RA is a Risk Factor for Osteoporosis

Osteoporosis is silent. People’s bones can gradually become weaker and weaker with no outward hints that there is a problem — until suddenly bones break.  Spontaneous compression fractures of the spine can be quite painful and lead to deformity, chronic pain, and premature death.  Broken hips are another risk factor for early death — approximately 20% of people with a broken hip die within one year of the fracture.

In an ideal world, osteoporosis would not occur.  In theory, osteoporosis is entirely preventable.  Since we don’t live in an ideal world, it is crucial that osteoporosis be identified early and treated aggressively.

DEXA is the gold-standard in osteoporosis testing.  DEXA scanners (Dual-Energy X-ray Absorptiometry) (also called DXA) use two separate very low-radiation x-ray beams – about 1/10th the radiation of standard x-rays — to image the hips and spine to measure bone mineral density.  As we would expect from the “dual energy” portion of the name, these two x-ray beams have different energy levels.  Bone mineral density is calculated by measuring the difference between what is absorbed from the first beam and the second.

Test results will provide a variety of numbers.

  • Bone Mineral Density
  • T-Score
  • Z-Score

Bone Mineral Density (BMD) is a raw number indicating the average concentration of minerals in your bones. The higher the number, the higher the bone mineral density and the stronger the bones.  Lower numbers indicate weaker bones.

T-score and Z-score are based on statistics.  Compiling the results from many people has allowed scientists to determine what is normal bone mineral density, and what constitutes strong or weak bones.  Graphing the data forms a picture shaped somewhat like a bell.

A brief aside about statistics:  in statistics, the mean is the average — it tells us what is normal. The standard deviation tells us how far away something is from what is normal. 68% of all data will only deviate slightly from the average (will be within one standard deviation of the mean) — this makes sense because obviously most things should be close to what is normal. On a bell curve (pictured below), the mean does not deviate at all from what is normal, thus the center of the curve deviates zero (labeled 0), and most of the data clusters close to the middle — one standard deviation is labeled +1 (above zero) and -1 (below zero).  95% of the data will be within two standard deviations of the mean (labeled +2 and -2), and 99.7% of the data will be within three standard deviations of the mean. It is very rare for something to deviate significantly from what is normal.

T-score and Z-score numbers indicate standard deviations from the mean on a bell curve.  A T-score compares your BMD with healthy young adults who have good bone mineral density.  A Z-score compares your BMD with others of your age and ethnicity.  Doctors are most concerned with the T-score.


A bone mineral density scan T-score that is more than one standard deviation below the mean is bad. Between one and 2.4 standard deviations below normal is osteopenia, while a T-score of 2.5 or more standard deviations below the mean is osteoporosis.

Who should get a bone density scan? The general rule is women at age 65 or men at age 70.  Before age 65, the test is only considered if you have risk factors, and if treatment would occur based on test results.  If you wouldn’t be treated, there’s no point in having the test done.  Bone density scans are rarely done on premenopausal women; until menopause, high estrogen levels seem to provide protection against broken bones even in people with low bone mineral density.  The question is, what are the risk factors?

Rheumatoid arthritis is just one of many risk factors for development of osteoporosis.  Other risk factors include:

  • history of taking 5mg or more of corticosteroids for more than three months
  • taking methotrexate (other meds, too)
  • family history of osteoporosis
  • history of an immediate family member with a fragility fracture
  • history of bone fracture as an adult
  • loss of height
  • weight of less than 127 pounds
  • being a smoker
  • menopause
  • eating a diet low in calcium
  • avoiding sunlight (indicative of low vitamin D production)

Given these risk factors, it is no surprise than rheumatologists refer patients for bone density scans.

Everything published about DEXA says that it is painless.  This information is obviously prepared by people who have never had the test.  Although it is technically true that the x-rays themselves do not inflict pain, before the scan is taken you’re strapped to a table in an uncomfortable position and required to stay tied down for the duration of the 15-20 minutes of the test. Although the average person might not be physically injured by the scan, it is inaccurate to say that the test is painless.  More accurately, the test is uncomfortable, but not unbearable.

After the test is complete, the referring doctor will receive a report showing your Bone Mineral Density, your T-score, and your Z-score.  Your report might also include use of the World Health Organization’s Fracture Risk Assessment Tool (FRAX) . This attempts to calculate a person’s probability of fracture within the next ten years with the goal of frightening patients into taking osteoporosis seriously.  A 28% risk of fracture within ten years is about 2.8% per year.  2.8 doesn’t sound nearly as scary as 28%, though, thus the use of ten-year risk estimates.  If you click on the link, select “calculation tool” and then select your continent/country and complete the questionnaire.  The calculation can be made either with or without results of a bone density scan.

Measuring Inflammation

Remember those old childhood cartoons where a guy hits his thumb with a hammer?  The thumb turns bright red, swells to three times its normal size, and hurts so much that painful rays emanate for all to see.

I remember the day I awoke in excruciating pain, my entire hand red and throbbing as if it was a model for one of those old hammer-to-thumb cartoonists.  In the cartoons, it’s funny – not so much in real life.

There have also been times my hands swelled to a lesser extent – not enough for anyone else to notice, but enough that it cut off the circulation in my ring finger.  When fingers swell so much that a perfectly sized wedding ring cuts off circulation and the finger turns blue, it’s a safe bet that there’s a fair amount of inflammation going on.

One would think that a doctor could write “significant swelling” as documentation of such events, but doctors seem to have a preference for numbers to quantify everything, including inflammation.  ESR (erythrocyte sedimentation rate) and CRP (C-Reactive Protein) are two lab tests that can be done to “measure” inflammation.  Unfortunately, those tests aren’t perfect.  People can have significant inflammation but perfectly “normal” lab results.  How ironic that someone’s feet can be too swollen to fit into shoes, hands can be too swollen to do anything, and a doctor can say, “I’m sorry, but according to your lab work, there is no inflammation.”  Many RA patients have “normal” inflammatory markers – accompanied by enough disease activity that joints are destroyed.

I’ve wondered why, if pharmaceutical companies can develop drugs to inhibit TNF-α, nobody can come up with a test to measure TNF-α in the bloodstream.  Same with interleukin-6 and the other proteins that are thought to be associated with disease activity in RA.  If numbers are so important, there should be a way to measure those things.

Scientists have been working on it, and have a new test.  This test doesn’t diagnose RA, but gives the doctor an objective number to indicate how active the RA monster is.  Announced late last year, the Vectra Disease Activity Test measures twelve proteins, applies a convoluted formula (take the logarithm of 1+CRP, multiply by .36, add the square root of this, multiply by that…) and produces a single number to quantify disease activity.

Yay!  With luck, this will be a better test.  Questions remain, though.

Given the number of RA patients with normal CRP, I don’t understand why that information is used in the new test’s calculations.  The testing company’s website compares the results to DAS28. I’d rather see some comparisons that show Vectra DA to be superior to existing tests.  What I’d really like to see is data from hundreds of RA patients with obvious disease activity but normal ESR & CRP, and see that this new test returns a high number, regardless of the normal ESR/CRP.  Show us the data.

Tuberculosis Testing & Methotrexate

Remember those old television commercials showing kids playing with their alphabet soup and AlphaBits?

I think that the scientists who write about tuberculosis miss the days of their childhood spent playing with their food.  There sure are a lot of mixed-up letters in the literature on this topic!  The DTBE of the CDC established the TBESC for purposes of TB research.  How accurate is PPD in people who’ve had prior BCG?  Is IGRA more accurate than TST?  What is the difference between T-SPOT.TB and QFT-G?*

Whew!  By now you’re asking (if you’re even still here), what does all of this have to do with methotrexate, anyway?

There are a zillion hoops to jump through before starting methotrexate:

  • lab tests
  • chest x-ray
  • tuberculosis test

Yep.  The rheumatologist should make sure that you don’t have TB (or LTBI) before prescribing mtx.

I was curious, because I remember my rheumy saying that I needed a TB test and silently groaning to myself, “Oh, no!  That means I have to come back here in a couple days to have it read.”  With a skin test for tuberculosis, a needle is used to inject a small amount of tuberculin purified protein derivative just beneath the skin, making a tiny red bump (a little bit like an insect bite).  Then, a couple days later, the person being tested must return so that a nurse can look at the little bump, measure it, and exclaim over its progress (or, hopefully, the lack of progress).  It’s not very convenient – but much more convenient than dealing with the disease.

Event though my doctor said I needed a TB test, and wrote TB on the lab slip (in addition to all the regular tests ordered), a skin test wasn’t done.  After a one-hour drive to the doctor’s office, a long wait because she was uncharacteristically behind schedule, then waiting forty minutes at the lab for a blood draw, and adding another hour in radiology for x-rays, I still faced an extra hour to drive home… I was exhausted!  I just wanted to get home and was quite willing to address the need for another test on a different day, so decided not to ask any more about the TB test.

Fortunately, a few days later my lab results showed up.  I discovered that there is a blood test for tuberculosis.  I’d only known of the skin test.  In fact, there are (at least) two blood tests for tuberculosis.

These tests are considered interferon-gamma release assays (IGRAs), and are performed in a test-tube on a blood sample.  Both tests appear to be more accurate than the skin test.  You can read more about it at MedPage Today

* * * * *

  • TB:  tuberculosis disease
  • LTBI:  latent tuberculosis infection
  • BCG:  Bacille Calmette-Guérin (tuberculosis vaccine)
  • TST:  tuberculosis skin test
  • PPD:  purified protein derivative (another name for the skin test)
  • AFB Culture:  Acid-Fast Bacillus smear and culture and sensitivity
  • INH:   isoniazid (antibiotic to treat tuberculosis)
  • MDR TB:  Multi-Drug Resistant tuberculosis
  • XDR TB:  Extensively-Drug Resistant tuberculosis
  • TBESC:  Tuberculosis Epidemiologic Studies Consortium
  • IGRA:  Interferon-Gamma Release Assays
  • QFT-G:  QuantiFERON®-TB Gold
  • TSPOT/ T-SPOT.TB:  blood test that counts the number of effector T-cells that produce gamma interferon