Who are we worried about?

• Someone who gets non-traumatic fractures (for example, a collapsed bone of your spine without injury).

• When a bone density scan, known as a DEXA, gives a T-score of less than -2.5.

• When the FRAX tool predicts a >20% chance of fracture in the next ten years.

The simple answer is post-menopausal women. This is because approximately 80% of those who meet the definition of osteoporosis fall into this category.

Who should we screen?

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• Women should be screened when they reach age 65.

• Women between 50 and 65 who have risk factors for osteoporosis, such as:

  • A history of fractures

  • A history of tobacco use

  • Low body weight

  • Use of corticosteroids

  • A family history of osteoporosis

• Men should be screened when they reach age 70, typically if they have risk factors similar to those noted above.

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Follow-up screens are often done every 2 to 5 years, with the large variability based on clinical judgment

How to treat Osteoporosis?  There are three major choices.

• Bisphosphonates (these include Fosamax, Actonel and Reclast)

• Prolia

• Parathyroid hormone analogues (these include Forteo and Tymlos)

I’m realizing this discussion seems to have the rule of threes.  Another one would be why do we treat?

• To reduce risk of fractures (just improving bone density is not the goal)

• To improve mobility.  (those that fracture become, at least temporarily, more dependent)

• To save money.  It’s cheaper to prevent a fracture than to treat one.

How do we actually diagnose osteoporosis?

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The DEXA Scan: A DEXA scan (Dual-Energy X-ray Absorptiometry), also known as a bone density scan, is a non-invasive test.

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How It Works:

• Dual-Energy X-rays: The DEXA scan uses two different X-ray beams to measure bone density. These beams allow for better distinction between bone and soft tissue, giving a highly accurate measurement of bone density.

• Process: During the scan, you lie on a padded table while the scanner passes over your body. The procedure is quick, typically taking 10-20 minutes, and it’s painless. Generally, there’s no special preparation needed, though you might be asked to avoid taking calcium supplements for 24 hours before the test. The amount of radiation used is very low, much less than a standard chest X-ray.

The results are often confusing for most people because they use ‘standard deviation’ to assess risk. This involves a bell-shaped curve. Quite confusingly, for almost everyone who gets the tests, the scores are in NEGATIVE numbers, meaning a -0.8 is a lot better than a -2.1. Even more confusing is that they give two separate scores: the T-score and the Z-score.

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• Z-Score: Compares your bone density to the average bone density of people of the same age, sex, weight, and ethnic or racial background. This is helpful if you wish to predict where you might end up in time.

• T-Score: Compares your bone density to the average peak bone density of a healthy young adult of the same sex. The T-score is the one that matters most because it predicts your likelihood of having a fracture NOW.

There are three categories (of course three):

• Normal: A T-score of -1 or higher.

• Osteopenia: A T-score between -1.0 and -2.5.

• Osteoporosis: A T-score of -2.5 or lower.

The general rule is to NOT treat those with osteopenia, as the drugs were not shown to be particularly effective at reducing the risk of hip and arm fractures. However, there was significant reduction regarding vertebral fractures.

Are there any other helpful tools? Yes.

The FRAX tool is an online tool developed by the World Health Organization (WHO) to assess an individual's 10-year risk of experiencing a bone fracture due to osteoporosis. It is widely used in clinical practice to help guide decisions about the need for treatment, particularly in individuals with osteopenia or other risk factors for fractures.

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How the FRAX Tool Works:

1. Data Input: The tool requires input of several factors that influence fracture risk, including:

   • Age: Risk increases with age.

   • Sex: Women are at higher risk than men.

   • Weight and Height: Used to calculate Body Mass Index (BMI), with lower BMI being associated with higher risk.

   • Previous Fractures: A history of fractures, particularly after age 50, increases risk.

   • Parent Fractured Hip: A family history of hip fractures increases risk.

   • Smoking: Current smoking status contributes to higher risk.

   • Glucocorticoid Use: Long-term use of corticosteroids (like prednisone) is a risk factor.

   • Rheumatoid Arthritis: This condition is associated with an increased risk of fractures.

   • Secondary Osteoporosis: Conditions such as type 1 diabetes, untreated long-standing hyperthyroidism, hypogonadism, and others can increase risk.

   • Alcohol Intake: High alcohol consumption (3 or more units/day) is a risk factor.

2. Bone Mineral Density (BMD): The T-score from a DEXA scan, particularly at the femoral neck, is a key factor in the calculation.​Calculation: The tool uses these inputs to calculate the 10-year probability of:

   • Major Osteoporotic Fractures: This includes fractures of the hip, spine, forearm, or shoulder.

   • Hip Fracture: The probability of experiencing a hip fracture specifically.

3. Thresholds for Treatment:

   • The results are expressed as percentages, indicating the risk of fractures over the next 10 years.

   • Clinical guidelines often suggest considering pharmacological treatment if the 10-year probability of a major osteoporotic fracture is ≥20% or if the 10-year probability of a hip fracture is ≥3%.

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Now, for those that want more in-depth analysis read on…

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I always find it important to know how well the interventions actually work. To do so I don’t think it makes sense to only look at what the drug company (and physicians) tell you. Things such as, “we reduce risk of fractures by 50%” This sounds absolutely incredible and you’d have to be a real contrarian not to take the treatment. But, let’s look deeper into the numbers.

The Fracture Intervention Trial (FIT) was the landmark trial from Fosamax (Alendronate)

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Number of Participants: The FIT trial included 6,459 postmenopausal women aged 55 to 80 years.
Inclusion of Men: The trial focused exclusively on postmenopausal women with low bone mass and did not include men.
Length of trial:  Three to four years

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Hip Fractures

• Treated Group (Fosamax): Approximately 50 hip fractures occurred in the treated group.

• Placebo Group: Approximately 98 hip fractures occurred in the placebo group.

Wrist Fractures

• Treated Group (Fosamax): Around 60 wrist fractures were reported in the treated group.

• Placebo Group: Around 115 wrist fractures occurred in the placebo group.

Lumbar Spine (Vertebral) Fractures

• Treated Group (Fosamax): About 214 vertebral fractures were reported in the treated group.

• Placebo Group: Around 427 vertebral fractures occurred in the placebo group.

Breaking this down you can say the results in two separate ways.   Over the four years of the study there were reductions in fractures at the 

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--hip by 50%
--wrist by 48%
--spine by 50%

OR

--hip  48 fewer fractures in the 3,230 women over four years.  1.4% difference
--wrist 55 fewer fractures in the 3,230 women over four years.  1.7% difference
--spine 213 fewer fractures in the 3,230 women over four years. 6.6% difference

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How to interpret what seems like a huge difference.  The bottom line.  Most women didn’t have any fractures over the four-year period.  For example, in the area that most are concerned with, hip fractures, in the non-treated group there were only 98 fractures in the 3,230 women.  That’s just 3%.  

Fracture Reduction Evaluation of Denosumab in Osteoporosis Every Six Months.(Freedom) was the landmark trial for Prolia.

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Number of Participants: The trial enrolled 7,808 women with Osteoporosis
Age Range: The participants were women aged 60 to 90 years.
Inclusion of Men: The FREEDOM trial did not include men. 
Length of trial:  Three years

Hip Fractures

• Reduction in Risk: Prolia reduced the risk of hip fractures by approximately 40% 

Wrist Fractures

• Reduction in Risk: Prolia showed a reduction in wrist fracture risk, although the exact percentage was not as high as for hip and vertebral fractures. The reduction in risk was approximately 16%.

Lumbar Spine (Vertebral) Fractures

• Reduction in Risk: Prolia was particularly effective in reducing the risk of vertebral fractures, with a risk reduction of approximately 68%.

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But, let’s look at the actual numbers.

Hip Fractures

• Prolia Group: 20 fractures out of 3,902 women (approximately 0.5%).

• Placebo Group: 35 fractures out of 3,906 women (approximately 0.9%).

Wrist Fractures

• Prolia Group: 71 fractures out of 3,902 women (approximately 1.8%).

• Placebo Group: 91 fractures out of 3,906 women (approximately 2.3%).

Lumbar Spine (Vertebral) Fractures

• Prolia Group: 86 fractures out of 3,902 women (approximately 2.2%).

• Placebo Group: 264 fractures out of 3,906 women (approximately 6.8%).

Two things to note.  Again, the vast majority of women didn’t fracture at all.  90% in the placebo group, for example.  And, it’s hard to compare the trials exactly as the ages are slightly different and the time was shorter in the Freedom trial.  

The Fracture Prevention Trial was the trial used to examine Forteo (a daily injectable)

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Participants: The primary trial for Forteo, often referred to as the Fracture Prevention Trial, included both postmenopausal women and men with osteoporosis.
Number of Participants: The trial enrolled approximately 1,637 participants, including 1,137 postmenopausal women and 292 men with osteoporosis.
Age Range: The participants were generally aged between 45 and 85 years.
Inclusion of Men: Yes, men were included in this trial, which distinguishes it from some other osteoporosis trials that focused exclusively on women.
Length of trial:  21 months

Hip Fractures—Interestingly, these weren’t reported.  They say because there were just too few in both groups to make a meaningful comparison.  
Wrist Fractures—Forteo reduced wrist fractures by ?  We don’t know for sure.  They just lumped them together with all ‘non-vertebral fractures’ 
Non-vertebral Fractures—This showed a 53% reduction. 5% in treated group, 10% in placebo
Vertebral Fractures—Forteo showed a 65% reduction  3% in treated group, 14% in placebo

Lumbar Spine (Vertebral) Fractures

• Treated Group (Forteo): 10 out of 541 participants (approximately 1.8%).

• Placebo Group: 30 out of 544 participants (approximately 5.5%).

Nonvertebral Fractures (Including Wrist)

• Treated Group (Forteo): 22 out of 541 participants (approximately 4.1%).

• Placebo Group: 37 out of 544 participants (approximately 6.8%).

Hip Fractures

• Treated Group (Forteo): The exact number of hip fractures was very low, and specific data on hip fractures alone were not prominently reported due to the low incidence.

• Placebo Group: Similarly, the number of hip fractures was low, and a statistically significant reduction was not observed.

As we all know with commercials of medications, they will give a list of literally every possible side effect.  I don’t plan to do that here. But I do think it’s fair to acknowledge that medicines don’t only provide benefit. There can be drawbacks.  
 

Fosamax and other bisphosphonates

• They are difficult to tolerate. Most literally go right through you. i.e. you poop out about 99% of the medication. So, you must take with an empty stomach and a full glass of water. (Typically, Fosamax is taken orally once per week)

• You have to stay upright for at least half an hour as it will tend to irritate the esophagus and stomach if you don’t. Potentially even causing ulcers.

• It can cause a very rare but horrible destruction of the jawbone known as Osteonecrosis of the Jaw. Typically, only when given in the IV form and when someone is on chemotherapy.

• It can cause atypical femur fractures. Meaning fractures in the middle of the thigh. These are particularly difficult to repair.

• It doesn’t help to take for too long. This was shown in the FLEX trial. They compared data for those who took for 5 years versus 10 years and…the rates of non-vertebral fractures was basically the same. But there were more atypical femur fractures. This led to the recommendation to stop after five years.

Prolia. This is a monoclonal antibody given in injections every six months.

• Back pain 35% of the time

• Musculoskeletal pain 30-35% of the time

• Osteonecrosis of the jaw, similarly very rare

• Slightly increased risk of developing a serious infection as it lowers your immune system slightly like other monoclonal antibody therapies.

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Forteo. This is something the patient injects into themselves daily for two years.

• Injection site pain or irritation

• Nausea in about 10%

• Joint pains 10%

• Dizziness 10%

• Leg cramps 5%

• Too much calcium, kidney stones

There is also a black box warning that in high dose animal studies it rarely caused osteosarcoma, a form of bone cancer. Again, not something that has been shown in humans.

In Summary: What to do with your bone DEXA results? I would tend to lean against medicine therapy if you fall into the Osteopenia category. This is due to limited benefit of the drugs here along with known side effects. But I would ensure good Vit. D and Calcium levels and try to do regular exercise. And, I’d be remiss if I never stated doing balance exercises, using assistive devices, and keeping the house free of clutter to help prevent falls in the first place.

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Once in the Osteoporosis category, I’d still say all of the non-medicine things should be done if possible. Which treatment to use is tricky. I’d say that my experience is that endocrinology tends to lean to the Bisphosphonates as they are simple to use, they are cheap and their efficacy is quite similar to the other more complicated and expensive treatments.