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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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Dr. Susan E. Brown

Am I Losing Bone Right Now? The NTx Test

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Every day women are worried because they’ve been told that a DEXA test shows their bone density is that of an 80-year-old, or that they “must” take bone drugs.

But what worries me is that most of these women have NOT been told whether or not their bone loss is ongoing or if it occurred in the past. Knowing if your bone loss is still taking place is critical when it comes to your risk of excessive bone loss, osteoporosis and fracture.

The NTx test measures current bone loss

I recommend anyone worried about bone loss get an NTx (N-telopeptide) test. Unlike bone density tests which only provide a static snapshot of your bones, an NTx test tells you if your bones are currently breaking down. It does this by measuring molecules from bone excreted in the urine.

First: Download this free guide to share with your Doctor about this test & resources.

NTX Booklet for You and Your Doctor

Second: Watch This Video:

 

Third: Ask Your Doctor to order the NTx test using our manual above

. . . Or order it yourself online.

New Offering from the Better Bones Foundation

Skip the doctor and order your tests online! So many times we hear from our clients and readers that their MDs are not willing to order the tests that they request. This is such a frequent occurrence that we wanted to find a way for women to obtain these necessary tests. In partnership with The Better Bones Foundation and Evexia Labs, we are now able to offer low-cost self-pay tests for those who want to know WHY they are losing bone.

The process is easy . . .

#1 Select the tests that you are interested in and submit your form below. Make sure you include your full address with city, state, and zip code. We will pass this information on to the lab on your behalf.

#2 Wait for an email from Evexia Lab with your username and password (also check your spam folder). Once you log in you will then be able to see the cost of the tests and can choose to self pay (no insurance accepted). After you pay them, Evexia will email you a requisition form for the lab.

#3 Print your requisition and take it to the nearest LabCorp facility. You can find a LabCorp close to you using this link: https://www.labcorp.com/labs-and-appointments. Self-pay testing is not available in NY, NJ, and RI.

#4.  In 2 to 4 weeks after getting the tests done, you will receive your lab results via an email notifying you that the results are ready. They can be viewed in your account or you can print them out and take them to your doctor for interpretation.

I am inquiring about the following tests: (Check all that apply)

Other reading resources for Medical Testing for Bone Health

What’s the cause of your osteoporosis? Diagnostic tests and what they mean

Bone testing — assessing bone breakdown and bone loss

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.

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 bone drug raloxifene (Evista™)

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Recently, Sarah came to my office reporting that her doctor wanted her to take the bone drug raloxifene (Evista™). She wanted to know if I thought this medication would benefit her, so I sat down to take a fresh look at the first and largest controlled study on this drug.

The short version of what I discovered: there is limited benefit and substantial risks with this bone drug.  But to understand why, you need to know the long version: what this drug does, and what it doesn’t do.

What is raloxifene (Evista™)?

Raloxifene is a “selective estrogen receptor modulator (SERM),” which puts it in the same family as the breast cancer drug tamoxifen (it was studied for breast cancer, but proved less effective than tamoxifen). SERMs bind to estrogen receptors and mimic estrogen’s effects; the idea is that you can get estrogen’s beneficial impacts on bone, but without the negative estrogen effects of on the uterus endometrial and breast tissue.

What raloxifene’s fracture prevention trial reveals

Back in the late 1990s, researchers conducted the first (and largest) placebo-controlled fracture prevention trial to determine what raloxifene might offer for osteoporosis. This trial involved 6,828 postmenopausal women divided into two treatment groups: One that was given a placebo, and the other given raloxifene in either 60 or 120 mg daily doses.

All of the study subjects had osteoporosis as determined by bone density measurement (–2.5 T score), and some of the women had already experienced a spinal fracture. The study was three years in duration.

Fracture reduction at three years:

  • Of the 6,828 women in the study, 503 (7.4%) experienced at least one new vertebral fracture during the study period.
  • In the placebo group, 10.1% experienced a vertebral fracture visible on x-ray (not necessarily symptomatic) during on the 3-year study.
  • In the treatment group using 60-mg doses of raloxifene, 6.6% experienced a new vertebral fracture. This represents an absolute risk reduction of 3.5% — that is, among those using raloxifene, 3.5 fewer vertebral fractures occurred per 100 women as compared to those not taking the drug.
  • Importantly, there was no significant reduction in hip fracture or other non-vertebral fractures with the use of raloxifene. While spinal fractures are a key warning sign for osteoporosis, they don’t affect quality of life nearly as much as hip fractures do.

All in all, this very large study showed that this drug had a small effect on reducing vertebral fractures and no significant effect on reducing hip or other non-vertebral fractures. 

The risks of raloxifine lead to FDA black box warning

Unfortunately, even this very first study on raloxifene reported serious adverse effects, most notably a three-fold increase in the risk of potentially life-threatening venous blood clots (thrombosis).

Ten years after the drug was approved, the FDA issued a black box warning about this side effect — which is the most serious notification of potentially life-threatening adverse effects the FDA can require, short of withdrawing the drug from the market. I’ve reproduced it here so you can see what it says.

 

Is there a better way?

After looking at this information and comparing the mild possible benefits to the significant potential harms, Sarah and I have to ask the question: Is there a better way?

Currently, there are number of bone drugs prescribed to intervene with the mechanisms of skeletal weakening, and many more are in the pipeline. Given that up to half of the women 50+ in this country will be told to take a bone drug at some point, it’s a great idea to take a look at what these drugs do, the degree to which they really prevent fracture, and their potential risks, and what other avenues might be available to you.

Then make up your own mind.

Here at the Center for Better Bones we know there is a better way and it is our mission and passion to share with you our time tested, fully life-supporting Better Bones, Better Body Program.

References
Cranney A, Adachi JD. Benefit-risk assessment of raloxifene in postmenopausal osteoporosis. Drug Saf. 2005;28(8):721-30.
Duvernoy CS1, Yeo AA, Wong M, Cox DA, Kim HM. Antiplatelet therapy use and the risk of venous thromboembolic events in the Raloxifene Use for the Heart (RUTH) trial. J Womens Health (Larchmt). 2010 Aug;19(8):1459-65. doi: 10.1089/jwh.2009.1687.
Ettinger B, Black DM, Mitlak BH, et al. Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene: results from a 3-year randomized clinical trial. Multiple Outcomes of Raloxifene Evaluation (MORE) Investigators. JAMA 1999;282(7):637-645.

Dr. Susan E. Brown

Estrogen therapy isn’t an option for osteoporosis anymore

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When the American College of Physicians (ACP) recently updated its guidelines for treating osteoporosis (Qaseem et al, 2017), tucked in with the usual recommendations for drug therapy was something major: The ACP reversed its position on estrogen therapy for osteoporosis.

In 2008, ACP guidelines supported estrogen therapy based on “high-quality evidence that estrogen therapy was associated with reduced risk for … fractures in postmenopausal women.” In direct contrast to this, the new guidelines state that “[m]oderate-quality evidence showed no difference in reduced fracture with estrogen treatment in postmenopausal women with established osteoporosis.”

Why guidelines on estrogen therapy for osteoporosis have changed

How is it possible to have “high-quality evidence” that something works and a few years later, it somehow doesn’t? 

It’s all about how you look at the data. The 2008 guideline based its recommendation on studies showing estrogen decreased fracture risk—but, as the 2017 guideline points out, “many of these studies focused on postmenopausal women with low bone density, or on postmenopausal women in general rather than those with established osteoporosis.” In other words, the 2008 evidence came from women who did not have osteoporosis — the problem the guidelines are meant to address.

In the intervening years, a bunch of randomized clinical trials were done examining estrogen’s effects on women with osteoporosis to offer better information. Since estrogen offers little benefit and has known harms, like increased risk of stroke or breast cancer, the ACP’s decision to change their recommendation makes perfect sense. It also highlights two important points when it comes to science — one, it’s always changing with new information, and two, a lot depends on the assumptions of the people looking at the evidence.

It’s enlightening to look at the ACP osteoporosis guidelines side-by-side with the 2013 European Union osteoporosis guidelines (Kanis et al., 2013). The European recommendations start by discussing mobility, falls, and diet and nutrition before weighing the pros and cons of bone drugs. The ACP guideline starts with drug therapy and mentions nutrition only in passing (the usual suspects, calcium and vitamin D, nothing more) and devotes only three lines to exercise.

The ACP’s guideline assumes that drug therapy is the best approach. The Europeans look at it differently — and so do I. My Better Bones, Better Body approach has stayed pretty consistent over the years because it’s based on the understanding that the body knows how to heal itself if it has the resources it needs!

References


Kanis JA, McCLoskey EV, Johansson H, et al. European guidance for the diagnosis and management of osteoporosis in postmenopausal women. Osteoporosis Int 24(1):23–57.

Qaseem A, Forceia MA, McLean RM, Denberg TD, for the Clinical Guidelines Committee of the American College of Physicians. Treatment of Low Bone Density or Osteoporosis to Prevent Fractures in Men and Women: A Clinical Practice Guideline Update from the American College of Physicians. Ann Intern Med 2017;166(11):818-839.