Wednesday, July 25, 2012

Osteoporosis

     Several readers have asked me to write a blog on osteoporosis. They are confused by the welter of stories about whether or not there is a reliable way to prevent osteoporosis, the benefits and side effects of treatment of osteoporosis with bisphosphanates, and what exactly a bone density study measures and its reliability as a clinical tool. Again, all of my comments are general observations and conclusions based upon my training as a physicist and experience as an internist, and the final decision should ideally be made in concert with your doctor. I will restrict my comments to the results of clinical studies, and indicate the unknowns as well.

     In order to make bone, the body needs calcium in the form of the (Ca++)  cation, vitamin D, phosphate in the form of the (PO4---) anion, and parathyroid hormone. The body does NOT care and canNOT tell the difference between various sources of calcium: milk, calcium supplements with vitamin D added, calcium carbonate (as is contained in TUMS),  calcium from oyster shells, calcium from the white cliffs of Dover,  pills containing calcium-phosphate compounds, etc. The biochemistry of the body just looks for (Ca++), and the source is immaterial. In a similar fashion, the body will utilize the vitamin D that sunlight creates in your skin from cholesterol equally well with any vitamin D supplements you ingest. (To be precise the UV waves present in sunlight activate the 7-dehydrocholesterol that is normally present in your skin into vitamin D.) The use  of cod liver oil as a source of vitamin D originated in public health suggestions in the 1800's  when children in industrial countries growing up in tenements and working 12 hours a day 6 days a week in factories were observed to develop rickets in their growing bones because of their  insufficient exposure to sunlight, as opposed to children growing up on farms who had  an adequate supply of both milk and  sunlight.

     Wolff's law is an expression of the clinical observation that under a load bone will thicken its shaft to help it withstand the load. The most direct example of this is the bunions that women but not men develop. When walking in high heels, the foot tends to slide forward, and much of the body's weight is transferred to the medial part of the metatarsal joint of the first toe, known as the hallux. The bone's response is to thicken at the base of this hallux metacarpal joint to the extent that wearing shoes eventually becomes painful because the periosteum, or covering of a bone, is exquisitely supplied with pain nerves. In a similar fashion, I have played tennis my whole life, usually singles, on an average of two to three times a week, beginning at age eight. I have an Eastern forehand grip, which means that at the moment of contact my wrist is locked into a right angle. Much of the force of the forehand stroke is transferred to the base of the metacarpal bone that is proximal to my first finger, and this bone has a palpable swollen end just distal to my right wrist.

     There is no clinical practice that is proven to prevent osteoporosis, but we know several ways to avoid osteoporosis or, to be precise, we know what predisposes a patient to developing osteoporosis: getting older, bed rest, alcoholism (by depleting the phosphate ion and  in your body), smoking, menopause, hyperthyroidism, and treatment with glucocorticoids. The most rapid development of osteoporosis occurs with surgically induced menopause (i.e. removal of both ovaries) or with treatment with prednisone. The bone loss with the latter is so rapid that most authorities recommend instituting Fosamax or other bisphosphanate treatment simultaneously with the initiation of steroid treatment. If there is to be screening for osteoporosis, it would make clinical sense to screen individuals at risk more frequently than the rest of the population. A case could also be made for screening anyone who develops a bone fracture, compression or otherwise, for osteoporosis.

     This is the appropriate place for some definitions. A DEXA or bone-density scan measures the absorption of two different x-rays of different energies by the calcium in your bone. Every element absorbs only certain x-ray wavelengths, so the results are specific to calcium. There is no dangerous exposure to radiation in this procedure. Your T-score compares your measured bone density to that of a mythical 30 year old adult. Your Z-score compares your bone density to other patients of your age and sex. Therefore the T-score is absolute, and the Z-score is relative. The measurement of the  bone density of 30 year olds, is distributed in a Gaussian curve, the familiar error curve. The most common density is called the mean, or average density, and this is what your density is referred to. The width of the curve of measurements is determined by the standard deviation---by definition 67% of the measurements will fall within one standard deviation higher or lower than the mean value. In addition, 2.5 standard deviations encompasses approx. 98% of all the measurements, with 1% being higher than the mean plus 2.5 standard deviations, and 1% being lower than the mean minus 2.5 standard deviations. By consensus (or definition, the two words are used interchangeably here) if your T score is minus 1 or less, meaning that you have 33% less bone density than the average 30 year old, you are labeled as having osteopenia. Similarly, if your T score is minus 2.5 or less, meaning that you have 98% less bone density than the average 30 year old, you are labeled as having osteoporosis.

     Now come the myriad of questions, some of which we can answer from clinical studies, and some of which we cannot (as yet).  All my following statements apply to the average patient, with no known risk factors for osteoporosis. And again, final decisions should be made in consultation with your doctor. In what follows, "may" means that the data is suggestive but not statistically significant.

     1) No one knows if treating osteopenia prevents progression to osteoporosis.

     2) Treatment of osteoporosis with bisphosphanates prevents hip and back fractures.

     3) No one knows for how long you should be treated with bisphosphanates but we do know that the bisphosphanate molecule binds to your bone and stays there for between 5 and 10 years.

     4) No one knows at what age DEXA screening should start, nor how often you should be screened (a) if you have normal bone density, (b) if you have osteopenia, or (c) if you have started treatment.

     5) Patients who have taken bisphosphanates have an increased incidence of osteonecrosis of the jaw, which often appears after tooth implants. There may or may not be an increase in atypical fractures of the femoral neck---two conflicting studies have been published.

     6) Calcium supplements alone (assuming your diet has the proper amount of calcium) will not prevent osteoporosis.

     7) Daily calcium plus 400 Units of Vitamin D appears to confer no benefit, but daily calcium supplements plus 800 Units of Vitamin D may prevent hip fractures. In this case I say "may" because the positive conclusion was drawn from a meta-analysis of several studies, and meta-analyses have statistical problems and rest on an unproven mathematical assumption. (The interested reader is referred to two earlier blogs of mine as well as my article in "Chance", a statistical journal.)

     8) Daily exercise will increase bone density and may or may not prevent hip fractures.

     9) Bisphosphanates can cause reflux esophagitis, or make existing GERD worse, and there are no studies to show if taking stomach acid inhibitors prevents this effect.

     I am sure that there will be other clinical studies published in the future, because of the paucity of definitive clinical answers. And your decision will depend, in part, on how you feel about taking medicine for prophylaxis against an event that may or may not happen. Will you blame yourself if you do not take a bisphosphanate and develop a hip or spine fracture, or will you blame yourself if you do take this medicine and develop an unfortunate side effect? Either way, as I tell everyone, please don't second-guess yourself.

   


4 comments:

  1. I should mention again that designating a T score of (-1) as the beginning of osteopenia and (-2.5) as osteoporosis is quite arbitrary, and there is no clinical evidence to show if patients would be better or worse off if we designated (-1.5) as osteopenia and (2.0) as osteoporosis and the number at which to begin treatment.

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  2. Added note: As an example of the necessity for weight-bearing exercises or at least body motion in maintaining bone mass and density, the astronauts, who experienced zero gravity and therefore had no weight pressing down on their bones despite their mass, developed osteoporosis that was so severe that it limited the amount of time they could stay up in orbit.

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  3. Several readers have asked about the necessity of taking magnesium with calcium. Both elements appear in your body as divalent cations (charge ++) and therefore can precipitate out together in a chemical reaction. However, you do not need magnesium to make bones, so magnesium supplements are unnecessary. And don't forget that milk of magnesia, which contains magnesium, is a laxative.

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  4. To clarify paragraph 5: a T score of -1 means that you have less bone density than 67% of 30 year olds of your sex, not that your numerical number is 67% less.

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