Wednesday, 13 November 2013

Osteoporosis : forget calcium and vitamin D - but what about HRT ?


Osteoporosis : forget calcium and vitamin D - but what about HRT ?

Osteoporosis is nothing to do with vitamin D, and so why is it that we see headlines such as:


And this was in the British Medical Journal! It also appeared on the inner pages of national newspapers. There was no biological reason to expect vitamin D to be helpful in the treatment of osteoporosis, and this had been demonstrated in an earlier trial.  

Osteoporosis is a serious, disabling, and chronic disease, especially in elderly women  the number of which is increasing considerably. The absence of effective treatment of osteoporosis creates therapeutic desperation, and as a result the vitamin D trials came into being. The absence of benefit can hardly be attributed to be a so-called “failure” of vitamin D, but that is how it has appeared. 

It is important to understand osteoporosis, and to do so it is necessary to take a look at the biology of bone. Osteoporosis and vitamin D are both something to do with bone, but that is where the connection ends. But vitamin D has many benefits unconnected with bone.

Osteoporosis

Bone formation starts as the production of a fibrous substance called osteoid, which is laid down in a structural pattern called matrix. This is obviously of fundamental importance and is is this step that is impaired in osteoporosis. When matrix is inadequate the bones become brittle and they easily break.

Bone and its matrix are continually being regenerated - old bone is destroyed by cells called osteoclasts (= “bone destroyers”) and new osteoid matrix is created. At any one time about 10% of bone is being replaced. This occurs in ways that are not fully understood. In fact understanding is extremely poor otherwise the nature of osteoporosis would be clear, but it isn’t. 

Head and neck of femur - normal and osteoporotic bone
The pattern of matrix varies in different parts of the body depending on the physical stresses at particular parts of the skeleton. The density of matrix is much greater in weight-bearing parts, especially the neck of the femur and the vertebral bodies of the spine. It has been noted that as a result of weightlessness, astronauts lose bone density and develop osteoporosis. In healthy people this is rapidly reversed in normal physical circumstances. 


Ossification and osteomalacia

Matrix is converted into mature bone by specialised cells called osteoblasts (= “bone creators”). They add to the matrix a complex calcium-containing compound, a process that is called ossification. Osteoblasts are controlled by calcitriol, the active form of vitamin D. When vitamin D is deficient the ossification process fails. This means that bone remains prodominently osteoid matrix and therefore it is not rigid but can bend. This bone disease is called osteomalacia (“soft bone”). 

In osteoporosis there is not enough matrix, but the matrix that is present is fully ossified. This means that that the bone density is low - the bones are thin, delicate and prone to fracture. In practice bone density is measured as the density of calcium rather matrix, as usual measuring what it is easy to measure rather than what it is most important to measure.

On the other hand osteomalacia is completely different. There is normal matrix but it is not fully ossified. The bones are therefore soft rather than brittle. They can bend and deform especially during growth in childhood.

X-ray of tibia and fibula in rickets showing typical bend of soft bone
Bow legs, typical of rickets



Rickets is a disorder of vitamin D deficiency affecting growing bone and is thus seen as an active disease in children, the childhood form of osteomalacia.  Skeletal deformities can result and can persist into adult life. The characteristic deformity is bow-legs. A much more serious deformity is contraction of the pelvis due the thrust from the legs pushing the hip-joints inwards. When rickets was more common in the industrial cities during the 19th and early years of the 20th century,  the contracted pelvis in young women led to terrible problems with obstructed labour.

Vitamin D is vital for bone health especially in childhood.

Osteporosis in the 21st century

Now that we are in the 21st century osteoporosis will become a major problem. It is a condition found almost exclusively in elderly women and their number is increasing steadily. The main reason for this is that deaths from coronary heart disease, the major killer of the latter half of the 20th century, have virtually come to an end. Death rates from stroke have decreased substantially and those from cancer significantly. The major problem is now old age with associated infirmity, and this is causing great pressures on health services.

X-ray of spine showing vertebral collapse and osteoporotic bone
Osteoporosis results in brittle bones that fracture easily. This occurs most commonly in the spine. The vertebra can collapse vertically causing temporary pain but irreversible shortening of the trunk. This is accentuated as with age the intervertebral discs become dehydrated and also lose their height. The vertebra may collapse asymmetrically, the front collapsing into what is called a “wedge fracture”. This causes shortening, but also a frontwards leaning. This leads to a curvature of the spine called a kyphosis, or historically a “Dowager’s hump”, indicating its characteristic appearance in elderly women.



X-ray of pinned neck of femur


Fractures can occur in any bone but the most serious is the neck of the femur. This can be a terminal event in very old people, but for the majority a “quick fix” can be given by  the surgical insertion of fixing pins, or even a total hip replacement.





The significance of the menopause

The synthesis of bone osteoid matrix is controlled to a significant extent by the sex hormones testosterone in men and oestrogen in women. Deficiency of these hormones can lead to reduction in the synthesis of bone matrix and thus osteoporosis. Testosterone deficiency in men is rare, but oestrogen deficiency in women is universal. 

As the ovaries cease to function at about the age of 50 years, oestrogen production inevitably comes to an end. This is the menopause, and it can occur naturally usually between the ages of 45 and 60. It obviously occurs earlier if the ovaries are surgically removed, and in some women spontaneously.

The menopause can be identified by the cessation of menstruation, but this is not obvious if hysterectomy has been performed. A women will probably identify night-time hot sweats and flushing as menopausal symptoms. Biochemical tests can also indicate menopause. 

The way in this works is as follows. The ovaries are stimulated by hormones produced in the pituitary gland, the time controller. The pituitary secretes the hormone FSH (follicle stimulating hormone) and this activates follicle maturation within the ovaries. This is followed by the secretion of LH (lutenising hormone) by the pituitary, and this leads to release of the ovum, the egg, from the follicle. The follicle secretes oestrogen, and this together with the failure of fertilisation of the ovum leads to inhibition of secretion of FSH and LH by the pituitary gland, which then comes to the end of its monthly cycle. Menstruation follows immediately and then the cycle starts again, with commencement of FSH secretion by the pituitary. 

When the ovaries ultimately fail, the blood levels of FSH and LH are maintained at a very high level, and this becomes evidence of the menopause. It is sometimes puzzling to women as to why when the ovaries stop working hormone levels in the blood increase, but these are only stimulating hormones and not active sex hormones. There is  a failure of what is called “feed-back inhibition”. The same thing happens with the thyroid in which organ failure, hyothyroidism or myxoedema, leads to an increase in the blood level of TSH, thyroid stimulating hormone also produced by the pituitary.

Post-menopausal osteoporosis

The development of osteoporosis
After the menopause a woman has low production of oestrogen, and this is not a good thing. It leads to osteoporosis. Before the menopause women have a distinct health advantage over men, but this is lost after the menopause. It is interesting to note that in a variety of mammals there is equality of susceptibility to infections and infestations between young males and females, but after puberty the females gain an advantage, again pointing to a benefit from oestrogen. Menopause occurs very rarely in non-human mammals and so its effect is not available for study. It is usual in nature for death of a female to occur shortly after, or perhaps before, the end of reproductive functions. 

In human beings, if a woman dies at the age of about 70 years she would have been deprived of oestrogen for just 20 years. This is long enough for osteoporosis to develop without it usually being a major problem. But now more than 40% of women die after the age of 85 years, and the proportion living to 100 is expected to increase substantially. The menopause can now be expected to occur at only half-way through a woman’s life. For a woman to live perhaps 50 years without oestrogen gives an extremely high risk of serious osteoporosis.

Prevention of osteoporosis

What can be done about this? First, physical exercise during earlier life can produce the natural stresses on the skeleton that will lead to optimum deposition of osteoid matrix. Second, sun exposure and vitamin D should be maximised to make certain that ossification of matrix is perfect. Third, diet should be good with adequate protein to help build up matrix. Fourth, avoidance of obesity avoids undue vertical pressure on bones, especially the spine and hips.

Treatment with corticosteroids, prednisolone, should be minimised but it is sometimes essential even intermittently for suppressing serious illnesses, especially chronic inflammatory conditions (eg asthma, ulcerative colitis, lupus). Prednisolone can lead to severe osteoporosis due to an imbalance of bone turnover, increased osteoclast activity or reduced synthesis of osteoid matrix. Its effect is additive to that of the menopause. It is recommended that older people who take steroids should also take calcium and vitamin D tablets. There is no evidence that these are of any benefit in osteoporosis but clearly vitamin D will be helpful if there is associated but unrecognised deficiency of vitamin D. Calcium and vitamin D tablets are prescribed widely, but unpleasant and ineffective, they are also very cheap. The vitamin D given will however improve health in several other ways.

A group of pharmaceuticals called biphosphanates can be helpful in perhaps minimising the progression of osteoporosis but not reversing it. Biphosphonate is often given as a single weekly dose of alendronate, although this can have detrimental effects on the oesophagus and much more serious but less common effects on the jaw.

Strontium can also be given in established osteoporosis, again to reduce deterioration rather than to reverse. It is probably equally effective as biphosphonates.

The guidance that doctors receive is that these pharmaceuticals should only be given when osteoporosis is established. This is reasonable considering long-term therapy with medicines that have significant undesirable effects. The presence of osteoporosis can be detected by bone density scans, but the usefulness of these is doubtful if we are interested in the prevention of osteoporosis, and we must be.

Hormone replacement therapy

The greatest benefit must lie in preventing osteoporosis. This is the role of HRT – hormone replacement therapy. This is started at the time of the menopause and it is usually used as short-term treatment for suppressing menopausal symptoms. However its value in preventing osteoporosis demands long-term use. HRT should most certainly be given to women who have an early menopause. In the woman with a menopause after the age of 50, how long HRT should be given is far from clear but perhaps until about 20 years before death. For most women this might mean until the age of 80 years! 

It is difficult to get our minds around this but we must remember two vitally important facts. This first is that osteoporosis cannot be reversed and can only be prevented. The second is the remarkable long lives that pre-menopausal women of today must expect. To have a long life-expectancy is wonderful, but only if health is maintained and serious disability with osteoporosis is avoided. 

Women who are 100 years old today were born before the First World War. The younger women who are approaching the menopause today were born in the latter half of the 20th century and they can expect to live to the age of 100. The decision as to whether to take HRT is very relevant for them and it cannot be put off. It is necessary to deal with judgement as the full information about the value of HRT is not likely to be available for perhaps another 20 years. What we must do in the meantime is assess the balance of risks. There is as usual a great deal of fear given to women, especially if "trying to interfere with nature". But if nature means either an early death or crippling osteoporosis then perhaps it is best to interfere with it. 

Breast cancer in younger women is usually oestrogen dependent. Part of the treatment and long-term suppression therapy is Tamoxifen, which  functions by blocking oestrogen receptors. This creates menopausal symptoms and most women are able to cope with these. It follows therefore that to give oestrogen-containing HRT to women with previous breast cancer or with a high family risk of breast cancer would be unwise - it should not be given. But be clear that HRT does not “cause” breast cancer.

There is potentially a huge amount to be gained by so many young women in the prevention of osteoporosis. Hopefully other methods of prevention will come available in the future. At the moment there is only HRT, and this means natural hormone levels. 


4 comments:

  1. This comment has been removed by the author.

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  2. A friend has been put on 800 units vit d by her doctor against osteoporosis. Highly ironical as she was already taking 5000 units per day on my recommendation which he says is too much!
    I immediately referred her to your blog that I thought had the message that vit d is specifically useless against osteoporosis ( other than of course that general bone health and absence of rickets is very relevant to vit d)
    I wanted to tell her that her doctor was an idiot but as I read past your headlines I was left confused whether or not you would approve of a doctor putting someone onto vit d for osteoporosis.
    David I love your blog and books but I think you should be more definite and stamp the floor a bit more about your message.
    If your article really does say that research shows what was already known, that vit d was not beneficial to osteoporosis the cynic in me wonders who funded research that was destined to show vit d in a poor light.
    Confused from Seaton Ross

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    1. I am well aware that very many people are put on calcium and vitamin D tablets, supposedly to prevent osteoporosis.
      I am not unhappy with this. The calcium is not necessary as we are not calcium deficient in respect of diet. We require vitamin D in order to absorb calcium from our food into or bodies. The vitamin D prescribed will be beneficial, although the dose given, usually 800 units per day, is not as high as it should be, about 2,000 units per day.
      I am all for vitamin D supplement, but it is not a panacea, it does not prevent or cure everything. It does not affect the development of the serious condition of osteoporosis.
      I am concerned about osteoporosis and I am concerned that many doctors are misinformed by official guidelines that Ca & Vitamin D will prevent it. I want to improve awareness of the dangers of osteoporosis, especially now that we (especially women) are living longer. HRT is the best bet, but fine to take vitamin D for other heath benefits.
      And of course vitamin D is important in earlier life, for bone health and other health advantages.

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  3. Thank you for your helpful reply especially as I was a little concerned about my comments being a little forthright and loquacious as a result of a glass to two of wine!

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