The Better Bones Blog

by Dr. Susan Brown, PhD.

prolia-blockbuster or bust?

Prolia for Bone Fractures — I’m Still Not Impressed

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.

Is a 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 it just doesn’t work.


Anastasilakis AD, Polyzos SA, Makras P, Aubry-Rozier B, Kaouri S, Lamy O. Clinical features of 24 patients with rebound-associated vertebral fractures after denosumab discontinuation: systematic review and additional cases. J Bone Miner Res. 2017 Jun;32(6):1291-1296. doi: 10.1002/jbmr.3110. Epub 2017 Mar 13.

Cummings SR, Ferrari S, Eastell R, Gilchrist N, Jensen JB, McClung M, Roux C, Törring O, Valter I, Wang AT, Brown JP. Vertebral fractures after discontinuation of denosumab: a post hoc analysis of the randomized placebo-controlled FREEDOM Trial and its extension. J Bone Miner Res. 2017 Nov 4. doi: 10.1002/jbmr.3337. [Epub ahead of print]

Lamy O, Gonzalez-Rodriguez E, Stoll D, Hans D, Aubry-Rozier B1. Severe rebound-associated vertebral fractures after denosumab discontinuation: 9 clinical cases report. J Clin Endocrinol Metab. 2017 Feb 1;102(2):354-358. doi: 10.1210/jc.2016-3170

Polyzos SA, Terpos E. Clinical vertebral fractures following denosumab discontinuation. Endocrine. 2016 Oct;54(1):271-272. Epub 2016 Jul 8.

Popp AW, Zysset PK, Lippuner K. Rebound-associated vertebral fractures after discontinuation of denosumab-from clinic and biomechanics. Osteoporosis Int. 2016 May;27(5):1917-21. doi: 10.1007/s00198-015-3458-6. Epub 2015 Dec 22.

Zanchetta MB, Boailchuk J, Massari F, Silveira F, Bogado C, Zanchetta JR. Significant bone loss after stopping long-term denosumab treatment: a post FREEDOM study. Osteoporosis Int. 2017 Oct 3. doi: 10.1007/s00198-017-4242-6. [Epub ahead of print]

interval training for better bones

Take a minute for your health in the new year

I’m a big believer that any step you take to improve your health, no matter how minor it may seem, can have profound effects on all the body’s interconnected systems.

Case in point: a recent study on interval training found that exercising a few times week for 10 minutes — with just 60 seconds of maximal effort per session — was enough to boost insulin sensitivity, cardiorespiratory fitness, and skeletal muscle strength.

In the study, the researchers took an interval training regimen developed some years ago that used 20 to 30 minutes of cycling per session and pared it down to a 10-minute program to see if the benefits could be obtained with even less time commitment. Over the course of 12 weeks, previously sedentary men engaged in interval training 3 times per week for 10 minutes per session. Their workouts consisted of:

  • 2 minutes of low-intensity cycling followed by a maximum-effort burst lasting 20 seconds (performed 3 times)
  • A 3-minute cool-down to end the session.

Meanwhile, a continuous training group did a 2-minute warm up, followed by 45 minutes of cycling at 70% max heart rate, then a 3-minute cool down.

Just 60 seconds is all it takes

The astonishing conclusion was that the sprint interval training regimen — a total time commitment of 30 minutes per week, with just 60 seconds of maximal effort per session — was as effective as 150 minutes per week of moderate-intensity continuous training. And more amazing is that benefits were seen across the board — increasing insulin sensitivity, cardiorespiratory fitness, and skeletal muscle mitochondrial content. (I should note here that although this particular study was done with men, other research suggests interval training has a similar effect among women.)

This is an absolutely incredible finding! It reinforces the idea that even a small commitment of time and effort and can have big benefits. So go all out for a minute to improve your bone health — and total health — this year!

Gillen JB, Martin BJ, MacInnes MJ, et al. Twelve weeks of sprint interval training improves indices of cardiometabolic health similar to traditional endurance training despite a five-fold lower exercise volume and time commitment. PLoS One. 2016 Apr 26;11(4):e0154075. doi: 10.1371/journal.pone.0154075.

how do you want to be, feel, and look in 2018?

2018: The Year of Deliberate Creation

On these long winter nights, my attention is often drawn inward. Cozying up to a blazing wood stove, I am ready for my favorite topic of contemplation:

“Knowing that my choices will determine my life experience, what life experiences and personal transformation do I want in 2018? More important, what deliberate actions am I willing to take to achieve my goals?”

As the new year begins, I encourage you to take advantage of these quiet winter nights to answer your own soul-searching questions:

  • How do you want to be, feel and look in the coming year?
  • Have you joined the critical mass of women taking responsibility for their health, perhaps starting with bone health?
  • The ancient Chinese proverb notes, “If we keep going in the same direction we will end up right where we are headed.” Where are you headed, and is that the direction you want?

As for me, I’m using the winter’s quietude to reset my sights and plant new seeds, knowing that after a few months of rest, these uplifting initiatives will sprout, bringing joy, growth, and fulfillment in 2018.

Here’s my plan for 2018:

  • Working with my colleagues at the Center for Better Bones, we will build an even stronger, more informed tribe of women willing and able to take charge of their bone and overall health.
  • I will share my knowledge with women worldwide so they may do what women have done throughout the ages: protect and nurture the fires of health and well-being.
  • I’ll offer a new weekly “Wisdom” social media posting for you to consider, respond to, and share with others. Together we can create an uplifting, positive energy capable of moving everyone forward.
  • My dedicated team at the Center for Better Bones will make our time-tested Better Bones, Better Body Program more affordable and available to every interested woman through our new community online classes. (More on this coming soon!) Together we’ll transform both the way women themselves,and the medical profession, view and treat bone health concerns.
  • Finally, in a spirit of sisterhood and joy, we at the Center for Better Bones are offering “Love Your Bones, Love Your Life,” our first ever 4-day education/inspiration retreat in North Myrtle Beach, South Carolina, March 2018. (Learn more.) Don’t worry if you can’t attend this time… there will be other retreats!

New Year’s is a logical time of year to appreciate your personal growth and plan for the coming year. I invite you to join me as we create Better Bones and a Better Body in 2018. I’ll be here to support you all along the way.

Together will rewrite the book on women’s bone health!

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