The next big new bone drug is about to 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 hear about a new bone drug, 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.
Question #1: What is 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 that 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 6600 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 benefitted, 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 facture. Among the 3327 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 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 bone today?
Cosman, Felicia et al., Romosozumab Treatment in Postmenopausal Women with Osteoporosis. New England Journal of Medicine
October 20, 016:375.532-1543.
Scientists have noticed that we tend to reflect the people we’re closest to — if our friends are optimists, it makes us more cheery, and if they have healthy lifestyle habits, we often improve our own. Large, long-term studies have begun decoding how social networks influence not only our moods but also our total health. Here’s what they found:
- The more social ties people have at an early age, the better their health at both the beginning and end of their life. Young people with a large social network over their life are less likely to have abdominal obesity, inflammation, and high blood pressure.
- Fewer social ties can lead to health problems. Social isolation increases risk of inflammation by the same amount as physical inactivity, and social integration protects against abdominal obesity.
- In middle adulthood what matters most is the amount of social support or strain provided by the social network. At this mid life stage, quality of the social network was more important than network size.
- In old age, social isolation is more harmful to health than diabetes with respect to hypertension risk.
Researchers also learned these things about happy people
- Happy people tend to be located in the center of their local social networks and in large clusters of other happy people.
- The happiness of an individual is associated with the happiness of people up to three degrees removed in the social network. For example, a friend who lives within a mile and who becomes happy increases the probability that you will be happy by 25%.
Happiness is, researchers suggest, a property of groups of people, and changes in individual happiness can ripple through social networks and generate large-scale change.
The happiness bottom line
We are social creatures, weaving social webs that influence our physical, emotional, psychological and spiritual well-being, similar to the Buddhist analogy of a jeweled net in which each jewel, representing one individual, is linked to all other jewels by a complex woven structure. Your actions, deeds, and thoughts influence the whole. Be the shining jewel that you are!
Yang Claire Yang et al., Social relationships and physiological determinants of longevity across the human life span. Proc Natl Acad Sci USA 2016;113(3):578-583.
Fowler JH, Cristakis N. Dynamic spread of happiness in a large social network: longitudinal analysis over 20 years in the Framingham Heart study. BMJ 2008;337:a2338.
Here is the scenario. A woman seeks my services, concerned and even fearful after having been told she has osteoporosis and should take a bone drug. We sit down and after a careful review of her case, I am led to ask, “What’s the real problem here? Is osteoporosis really the major issue?” Quite often, the answer is “no,” and then I ask, “Should we start by addressing bone, or is it more effective to start on another level?”
Here’s an example that reveals why:
Barbara came to consult with me about her doctor’s recommendation she should begin bone drugs. Barbara, a nurse, had suffered from an autoimmune disease for years that caused debilitating digestive issues. Between the ages of 47 and 50, she experienced an autoimmune flare that left her only able to eat a small amount of food at each meal. She became extremely debilitated and lost 25% of her body weight — and 14.9% of her spinal bone density — before she had identified dietary and lifestyle modifications that could quiet the autoimmune activity.
Her doctor’s insistence she use bone drugs was based on this rapid decrease in spinal bone density. But Barbara was now 53, her digestive issues were better, and her most recent DEXA showed only an insignificant loss in the spine — she’d even gained a bit in the hip.
Was osteoporosis really the problem to address first?
We realized that Barbara’s spinal bone density loss coincided with her serious, prolonged problem with esophageal spasms stemming from her autoimmune disorder and its related allergic responses. Rather than concentrate on her bones, it made more sense to address her autoimmune disorder, which was the likely root cause of her bone loss.
Changing our focus was also important because while Barbara’s bone density had stabilized and her digestion was better, she was still experiencing occasional esophageal spasms, palpitations, chest pain and fatigue. Any flare of these symptoms could lead to another bout of rapid weight and bone loss.
To help alleviate these concerns, I suggested Barbara undertake a partial elimination diet, alkalize her pH, use a few immune-enhancing and bone-building nutritional supplements, exercise and meditate daily. Within one month, Barbara reported she was feeling healthier and stronger than she had felt in the past six years. Our plan now is to undertake a comprehensive Better Bones, Better Body program for building both Barbara’s immunity and her bone strength. “Nourish the root to receive the fruit” is an ancient aphorism I keep in my back pocket — in this case to Barbara’s benefit.
Barbara’s happy to share my short video interview above with you. We both hope it will encourage each of you to look for the root causes of any excessive bone loss.