Calculator for Length of Use of Bisphosphonates (CLUB)

Osteoporotic fractures are a major public health problem, especially for older persons.
Bisphosphonates (BPs) are an inexpensive therapeutic class of drugs effective at preventing
these fractures. However, there has been a substantial decline in use of BPs for osteoporosis at
least in part because of concerns for rare, albeit potentially serious side effects, namely atypical
femoral fractures (AFF) and bisphosphonate medication related osteonecrosis of the jaw
(MRONJ). Duration of treatment is a risk factor for long-term side effects from BPs, including
AFF, and to a lesser extent, MRONJ. To assist with decision-making regarding duration of use
of BPs, the FDA and professional societies developed guidelines suggesting that after three to
five years of oral or three years of intravenous BP use, that reassessment of fracture risk with
possible provision of a drug holiday be done. However, these recommendations were based on
very limited evidence largely derived from white, healthy, community-dwelling postmenopausal
women. Moreover, the risk associated with drug holidays is uncertain, as emerging reports
suggest that a number of women have sustained osteoporotic fractures while off therapy. It is
paramount to better understand the risk-benefit profile of long-term BP therapy and drug
holidays, in both men and women, all races and ethnicities, and those with serious
comorbidities. To accomplish this, we have amassed an expert multidisciplinary team to study
large and diverse patient populations ranging from community dwelling to long-term care
residents from Kaiser Permanente (KP; Northern California, Georgia, and Mid-Atlantic regions),
Health Partners (HP; Minnesota), and the national Veterans Health Administration (VHA),
spanning 30 years (1996 to 2025) and including over half a million older U.S. adults who
initiated osteoporosis treatment with a BP. Utilizing this population, we will determine risks and
benefits, health care costs and cost effectiveness of uninterrupted continuation of BPs versus
BP drug holidays. These information will be utilized to develop a risk factor calculator to
determine if a drug holiday should be done (Calculator for Length of use of Bisphosphonates
(CLUB)). An expert panel including both clinician and consumer voices will inform the final
design of CLUB. We anticipate that CLUB will be a clinically useful point-of-care tool to guide
shared decision-making on BP use and optimize care for older patients at risk for fracture.

Grant Number: 3R01AG079118-04S1
NIH Institute/Center: NIH
Principal Investigator: LAURA CARBONE