Pathways to Prevention (P2P) Program
Appropriate Use of Drug Therapies for Osteoporotic Fracture Prevention
New Workshop-Related Funding Opportunities
RFA-AG-22-018 and NOT-AR-21-006 encourage more intensive analysis of the risks and benefits of long-term osteoporosis treatment.
More than 10 million people in the United States have osteoporosis1, a skeletal disorder that causes bones to become weak and fragile as a result of low bone mass. The condition makes people more susceptible to fractures, which can impair their ability to live independently and even threaten their lives2. The social and economic burden of osteoporotic fractures is substantial3. Reducing osteoporosis prevalence and hip fracture incidence are among the major objectives of Healthy People 2020, the U.S. Department of Health & Human Services’ national health promotion and disease prevention initiative.
Lifestyle changes—including getting adequate nutrition and regular exercise, quitting tobacco use, limiting alcohol use, and preventing falls—can help reduce a person’s risk of osteoporotic fractures. However, medications may be prescribed to prevent fractures if a person has very low bone mineral density or has experienced a prior fragility fracture.
The U.S. Food and Drug Administration has approved several types of drugs to prevent osteoporotic fractures. Clinical guidelines by various medical organizations recommend bisphosphonates (BPs) as a first line of treatment for most people who have osteoporosis. BPs are effective for short-term use (up to 3–5 years) by people who are at high risk of fracture. However, the benefits and risks of longer-term treatment are less clear. Reports of rare but serious adverse events such as atypical femoral fractures and osteonecrosis (death of cells) of the jaw have raised questions about the safety of osteoporosis drug use, especially in people who use the drugs for more than 3–5 years or who had a low risk of fracture when they began treatment.
There is a gap in scientific data about the appropriate long-term use of many osteoporosis drugs. There are uncertainties about which people will benefit or may be harmed if they take the drugs long-term. Public concern about these and other unanswered questions has coincided with a significant decrease in use of osteoporosis drugs and a leveling off in what had been a promising decline in the incidence of osteoporotic fractures4,5. These changes have raised concerns within medical and professional communities that many people who might need the drugs are not being prescribed them, and those who are prescribed them are not taking them.
In addition, evidence is limited regarding the initiation and length of “drug holidays” (a medical practice in which a patient stops taking medications for a period of time and then resumes treatment again, if the patient or their doctor believes it could be in their best interests), whether stopping treatment reduces the risk of serious adverse events while maintaining fracture prevention benefit, and which individuals should change treatments instead of simply taking a drug holiday from their current medication.
Innovative research strategies are needed to address these knowledge gaps and to help better inform individuals and physicians in their decision-making about osteoporosis treatment.
This P2P workshop assessed the available scientific evidence to better understand the appropriate use of drugs for osteoporotic fracture prevention, specifically addressing the following questions:
- What are the benefits and risks (including major adverse events) of osteoporotic drugs with short-term use (from first-use up to 3–5 years of treatment)? What factors influence outcomes?
- What are the benefits and risks of osteoporotic drugs over the longer term (for treatment periods longer than 3–5 years)? What factors influence outcomes?
- Do drug holidays improve outcomes?
- What patient and clinician factors impact the use of and adherence to osteoporotic drugs?
Sponsoring Institutes, Centers, and Offices
The workshop was co-sponsored by:
- National Institute of Arthritis and Musculoskeletal and Skin Diseases
- National Institute on Aging
- NIH Office of Disease Prevention
1Wright NC, Looker AC, Saag KG, et al. The recent prevalence of osteoporosis and low bone mass in the United States based on bone mineral density at the femoral neck or lumbar spine. Journal of Bone and Mineral Research. 2014;29(11):2520–2526. doi: 10.1002/jbmr.2269.
2Sattui SE, Saag KG. Fracture mortality: associations with epidemiology and osteoporosis treatment.Nature Reviews. Endocrinology. 2014;10(10):592–602. doi: 10.1038/nrendo.2014.125.
3Burge R, Dawson-Hughes B, Solomon DH, et al. Incidence and economic burden of osteoporosis-related fractures in the United States, 2005-2025. Journal of Bone and Mineral Research. 2007;22(3):465–475. DOI: 10.1359/jbmr.061113.
4Wysowski DK, Greene P. Trends in osteoporosis treatment with oral and intravenous bisphosphonates in the United States, 2002-2012. Bone. 2013;57(2):423–428. doi: 10.1016/j.bone.2013.09.008.
5Michael Lewiecki E, Wright NC, Curtis JR, et al. Hip fracture trends in the United States, 2002 to 2015.Osteoporosis International. 2018;29(3):717–722. doi: 10.1007/s00198-017-4345-0.