Bones are really quite interesting and underestimated. Most of us walk around each day and take our bones for granted.
Bones are not just a chassis for humans. Bones don’t just give us structure. Sure, they allow us to move around. But they are actually essential to our survival. How so? They protect our vital organs. They play an essential role in breathing.
Equally, bones are not static. Bones are also highly dynamic structures. They are continually being remodeled. New bone is made by specialized cells called osteoblasts and old bone is resorbed by other specialized cells called osteoclasts.
And the best part of all is that this all happens without any input from us.
Table of Contents
- What is Osteoporosis?
- Who Gets Osteoporosis?
- How Does Osteoporosis Present?
- How is Osteoporosis Diagnosed?
- Is There any Research on Osteoporosis?
- How is Osteoporosis Treated?
- Lifestyle Factors for the Management of Osteoporosis
- Treatments for Osteoporosis
- Comparative Effectiveness of Osteoporosis Options
- Other Treatment Options
What is Osteoporosis?
Osteoporosis refers to the thinning of the bones. It is defined as "low bone mineral density caused by altered bone microstructure leading to skeletal fragility and fracture." The main risk of osteoporosis is that it puts people at risk of fractures.
Osteopenia is the term used for a milder form of bone thinning that can progress to osteoporosis over time.
Who Gets Osteoporosis?
Over 10 million people in the US are thought to have osteoporosis (1).
Rates of osteoporosis increase with advancing age.
Who are these 10 million people?
There are known risk factors for developing osteoporosis.
Risk factors for any disease can be summed up by the equation:
Total Risk = Genetic Factors (DNA) + Epigenetics Factors (Lifestyle)
It is thought that up to 60% of our bone health is determined by our genetics or DNA. That being said, that leaves us with up to 40% of epigenetic factors or lifestyle factors that we can work on.
These epigenetic factors for osteoporosis include:
- hepatitis C
- kidney disease
- thyroid disease
- diabetes and
- medications such as some anti-HIV drugs, steroids, and anticonvulsants.
How Does Osteoporosis Present?
Osteoporosis is sometimes called the "silent disease" as the vast majority of people have no symptoms of osteoporosis until they have an actual fracture. Depending on the level of the osteoporosis, these fractures can occur with minor trauma or even with no trauma.
The problem with osteoporosis is the fact that a fracture can have really significant effects on an older person. It is often a critical tipping point. All too often, we see an elderly person lose their ability to function independently because of complications from an osteoporotic fracture.
How is Osteoporosis Diagnosed?
Osteopenia and osteoporosis can sometimes be diagnosed on plain x-ray. This happens when an x-ray is done for some other reason (eg a suspected fracture) and bone thinning is noted. X-rays are not usually used to diagnose osteopenia or osteoporosis.
The gold standard for diagnosing osteoporosis is known as a DXA or DEXA scan (Dual-energy X-ray absorptiometry). This is pronounced DEX-AH. The result of a DXA scan is called a T-score or a Z-score.
A T-score compares the result of a DEXA scan to that of a young healthy person.
A Z-score compares the result of a DEXA scan to the expected bone density for that age group and gender.
Just to be all nerdy about this, people with a T-score which is -2.5 standard deviations below that of a young person is diagnosed as having osteoporosis. Standard deviations are a statistical measurement of how far things are part.
If we drew a line with the results of lots of people who had DEXA scans, then people with a T-score of -2.5 standard deviations below that of a healthy young person are probably in the lowest 5% of the population. If there are any statisticians reading, please forgive the amateur statistics.
A commonly used tool for grading the severity of osteoporosis is the FRAX (Fracture Risk Assessment Tool) score. (2). This is an algorithm that gives the ten-year risk of fracture for any patient taking into account their risk factors and bone mineral density at the femoral neck.
There is a handy downloadable app in 28 languages that can be used for quick fracture risk assessment.
Is There any Research on Osteoporosis?
There are over 80,000 publications on osteoporosis and this includes 5000 clinical trials. To put this into context, there are only 34,000 publications including 2197 clinical trials on fractured hips.
When writing this paper, I was really struck by the fact that there is quite a lot of ongoing research into osteoporosis as evidenced by the high number of publications from this year and even from this month.
How is Osteoporosis Treated?
There are over 50 key groups who develop guidelines for the prevention and management of osteoporosis. These include:
- The US National Osteoporosis Foundation
- American Association of Clinical Endocrinologists
- National Osteoporosis Foundation (NOF)
- North American Menopause Society (NAMS) and
- American College of Physicians.
The American College of Physicians published comprehensive guidelines on the management of osteoporosis in 2008. These guidelines were updated in 2017 with the inclusion of randomized trials, systematic reviews, observational studies and case reports (3).
As we know, guidelines are always evolving. A paper from June 2018 complains that the 2017 American College of Physicians osteoporosis guidelines are out of date already (4). To be honest, lots of guidelines are out of date by the time the ink dries.
Lifestyle Factors for the Management of Osteoporosis
Step #1 in the management of patients with osteoporosis is reducing the risks of ongoing damage by getting the basics right. Sorting out the epigenetic 40%.
One practical and helpful intervention is to advise patients to stop smoking (5).
A study in twins where one twin smoked and the other did not smoke shows that for every 10 pack-years of smoking, the bone density of the twin who smoked more heavily was 2.0 percent lower at the lumbar spine.
I am not saying it is easy to give up smoking but it can certainly help bone density.
Another practical intervention is making sure that people have an adequate intake of calcium and vitamin D.
The daily recommended dose of calcium is 1200mg but the specific optimal dose has not been definitively established (6).
This can come from diet or supplements and many people use a combination of diet and supplements to achieve this target intake.
The daily recommended intake of vitamin D is and the vast majority of people have to take vitamin D supplements to achieve this target (7). Vitamin D affects bone formation, bone resorption, and bone quality.
Exercise is another key intervention in the management of osteoporosis. Exercise increases actual bone mass and also muscle tone and balance which helps prevent falls.
Glaswegian researchers did a full Cochrane review of exercise in post-menopausal women and found 43 trials with 4320 participants (8). The quality of the studies was low. There was a small but statistically significant effect of exercise on bone density.
The most effective type of exercise intervention for the neck of the femur seemed to be progressive resistance strength training for the lower limbs while combination exercise programs were best for the spine.
That all sounds great until we get into the small print which says that exercise had no effect on fractures in this analysis.
The issue of balance deserves a special mention. A systematic review published just this month looked at the effect of balance training in falls prevention in patients with osteoporosis (9). They synthesized data from six randomized controlled trials and found that balance training interventions significantly reduced the frequency of falls in these patients.
The hope is that by preventing falls, there would be a reduction in the fracture rate in people at risk.
The final piece of lifestyle advice is reduction in alcohol consumption. Alcoholism is a risk factor for osteoporosis, but the question that many people ask is "Doctor, I know I have osteoporosis now but if red wine is good for my heart health, how about some moderate alcohol intake?"
Researchers in the Bronx looked at data from 33 relevant studies to try to answer this question (10). The results are a bit confusing and not something that I can easily turn into a lifestyle recommendation for my patients. Here goes.
Compared with abstinence, consuming 1 drink or less per day is associated with a lower risk of hip fracture, whereas consuming more than 2 drinks per day is associated with higher hip fracture risk.
So far so good.
The study showed that greater alcohol consumption (up to 2 drinks per day) is linearly associated with higher bone density.
The analysis could not identify the sweet-spot i.e. that ideal alcohol intake that builds bone as opposed to puts people at a risk of osteoporosis.
I have two practical observations on this issue.
Alcohol intake that impairs balance can lead to falls and be a disaster in osteoporosis. That split-second delay in judgement or correction of balance can make all the difference.
Many people can be very liberal in their definition of "moderate" alcohol (and even the size of one drink). Trust me on this one - I am Irish after all.
Treatments for Osteoporosis
The mainstay of drug treatment for osteoporosis is a group of drugs known as the bisphosponates (alendronate, risendronate, zoledronic acid).
They are the darling of osteoporosis treatment. They act by binding to the surface of bones and especially bone that is being resorbed. When the osteoclasts start to resorb bone, the bisphosphonate is released and blocks the osteoclast from doing its work. A bit like a Trojan horse.
They can be given orally or intravenously and can be administered daily weekly monthly or even yearly.
Some people find it hard to tolerate bisphosphonates. They can cause local irritation in the esophagus (bad heartburn). For this reason, it is recommended that bisphosphonates should be taken with a glass of water. Additionally, people who take bisphosphonates should sit upright for at least 30 minutes.
This allows time for the medication to be absorbed and prevents reflux. Bending over or lying down before the bisphosphonate is absorbed can lead to gastrointestinal upset as the medication can reflux back up the esophagus. It is actually incredibly difficult to stay upright for 30 minutes.
It seems that there are so many reasons to bend over (picking up a cellphone, putting on socks, open a car door, turn on dishwasher). Other side effects of bisphonates include low calcium, muscle pains, and blurred vision.
A rare but really important side effect of bisphosphonates is osteonecrosis of the jaw. This means the death of jaw bone. I have only seen this once in my practice.
Finally, some people are allergic to bisphonates
Bisphosphonates are not recommended in people with chronic kidney disease.
There is high-quality evidence that some of the bisphonates reduce vertebral, nonvertebral and hip fractures when compared with placebo in postmenopausal women. The evidence in men is less convincing.
A meta-analysis from May of this year from Korea reviewed data from 12 trials involving 5670 subjects (11). This meta-analysis looked at the effect of bisphosphonates on people who had already sustained a fragility fracture. They found that bisphosphonates prevented subsequent fractures and reduced mortality.
Kappa B Ligand Inhibitors
Kappa B ligand inhibitors are also known as biologic inhibitors, monoclonal antibodies or Receptor Activator of Nuclear factor-Kappa B (RANKL) inhibitors. Simply put, RANKL is a protein that is essential for osteoclasts resorption of bone. RANKL inhibitors such as denosumab prevent the breakdown of bone during bone remodeling.
French and Senegalese researchers published a meta-analysis of denosumab for osteoporosis in 2015 (12). The meta-analysis found a 70% reduced risk of vertebral fracture and a 40% reduced risk of hip fracture.
They are usually reserved for second-line treatment of osteoporosis in people who cannot tolerate bisphonates.
Hormone therapies such as estrogen-progestin have been shown to reduce hip and vertebral fracture. The main study quoted in relation to this was the Women's Health Initiative which dates back to 2002 (13). This study was co-ordinated by the National Heart, Lung, and Blood Institute, Bethesda, USA.
The study assessed the risks and benefits of estrogen-progestin therapy in 166608 women aged 50-79 from across 40 academic centers in the USA. It is pretty hard to argue with those numbers.
Clinical trials usually have a Data Safety and Monitoring Board (DSMB). The function of the DSMB is to review the data before the end of the study to make sure that the trial intervention is safe. Most well-conducted studies have 'stopping rules' which say that the study should be stopped if a certain number of people have side effects or die (regardless of how great the treatment might be).
After all, we physicians are bound by the rule of "Above all else, do no harm."
The DSMB for this study prematurely terminated the study because they found an unacceptably high risk of breast cancer, stroke, and clots in the intervention arm of the study. The full study analysis showed a reduced risk of hip fracture in the intervention arm of the study.
Despite this, they are not routinely prescribed for the treatment of osteoporosis in post-menopausal women over the age of 60 because of the increased risks of cancer, stroke, and clots (14).
Parathyroid Hormone Analogues
Parathyroid hormone analogues (teriparatide) stimulate bone formation (unlike bisphosphonates and RANKL inhibitors which prevent bone destruction).
In 2008, Brazilian investigators carried out a systematic review of teriparatide for osteoporosis and found that the drug 'reduces the incidence of vertebral fractures (67%) and non-vertebral fractures (38%) and increases bone mineral density in the lumbar column and femur' (15).
Currently, teriparatide is reserved for people with severe osteoporosis.
Comparative Effectiveness of Osteoporosis Options
A 2014 paper compared the effectiveness of drug therapy to prevent osteoporotic fractures in adults with osteoporosis (16). They screened 52,000 titles and identified 321 relevant publications.
They found 'high-strength evidence that bisphosphonates, denosumab, and teriparatide reduce fractures compared with placebo, with relative risk reductions from 0.40 to 0.60 for vertebral fractures and 0.60 to 0.80 for nonvertebral fractures'.
It is not often that systematic reviews find "high-strength evidence."
Other Treatment Options
Other agents that are sometimes used by experts for complex patients include SERMs (selective estrogen receptor modulators) and calcitonin. We are just mentioning them here for the sake of completion.
Surgical treatments are usually reserved for people with osteoporotic fractures. Kyphoplasty involves putting a balloon into a fractured vertebra (back bone) and injecting cement into the vertebra to give it some extra structure.
A 2017 meta-analysis from Hong Kong reviewed 9 studies with 1222 participants and found that tai chi (especially long term tai chi) can improve bone mineral density and may help prevent osteoporosis (17).
Finally, a meta-analysis of studies in English and Chinese language literature relating to acupuncture for osteoporosis identified 35 studies involving 3014 patients and concluded that acupuncture (especially warm acupuncture) could be beneficial in the treatment of osteoporosis (18).
Osteoporosis has a number of unique features. It is usually a silent disease that presents first with an actual fracture. While usually considered as a disease of aging, it can affect younger people. We know who these younger people with osteoporosis are and in some cases, we know lifestyle modifications that can slow down the disease process.
I think that this might be my very first article for #HBS that found a systematic review with "high-strength" evidence for any treatment or intervention.
Osteoporosis is so much more than just DXA scores and systematic reviews. All too often, a simple fall resulting in an osteoporotic fracture is the tipping point when an elderly person never gets back to independent living and needs long-term residential care.