The next big new bone building drug has 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 research any new bone building drugs, 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.
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 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.
This study looked at 7180 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).
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.
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:
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.
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 bones today?
Reference:
Cosman, Felicia et al., Romosozumab treatment in postmenopausal women with osteoporosis. New England Journal of Medicine 2016;375:1532-1543.