Bisphosphonate Drug Holiday: Choosing Appropriate Candidates

Abstract

Osteoporosis related fractures contribute to morbidity and mortality in U.S. patients, placing a heavy financial burden on society. Randomized clinical trials involving over 30000 subjects have established bisphosphonates’ efficacy in reducing the incidence of fragility fractures. However, as bisphosphonates are retained for years in the skeleton, reports of adverse events from prolonged use are surfacing in the literature, namely, esophageal cancer, atrial fibrillation, osteonecrosis of the jaw, and atypical fracture development. The concept of a drug holiday has been proposed to potentially reduce incidence of these adverse events. This review will highlight the benefits and risks of bisphosphonate therapy and discuss the extension data available from the bisphosphonate trials. As randomized clinical trial evidence is not yet available on who may qualify for drug holiday, this review will provide suggestions for clinicians on identification of possible candidates and monitoring during a bisphosphonate drug holiday.

“Bisphosphonates: Possible Modes of Action and Implications for Dental Implant Treatment. A Review of the Literature”

“…Those who discontinued alendronate experienced a reduction in BMD without an increase in non-vertebral fractures though the risk of clinically recognised vertebral fractures was higher compared with the continuous users. In the continuous user (Alendronate group), the effect of alendronate/ placebo for 10 years was positive with 1-3% increase in BMD, compared to a 5-10% loss in untreated women of similar age [22,95]. In this study markers of bone turnover gradually increased after discontinuation but remained lower than baseline even after 5 years without alendronate [22].…”

“…Existing dental prostheses should be assessed carefully and proposed dental prostheses carefully designed. Mucosal breakdown is the second most common reason for the development of BRONJ lesions [95].…”

Effects of sequential osteoporosis treatments on trabecular bone in adult rats with low bone mass

“…Clinical studies of fracture risk that include a bisphosphonate drug holiday have reported that fracture risk may rise, leading to recommendations that drug holidays be limited to patients with low or moderate fracture risk [29] and then only with intermittent monitoring for bone loss or fracture [30]. Our results show that despite better bone mass and microarchitecture in the drug holiday group than in untreated OVX rats, bone strength is not better.…”

Role of the Pharmacist in Medication Therapy Management Services in Patients With Osteoporosis

“…Figure 8 provides a modified example of such an algorithm that has been proposed by bone health specialists. 41 CONCLUSIONS Treatment of chronic disease states, including osteoporosis, requires careful monitoring. The risk versus benefit of a therapy must be continually evaluated to determine the appropriateness of continued treatment.…”