Bone Drugs Archives - Page 2 of 4 - Better Bones, Better Body
Questions? Text 1-315-595-5564

Archive for category: Bone Drugs

You are here: Home / Bone Drugs
Dr. Susan E. Brown

New bone drug Tymlos — is it safe?

/in /by

Another new bone drug — Tymlos (abaloparatide) — recently hit the market, approved by the FDA for treating osteoporosis in postmenopausal women.

As always when we get a new entry into this ever-more-crowded market, I wanted to see how Tymlos works in the body and what downsides could be lurking behind all the hype. Is Tymlos safe? I wish I had a new and different message for you about Tymlos. Believe me, it would be nice to be able to say, for once, that the newest product on the bone drug market really is good for bones — and safe for those who take it. Unfortunately, I can’t say this.

Tymlos — how does it work?

Tymlos, like Forteo before it, works by imitating a natural bone-building process in the body to increase the patient’s bone density. It’s similar to Forteo in that it focuses on the parathyroid hormone (PTH) pathway, except that while Forteo mimics PTH itself, Tymlos mimics a peptide called human parathyroid hormone-related protein (PTHrP) — but the end result is the same: stimulation of the PTH pathway to increase osteoblast activity, with the goal of building denser bone. If Tymlos works along similar lines as Forteo, then it stands to reason that it’s going to have similar drawbacks — and it does.

The side effects of Tymlos — a deeper look

Like Forteo, Tymlos comes with a warning about osteosarcoma, a rare bone cancer. The warning is based on animal studies that have shown increased rates of this cancer in animals dosed with abaloparatide (Tymlos). Rather ironically, one study cheerfully noted that their results “suggest no increased risk of osteosarcoma would be expected in patients treated with [Tymlos]” in comparison to Forteo — which itself offers a greater-than-normal risk of osteosarcoma, so that’s not much of a recommendation.

Another adverse effect in the warning list is orthostatic hypotension — that is, low blood pressure upon standing, which could lead to fainting or falls (not something you want in a person at high risk of fracture!). High blood or urine calcium levels (the latter in association with kidney stones) are also concerning side effects.

Further, the effects of this drug on the immune system is really unexplored and only lightly touched upon in the safety trials. Half of the individuals using the new drug developed antibodies to the drug which in some cases lead to cross-reactivity, and in all cases squantered precious immune system focus and energy.

It’s also notable that a large, double-blind clinical trial with 2,463 women (age 49–86) comparing Tymlos directly to Forteo and placebo, Tymlos significantly outstripped both the placebo group and the Forteo group in terms of participants who had to stop treatment due to side effects such as nausea, dizziness, headache, and palpitations; where the Forteo group had about an 0.7% absolute increase in such side effects over the placebo group (a relative increase of 11%), the Tymlos group experienced a whopping 3.8% increase (a 61% relative increase) in these effects over the placebo group.

How much does Tymlos really reduce fracture?

I bring up the “absolute” vs. “relative” increases in side effects for a reason: The 43% nonvertebral fracture risk reduction in Tymlos-treated patients sounds fantastic until you realize it’s relative risk, not absolute risk. In absolute terms, the placebo group had 2% more nonvertebral fractures than the Tymlos group — meaning for every 100 women who took this drug and dealt with its side effects, 2 were spared a nonvertebral fracture who would’ve had one if they’d done nothing. And how about vertebral fractures? This new drug was only slight more successful at reducing vertebral fractures — reporting a absolute reduction of 3.64%. One hundred women have to be treated for 3.64 spinal fractures to be prevented.  (Given the exorbitant cost of this drug, that’s not such a great return on investment!)

Ultimately, this drug has the same problems most of the others have — it hijacks the body’s natural processes to force a result without consideration for the unintended consequences. Which begs the question: Why not work with the body to strengthen bones the way nature intended?

References

Hattersley G, Attalla B, Varela A, Smith SY. Comparison of osteosarcoma incidence between abaloparatide (BA058) and PTH (1–34) in long term rat studies. Bone Abstracts (2014) 3 PP302 | DOI: 10.1530/boneabs.3.PP302

Miller PD, Hattersley G, Riis BJ, et al; for the ACTIVE Study Investigators. Effect of Abaloparatide vs Placebo on New Vertebral Fractures in Postmenopausal Women With Osteoporosis: A Randomized Clinical Trial. JAMA. 2016;316(7):722-733. doi:10.1001/jama.2016.11136

Tymlos Prescribing Information. Radius Pharmaceuticals. Web. http://radiuspharm.com/wp-content/uploads/tymlos/tymlos-prescribing-information.pdf

 

You need to install and activate the WooCommerce Shop Plugin to display WooCommerce Products

You need to install and activate the WooCommerce Shop Plugin to display WooCommerce Products

 

Dr. Susan E. Brown

A look at the bone drug raloxifene (Evista™)

/in /by

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

Dear doctor, please treat me like a man

/in /by

Our skeletons were meant to last a lifetime, so when they show signs of not living up to this promise, we need to stop and ask ourselves, “What’s causing bones to weaken?”

Seems only logical, right?

While this is how thoughtful osteoporosis treatment begins, having spoken with thousands of individuals diagnosed with osteoporosis, I can’t help but notice a glaring difference between how women and men are treated when a bone health concern arises.

The double standard of conventional osteoporosis treatment

As a rule, women are told to take bone drugs when their T scores get to -2.5 or greater — without any investigation into the possible causes of their bone weakening. Often, they’re not even carefully questioned about their history, or even given a simple test for vitamin D adequacy.  For a man with similar bone density or fracture history, however, a medical workup is usually ordered; he’s not simply handed a bone drug script.

Let me illustrate these statements with the cases of Sally and Robert.

Sally, a 61-year-old woman, experienced a spinal compression fracture and was found to have low bone density. Her hip and spine T-scores were -2.5 and -2.7, so she was diagnosed with osteoporosis. The doctor felt Sally’s osteoporosis was potentially dangerous, so he recommended bone drugs, despite all their limitations and unwanted side effects, as treatment. His recommendation was accompanied by remarks like, “You’ll fracture if you don’t.” When Sally expressed doubts, she heard, “You’ll end up disabled.”

At the Center for Better Bones, we take the position that if the doctor thinks the problem is serious enough to warrant bone drug use, then it is surely serious enough to warrant a search for the causes of this problem. Yet Sally wasn’t given even one of the medical tests commonly used to identify causes of bone weakening. She was simply and forcefully told to take bone drugs.

Richard, a slender, 55 year-old man with T-scores of of -3 in the hip and -2.5 in the spine, had no fractures. Like Sally, Richard was diagnosed with osteoporosis and offered bone drugs — but beforehand, he was subjected to one of the most comprehensive osteoporosis workups I’ve ever seen. He was tested for vitamin D, parathyroid hormone, loss of calcium in the urine, blood calcium, bone formation markers, celiac disease, autoimmune factors, a hormone panel, comprehensive nutrition testing — even tests looking for unusual bone marrow disorders. The irony is, men in his family have a tendency to have low bone mass, yet none ever had a significant osteoporotic fracture — so he was given this battery of tests (and offered drugs) despite personal and familial history suggesting his fracture risk was low.

While these are just two cases, this is something I typically see in my clients: women are rarely given the same sort of medical workup for osteoporosis as men, even when (as in Sally’s case) they have already had an osteoporotic fracture.

Finding hidden causes of osteoporosis

Of course, we should all review and correct any shortcomings in diet, lifestyle, exercise, behavior, and even thought patterns that contribute to less-than-ideal bone health. But if you have excessive bone loss or low-trauma fracture, women especially should seek out a physician who will look for underlying medical causes of bone weakness. As a guide, you might print out my list of osteoporosis workup medical tests to give your doctor. Follow this up by politely asking to be treated… like a man.

Bisphosphonates make bones weaker
Dr. Susan E. Brown

Bisphosphonates make bones weaker, not stronger

/in /by

I’ve argued for years that bisphosphonates — the knee-jerk bone drugs  recommended for those with osteoporosis regardless of their actual fracture risk — quite often offer no benefit to those who are prescribed them, and for many, do more harm than good. That’s why I was alarmed, but not surprised, by a recent study that found bisphosphonate drugs may be leaving bones weaker — not stronger — at the microscopic level (Ma et al, 2017).

In the study, researchers obtained samples of trabecular bone from three groups of subjects: (1) normal, healthy older adults who had no fractures, (2) individuals who had fractured a bone after at least 1 year of treatment with bisphosphonates, and (3) individuals who’d had fractures but were not being treated for osteoporosis.

They first examined the bones’ microstructure and identified areas of osteoclast activity (“perforations”) versus microscopic fractures (“microcracks”). Then they subjected each sample to load-controlled tensile testing to determine how much strain the bone could withstand.

The results were revealing. The first group (no fractures) had the least amount of either perforations or microcracks. Both the second (untreated with fractures) and third (bisphosphonate-treated with fractures) groups had roughly equivalent amounts of perforations and microcracks. But the big difference was the volume of perforations versus microcracks: the untreated group had a significantly higher volume of perforations while the bisphosphonate group showed a significantly higher volume of microcracks.

Bisphosphonates and bone fracture risk

I’ve always maintained that the greatest issue when it comes to bone health isn’t thin bones — it’s weak ones. In healthy bone, microfractures stimulate bone turnover, which ultimately renews bone and makes it stronger — unless the activity of bone-building osteoblasts is outstripped by bone-removing osteoclasts.

It’s pretty clear that the untreated patients who’d had fractures were undergoing high bone turnover — that’s why they had more (and larger) osteoclastic perforations. But the bisphosphonates-treated group had significantly larger microcracks — which suggests that in the bisphosphonate group, either the bone is much less resilient and more prone to cracking under strain than normal bone, or the usual repair mechanisms aren’t working up to standard. Or both at the same time!

More to the point, it suggests that people treated with bisphosphonates have bones that are significantly weaker and more prone to fracture than either healthy people or people with high bone turnover.

The tensile strength testing performed on all three groups’ samples confirmed this: Where the normal group had a tensile strength (measured in megapascals) of 1.62 MPa, the untreated fracture group’s tensile strength was decreased by about 47% (to 0.86 MPa) — and the bisphosphonate group’s tensile strength was an astonishing 64% (0.58 MPa) below the normal group’s level.

This means that people treated with bisphosphonates have much weaker bones than even people at high risk of fracture due to high bone turnover!

So if using bisphosphonates leaves patients with slightly denser but significantly weaker bones, increasing the likelihood of a catastrophic fracture (never mind the other side effects), this leaves us asking, “What exactly is their benefit?”

Reference  

Ma S, Goh EL, Jin A, et al. Long-term effects of bisphosphonate therapy: perforations, microcracks and mechanical properties. Sci Rep 2017;7:43399; DOI: 10.1038/srep43399.

Dr. Susan E. Brown

Estrogen therapy isn’t an option for osteoporosis anymore

/in /by

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.

Dr. Susan E. Brown

Conflicting advice on bone drugs — what does the evidence say?

/in /by

It’s no secret that I’m no fan of bone drugs in general. I’ve found the arguments for their use deeply unconvincing for decades. And now, European researchers looking at the accumulated evidence about the various drugs’ long-term effects are starting to come to the same conclusion:

Except in extreme cases, bone drugs don’t offer enough benefit in reducing the risk of fractures to be worth the price paid in terms of both short- and long-term side effects.

A European/Canadian research group reviewed the evidence on bisphosphonates like:

  • alendronate (Fosamax),
  • ibandronate (Boniva) and zoledronic acid (Zometa or Reclast)
  • teriparatide (Forteo)
  • denosumab (Prolia)
  • two treatments not used in the U.S.: calcitonins and strontium ranelate

Their findings struck me as good general “lessons” for all of us to learn.

‘Denser’ bones are not always stronger bones

The review found that the majority of osteoporotic fractures happened in those who did not have “osteoporotic bone density.” This helps confirm: Bone density alone cannot predict fracture risk.

Other recent studies show a large percentage of people who fracture have only osteopenia or even normal bone density. Many people with an osteoporotic bone density never fracture.

Not all fractures are created equal

When it comes to assessing bone drugs’ effects, a painless vertebral fracture or a toe fracture (painful, but not life-altering) shouldn’t be considered as clinically important as a hip fracture, which is life-changing.

Yet many drug trials either focus on vertebral fractures or on “non-vertebral” fractures as an endpoint. The stubbed toe becomes equivalent to a hip fracture in determining how effective the drugs are in fracture prevention.

Not surprisingly, when hip fractures are looked at specifically as the endpoint of choice, the researchers discover something different. They found that the data on less serious fractures of toes, wrists and so forth obscure the fact that the drugs don’t do much to prevent the most serious and dangerous osteoporotic fractures.

Bone drugs’ benefits remain inconclusive

The benefits of taking a bone drug must outweigh the costs for it to be worth recommending. And even in high-risk older adults, such benefits have not been shown conclusively.

In weighing the risk-benefits of bone drugs, researchers took a hard line on the importance of evaluating all costs. “Clinical trials evaluating harm-benefit balance in osteoporosis or fracture prevention should be well-powered long-term studies that include hard endpoints,” they note. “Total mortality, total serious adverse events, hip fractures, and functional status are essential outcomes.”

New U.S. osteoporosis guidelines miss the mark

What’s frustrating to me is that experts in the U.S. still focus uncritically on the flawed studies that the review critiques. They glibly parrot the ideas that bone density is the same thing as fracture risk and that drugs offer protection from fractures.

Case in point: The American College of Physicians’ latest osteoporosis guidelines, which were published virtually simultaneously with the European review. They make a “strong recommendation” for the use of bisphosphonate drugs “to reduce the risk of hip and vertebral fractures.” Most galling to me, they openly equate bone mineral density with fracture risk: “most women with normal DXA scores” it notes, “do not progress to osteoporosis within 15 years.”

To which I respond with the European review’s first lesson: Denser bones ≠ stronger bones.

References:
Erviti J, Gorricho J, Saiz LC, Perry T, Wright JA. Rethinking the Appraisal and Approval of Drugs for Fracture Prevention. Front Pharmacol. 15 May 2017 | https://doi.org/10.3389/fphar.2017.00265

Qaseem A, Forciea 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;166:818–839.

Dr. Susan E. Brown

Strontium: bone drug or nutrient?

/0 Comments/in , /by

Quite frequently women write me to ask: What is strontium and why do you include it in your Better Bones Builder?

Well, there’s a short answer and a long answer to that question. Here’s the short answer: Strontium is an element very much like calcium and naturally present in our food and water. If you are eating a typical diet, you might getting anywhere from 1 mg to more than 10 mg of strontium per day. The reason it’s in the Better Bones Builder is that the elemental form (that is to say, the non-radioactive version found in nature) has been shown to promote formation of healthy teeth and bones. So it makes sense to include dietary doses of strontium in comprehensive bone-building formulas such as our Better Bones Builder because low-dose strontium is a companion nutrient that works with calcium and other minerals to promote bone health.

Low-dose vs. high-dose strontium

Now let’s get to the long answer. Where confusion sets in is when people hear about strontium being used by itself to build bone. What most people don’t realize when they read about strontium as “the solution” for bone health is that such talk isn’t referring to dietary doses of elemental strontium — rather, it’s referring to the extremely high-dose strontium that has been developed and patented as a drug therapy for osteoporosis in Europe. This drug, known as Protelos®, contains 680 mg of elemental strontium and two grams of strontium ranelate, a synthetic salt that combines strontium with ranelic acid.

Risks of high-dose strontium

Elemental strontium is different

Elemental strontium is a natural part of the earth’s crust and is very different from “strontium 90” which is a hazardous radioactive nuclear fallout product from aboveground nuclear testing. All strontium used in bone-building health products is elemental strontium.

One goal of Protelos® is for a small number of strontium atoms to displace calcium atoms in bone. For this effect it is necessary that the strontium drug be taken at least two hours apart from calcium. This separation of calcium from strontium is not necessary for low-dose strontium (22 mg) like that in my bone-building formula, which is used as a nutrient to aid the development of healthy bones. Unlike dietary strontium, the strontium drug has been found to have various adverse side effects including nausea, diarrhea, and, more rarely, memory problems, serious skin rashes, and venous clots. For the first 10 years of its use as an osteoporosis drug, however, more serious drug-induced problems were detected as the strontium drug (Protelos®) was found to substantially increase the risk of heart problems, including heart attack. In 2014, the European Medicines Agency Pharmacovigilance Risk Assessment Committee (PRAC) concluded that the risks of the strontium drug outweighed the benefits and they recommended suspension of its use.

Specifically, PRAC reported in 2014 that:

  • For every 1,000 patient years of use of the strontium drug (Protelos®) there were 4 more cases of serious heart problems and 4 more cases of blood clots or blockages of blood vessels than there were with the placebo.
  • As for benefits, the strontium drug had only a modest effect in osteoporosis, preventing 5 non-spinal fractures, 15 new spinal fractures, and 0.4 hip fractures for every 1,000 patient years.

Later in 2014 this same European committee revised its recommendation allowing the strontium drug to be used by patients who could not be treated for osteoporosis by other bone medicines, but requiring that patients using the strontium drug be carefully monitored. In addition, those with a history of heart or circulatory problems were not allowed to use this medication.

The high-dose strontium drug is not available in the U.S.

Keeping strontium in perspective

To avoid any confusion, let me be perfectly clear: In the U.S. the strontium drug Protelos® is not approved for use as a bone drug, and it is not available here for purchase. In the U.S. and Canada, however, one can purchase equally high dose natural forms of strontium as strontium citrate or strontium carbonate and some companies promote bone support formulas with 680 mg elemental strontium (the same strontium dose as in the Protelos® strontium drug formula). Keep in mind that this high-dose strontium, be it natural strontium as sold in the U.S. or synthetic as in Protelos®, is best viewed as a “bone drug,” and, as with all bone drugs, it should be used with great caution. While the synthetic strontium drug (Protelos®) has been shown to carry serious adverse effects, to date there have been no studies on the safety or efficacy of high-dose (680 mg) natural strontium as sold here in the U.S.

Here at the Center for Better Bones our mission is to explore the full human potential for natural, life-long bone health. We strive to work with nature and in accord with nature when at all possible. The Better Bones, Better Body program includes small low doses of supplemental strontium, while not generally recommending the use of high-dose strontium (680 mg) or conventional bone drugs.

I hope this helps clear up the confusion when it comes to strontium. I will be writing more on strontium in the future, so stay tuned!

Best wishes to everyone.

References: 

2014 European Medicines Agency. PRAC recommends suspending use of Protelos/Osseor (strontium ranelate),Jan 10. EMA/10206/2014  http://www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_events/news/2014/01/news_detail_002005.jsp&mid=WC0b01ac058004d5c1

2014 European Medicines Agency. PRAC. Protelos/Osseor to remain available but with further restrictions. April 14, EMA 235924/2014

Strontium Ranelate

Strontium Ranelate

Dr. Susan E. Brown

3 types of medications that cause bone loss

/in /by

Are your medications dangerous to your bone health? While we all know that medications have some side effects, we may not recognize that certain medications, especially used long term, can seriously harm your bones.

Let’s look at the 3 most commonly used classes of medications known to increase fracture risk.

Which medications damage bone?

Corticosteroids. This class of drugs interferes with bone formation while simultaneously stimulating bone resorption, thus accelerating bone loss significantly.  At one point, scientists estimated that approximately 20% of all osteoporosis in the U.S. was the result of corticosteroid use, and it is estimated that up to 50% of patients using long-term oral corticosteroids will develop bone fractures.

While short-term, very occasional steroid use has less potential to weaken bone, longer-term use of oral and even inhaled steroids clearly jeopardize bone strength and increase fracture risk. Doses as low as 5 mg a day have been shown to increase fracture risk.

It is wise to seek alternatives to steroid therapy, use them when only truly necessary and for the shortest period  of time possible, and to fully support your bone health while using them to help offset the drug’s effects.

Common corticosteroids

    • Beclomethasone (inhaled)
    • Betamethasone (lotion or cream for skin)
    • Budesonide (oral capsule, inhaler and nasal spray)
    • Ciclesonide (inhaled)
    • Cortisone (oral, injection)
    • Dexamethasone (oral)
    • Ethamethasone (oral, injection)
    • Flunisolide (inhaled)
    • Fluticasone (inhaled)
    • Hydrocortisone (spray, liquid, lotion, gel, cream, ointment)
    • Methylprednisolone (oral)
    • Mometasone (inhaled)
    • Prednisolone (oral)
    • Prednisone (oral)
    • Triamcinolone (oral, injection)

 

Antacids

Antacids. Proton pump inhibitors such as esomeprazole (Nexium) and lansoprazole (Prevacid) are commonly used antacids. These antacid drugs powerfully reduce the production of stomach hydrochloric acid and thus likely weaken nutrient absorption.  Proton pump inhibitors have been repeatedly documented to increase the risk of hip, wrist and spine fractures.

H2 receptor antagonist drugs like cimetidine (Tagamet) and ranitidine (Zantac) are also used to suppress acid production, which suggests that they might impair nutrient absorption similarly. However, studies have suggested that they do not seem to increase fracture risk as do proton pump inhibitors. One reason may be that they work by blocking the action of histamine — a chemical released in immune responses. Histamine tends to promote bone resorption. So these drugs are less likely, long term, to promote bone loss. Even so, there are studies showing that bone loss occurs in people taking H2 receptor antagonists if they do not have good intake of specific key bone nutrients, such as calcium and Vitamin D.

Antidepressants

Antidepressants. A specific class of antidepressant medications called selective serotonin reuptake inhibitors (SSRIs) is associated with a significant increase in fracture risk. One study noted that there are some indicators that the medications have direct effects on bone, but they’re not well determined. However, the impact of SSRIs on balance and alertness are well established.

What it boils down to is this: if you take SSRIs, it’s important to look carefully at your bone health. Even in the absence of a direct effect on bones, falling is the primary cause of fracture in those with weakened bones.

Take action!

I realize that it’s not always possible to avoid these medications, but there often exist dietary and lifestyle changes and alternative medical approaches that go to the root of the disorder and reduce the need for bone-damaging medications.  Also, once you know your medication may harm your bones, you can take steps to protect your skeleton. Plus, by knowing what the medications are, you can talk with your practitioner to determine whether there are less bone-damaging alternatives and support your body’s natural healing processes as much as possible.

References:
Halpern MT, Schmier JK, Van Kerkhove MD, et al. Impact of long term inhaled corticosteroid therapy on bone mineral density results of a meta-analysis. Ann Allergy Asthma Immunol 2004;92:201-207.

Hodgson SF. Corticosteroid-induced osteoporosis. Endocrinol Metab Clin North Am 1990;19: 95-111.

Jones A, Fay JK, Burr M, et al. Inhaled corticosteroid effects on bone metabolism in asthma and chronic obstructive pulmonary disease. Cochrane Database Syst Rev 1, 2006.
Low Dose Steroids Can Increase Fracture Risk. Medsafe, NewZealand Medicines and Medical Devices Safety authority, 2017 http://www.medsafe.govt.nz/Profs/PUarticles/bone.htm

Vestergaard P, Rejnmark L, Mosekilde L. Proton pump inhibitors, histamine H2 receptor antagonists, and other antacid medications and the risk of fracture. Calcif Tissue Int. 2006 Aug;79(2):76-83. Epub 2006 Aug 15.

Warden SJ, Fuchs RK. Do selective serotonin reuptake inhibitors (SSRIs) Cause Fractures? Curr Osteoporos Rep. 2016 Oct;14(5):211-8. doi: 10.1007/s11914-016-0322-3.

Wiercigroch M, Folwarczna J. [Histamine in regulation of bone remodeling processes]. Postepy Hig Med Dosw (Online). 2013 Aug 26;67:887-95.

Yu EW, Bauer SR, Bain PA, Bauer DC. Proton pump inhibitors and risk of fractures: a meta-analysis of 11 international studies. Am J Med. 2011 Jun; 124(6): 519-526.doi: 10.1016/j.amjmed.2011.01.007

Yu EW, Blackwell T, Ensrud KE, Hillier TA, Lane NE, Orwoll E, Bauer DC. Acid-suppressive medications and risk of bone loss and fracture in older adults. Calcif Tissue Int. 2008 Oct;83(4):251-9. doi: 10.1007/s00223-008-9170-1. Epub 2008 Sep 24.

Zhou B, Huang Y, Li H, Sun W, Liu J. Proton-pump inhibitors and risk of fractures: an update meta-analysis. Osteoporos Int. 2016 Jan;27(1):339-347.

 

Dr. Susan E. Brown

New analysis looks at bone drug risks vs. benefits

/0 Comments/in /by

Wouldn’t it be valuable if there was one study to answer the important questions about bone drugs, including:

  • How effective are bisphosphonates?
  • How well do they actually work to prevent hip fractures?
  • What’s the possibility of harm from these bone drugs?

Now, there is one — thanks to researchers who conducted a detailed systematic analysis of clinical trials using bisphosphonate drugs to treat osteoporosis and prevent hip fractures.

Benefits vs. risks of bisphosphonates

Here are two striking numbers researchers discovered when looking at how bisphosphonates help or hurt the women who take them:

  • 175 postmenopausal women with bone fragility had to be treated for three years to prevent one single hip fracture.
  • Treating 300 people with bisphosphonate drugs for three years will result in one person being harmed from serious side effects.

What’s more, researchers noted that hip fracture rates in developed countries are declining, yet sales of bisphosphonate drugs tripled between 2001 in 2008 and are forecast to exceed $11 billion in 2015.

Also, while 80 is the average age at hip fracture, the evidence suggests no benefit from bisphosphonate bone drugs for this age group.

“Pharmacotherapy (for hip fracture prevention) can achieve at best a marginal reduction of hip fractures at the cost of unnecessary psychological harms, serious medical adverse events, and forgone opportunities to have greater impacts on the health of older people,” said Dr. Barbara Mintzes, one of the study authors.

I really appreciate that they took into account the psychological impacts of osteoporosis overdiagnosis, which is something I see often in my work.

Listen: The trouble with bisphosphonates

You can listen to Dr. Mintzes detail more about the research findings in the first 13 minutes of this interview that aired on Australian national radio titled “The trouble with bisphosphonates” here.

 

Reference:
Jarvinen, T.L., et al, Overdiagnosis of bone fragility in the quest to prevent hip fractures. BMJ 2015;350:h2088, 2015 May 26 (http://www.bmj.com/content/350/bmj.h2088)

Better Bones Blog
Dr. Susan E. Brown

Bisphosphonate bone drugs caught in compromising position

/0 Comments/in /by

JCEM

While you may not think to turn to The Journal of Clinical Endocrinology & Metabolism for breaking scandals, I recently saw troubling news about bisphosphonate bone drugs that I believe deserves some big headlines.

A new study shows that the popular bone drug therapy — Fosamax, Actonel, Boniva and Reclast — actually blocks the effectiveness of two natural bone builders.

Specifically, a team of international researchers showed there’s a vicious circle effect when it comes to the relationship between nitrogen – bisphosphonates and the levels of coenzyme Q10 (CoQ10) and vitamin E. In the case of CoQ10, the drugs compromise the metabolic pathways essential for its synthesis, resulting in lower levels in those using drugs. Plus, researchers suggested that the lack of the needed CoQ10 places additional demands on vitamin E, resulting in significantly reduced levels of that key antioxidant too!

If you don’t have the proper levels of CoQ10 and vitamin E in your body, here’s what your body is missing:

Benefits of vitamin E:

  • Protects essential lipids from oxidative damage body-wide.
  • Works synergistically with vitamin C for halting spinal bone loss in elderly women.
  • Low levels are associated with osteoporosis and low spinal bone density in early postmenopausal women.

Benefits of CoQ10:

  • Enhances immunity, and protects the heart and skeletal muscles.
  • Known to play a key role in cellular energy production and is found in nearly all cell membranes.
  • Works in conjunction with vitamin E to protect against free radical damage.
  • Inhibits the development of osteoclast bone-breakdown cells.

Remember that my intention #4 for 2014 is Sharing the truth about bone drugs. The more you know about bone drugs, the more you are empowered to make the right decision for your individual situation.

 

References:

Kalyan, S, et al. Nitrogen – bisphosphonate therapy is linked to compromise coenzyme Q 10 and vitamin E status in postmenopausal women. Jr Clin Endocrin, Jan 13, 2014 me

Xu. Et al. Vitamin E Stimulates trabecular bone formation and alters epiphyseal cartilage morphometry. Calcif Tissue Int. 1995 Oct; 54(4):293-300.

Chuin A, et al., Effect of antioxidants combined resistance training on BMD in elderly women: A pilot study.Osteoporosis Int., 2009, Jul; (20 (7):1253-8

Mata-Granados JM, et al. Lower vitamin E serum levels are associated with osteoporosis in early postmenopausal women: a cross-sectional study, J Bone Miner Metab 2013, Mar 28

Moon, H-J, et al., Coenzyme Q10 regulates osteoclast and osteoblast differentiation. Jr of Food Science, Vol. 78, issue 5, May 2013: H785-H791. DOI:http://dx.dol.org/10.1210/jc.2013-3648 Moon, H-j et al. Antioxidants, like CQ 10, selenite and curcumin inhibit osteoclast differentiation by suppressing reactive oxygen species generation. Biochem and Biophys Res. Comm. Vol 418, issue 2, Feb 10, 2012:247-253.