Business Club May 27th, April 15th, the State Food and Drug Administration issued an adverse reaction information bulletin to report adverse reactions to bisphosphonate-induced jaw osteonecrosis, musculoskeletal pain, esophageal cancer, and renal failure. . Recently, both the NEJM Weekly and the JAMA have published research papers on the risk of bisphosphonate-induced fractures. At one time, the risk of bisphosphonate causing fractures has become the focus of scholars' attention.

Bisphosphonate causes fracture risk was confirmed

Drug bisphosphonates used to reduce the risk of brittle bones and the incidence of osteoporosis have been put into use since the 1990s. Bisphosphonates can reduce the viability of cells that cause bone fragility, thereby reducing fractures caused by brittle bones. However, it has been suspected for some time that bisphosphonates can cause other forms of fractures, such as fatigue fractures, because it can prevent the natural renewal of bones. Bones cannot be renewed, which in turn can cause certain types of bone cracks not to heal naturally.

Foreign scholar Pell Aspenberg and colleagues confirmed these speculations. They studied 12,777 women 55 years or older. Fifty-nine femur fracture subjects were diagnosed as fatigue fractures (often referred to as atypical femoral fractures). Of these 59 people, 78% used bisphosphonates. Research on these findings has been published in the New England Journal of Medicine (NEJM).

Prof Asperberger said: "At present, the international community is controversial about the side effects of bisphosphonates. The results of this study may lead to controversy. The link between bisphosphonates and fractures is very close. We believe that there is a causal relationship."

The study also pointed out that once patients stop using bisphosphonates, the risk of fatigue fractures will be reduced. After one year of withdrawal, the risk of fractures is reduced by 70%. "This may indicate that people should minimize the use of bisphosphonates and should conclude with this drug after several years of treatment." The conclusions of the research paper are expressed as such.

Swedish scholar Dr. Schilcher and co-authors conducted a review of the Swedish national patient registration records and found 12,777 women aged ≥55 years who suffered a femoral fracture in 2008. Of these, 1271 had a subtrochanteric or diaphyseal fracture. Researchers reviewed 1,234 women's X-rays. A retrospective study of these radiographs revealed 59 cases of atypical femoral fractures in this group of women. In 59 subgroups with atypical femoral fractures, 46 patients (about 78%) had used bisphosphonates.

Postmenopausal women are concerned about skeletal safety

According to the report of the Journal of the American Medical Association (JAMA), postmenopausal women taking bisphosphonates can increase the risk of subtrochanteric or femoral shaft fractures.

About 50% of women over the age of 50 experience osteoporotic fractures. Randomized trials have confirmed that taking bisphosphonates can reduce the risk of osteoporotic fractures. However, recent studies have shown that because bisphosphonates can inhibit bone remodeling and adversely affect bone strength, female long-term administration of bisphosphonates can cause subtrochanteric or femoral shaft fractures.

Dr. Laura Y., of the Li Ka Shing Institute, Michael Hospital, Toronto, Canada. Park-Wyllie and colleagues investigated the association of long-term administration of bisphosphonates with subtrochanteric or femoral shaft fractures in postmenopausal women.
The researchers identified a total of 205,466 women aged 68 years and older who were taking bisphosphonates continuously between April 2002 and March 2008 and were followed up until March 31, 2009. During the study period, 716 patients had subtrochanteric or femoral shaft fractures (411 cases with subtrochanteric fractures and 305 with femoral shaft fractures) when initially receiving bisphosphonate treatment.

The primary analysis found that patients who were on bisphosphonates for continuous treatment for 5 years or more were 2.7 times more likely to be hospitalized for patients with subtrochanteric fractures and femoral shaft fractures than patients on short-term bisphosphonates (over 100 days total). The secondary analysis investigated the risk of a typical osteoporotic fracture during treatment with bisphosphonates in 9,723 women. Patients who used bisphosphonates for more than 5 years had a 24% reduction in fracture risk compared to short-term users. Patients who took bisphosphonates for 3 to 5 years had a similar risk of fractures as patients who were 5 years old. In patients who took bisphosphonates for only 100 days to 3 years, the fracture risk was not significantly reduced. Further analysis showed that more than half of patients who used bisphosphonates for more than 5 years had subtrochanteric or femoral shaft fractures occurring after the fifth year of taking bisphosphonates. Of the 52,595 patients taking bisphosphonates for at least 5 years, 71 (0.13%) had sub-trochanteric or femoral shaft fractures within the 6th year of treatment, and 117 within the 2nd and 7th years of the 6th year. (0.22%).

The researchers stated that although the absolute risk of subtrochanteric or femoral shaft fractures is low, this conclusion demonstrates that prolonged bisphosphonate treatment may increase the risk of subtrochanteric or femoral shaft fractures. This also suggests that doctors should fully evaluate fracture risk when deciding whether patients need to use bisphosphonates for more than 5 years in order to ensure that the long-term users have the lowest risk of fractures. For patients who have been on bisphosphonates for more than five years, stopping the drug may be an appropriate method to reduce fractures, but further study is needed.

Finally, the researchers emphasized that this result also confirms the benefits of bisphosphonate treatment for the prevention of typical fractures and also provides evidence that bisphosphonate deficiency does not reduce the risk of fracture. Therefore, indications should not be prohibited. The patient took bisphosphonates.

Revenue still exceeds risk

Pell Aspenberg and colleagues, while writing in the weekly New England Journal of Medicine (NEJM), confirmed the risk of bisphosphonate fractures. However, he believes that the benefits of bisphosphonates far outweigh the side effects. He wrote in the article that the fundamental role of bisphosphonates is that it can greatly reduce the risk of osteoporosis-induced fractures. Therefore, even if there are side effects, only a small number of people and very little risk are involved. Bisphosphonates prevent far more fractures than they cause. All drugs have side effects and people should understand this. It is important to use medicine only when it is needed, and healthy people should not use medicine at will.

In addition, studies conducted by Dr. Schilcher and colleagues show that for patients with bisphosphonates, correction of atypical femoral fractures (a thorough horizontal fracture that can spread from the side with slight or no atraumatic) The relative risk after age is 47.3%. The crude incidence of this fracture in women who have not used this type of drug is 0.09 per 10,000 patient-years, and the crude incidence of this fracture in women who have used this type of drug is 5.5 per 10,000 patient-years. These results "should allow patients with bisphosphonates to feel at ease." The research leader, Schilcher, MD, of the Department of Experimental and Clinical Medicine, Faculty of Health Sciences, Linkoping University, Linkoping, Sweden, and colleagues, said, “With correct guidance, the role of this class of drugs in the prevention of fractures will far exceed its role. Induces atypical femoral fracture risk."

For the Swedish study, Dr. Sundeep Khosla, professor of medical physiology at the Mayo Medical Center in Lochester, Minnesota, chairman of the American Society of Bone Mineral Research (ASBMR), called the study very credible. The study not only included a lot of Participants conducted a study (incorporating a total of 1.5 million Swedish women aged 55 years or older in 2008) and also reviewed X-rays of almost all types of femoral fractures. (Reporter Chen Xi, according to "New England Journal of Medicine", "Journal of the American Medical Association", EU Drug Administration website information)