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Feature Story

Taking a ‘Drug Holiday’ to Avoid Bone Injuries

March 29, 2018



Three senior women smiling

Annette L. Adams, PhD, MPH, is committed to helping women avoid bone injuries that limit their mobility, and in some cases, end their lives.

During her eight years as a research scientist at the Kaiser Permanente Department of Research & Evaluation, in Pasadena, California, Adams’ interest in osteoporosis has led her to investigate many aspects of bone health, especially hip fractures and atypical femoral fracture, rare fractures of the thigh.

One of her studies, published this week in the Journal of Bone and Mineral Research, focused on bisphosphonates, a group of osteoporosis drugs. She wanted to know if women who took a “drug holiday” — or a strategic interruption in their medication treatment plan — from bisphosphonates had an increased risk of getting fractures.

The study was supported by the Kaiser Permanente Center for Effectiveness & Safety Research, a national center that leverages the expertise of Kaiser Permanente’s eight regional research centers and selected operational analytical groups to answer comparative effectiveness and safety questions that affect health and care delivery.

Annette L. Adams, PhD, MPH

Annette L. Adams, PhD, MPH

We recently talked with Adams about the study and the potential impact of its findings on patients and clinical care.

What did you investigate in this study?

The most commonly used treatments for osteoporosis are medications called bisphosphonates. They reduce the chance of fractures. Hip fractures are the most serious consequence of osteoporosis.

In the last 10 years, we’ve seen reports of rare but potentially serious problems associated with bisphosphonates, including atypical femoral fractures. These fractures seem to occur in younger, healthier women. There are many questions about the related risk factors, including who gets the fractures and how to prevent them. Researchers and clinicians have discussed the idea of stopping the bisphosphonates after women have gotten the maximum fracture protection. Our study looked at drug holidays for bisphosphonates and how they affected the risk of fractures.

Our study included more than 39,000 woman aged 45 years and older from five states that Kaiser Permanente serves. Each had taken bisphosphonates continuously for three years. We then compared fracture outcomes for women in the group who subsequently went for 12 months without bisphosphonates (the drug holiday group) to women who continued to use them regularly and to those who continued to use them intermittently.

What was the key finding?

Women who take a year-long holiday after three years of continuous bisphosphonate use don’t appear to be at any increased risk for osteoporosis-related fragility fracture, hip fracture, or fracture of the vertebrae of the spine, when compared to women who continue to use bisphosphonates regularly or women who continue to use bisphosphonates intermittently.

What does that mean for patients and clinicians?

The findings suggest that taking a break from bisphosphonates remains a reasonable option for some women. In some instances, this might mean having women switch to a different drug while continuing to closely monitor the potential for these atypical stress fractures.

Osteoporosis-related fractures are a big deal, especially hip and vertebral fractures. For many women, an injury can lead to loss of mobility or can be life threatening, even life ending. The more I learn about these fractures, the more I want to prevent them. The surgery and care are very costly in economic and human terms, and the injuries are largely preventable.

How did you decide to focus this specific topic?

A few years ago, the Kaiser Permanente Center for Effectiveness & Safety Research surveyed clinical leaders asking about comparative effectiveness or safety questions that are unanswered and could affect clinical practice. The center chose several topics, then found scientists who could work on the questions. This study came out of that process. It is a natural extension of work I had already been doing, so I was asked to lead the CESR study. It’s a nice example of how research scientists can interact with our care delivery system leaders and improve the care we offer patients. Research findings like these can influence organizational policy and practice.

It’s our hope that these findings will be considered by physicians as they make decisions about whether to implement drug holidays for some of their patients who have been on bisphosphonates for more than three years.

Co-authors on the study were: John L. Adams, PhD, Kaiser Permanente Center for Effectiveness & Safety Research, Pasadena, California; Marsha A. Raebel, PharmD, Institute for Health Research, Kaiser Permanente Colorado, Denver; Beth T. Tang, MA,  Kaiser Permanente Center for Effectiveness & Safety Research; Jennifer L. Kuntz, PhD, the Center for Health Research, Kaiser Permanente Northwest, Portland, Oregon; Vinutha Vijayadeva, PhD, MPH, the Center for Health Research, Kaiser Permanente Hawaii, Honolulu; Elizabeth A. McGlynn, PhD, Kaiser Permanente Center for Effectiveness & Safety Research; Wendolyn S. Gozansky, MD, MPH, Institute for Health Research, Kaiser Permanente Colorado.

About the Kaiser Permanente Southern California Department of Research & Evaluation
The Department of Research & Evaluation conducts high-quality, innovative research into disease etiology, prevention, treatment and care delivery. Investigators conduct epidemiologic research, health services research, biostatistics research, and behavioral research as well as clinical trials. Major areas of study include chronic disease, infectious disease, cancer, drug safety and effectiveness, and maternal and child health. Headquartered in Pasadena, California, the department focuses on translating research to practice quickly to benefit the health and lives of Kaiser Permanente Southern California members and the general public. Visit kp.org/research.

About Kaiser Permanente
Kaiser Permanente is committed to helping shape the future of health care. We are recognized as one of America’s leading health care providers and not-for-profit health plans. Founded in 1945, Kaiser Permanente has a mission to provide high-quality, affordable health care services and to improve the health of our members and the communities we serve. We currently serve more than 11.8 million members in eight states and the District of Columbia. Care for members and patients is focused on their total health and guided by their personal Permanente Medical Group physicians, specialists and team of caregivers. Our expert and caring medical teams are empowered and supported by industry-leading technology advances and tools for health promotion, disease prevention, state-of-the-art care delivery and world-class chronic disease management. Kaiser Permanente is dedicated to care innovations, clinical research, health education and the support of community health. For more information, go to: kp.org/share.