Save Our Bones Bulletin: Positive Bisphosphonate Study Disproven, New Osteoporosis Drug On The Horizon, Major Changes To FDA Osteoporosis Drug Testing Guidelines

This month's Save Our Bones Bulletin tackles news about osteoporosis drugs and the pharmaceutical industry. We'll examine newly published studies to ensure that you have the most accurate and up-to-date information about bone health.

First we'll look at two studies with opposing findings about the relationship between bisphosphonates and mortality risk.

Then you'll get the latest breaking news about a potential new osteoporosis drug.

We'll end on an encouraging note. The FDA is finally acknowledging that bone quality is an essential metric of bone health. Read on to learn more about how its policies are changing and much more.

Study Debunks False Claim That Bisphosphonates Reduce Risk Of Premature Death

A pair of studies released earlier this year concluding that bisphosphonate use reduces mortality risk have been proven wrong by a meta-analysis. The latter is a report that compares the findings of a large number of existing studies.^1,2

The first study compared the lifespan of 6,000 individuals, divided into groups of bisphosphonate users and non-users. Based on that comparison, the researchers concluded that using bisphosphonates reduced the risk of premature mortality by 34%.¹

A follow-up study looked at the same data to consider the relationship between bone density and mortality risk. This study concluded that 39% of the reduction in premature mortality risk was due to a lower rate of bone loss.¹

However, a meta-analysis of 38 studies on bisphosphonate use completely contradicts the above studies, concluding that bisphosphonate use does not confer any benefit to mortality risk.²

Relevant Excerpt:

“The meta-analysis included 38 randomized placebo-controlled trials involving a total of 101,642 individuals, of whom 56,048 were treated with a pharmacologic therapy for osteoporosis while 45,594 were given placebo.

There was no significant difference in mortality rates among patients given an osteoporosis drug versus placebo, neither when all drugs were evaluated together (rate ratio [RR]=0.98) nor when the analysis was restricted to 21 trials of bisphosphonate treatments (RR=0.95).
Similarly, mortality rates were not significantly different among patients treated with zoledronate compared with placebo in six randomized trials, but Cummings et al note that “there was evidence for heterogeneity of the results.”

The current findings “suggest that observational studies reporting that patients receiving bisphosphonate therapy had lower mortality may not have measured confounding factors that may have contributed to lower mortality [risk],” they say.”²

The researchers of the pair of studies mentioned earlier failed to consider that their results were skewed by neglected factors. This mistake illustrates why any single study isn't enough to draw a clear conclusion. It's important to seek out high-quality studies with results that have been confirmed by further research.

Synopsis

A pair of studies that concluded that bisphosphonates reduce mortality risk were proven to be incorrect by a meta-analysis of 38 other, higher-quality studies.

Potential New Osteoporosis Drug In Research Phase

A research group at Duke University has isolated a compound that they intend to chemically reproduce in an attempt to create a new osteoporosis drug. It is called adenosine, and while we already knew about this compound, researchers have uncovered its role in osteoporosis. They performed studies concluding that adenosine encourages the production of bone, and that its levels decrease with age, and in particular with decreasing estrogen levels.

In experiments on mice, the researchers found that increasing adenosine levels enhanced bone production, but adenosine isn't a viable treatment.

Relevant Excerpt:

“The researchers then sought to see if they could undo the destructive effects of the disease by increasing the adenosine levels. Instead of pumping in adenosine itself, they injected a non-hormonal small molecule produced by Bayer that activates the A2B receptor.

Still, the challenge remains of creating a small molecule drug-specific enough to be free of side-effects. Adenosine is made naturally in the body and serves many functions that include neuron modulation and regulation of blood flow to various organs. Adenosine cannot simply be administered through the blood in an effort against bone degradation without flooding other parts of the body. Molecule specificity is key to minimizing side-effects.

At least with the A2B receptor singled out, Varghese and others can begin researching into ways to deliver activators that bind only to receptors in the bones. For example, one of Varghese's students has commenced methods to tether adenosine-like molecules to carriers that target bone tissue. Her lab is also pursuing a sort of bandage that can convey growth-supporting drugs straight to damaged or broken bones.”³

The potential side effects are already evident: brain damage and cardiovascular problems.³ The risk of those side effects isn't worth the expected benefits. The same is true of osteoporosis drugs currently prescribed. We already have natural treatments for preventing and reversing osteoporosis.

Synopsis

Researchers have isolated adenosine, a protein that encourages bone growth, but that decreases with reduced estrogen levels. They are attempting to synthesize a drug that will imitate the action of the protein on bone, but the potential side-effects of such a drug are unlikely to be safe or tolerable.

FDA Requires Bone Quality Assessment For Osteoporosis Drug Trials

On a brighter note, the FDA is finally recognizing the failure of osteoporosis drugs. After ignoring decades of clear evidence that osteoporosis drugs decrease the quality of bone, from now on the FDA will require pharmaceutical companies to conduct bone quality tests in addition to bone density tests as part of their drug trials.

Relevant Excerpt:

“In addition to the pharmacology and toxicology studies required to support development of a new drug or biologic, long-term nonclinical studies, including bone-specific pharmacologic and toxicologic endpoints to evaluate the effects on bone quality, need to be conducted in appropriate animal models,” FDA writes.

FDA says such studies are necessary due to concerns over long-term adverse effects of drugs on bone quality and because “there are no validated and reliable methods for the noninvasive assessment of bone quality in humans.”

The eight-page guidance finalizes a draft version issued for comment in June 2016 and includes minor changes to the agency’s recommendations for conducting bone quality studies as well as some reorganized sections.⁴“

The Save Institute has spent years disseminating scientific research showing that bone quality is a vital measurement of bone health that must be considered in addition to bone density. The FDA is sorely late in considering the full picture of bone health, but it's a step in the right direction. It remains to be seen if this shift will have a meaningful impact.

That's not the only change to current FDA policy in regards to osteoporosis. Below are the rest of the new guidelines:⁴

• For already approved osteoporosis treatments, additional animal studies may be required “depending on the level of scientific concern.”
• The final guidance lowers the initially recommended number of drug dose levels that should be investigated in the bone quality studies from three to two—a dose achieving an optimal pharmacological effect and a high dose. The low dose option will be optional.
• Clinical treatment study duration for animal trials is recommended to last the intended duration- adjusted for the difference between animal and human bone remodeling cycles. However, the final guidance still provides species recommendations that only equal three years of human exposure.
• Recommends that bone quality studies should be conducted in two animal species for drugs, and a single study for biologics (which are drugs derived from living organisms)
• For postmenopausal osteoporosis, bone quality studies are recommended to be conducted in ovariectomized rats and a larger ovariectomized nonrodent species.

Synopsis

The FDA will now require drug manufacturers to test their drugs' impact on bone quality, in addition to bone density.

Ignore The Drugs To Improve Your Bone Health

As Savers know, the best way to increase bone quality doesn't require FDA approval because it isn't a drug at all: it's the actions you take every day. That's why we created the Osteoporosis Reversal Program.

Instead of risking side-effects and, ironically, causing a loss of bone quality by taking drugs, choose to follow an 80/20 pH-balanced diet and practice bone-strengthening exercises on a regular basis.

These easy lifestyle changes will do more than just improve the quality of your bones- they will improve your overall well-being and quality of life.

References

¹ https://www.sciencedaily.com/releases/2019/08/190812155456.htm

² https://rheumatology.medicinematters.com/osteoporosis/bisphosphonates/meta-analysis-questions-osteoporosis-treatments-reduce-mortality/17097774

³ https://www.ibtimes.com/protein-could-reverse-bone-damage-osteoporosis-found-2817830

⁴ https://www.raps.org/news-and-articles/news-articles/2019/8/osteoporosis-fda-finalizes-nonclinical-developmen