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?
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
Wrist fractures are “sentinels” of bone fracture risk; in fact, having a low-trauma wrist fracture may be more important than a diagnosis of osteoporosis in determining risk for subsequent hip fracture.
It makes perfect sense — when we fall, the reflex to throw out our hands and take the impact on the wrists protects our hips from being injured far more seriously. As we get older, that reflex isn’t as quick, and thus we have greater frequency of hip rather than wrist fractures.
So how do you know if your wrists are strong enough to stop your fall? And if they’re not — what do you do about it?
Get a grip on your grip strength
To start, figure out how strong your grip is. Grip strength is a marker of overall muscle strength. As studies have shown, muscle weakness as measured by grip strength is a predictor of unhealthy outcomes including cardiovascular and metabolic diseases, disability and even early mortality (Correia Martins et al., 2018).
One sign that your grip may be getting weaker is if you notice that opening jars is getting a bit harder. My favorite tool for measuring grip strength is a simple hand held-dynamometer. Simply squeeze the handle of this device as strongly as you can to measure your grip strength. Grip strength norms by age have been well established, so it is easy to see how yours compare (Massey-Westropp et al., 2011).
Exercise to strengthen your wrists
If your wrists aren’t as strong as you’d like, there’s certainly much you can do to change that. But first, understand that dominance has a profound effect on strength of the wrist and the bone mineral density of the wrist and forearm.
You might want to jot down the grip strength difference between your dominant and non-dominant arm and then exercise and non-dominant arm specifically to bring it up to the same strength level as a dominant arm. After all, we might have to stop a fall with either wrist, so we want to have both wrists as strong as possible.
Here are some basic exercise principles to strengthen your wrists:
- The impact of exercise is “site-specific” — that is, if you strengthen the muscles around the wrist, you will strengthen the wrist. That means that you need to load, and thus strengthen, all the muscles around the wrist and arm.
- Simply doing one type of exercise, such as a wrist curl, isn’t going to cut it. It only exercises one set of muscles, so you need to include wrist exercises that involve a full range of motion of the hand and wrist. See our exercise graphic below for ideas!
- As with all exercises, start slow and build up. You do not want to overdo it.
Maintain a healthy skeleton
Of course, your wrists don’t exist by themselves, floating in midair — and anything you do to support your overall bone and body health will certainly help your wrists too. So in addition to wrist-strengthening exercises, you can also do full-body workouts to strengthen your muscles and bones as well as focus on getting the full suite of bone-building nutrients and alkaline diet that support better bones and a better body.
Your wrists are the first line of defense against a fall, so why not give them a helping hand?
Correia Martins A, Moreira J, Silva C, et al. Multifactorial Screening Tool for Determining Fall Risk in Community-Dwelling Adults Aged 50 Years or Over (FallSensing): Protocol for a Prospective Study. JMIR Res Protoc. 2018 Aug; 7(8): e10304. Published online 2018 Aug 2. doi: 10.2196/10304
Massy-Westropp NM, Gill TK, Taylor AW, Bohannon RW, Hill CL. Hand Grip Strength: age and gender stratified normative data in a population-based study. BMC Res Notes. 2011; 4: 127. Published online 2011 Apr 14. doi: 10.1186/1756-0500-4-127
Bone responds to certain levels of physical strain in a really interesting way — it gets stronger.
Any type of strain on bone that applies enough impact or compressive pressure to stimulate new bone growth is called “osteogenic loading.” Our wise body constantly monitors strain, and in the brief moment of impact, when strain is enough to slightly stretch, bend or compress the bone matrix, this impact sends a warning message: high loads are coming, and the bones should grow stronger to carry them. This signal tells the bone-building osteoblast cells to increase their minerals uptake and build bone —which is why we emphasize the importance of having those minerals in your diet or using a well-constructed multivitamin like our Better Bones Builder.
Osteogenic loading basics
Even when just standing upright, the simple act of resisting gravity puts a load on bone, but this is a one that our body is well adapted to. To build stronger bones, a much higher load — that is, greater compression and bending — is needed to encourage our bodies to spend the necessary energy and resources.
The load put on bone can be measured in terms of multiples of body weight. The higher the load, the better able the activity is to stimulate bone growth. Calculations of multiples of body weight look like this for common physical activities:
Swimming: 0 (Your load is actually lessened in water.)
Brisk walking : 1–2
Power jumping: 4+
Resistance, strength training: 4 to 10 (Depending on impact.)
Safe impact training programs for osteogenic loading
Most physical activity loads bone to a degree, but for strong osteogenic stimulation, the load needs to reach around 4 times body weight.
At these higher multiples of body weight, however, safety becomes an issue. Any bone will succumb to fracture under loads that exceed its capacity. When training with high multiples of body weight, professional guidance is mandatory.
Simple ways to enhance your osteogenic loading
- If you have a desk job, stand frequently and walk, or stomp/skip around every hour.
- Walk more, walk faster, jog if you can.
- Practice stepping down stairs with a thud, or walk downhill.
- Do 100 heel drops.
- Turn up the music and kick up your heels in dance.
- Practice jump rope or 1- or 2-legged hopping or jumping, if your knees permit.
- Begin a strength training program, even in a moderate one. Many studies report a gain of both bone and muscle mass with regular resistance training done just twice a week.
I have seen uncounted clients gain significant bone density doing our full Better Bones, Better Program while amplifying our exercise component with serious strength training. We are now documenting a variety of successful exercise programs and will be detailing them to you in this weekly blog and on our new Exercise Evolution Channel. Not everyone is suited to lifting heavy weights, but everyone can and should work to increase muscle mass and bone strength.
Bone Health and Osteoporosis: A Report of the Surgeon General. Rockville, MD: U.S. Department of Health and Human Services, 2004.
Jaquish J, Singh R, Hynote E, Conviser J. Osteogenic Loading: A New Modality to Facilitate Bone density Development. A: Jaquish Industrial Research, LLC, 2017.
Westcott W. Resistance training is medicine: effects of strength training on health. Current Sports Medicine Reports July/August 2012;11:4P209216.