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Dr. Susan E. Brown

Prolia for Bone Fractures — I’m Still Not Impressed

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When the bone drug Prolia (denosumab) first came out in 2010, I took a hard look at it because it used a completely different mechanism than widely used bisphosphonate drugs, focusing on the RANK/RANK-L/OPG system to prevent osteoclasts from being “activated” instead of decreasing their number like bisphosphonates. I wasn’t satisfied in 2010 that this drug was any safer or more effective than bisphosphonates, and sad to say my skepticism has been borne out by recent research.

Dr. Brown’s 2024 Update:

Is Prolia a blockbuster bone drug — or a bust?

The FREEDOM Trial, which studied Prolia use in postmenopausal women for 3 years, found very little reduction in fracture risk. Vertebral and hip fractures were reduced 4.8% and 0.3% — meaning for 100 women they treated, only 5 saw fewer vertebral fractures than you’d expect with a placebo, and not even one woman was spared from a hip fracture by the drug. Given that hip fractures are considerably more harmful than vertebral fractures, these are minimal benefits indeed.

Although gains in bone density were observed, those gains were lost within 1 year of halting the drug (Cummings et al., 2017).

Furthermore, once they stopped using Prolia, patients’ risk of vertebral fracture quickly (<1–2 years) reverted to the same risk seen in those who’d never taken the drug in the first place (Cummings et al., 2017). They also lost a significant amount of the bone they’d gained by using Prolia — 35.5% of the total gain in the spine, 44.6% of the total gain in the femoral neck and 103.3% in the total hip (Zanchetta et al., 2017). In other words, the drug offered no lasting benefit.

Much more concerning: the finding that patients were more susceptible to having multiple vertebral fractures after discontinuing Prolia than patients who’d never taken the drug at all — and it was especially high in those who’d had such fractures prior to going on the drug in the first place (Cummings et al., 2017; Anastasilakis et al., 2017). This finding confirmed a number of earlier case reports of “rebound fractures” in patients who had discontinued Prolia within the preceding 12 months. Researchers speculated such fractures were a consequence of sudden renewal of bone resorption after the drug was stopped in combination with the absence of repair mechanisms during its use (Anastasilakis et al., 2017; Lamy et al., 2017; Polyzos & Terpos, 2016).

I’ve said repeatedly that working against nature invites unintended consequences, so I’m not surprised by these results. What is disappointing is the continued emphasis on the “magic bullet” approach to osteoporosis, when it has been clear for so many years that Prolia just doesn’t work.

 

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What is anabolic treatment?
Dr. Susan E. Brown

Forteo®, Tymlos® and Evenity®: How Much Do They Really Reduce Fracture Risk?

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The latest crop of recent bone drugs contains new anabolic drugs that enhance bone density. These drugs are designed to build new bone, while the older bisphosphonate bone drugs at best can only halt bone loss. Patients are told just that—that these new anabolic treatments will increase their bone density and also decrease fracture risk. Given the magnitude of this claim, I felt compelled to take a closer look at these medications to try to understand them a little better by asking the crucial question “How much do these new drugs really reduce fracture risk?” 

The following are the three anabolic bone–density-building drugs widely used today:  

All three drugs have five things in common: 

  1. They temporarily increase bone density substantially, at times by 10% or more. 
  2. However, any bone density gains that occur from the use of these drugs will be lost once the patient stops using the drug. Thus, upon stopping these new bone–density–building drugs, the patient must take one of the older bone drugs known to reduce bone breakdown (like Fosamax® or Prolia®). If they do not, then all bone density gains will be lost within a few years. 
  3. All 3 drugs carry “Black Box” warnings: Tymlos® and Forteo® for bone cancer risk and Evenity® for cardiovascular disease. 
  4. Each one can only be taken for up to 2 years, due to the Black Box warning of potentially life-threatening side effects. 
  5. Each of these new bone drugs is inordinately expensive. My local pharmacy gave me their costs without insurance:
    Tymlos®$31,140.00 per year
    Forteo®$56,988.00 per year
    Evenity®$28,896.00 per year 

The Critical Question: 

How much do these new drugs really reduce fracture risk? 

The answer is not very much according to a new 2019 meta-analysis of 16 different large clinical trials involving nearly 19,000 patients. Looking at the large clinical trials on these three drugs, the authors reported that: 

  • These drugs did not significantly reduce the risk of non-vertebral fractures (fractures of the hips, pelvis, or other parts of the body).  
  • Each of these bone–density-building drugs did “significantly” reduce the risk of vertebral fractures, but when you look carefully at each individual study, you find that the actual, absolute reduction in risk of vertebral fracture was only 1 to 4%. In other words, 100 people had to be treated with these expensive and risky bone–density–building drugs to prevent between one and four fractures. 

If you want to read more on Forteo®, Tymlos®, or Evenity®, click the links to more studies. 

Until recently, the major bone drugs were bisphosphonates, such as Fosamax®, Boniva®, Actonel® or Reclast®. These older bone drugs were only able to halt bone loss; they did not build new bone. The three new anabolic drugs discussed in this blog, each in their own way, trick the body into building new bone. But all gains are lost when the drugs are stopped. Thus, the recommendation is that they are followed up with the old drugs to halt any further bone loss. 

If you are thinking about taking these new “bone-building” drugs, there are two key things to keep in mind: 

  1. These new drugs by themselves reduce fracture by only a small percentage.  
  2. To maintain any of the bone density gains made, and hopefully to reduce fracture risk, you will need to take one of the older bone-halting drugs like Fosamax®, Reclast® or Prolia®, probably for the rest of your life. 
forteo
Dr. Susan E. Brown

Forteo for Osteoporosis — is this bone drug too good to be true?

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Forteo™ (teriparatide) is a new and different drug on the scene as a treatment for osteoporosis. Other bone drugs, like Fosamax, Actonel, Boniva or even estrogen work to halt bone breakdown. Forteo, on the other hand, works to increase new bone formation. Short-term studies, in fact, report a common 9% increase in lumbar spine bone density and a 2–3% increase in hip density accompanied by significant reductions in fracture incidence. Sound too good to be true? Sure does. So let’s take a second look and try to understand this new drug from what the manufacturer, Eli Lilly, tells us in their 2008 Forteo Product Monograph.

What exactly is Forteo?

Forteo is a man-made (well, E. coli-made) recombinant parathyroid hormone that has an amino acid sequence identical to part of the human parathyroid hormone (PTH). Forteo was approved by the US FDA in 2001 as an osteoporosis drug.

How does Forteo work?

In the body, natural parathyroid hormone serves to regulate bone metabolism in many ways. Chronic elevation of PTH, as in hyperparathyroidism, results in increased bone breakdown, a loss of calcium, and osteoporosis. On the other hand, daily injections of the PTH drug Forteo have the paradoxical effect of increasing bone mass and reducing osteoporosis. As scientists report, it seems to be that the pattern of exposure to parathyroid hormone determines its effect on the skeleton.

Through activation of various bone metabolic pathways, the PTH drug (Forteo) increases the number of active osteoblasts (bone-building cells), decreases the naturally programmed death of osteoblast cells, and recruits bone-lining cells as osteoblasts. This drug appears to act largely upon the bone-building osteoblast cells stimulating them to overactivity. Safety studies on this drug in rats, in fact, have shown findings of excessive new bone formation and bone cancer. Interestingly enough, the cancer this drug was found to cause in rat studies (osteosarcoma — I’ll say a little more about this shortly) is a cancer often associated with high osteoblast activity and rapid bone growth.

By how much does Forteo reduce fractures?

  • Reduction of spinal fractures — Among 1,637 postmenopausal women with severe osteoporosis and one or more vertebral fractures at baseline, the drug produced a 9.3% absolute fracture risk reduction over 19 months.
  • Reduction of hip, pelvis, wrist, rib, humerus and other fractures — Over 19 months in these same high risk women, Forteo reduced nonvertebral fractures by an absolute 2.9% reduction in fractures.

So, overall, the short-term studies on Forteo reported above show this drug to reduce fracture risk substantially more than the bisphosphonate drugs like Fosamax. In addition, Forteo in these studies increased bone density more than the bisphosphonates.

Just how much does Forteo increase bone density?

In this same 19-month study of high risk osteoporotic women, Forteo increased bone density by an average 9.7% in the spine and 2.6% in total hip, while the wrist lost bone density and total body mineral content remained the same.

Why are there just short-term studies on Forteo, and is it safe?

As the manufacturer reports, the longest studies on the safety and efficacy of Forteo were of only a two-year duration. Why are there only short-term studies on this new drug? There are only short-term studies because in the animal safety studies, Forteo was shown to cause a high incidence of osteosarcoma (a rare malignant, often fatal, bone tumor), as well as osteoblastoma (abnormal mass of tissue in bone) and osteoma (small benign bone lesions). As with all drug safety tests, the drug doses tested were from 3-, 20-, and at times, 60-fold higher than those used in human medications. Notably, bone tumors were observed at all Forteo doses, with the incidence reaching 40–50% in the higher-dose groups.

Given this major safety concern, human trials with this drug were terminated early and guidelines were set to limit the duration of its use in humans. In fact, as the manufacturer specifically states, “The safety and efficacy of Forteo have not been evaluated beyond two years (median 19 months in women and 10 months in men). Consequently, the maximum lifetime exposure to Forteo for an individual patient is 18 months.” Also, given the cancer-causing effect of the drug, the FDA required a “black box” label warning, clearly stating the increased cancer risk shown in rat studies.

Expensive, experimental, possibly cancer-causing and inconvenient

As near as I can calculate, since its development, studies on this drug have included only 1,943 patients. According to the manufacturer, a study of one year is considered “long term,” while the maximum length of any study was only two years. Thus, not only is Forteo relatively new, but it is also experimental and, I would say, inadequately tested. In addition, it is very expensive — the drug costs upwards of $600–$700 per month! Further, it is inconvenient to use as it must be given as a daily self-administered injection. Most importantly, since this drug has shown to cause cancer in rat safety studies, its use by humans is limited to two years or less. While there may be significant bone density gains while using Forteo, the research is clear that these gains are lost once the drug is stopped. To maintain bone density gains, antiresorptive drugs such as Fosamax must be used after stopping Forteo.

Is there a better way?

This is the question I constantly ask myself — is there a better way to increase bone strength and reduce needless osteoporotic fractures? Is there a way that does not run the risk of causing cancer, or lead to excessive new bone formation — a way that is not only safe, but also good for the entire body? Yes, in most cases there is another way, and that way is through a comprehensive, life-supporting bone-building program that enlivens natural human healing and the body’s regenerative capacity.

Read More : What do I really think of osteoporosis drugs, anyway?

 

To learn more on the topic of osteoporosis and bone loss, read our additional articles here:

Dr. Susan E. Brown

6 ways standard osteoporosis treatment is dead wrong: Part 3

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In my previous two blogs, I’ve given you 4 important reasons why I don’t believe standard osteoporosis treatment is effective. In this final blog of the series, I want to emphasize that there is no magic bullet for optimal bone health – despite what you may have heard about calcium or bone drugs.  Here’s why:

5.    The calcium-centered focus has distracted us from the fact that at least 20 nutrients are essential for bone health

I’ve pointed out that calcium doesn’t reduce fracture risk and excessive calcium intake holds increased risk of cardiac problems. But if calcium isn’t the “magic bullet” for bones, what is? Well for one thing, adequate vitamin D levels are essential, and  a lot of doctors are finally realizing how important vitamin D is for bone health.

Yet too little attention is still paid to other essential bone nutrients — especially vitamin K, which makes a major contribution to bone health and supports many other systems as well, but also zinc, magnesium copper, boron, folate, manganese and vitamin C.

6.    Bone drugs are far less effective and far more risky than commonly thought

Here’s where it really becomes frustrating. Our health system pushes high-dose calcium (which doesn’t work) as the solution to low bone density (which is not necessarily the problem). Then when there’s no improvement in bone density from overloading the body with calcium, the typical next step is to prescribe a bone drug.

I’ve always maintained that such medications should be used only as a last resort, for very severe cases where drastic measures are needed — for instance, a person experiencing low-impact fractures or excessive, uncontrollable bone loss. This is not the situation for most people who have relatively low bone density .

With that in mind, it shouldn’t be surprising that the results of bone drug therapy are often  very disappointing. Even worse, the evidence suggests no benefit from bisphosphonate bone drugs on real-world hip fracture incidence. Nor do these drugs benefit people 80 years old and older — which is, of course, the group most likely to fracture a hip!

What it all boils down to is this: If we’re to really help people to live long, healthy lives free from the fear of bone fractures, we don’t need more bone drugs.  Instead, we need to change our approach by:

  • Carefully assessing each individual case to identify whether excessive bone loss or weakness exists;
  • Detecting and correcting both obvious and hidden causes of excessive bone weakening;
  • Broad-spectrum, whole-body support with nutrition, exercise, neuroendocrine and hormonal balance, stress reduction, and resilience enhancement.

Such an approach would limit bone drugs to the few specific situations where obvious bone weakness cannot be offset by natural means and requires heavy-duty intervention.

Missed the previous blogs?  Read more.

Part 1

Part 2

* Information presented here is not intended to cure, diagnose, prevent or treat any health concerns or condition, nor is it to serve as a substitute professional medical care.

Dr. Susan E. Brown

6 ways standard osteoporosis treatment is dead wrong: Part 2

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I’ve written recently about two of my top six concerns about the standard approach to bone health.  And now, here are two more that emphasize how women are often being misled about how to best protect their bones:

3. Contemporary osteoporosis management treats bone as if it were separate and isolated from the rest of the body

It’s tempting to look at the body the way we look at cars — as a collection of independent parts, each with a specific job. But that’s not what the body is! It’s a set of dynamic, interconnected systems that are constantly changing in response to what goes on around us and inside us.

While most people lose some bone as they age, bones don’t just “wear out” over time, the way a car’s parts do. If bones are weak or rapidly become thin, it’s nearly always because of a larger systemic problem in the body. The most effective approach in this situation is a big-picture perspective that looks at bone health as an indicator of overall health — it’s been shown that older adults who experience a hip fracture have lower baseline health-related quality of life than those who don’t.

But the standard approach is to focus on the mechanics of bone breakdown and interfere with them. Most bone drugs work by targeting the cells that break bone down and stopping them from doing their job. Doing this doesn’t actually solve the problem — it just masks the effects.

Enduring bone health requires rebuilding strength and vitality. That’s why it makes sense to look at the complete body system — circulation, bone, acid-base balance — to find the places where something isn’t working right to cause bone loss, rather than focus in on halting bone loss itself, which is most often an effect of a larger problem.

4. High-dose calcium is still considered the first-line treatment, yet it does not prevent fracture, and may be harmful

Speaking of “larger problems,” let’s take a look at what happens when you try to address fracture risk with calcium supplements. There is tremendous controversy about calcium and bones, but now it’s becoming clear that high-dose calcium supplementation is not the solution.

Multiple studies show that calcium does not decrease fracture risk except in those with a very low calcium intake — and some studies suggest that taking high-dose calcium supplements can lead to an increase in arterial calcification, stroke, kidney stones.  In my own research, it’s quite clear that while adequate calcium is needed for healthy bones, using high doses is counterproductive.

It seems wise to obtain the total 1,200 milligrams of calcium daily from diet and supplements as recommended by the National Institute of Health. At the same time, we recommend you also learn about the other key bone nutrients and make sure you obtain adequate doses of all these essential bone builders.

Stay tuned for next week’s blog for my final two reasons the standard approach to bone health doesn’t make sense. And as you’ll see, are far less effective and far more risky than commonly thought!

See Part 1 here

See Part 3 here.

 

References:

Randall, AG et al., Deterioration in quality of life following hip fracture; a prospective study osteoporosis international 2000, 11(5);460-6.

Bischoff-Ferrari HA, et al., Calcium intake and hip fracture risk in men and women: a meta-analysis of prospective cohort studies and randomized controlled trials. Am J Clin Nutr. 2007
Dec;86(6):1780-90.

Bolland MJ, Leung W, Tai V, Bastin S, Gamble GD, Grey A, Reid IR. Calcium intake and risk of fracture: systematic review. BMJ. 2015;351:h4580. doi: 10.1136/bmj.h4580.
Bolland MJ, Grey A, Reid IR. Calcium supplements and cardiovascular risk: 5 years on. Ther Adv Drug Saf. 2013 Oct;4(5):199-210. doi: 10.1177/2042098613499790
https://ods.od.nih.gov/factsheets/Calcium-Consumer/

* Information presented here is not intended to cure, diagnose, prevent or treat any health concerns or condition, nor is it to serve as a substitute professional medical care.

Dr. Susan E. Brown

6 ways standard osteoporosis treatment is dead wrong: Part 1

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It’s no secret that I’m not a fan of the way bone drugs like Prolia® and Fosamax® are used these days. But people sometimes misinterpret my thinking as being “anti-drug” — yet it’s not just the drugs I object to. It’s how medicine in general approaches bone health and fracture risk.

I have at least 6 major objections to the standard approach, but for the sake of brevity, we’ll look at them two at a time over the next three weeks.

1.    Treatment is based on bone mineral density — but bone mineral density does not predict fracture

Having a low-side bone density isn’t actually a health problem. It doesn’t hurt or limit mobility — it doesn’t even necessarily mean the bones aren’t strong! It’s only when you fracture a bone that you have a health problem — and more, you cannot predict fracture by bone density alone. In fact, the majority of people whose bones are so fragile they experience a low-trauma fracture do not have an “osteoporotic” bone density.

That’s why treating low bone density bones as a “disorder” that “needs to be addressed” with heavy-duty medications makes no sense. Weak bones, on the other hand, need intervention. And, as far as weak bones go, there’s almost always an underlying problem causing the depletion of bone strength — whether it be nutritional, hormonal, bone-damaging medications, or some other hidden health condition or lifestyle factor. Properly detected and corrected these underlying causes can greatly reduce the risk of fracture. This is why a real fracture risk assessment and an assessment of underlying causes are so critical to developing a comprehensive bone-building program.


2.    The standard medical approach to osteoporosis is fear-based — and fear actually damages bone

Given that a low-side bone density does not necessarily indicate weak bones, why do you suppose doctors are so adamant that people with a low-side bone density need treatment? They’re afraid their patient will have a serious fracture.

But fear of fractures is itself bone damaging and can be a self-fulfilling prophecy — literally, as studies have linked higher levels of stress and the stress hormone cortisol with osteoporosis and increased fracture risk. A recent Danish study, for example, showed that just the perception of stress — seeing yourself as stressed — increases risk of osteoporotic fracture by 68%. It is bad enough that we have so many reasons to fall into stress and worry, we really do not need our health professional piling on more stress with unfounded fears of fracture. Again, what’s needed is a fracture risk assessment leading to a comprehensive bone building program — one that includes stress reduction and hope.

It’s interesting to note that Traditional Chinese Medicine holds that bone health is determined by the “kidney energy” and that fear is the emotion that disrupts the kidney energetic system. (And even Western medicine links osteoporosis with renal disease because the kidneys play such a central role in vitamin D metabolism, mineral reabsorption, and acid-base balance. (As I have discussed before, when kidneys can’t adequately buffer metabolic acids, calcium from bones is called upon to rescue essential pH homeostasis.) The ancient Chinese wisdom tradition suggests that the kidneys control bone and fear damages the kidneys — and I have found this to be true. All in all, we need less fear and more hope and bone-building solutions.

This isn’t all of course.  See Part 2 here.

References

References:

Adeva, M. M., and G. Souto. 2011. Diet-induced metabolic acidosis. Clinical Nutrition 30(4):416–421.

Azuma, K., Y. Adachi, H. Hayashi, and K. Y. Kubo. 2015. Chronic psychological stress as a risk factor of osteoporosis. Journal of UOEH 37(4):245–253.

Häussler, B., H. Gothe, D. Göl, G. Glaeske, L. Pientka, and D. Felsenberg. 2007. Epidemiology, treatment and costs of osteoporosis in Germany: The BoneEVA Study. Osteoporosis International 18(1):77–84.

Lu, Nan. 2010. Traditional Chinese medicine: A woman’s guide to a hormone-free menopause. TCMWF Publishing, New York.

Seeman, E., J. P. Devogelaer, R. Lorenc, T. Spector, K. Brixen, A. Balogh, G. Stucki, and J. Y. Reginster. 2008. Strontium ranelate reduces the risk of vertebral fractures in patients with osteopenia. Journal of Bone and Mineral Research 23(3):433–438.

Stone, K. L., D. G. Seeley, L. Y. Lui, J. A. Cauley, K. Ensrud, W. S. Browner, M. C. Nevitt, S. R. Cummings, and Osteoporosis Fractures Research Group. 2003. BMD at multiple sites and risk of fracture of multiple types: Long-term results from the Study of Osteoporotic Fractures. Journal of Bone and Mineral Research 18(11):1947–1954.

Fosamax® is a registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.

Prolia® is a registered trademark of Amgen Inc.

bone density measurement
Dr. Susan E. Brown

Bone density measurements were never meant to be treatment guidelines

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For years we have known that bone density does not itself predict fracture, yet how many men and women have been told, and continue to be told, that they should take osteoporosis drugs based on their bone density? So I was delighted to hear noted osteoporosis researcher Dr. Steven Cummings declare that bone density testing was never intended to serve as a guide to treatment. He made this statement on September 11, 2009 at the annual meeting of the American Society of Bone Mineral Research in Denver.

As Dr. Cummings detailed, the T score definitions of osteoporosis (defined as -2.5 T or more) and osteopenia (defined as -1 T or more) were developed by World Health Organization Committee in the face of expanding bone mineral density testing. Researchers felt the need to define what was “normal” bone density, so they developed the “T scores” rating system distinguish how similar one’s bone density was to that of a young person of the same sex. These definitions were supposed to be guidelines for establishing normal ranges, not signals of a need for treatment with bone drugs.

Dr. Cummings went on to suggest, as I have suggested before, that treatment guidelines should be based on an individual evaluation of multiple risk factors as is offered in the WHO’s FRAX tool, or better yet, in a more comprehensive fracture risk assessment like the one available on this site.

He also reminded his colleagues that another valuable way to assess risk of future fracture is by detection of previous fractures. While you well know if you have had a hip or wrist fracture, you may not know if you have a deformity, or fracture, of a vertebral body in the spine. An important new tool for detection of vertebral fractures is the “Vertebral Fracture Assessment” also known as a “Vertebral Deformity Assessment.” These tests, using either a spinal x-ray or a special picture from the bone density test can reveal of you have “hidden” vertebral fractures. If no deformities are found, no treatment is needed, but if such hidden fractures are found, taking action to strengthen bone is necessary. Existing fracture is the ultimate proof of bone weakness, and having such a fracture puts you at higher risk for further fractures.

Here at the Center for Better Bones, we try to give clients a realistic understanding of their fracture risk so that they know whether they need to take steps to improve their bone health. And we have a complete program that we tailor to their individual needs to help them do exactly that, without resorting to expensive bone drugs with unpleasant and unhealthy side effects. You can learn more about our ideas regarding natural bone health by reading the articles on betterbones.com.

 

Reference:

Cumming, Steven, “Identifying People Who Should be Treated to Reduce Fractures”. Presented at the “Osteoporosis: Focus on Fracture Prevention” Symposium, ASBMR Annual Meeting, Denver, 9-11-09.

 

osteoporosis drugs
Dr. Susan E. Brown

What do I really think of osteoporosis drugs, anyway?

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Those of you who read this blog and my articles regularly might think I’m against osteoporosis drugs altogether. That’s not truly the case. There are certainly people who have such catastrophic bone loss that it’s appropriate for them to use medications to slow or halt it — but these are usually people who have a serious health crisis going on. Cancer treatment, Paget’s disease of bone, those on long-term high dose prednisone treatment, and similar situations where bone is eroding rapidly are clearly circumstances where these strong medications can be beneficial. But my natural approach to support bones and overall health would be helpful in these patients as well.

Where I take issue with bone drugs is when they’re used to address low bone density without any effort to identify the reason for the bone loss — and that happens all too often. As most of my clients and some of my blog readers can attest, it’s not uncommon for physicians to simply hand out a script when they see a bone scan that indicates osteoporosis (or even osteopenia) without taking any steps to determine why bone is being lost, or even if bone is being lost!

Unfortunately, most physicians regard bone loss itself as a disease, when the vast majority of the time it’s really a symptom of some other, underlying health issue.

Treating the symptom with a drug doesn’t cure the disease — it simply masks the problem.  The “problem masking” in turn often brings with it significant life-damaging side-effects. And most physicians’ don’t mention that these are very powerful medications with a profound impact on the body’s most fundamental processes.

• Bisphosphonates put a halt first to osteoclast activity and over time to osteoblast activity as well.

• Teriparatide (Forteo) stimulates osteoblasts to work overtime in building new bone, but it has worrisome long-term risks that we discuss elsewhere.

• Denosumab (Prolia), a drug slated for FDA approval this summer, goes even farther, interfering with immune factors to prevent the natural process of bone breakdown and renewal.

What it boils down to is this: if your doctor finds your bone health situation so serious that she wants you to take these very powerful drugs — medications that affect not just bones, but other systems in the body too, then your situation is serious enough to warrant a full osteoporosis medical work-up looking for the causes of bone loss.  The case for bone drugs cannot be made on the basis of just one or even two DEXAs. The simple fact that a person is losing bone isn’t, in my opinion, reason enough to start someone on a drug as a knee-jerk reflex. If there is an identifiable underlying condition that is causing an individual to lose a lot of bone, rapidly, this should be uncovered and addressed. 

When a comprehensive natural approach to halting excessive bone loss fails, then can you make the case for bone drugs.  And when there isn’t an identifiable underlying health issue or an identifiable cause of bone loss, it still stands to reason that working to support bones by improving nutrient intake, getting more exercise, dealing with stress, and improving the body’s pH through an alkaline diet are much more sensible first steps than hauling out the “big guns”!

Postscript

Thank you all so much for telling your stories and adding your comments below. When I wrote this post, I did so out of concern that people who had significant health issues that resulted in bone loss would misunderstand my position on bone drugs and believe that I thought bone drugs serve no purpose. Your comments have shown me just how important it was to clarify that position! Many of you have exactly the kinds of health issues that cause rapid, catastrophic bone loss/weakening, so you fall into the category of people that I believe should consider medical therapies under a physician’s care and guidance. I don’t want anyone to feel that taking bone drugs to address this sort of bone loss is somehow wrong or incorrect, and certainly your physician is the first person to whom you should address any questions about medical treatment for bone loss — for the most part, it would not be proper for me to offer advice on whether someone should or shouldn’t use particular treatments, as I’m not familiar with your specific cases. At the same time, though, the alkaline diet and nutritional support that I recommend to all my clients is something that I encourage all of you to consider, as the more support you provide your system, the better it will respond to your treatment regimen. In my work with clients at the Center for Better Bones, I’ve found that these methods are a great support even to those patients who must use bone drugs to halt bone loss related to a medical issue. Best wishes to all of you, and thanks for reading my blog!

Getting to the Root of Osteoporosis

Dr. Susan E. Brown

The next big bone drug: big bang or little whimper? 5 questions to ask when evaluating bone building drugs

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The next big new bone building drug has hit your doctor’s office. Impressive claims that the drug reduces fractures by 73% are being tossed around. But bisphosphonates were once touted in similar terms and are falling out of favor due to side effects and limited efficacy.

Do the stats in these studies mean anything real?

Whenever I research any new bone building drugs, I look at the research and ask a set of key questions to see whether there is any good news. I’m sharing them with you so you have tools to help you assess what you hear.

5 questions to ask when evaluating bone building drugs

Question #1: What’s the nature and action of the drug? What will its long-term effects be?

The experimental bone drug I mentioned is a monoclonal antibody called romosozumab that inhibits action of a protein in the body known as sclerostin. Some time ago, it was discovered that sclerostin deficiency causes a rare genetic disorder characterized by high bone mass and resistance to fracture, so the pharmaceutical industry decided to make a drug to block this protein and see if it could reduce bone breakdown and enhance bone buildup.

Now Romosozumab is a drug that tinkers with both bone breakdown and bone formation in a whole new way, and its discoverers claim that “the risk of new vertebral fracture was 73% lower in those who took the drug.” Pretty impressive, if it’s true. So let’s take a closer look and continue asking questions.

To begin with, an important unanswered question is, “What are the many roles that sclerostin plays in the body, and what will be the long-term impact of suppressing this protein?” The current study does not address the issue of long-term impact or safety, and it often takes 10+ years to see the full effects of such tinkering with human physiology. For now, we know roughly how the drug acts, but we do not know what its long-term effects are.

Question #2: How many people participated in the study, and how were they selected?

This study looked at 7180 postmenopausal women ages 55 to 90 with a hip bone density T score between -2.5 and -3.5. The group was divided into two subgroups — 3325 who took the drug, 3327 who were given a placebo. So on the surface, this is a strong study — it includes a large sample of individuals who are similar in age, gender, and baseline bone density, and the groups are equivalent in size.

But a closer look shows that those at higher risk of fracture were excluded from the study. That includes women with a hip T score worse than -3.5, a history of hip fracture, or even one severe or more than two moderate vertebral fractures; those with a vitamin D below 20 ng; women with high or low blood or calcium as well as those with bone diseases or conditions affecting bone metabolism.

In other words, they chose participants based on low bone density rather than fracture risk (and if you’ve read my blogs, you know that the two aren’t necessarily the same).

Question #3: How long was the study?

Study subjects were only given the new drug, romosozumab, for 12 months and then switched to another monoclonal antibody bone drug, denosumab (Prolia®), in the second year. While researchers do not explain why they switched to another drug, I suspect they feared extended use of this new drug would result in serious longer-term adverse effects. This is not unlike the case with the drug teriparatide (Forteo®), the use of which is limited to two years due to potential life-threatening impacts.

Question #4: What is the real-life fracture-reduction benefit?

The length of the study is important because the short-term fracture reduction benefits may be very different from the long-term ones. In this case, all we have is a 1-year study with romosozumab and then another year-long study switching all study subjects (those on placebo and those on romosozumab) to the denosumab (Prolia®) bone drug. This makes the study a little confusing, but I’ll try to clarify the findings:

  • Only a few vertebral fractures were prevented by using either of the two drugs. The study had a total of 6,652 women, all of whom had a pretty low fracture risk to begin with. In the first year of the study using romosozumab versus placebo more than twice as many women (59) in the placebo group experienced vertebral fractures than the women in the romosozumab group (16). So when you look at how many women were spared from a vertebral fracture by taking the new drug (that is, 59 – 16 = 43 women), you realize that for every 1 woman who benefited, there were 76 others in the drug group who took the medication and got nothing out of it. If your doctor told you he had to treat 3,327 women to prevent just 43 vertebral fractures, you might look into other ways to strengthen your spine.
  • Both drugs put together had very little benefit on vertebral fracture. Among the 3,327 women who received placebo the first year and then were put on denosumab in the second year, there were 84 new vertebral fractures, whereas the women who took romosozumab the first year had only 21. Overall, then, 63 women out of 6652 were saved from having a fracture by taking bone drugs for both years. That’s not even 1% of the total number of participants.
  • The new drug had almost no impact on non-vertebral fractures. Vertebral fractures often cause no symptoms in those who have them, but others — like fractures in the wrist, collar, arm or hip — can be more serious and painful. Such fractures occurred in 56 patients on the new drug and 75 in the placebo group. That means the drug helped prevent only 19 of the 3,327 women avoid non-vertebral fractures with over 1 year of treatment. So you’d have to treat 175 women to save just 1 woman from fracturing a hip. And when you take the second year into account, when all the participants took bone drugs, you find no significant difference in risk between the romosozumab group and the placebo group. So if you were looking to prevent fractures of the hip, wrist, collarbone, arm, or other non-vertebral fracture, the new drug was no help at all.

Question #5: What are the reported and potential adverse effects of the drugs?

In this 1-year trial of romosozumab, adverse effects included the following: hypersensitivity to the injection; 2 cases of osteonecrosis of the jaw; 1 atypical femur fracture; a high incidence of anti-romosozumab antibodies (the impact of this on the immune system is yet unknown); and lowered serum calcium levels in those using romosozumab. These are all fairly serious problems.

Is there a better way to reduce needless fractures?

From my nearly 3 decades of clinical practice and bone health research, I confidently say yes, there is a better way! And that better way is one that builds Better Bones and a Better Body naturally, without the many risks of bone drugs.

Approaches like my Better Bones Program enhance health, vitality, and fitness while reducing fracture risk. Why not take a few minutes to review the steps to the Better Bones, Better Body Program and get started strengthening your bones today?

Reference:
Cosman, Felicia et al., Romosozumab treatment in postmenopausal women with osteoporosis. New England Journal of Medicine 2016;375:1532-1543.

Dr. Susan E. Brown

A look at the latest bone drug, Evenity

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In April 2019, the FDA approved romosozumab (Evenity), a new osteoporosis drug targeted at postmenopausal women with high risk for fracture. I looked at the data used by the FDA in granting approval for the drug — and it’s far from confirming the runaway success of Evenity that Big Pharma would lead us to believe. So before you fill that prescription, here’s some information I think you should know.

New bone drug Evenity — how does it work?

Evenity is a monoclonal antibody that suppresses a protein called sclerostin, which also regulates bone formation. In people who have a rare genetic disorder called sclerosteosis, sclerostin is very low, which allows osteoblasts to build bone at will. People who are born with sclerosteosis or a milder form called Van Buchem Disease have enhanced bone formation and denser, stronger bones than average — typically, Z-scores in the spine of as much as +7.7–+14.4. This might sound great to someone with osteoporosis, but the truth is, unimpeded bone building with nothing stopping it eventually causes serious harm, including entrapped nerves and enlargement of the skull, which puts pressure on the brain — and most people with sclerosteosis don’t live past their 30s. 

Knowing this, researchers looked for a way to inhibit sclerostin in women with low bone mass to see if it would cause them to develop greater bone density. And it does — although this shouldn’t surprise anyone. The principle of “use the body’s own mechanisms to build bone” is a fairly sound idea on the face of it. Where it runs into problems — and Evenity is no exception — is when you put normal bodily mechanisms on overdrive, as most of these medications do. 

What did the studies show?

The data used for the drug’s approval comes from two trials: The FRAME study (FRActure study in postmenopausal woMen with ostEoporosis) and the ARCH study, both of which looked at postmenopausal women at high risk for fracture.

The FRAME study enrolled 7180 postmenopausal women with a T-score of –2.5 to –3.5 at the total hip or femoral neck — so, definitely in the bone loss zone that defines osteoporosis. Half of these women were given Evenity, while the other half got a placebo. All of the participants also got at least 500 mg calcium and 600 international units (IU) of vitamin D supplementation daily, and anyone in either group who had serum 25-hydroxyvitamin D concentrations of 40 ng/mL or less (which was a whopping 77% of participants!) was given a loading dose of 50,000 to 60,000 international units of vitamin D within one week of randomization. After 12 months on Evenity, all of the participants were switch to Prolia for 12 months. 

The ARCH study was similar, except instead of following the year of Evenity or placebo with a year of Prolia, participants received alendronate (Fosamax). And as in the other study, the 4093 participants were all given 500 mg of calcium and 600 IU of vitamin D, and 74% had the same vitamin D loading dose as in the FRAME study.

So, how did the patients taking the drug fare? When you read the FRAME researchers’ publication in the Journal of Bone & Mineral Research, the numbers are staggering: “after 12 months of romosozumab, at the lumbar spine, 96% of patients achieved gains ≥3% from baseline, 89% of patients achieved gains ≥6%, and 68% of patients achieved gains ≥10%, compared with 22%, 6%, and 1% of patients receiving placebo” — amazing numbers! 

Are they too good to be true? You bet they are.

Did Evenity really make a big difference?

Let’s go back for a minute and consider the protocols used in the FRAME and ARCH studies. Each of the women enrolled had osteoporosis — it was a prerequisite for participating. All of them got vitamin D tested, and well over two-thirds in both studies were identified as being deficient and given a therapeutic dose of vitamin D. (It’s also interesting to see that the cutoff point for vitamin D deficit was set at 40 ng/mL, higher than the usual 30 ng/mL). 

While the results from the drug arm of the FRAME study are astonishing, what’s really interesting are the results from the placebo group in the FRAME study, where 29% of the participants had a 3–10% improvement in bone density just from the added vitamin D and calcium. Meanwhile, 47% had a decrease in bone density. The remainder (24%) saw no significant change.

What this means is that the vitamin D therapy alone enabled more than half (53%) of the women in the placebo group to halt their bone loss and, for some, start building bone. It’s problematic for the findings because this “placebo” arm did not actually use a placebo — what it did was identify a common cause of bone loss and treat it using nutrition (sound familiar?). How much more improvement would this groups have seen if they had also used weight-bearing exercise and the remaining key nutrients as part of its “placebo”?

Taking drawbacks into account

The findings from the FRAME trial’s placebo arm also imply something else: that nearly 2000 of the women who were given Evenity could have halted their bone loss and perhaps started to build bone even without the drug, just by improving their vitamin D status. 

However, they built even more bone with the drug, and that’s good, right? Well, if that were all the drug did, it certainly would be. But the bone drug Evenity comes with a black box warning of increased risk of heart attack, stroke, and death. One has to wonder if the risk of a heart attack is really worth it for the thousands of women who took this drug without realizing that the “supportive” treatment — vitamin D therapy — might be responsible for at least some of the bone-building effects. 

The news from the ARCH trial is no different: It found reductions in fracture incidence (which you’d expect) but increased cardiovascular events, as well as a few instances of the atypical fractures and osteonecrosis of the jaw — problems that have been associated with bisphosphonates in the past.

Not to mention, the reason these studies were constructed with only 1 year of Evenity followed by 1 year of a different drug is that Evenity stops working after 1 year. It’s a pity that the researchers didn’t follow a year of Evenity with a year of just nutritional support to see whether the gains seen in the women who took the bone drug Evenity were maintained. (Maybe they didn’t want to know the answer…)

 

References

Appelman-Dijkstra N, Van Lierop A, Papapoulos S. SOST-related sclerosing bone dysplasias. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews (Internet). Seattle (WA): University of Washington, Seattle; 1993-2019.

Cosman F, Crittenden DB, Adachi JD, et al. Romosozumab treatment in postmenopausal women with osteoporosis. N Engl J Med. 2016;375:1532–43.

Lewiecki EM. Role of sclerostin in bone and cartilage and its potential as a therapeutic target in bone disease. Ther Adv Musculoskelet Dis 2014;6(2):48-57.

Saag KG, Petersen J, Brandi ML, et al. Romosozumab or alendronate for fracture prevention in women with osteoporosis. N Engl J Med. 2017 Oct 12;377(15):1417-1427.

Sancar F. Caution with new osteoporosis drug. JAMA 2019;321(19):1862.