Atypical fractures of the femur can occur with bisphosphonate drugs, but the benefits exceed the risk. Evenity reduces the risk of vertebral fractures, but it does not significantly reduce the risk of hip or wrist fractures. Other drugs do.
I recently got an email from a woman who is 70 years old and is being treated for osteoporosis. Her rheumatologist had recommended Evenity injections (romosozumab) after she had failed to improve with Fosamax, Reclast or Prolia. When she read a newsletter by Al Sears, MD, she became confused and didn’t know what to think. She asked for a consultation and wanted to know my fee. I told her I am retired and no longer see patients, but I offered to look into Evenity and evaluate the research on its safety and efficacy.
Evenity (romosozumab) is an anabolic sclerostin inhibitor that stimulates bone formation and decreases bone resorption. It requires monthly injections. It carries a black box warning about increased risk of heart attacks, strokes, and cardiovascular death. There are many drugs available to treat osteoporosis. They were reviewed in The Medical Letter in the July 13, 2020 issue (#1602, subscription required). In clinical trials, Evenity was more effective than alendronate in reducing vertebral and clinical fractures and more effective than teriparatide in increasing hip bone mineral density. They concluded that it could be considered for initial treatment of women at very high risk of fracture.
Dr. Sears’ newsletter said that the FDA had rejected Evenity two years earlier, because it provided only a modest improvement in reducing bone fractures and because clinical trials had shown it increased the risk of heart attacks, strokes, and cardiovascular death. Why did it decide to reverse course and approve the drug now? He claims it was because the Big Pharma company’s existing osteoporosis drug’s patent was about to expire and they would lose billions in profits when it went generic, so they needed a new money-maker. Evenity was their solution; it would cost $22,000 a treatment.
His information is questionable. According to the company’s website, the list price is $1,825 per month, and financial assistance is available. (I don’t know where he got the $22,000 figure; he doesn’t tell us.) And the FDA doesn’t base its approval on a company’s desire for profits. In this case, it based its approval on a re-submitted application for a narrower patient population: postmenopausal women with osteoporosis who carry a high risk of fracture, or patients who have failed or are intolerant to existing osteoporosis therapies. Natalie Grover has a better description of what actually happened.
Sears says for years he has been warning patients to stay away from these “bone-building” drugs. He says they don’t work, and there are safer alternatives.
He explains osteoporosis as a result of an imbalance between the osteoclasts that break down bone and the osteoblasts that deposit new bone. He says the bisphosphonate drugs kill osteoclasts so they can’t remove more bone. They do that, and your bones become denser, but the denseness is made up of old bone and old calcium (what?). He says the osteoblasts won’t make new tissue if the old tissue is still there, so your bones become brittle and more prone to fracture. They look strong on a scan, but in reality they are weak and fragile. These drugs cause the exact thing they are supposed to prevent: broken bones. (Really? But weren’t they approved by the FDA because studies showed they reduced the incidence of fractures?) The reference he cites is “Atypical Fractures of the Femoral Diaphysis in Postmenopausal Women Taking Alendronate” by Lenart et al. published in 2008 in The New England Journal of Medicine. It was not a peer-reviewed study, but only a letter to the editor. It reported on 15 patients who had “low energy” fractures occurring in a fall from a standing height or less. They found a unique radiographic pattern of cortical thickening in 10 of the 15 patients; those patients had been taking alendronate for longer (7.3 years) than the 5 patients who lacked that pattern (2.8 years). They called for additional studies. Sears’ description of this reference is simply wrong. He says it was a study of women taking alendronate who “had experienced some sort of fracture” and that 65% had the same rare fracture of the middle of the thigh bone, a place where people rarely get a fracture. That’s such a completely false misrepresentation that I found it hard to believe that Dr. Sears had actually read the article and understood it.
A 2020 study by Black et al., “Atypical Femur Fracture Risk versus Fragility Fracture Prevention with Bisphosphonates” was subsequently published in The New England Journal of Medicine. It said bisphosphonates were effective in reducing hip and osteoporotic fractures, but that concerns had been raised over atypical femur fractures in women taking the drugs. They followed 196,129 women for ten years; 277 women had atypical femur fractures. The risk increased with the duration of bisphosphonate use, rapidly decreased after bisphosphonate discontinuation, and was greater in Asians than in Whites. In their conclusion, they stressed that the absolute risk of atypical femur fracture remained very low as compared with reductions in the risk of hip and other fractures.
The advantage of Evenity is that it works more quickly than other drugs. It is intended for short-term use – 12 months – to reduce risk in patients with imminent risk of fracture, to be followed by an antiresorptive drug such as Prolia. Unfortunately, it does not reduce the risk of non-vertebral fractures (hip and wrist, which are the most consequential complications of osteoporosis). Other drugs (Tymlos and Forteo) reduced the risk of non-vertebral fractures by 43-53%, while Evenity showed only a non-significant reduction of 25%. Both Tymlos and Forteo require daily dosing compared to Evenity’s once-a-month injections, and both of them also carry black box warnings – for osteosarcoma – but these are based on animal studies and not verified in humans.
Side effects of Evenity
In addition to the black box warnings, the company’s website lists these other risks of Evenity treatment: serious allergic reactions, low calcium levels, osteonecrosis of the jaw bone, and unusual thigh bone fractures. But they say the most common side effects are joint pain and headaches.
What does Dr. Sears recommend?
He dismisses prescription drugs, claiming that there are safer alternatives. He offers the “Big 3” bone strength boosters: vitamin D3, boron, and vitamin K2, which he calls “bone glue.” He cites references, but they are far from convincing and don’t say what he seems to want us to think they say. And of course, there are no controlled clinical studies comparing drugs to Dr. Sears “Big 3” for preventing osteoporotic fractures.
Who is Dr. Sears?
Should we believe Dr. Sears? He is an MD, but he says a lot of things that don’t make sense. He misrepresents the references he cites so badly we can only wonder if he actually read them. He practices integrative medicine and bills himself as America’s #1 anti-aging authority. Integrative medicine is a mish-mash of ideas that are based on science and ideas that are not. As Mark Crislip famously said, “If you integrate fantasy with reality, you do not instantiate reality. If you mix cow pie with apple pie, it does not make the cow pie taste better; it makes the apple pie worse.”
Conclusion: Sears is not a credible source of information
IMHO, my correspondent can safely disregard the statements in Dr. Sears’ newsletter that confused her. She would be better off trusting the advice of a science-based rheumatologist who is familiar with her case.