given treatment to prevent bone reabsorption. One can also check on patients to see if they are compliant to the treatment.

What is the treatment of Osteoporosis and who should be treated with what?

Osteoporosis (OP) is a silent disease; hence it is under treated in most countries of the world.  The other problem is poor patient compliance due to forgetfulness, side effects and not understanding the consequences of the problem. We have to overcome these problems with education, good reminder methods, minimizing the side effects or changing over to a drug more acceptable to a woman.  Prevention of OP starts in childhood with good nutrition exercise and sunshine. This should continue at all ages, a woman needs to take about 1000 to 1300 mg of calcium daily. Too much calcium can cause some cardiac problems; hence there is some international debate on this issue. This should be accompanied by 800 international units of Vitamin D (1 microgram of Vitamin D is = to 40 INU); this can be taken as a lump sum once a month. One of the main roles of Vitamin D is to absorb calcium from the gut, allowing calcium and phosphorus levels to control bone formation. It also keeps the parathyroid gland under control. Sunshine for a few minutes in summer is adequate to make up your Vitamin D, may be a short walk at lunch time, prolonged sun exposure does not keep increasing your vitamin D; however it increases your risk of skin cancer. If the UV index is more than 3, sun exposure should be avoided. This is to prevent the risk of skin cancer.

Lifestyle factors should be improved, such as; stop

smoking,  limit alcohol intake, along with soft drinks, tea, coffee and sugar. Try and decrease your weight, if you are very overweight and see if some of the drugs you take for other diseases can be readjusted. Some studies have shown a role of vitamin K, but at this stage it is not recommended for the treatment of OP.

Pharmacological treatment is recommended in almost all pre and post menopausal women under the age of 60. Initially they were prescribed a drug called PROFOX (a combination Prozac and Fosamax) which in my opinion was no good. Fosamax has its own side effects and Prozac is no good for OP. In the first 5 years of menopause not only do women lose 1% of their bone density, they lose collagen from the skin thus losing its thickness, losing intervertebral discs which make one fifth of the length of the spine, there are emotional changes due to lack of oestrogens, at times of life cycle as postpartum, premenstrual, so in my view hormone replacement treatment will be the best treatment before the age of sixty. It will take care of all other symptoms for example: hot flushes, poor sleep, depression and all that goes with menopause and prevent losing bone. Many clinicians are reluctant to use HRT because they have not familiarised themselves with its use. Depending on if the woman has a uterus she can have oestrogens and progesterone, otherwise if she has no uterus oestrogens alone do very well. Many different types of oestrogens and progesterone can be taken by different routes to prevent side effects. They decrease risk of hip and spinal fracture, bowel cancer, heart attacks and mortality. After 5 years of treatment bone density has been shown to rise by about 10 %. The only risk is a very small risk of increase in breast cancer. The Thromboembolic risk (Thrombus) can be managed by using Transdermal (on the skin) oestrogens. The breast tenderness and vaginal bleeding problems are easily managed.

Bisphosphonates is the main group of drugs used by most clinicians as the first line of treatment.

Who should be given these drugs?

1) Those that have had a minimum trauma fracture have a high fracture risk with or without using BMD

2) Those with a T score of -2.5 or lower.

3) On high doses of corticosteroid for more than 3 months

4) High risk factors for OP

Various Bisphosphonates

Alendronate: 70 mg orally once weekly.  On the remaining 6 days women can take vitamin D and calcium in the usual dosage

The other Bisphosphonate often used is Risedronate: 35 mg orally once a week or 150 mg once a month.

Ibandronate: 150mg orally once a month or it can be given 3 mg IV every 3 months.

Zoledronic acid (another Bisphosphonate) is given

5 mg in 100mls IV slowly once a year.

Bisphosphonates are advised to be taken on an empty stomach first thing in the morning with a glass of water, after that keep standing, do not eat or drink anything else. Bisphosphonates attach to the surface of the bone thus slowing the activity of osteoclast cells. Bisphosphonates have many serious side effects. The main side effect of these is gastric upset and esophageal burning, nausea, vomiting, joint and muscle pains, fever, loosing of teeth, jaw pain, constipation and fatigue. One of the two very rare complications quoted are osteonecrosis of the jaw and atypical fracture of the femur. These usually, only happen if they are used in very high doses for bone cancer. There is no definitive date as to how long this therapy should be used. No therapy is indefinite, after 1-3 years or if there is another fracture it should be reassessed. It is believed that the benefit of Bisphosphonate treatment can last up to 5-10 years, however it is worth while repeating BMD , BTM , and fracture risk after 1-3 years.  During this time calcium and vitamin D should be continued. Combination therapy with other drugs does not provide any benefit.

Denosumab, is the latest achievement in the treatment of osteoporosis. It is used as a first line of treatment in some countries. It is a monoclonal antibody (like a vaccine) and attacks only one type of cell. It works by disabling the maturation and activity of osteoclasts, and the only problem is that its effect does not last when the drug is stopped. Before starting Denosumab assess the oral cavity to decrease the risk of osteonecrosis of jaw (this is very rare), and make sure there is no hypocalcaemia. There is some concern about its effect on the immune system (increased risk of infections) and its use after bisphosphonates, on the bone after treatment is stopped. The dose of Denosumab is 60 mg in 1ml given every 6 months subcutaneously, (meaning under the skin). It can cause side effects like any other drug and you can get this list from your caregiver. A 5 year trial with Denosumab has been very successful. Its use decreased the risk of spinal fractures by 70%, hip fractures by 40%. It does not have a cancer risk. The cap on the syringe is latex so let your caregiver know, that you have a latex allergy. There is a special programme called Provital, which can keep reminding you when your next treatment is due.

The other very simple treatment for OP is Raloxifene. This is a special oestrogen which has different actions in different organs, hence effective with bones; it does not cause breast cancer. The dose is 60 mg daily, taken orally and you do not have to fast. It should not be given to people who have a history of deep venous thrombosis or have been immobilised for a long time.

Teriparatide: Is a synthetic form of Parathyroid hormone and acts by decreasing bone resorption and improves bone formation. 20 micrograms are given daily by subcutaneous injection. Its use is restricted to 18 months as its long term use caused bone cancer in animals. It is recommended that it is followed by Bisphosphonates.
Abaloparatide is the latest drug that is being used in place of Teriparatide.

It is recommended that any treatment is followed every 1, 3, 5 years depending on the individual situation. Treatment should be offered for various disorders, which cause secondary osteoporosis.
There are many new drugs and treatments now available in different situations.

So much on osteoporosis why is it such a significant problem? Life expectancy is increasing hence the risk of osteoporosis is increasing. There are almost 200 million women in the world who have osteoporosis, may be many more about whom we do not know. There are 8.9 million known fractures caused in the world annually. It costs 70 -20 billion US dollars to treat them. Do not forget that in most parts of the world many are never treated. It was estimated that a fracture occurs in the world every 3 seconds. Osteoporosis is a silent disease, it causes untold problems to the individuals, pain, disability, poor quality of life, and death, too much cost to the nations, too much cost to the world. The good news is that health providers and the public are both becoming aware about it, so let us start with education, information and prevention. The new technologies are providing us with better and better treatments. Even surgery is used for correction of spinal defects caused by osteoporosis. The main prevention should start in childhood, good nutrition sunshine and exercise. Later focus on lifestyle factors, nutrition, calcium, vitamin D measures for fall prevention,(do not walk in the dark or cluttered spaces, be aware of the drugs that can cause dizziness), exercise and regular medical advice on your health. Do not ignore the treatment that is offered to you.

KEY POINTS:-
Start prevention early in life rather than later.
Regular exercise.
Good Nutrition.
Sunshine.
Vitamin D and Calcium.
Stop Smoking
Limited Alcohol