Bisphosphonate Drug Holidays Research Articles

Bisphosphonate drug holidays in postmenopausal osteoporosis: effect on clinical fracture risk.

BPs are the most widely used treatment for postmenopausal osteoporosis. The optimal treatment duration, however, remains unclear. The purpose of this study was to evaluate the fracture risk in postmenopausal women with osteoporosis after discontinuing BP treatment (BP "drug holiday"). A retrospective analysis was performed at Lille University Hospital (LUH) on postmenopausal women with osteoporosis who had taken a "drug holiday" or continued treatment after first-line BP therapy (3 to 5years). The occurrence of new clinical fractures during follow-up was also explored. Cox proportional hazards models were used to investigate the relationships between BP "drug holiday" and the occurrence of clinical fractures, while controlling for confounding factors. Survival without new clinical fractures was analyzed using Kaplan-Meier curves and log-rank tests. One hundred eighty-three women (mean age: 61.8years; SD: 8.7) who had previously undergone BP treatment for 3 to 5years were enrolled in our study. The patients had received alendronate (n=81), risedronate (n=73), zoledronic acid (n=20), and ibandronate (n=9). In 166 patients ("drug holiday" group: n=31; continuous-treatment group: n=135), follow-up ranged from 6 to 36months (mean duration: 31.8months; SD: 8.2). The incidences of new clinical fractures during follow-up were 16.1% (5/31) and 11.9% (16/135). After full adjustment, the hazard ratio of new clinical fractures among "drug holiday" patients was 1.40 (95% CI: 1.12-1.60; p=0.0095). After first-line BP therapy in postmenopausal women with osteoporosis, the risk of new clinical fractures was 40% higher in subjects who took a bisphosphonate drug holiday.

Can bone turnover markers help to define the duration of bisphosphonate drug holidays?

Searchable abstracts of presentations at key conferences on calcified tissues ISSN 2052-1219 (online)

Can bone turnover markers help to define the duration of bisphosphonate drug holidays?

Searchable abstracts of presentations at key conferences on calcified tissues ISSN 2052-1219 (online)

Bisphosphonate Drug Holiday? Celebrate?: Commentary on article by Jordan C. Villa, MD, Arianna Gianakos, BS, Jospeh M. Lane, MD Bisphosphonate Treatment in Osteoporosis: Optimal Duration of Therapy and the Incorporation of a Drug Holiday.

Bisphosphonate Drug Holiday? Celebrate?: Commentary on article by Jordan C. Villa, MD, Arianna Gianakos, BS, Jospeh M. Lane, MD Bisphosphonate Treatment in Osteoporosis: Optimal Duration of Therapy and the Incorporation of a Drug Holiday.

The cumulative incidence of and risk factors for latent beaking in patients with autoimmune diseases taking long-term glucocorticoids and bisphosphonates.

The incidence of beaking, which has been reported to precede atypical femoral fracture, was high and increased over 2 years in patients with autoimmune diseases who were taking bisphosphonates and glucocorticoids. Regular femoral X-rays are strongly recommended to screen for beaking, and bisphosphonate drug holidays should be considered. Atypical femoral fractures (AFFs) have been recently recognized as complications associated with bisphosphonate (BP) use. AFFs are considered to be stress fractures; localized periosteal thickening of the lateral cortex is often present at the fracture site; this thickening is termed "beaking." Beaking has been reported to precede AFF. The aims of the present study were to evaluate the incidence of latent beaking in patients with autoimmune diseases taking BPs and glucocorticoids and to identify risk factors for beaking. A total of 125 patients with autoimmune diseases who were taking BPs and glucocorticoids was included; 116 patients underwent X-rays and analysis of serum and urine bone metabolic markers annually for 2 years. Mean patient age was 54.5 years; there were 105 (90.5%) females and the mean duration of disease was 13.2 years. Focal lateral cortical thickening in femoral X-rays was defined as beaking. Beaking was detected in 15 femora of 10 patients (8.0%) at the time of recruitment. Over the 2-year observation period, the incidence of beaking increased to 21 femora of 12 patients (10.3%), and a complete AFF at the location of beaking occurred in one patient. Beaking was associated with a longer duration of BP treatment (6.1 ± 1.0 years vs. 5.0 ± 2.9 years, p = 0.01). Age 40-60 years, BP therapy ≥4 years, and diabetes mellitus were significantly associated with beaking. The incidence of beaking was high, and increased over 2 years, in patients with autoimmune diseases who were taking BPs and glucocorticoids. Regular femoral X-rays are strongly recommended to screen for beaking. Long-term BP/glucocorticoid use was a risk factor for beaking in patients with autoimmune diseases; BP drug holidays should be considered.

Current approaches to osteoporosis treatment.

Osteoporosis is a skeletal disorder in which bone strength is decreased leading to an increased risk of fracture. In line with advances in knowledge of bone biology, the past several years have held major therapeutic advances in osteoporosis treatment. In this article, we review the current approaches to osteoporosis treatment with a focus on issues of interest to the practicing rheumatologist. In addition to the bisphosphonates, the introduction of denosumab, teriparatide and selective oestrogen-receptor modulators, as well as the development of new therapeutic agents (romosozumab and odanacatib) has opened the door to new approaches, including individualization of treatment in different clinical circumstances based on patient comorbidities and preference; combination therapy to optimize treatment effect; and consideration of goal-based treatment. Postmarketing surveillance of bisphosphonates has revealed several safety concerns including osteonecrosis of the jaw and atypical femoral fractures. Bisphosphonate drug holidays should be considered in patients on bisphosphonate therapy because prolonged treatment may be associated with adverse events. Substantial progress has been made in the past several years in the understanding and modification of osteoporosis management. Many conditions encountered by rheumatologists are associated with bone loss; therefore, the rheumatologist needs to be aware of the current approaches in osteoporosis management.

Bisphosphonate Drug Holiday and Fracture Risk

Background/Aims: Among women with ≥ 3 years exposure to bisphosphonates (BPs), we compared the incidence of fragility fractures in those who discontinued BPs for ≥ 12 months (drug holiday) to those who continued to use BPs (persistent use).

Position Statement: Drug Holiday in Osteoporosis Treatment with Bisphosphonates in South Korea.

Bisphosphonates have been widely used in the treatment of osteoporosis with robust data from many placebo-controlled trials demonstrating its efficacy in fracture risk reduction over 3 to 5 years of treatment. Although bisphosphonates are generally safe and well tolerated, concerns have emerged about the adverse effects related to its long-term use, including osteonecrosis of the jaw and atypical femur fractures. Because bisphosphonates are incorporated into the skeleton and continue to exert an anti-resorptive effect for a period of time after the discontinuation of drugs, the concept of a "drug holiday" has emerged, whereby the risk of adverse effects might be decreased while the patient still benefits from anti-fracture efficacy. As randomized clinical trial evidence is not yet available on who may qualify for a drug holiday, there is considerable controversy regarding the selection of candidates for the drug holiday and monitoring during a drug holiday, both of which should be based on individual assessments of risk and benefit. This statement will provide suggestions for clinicians in South Korea on the identification of possible candidates and monitoring during a bisphosphonate drug holiday.

AB0813 Bisphosphonate Drug Holiday from Patient Perspective - Beliefs and Attitudes

BackgroundBisphosphonates are widely prescribed and highly effective at limiting the bone loss in senile osteoporosis in both men and women. Although they are generally well tolerated, potential adverse effects may...

SAT0466 Bisphosphonate Drug Holiday: Results from the ESTRATOS Survey

BackgroundLong-term treatment with bisphosphonates (BP) has been associated with atypical femoral fractures and other complications, so some experts recommend a temporary discontinuation of these drugs in patients with osteoporosis who...

Bisphosphonate Drug Holidays and Fall Prevention in the Reduction of Postmenopausal Fractures

Bisphosphonates are commonly used as first-line agents in the treatment of postmenopausal bone fragility. Recently, concern has been raised regarding the risk of atypical fracture with long-term therapy. A potential solution to obtaining the benefits while minimizing the risks of bisphosphonate therapy is the use of a drug holiday, or temporary cessation of medication. For drug holidays to be an effective approach, patients must maintain fracture protection while off therapy. One way to optimize fracture protection during this time is to prevent falls. Risk of atypical fracture and bisphosphonate drug holiday will be discussed, along with a summary of the most effective fall prevention modalities.

Bisphosphonate drug holidays: Can we recommend currently?

Bisphosphonates (BP) are the mainstay of treatment for osteoporosis. Subtrochanteric or diaphyseal fractures have been reported with long term use of BP, which raised world-wide debate on two aspects, i.e., for how long the BP is to be given and potential advantages/role of BP drug holidays. BP accumulates in bone with some persistent protective effect after therapy is stopped endorses the concept. Theoretically, a drug holiday may be a considerable option to decrease risks of BP, which continuing the protection from fractures but the level of evidence and data supporting the concept of drug holidays is a week. Hence, no specific recommendations are available on BP drug holidays from major available treatment guidelines on postmenopausal osteoporosis. Hence, before it is recommended it requires more robust research in this field.

Bisphosphonate 休薬期間が抜歯窩治癒過程に及ぼす影響についての実験的研究

Bisphosphonate 休薬期間が抜歯窩治癒過程に及ぼす影響についての実験的研究

Postmenopausal osteoporosis

The aim of this study is to provide a thorough updated review of the diagnosis and treatment of postmenopausal osteoporosis. There have been several important findings in the field of postmenopausal osteoporosis over the past 1-2 years. Fewer morphometric vertebral fractures were found in women treated for 6 years with zoledronic acid compared with those who stopped treatment after 3 years. Longer duration of bisphosphonate therapy is associated with a higher risk of atypical femur fractures. Combination therapy with teriparatide and denosumab appears to increase bone mineral density to a greater extent than either therapy alone in postmenopausal women at high risk for fracture. There are several novel therapies under investigation for the treatment of osteoporosis, which are in various stages of development. Nonadherence to osteoporosis therapies continues to be a major problem in clinical practice. There are numerous effective pharmacologic treatment options for postmenopausal osteoporosis. Bisphosphonate drug holidays continue to be an area of significant debate.

Long-Term Follow-up of patients on Drug Holiday from Bisphosphonates: Real-World Setting

ObjectiveAtypical femoral fractures and osteoporosis of the jaw have been associated with prolonged bisphosphonate therapy for postmenopausal osteoporosis. American Association of Clinical Endocrinologists guidelines suggest a drug holiday after 4 to 5 years of bisphosphonate treatment for moderate-risk patients and 10 years for high-risk patients, but there are minimal data on safe holiday durations. A recent U.S. Food and Drug Administration perspective suggests a treatment duration of 3 to 5 years. Our aim was to describe a group of patients on drug holiday and identify fracture risk. MethodsA retrospective chart review was conducted of 209 patients who started a bisphosphonate drug holiday between 2005 and 2010. Collected data included bone mineral density (BMD), markers of bone turnover, vitamin D status, and clinical and radiographic reports of fractures. ResultsEleven of 209 patients (5.2%) developed a fracture. Their mean age was 69.36 years (±15.58), and the mean lumbar spine and femoral neck T-scores were −2.225 (±1.779) and −2.137 (±0.950), respectively. All patients had a significant increase in bone-specific alkaline phosphatase at 6 months, which was more pronounced in the fracture group (3.0 ± 0.6083 μg/L vs. 1.16 ± 1.9267 μg/L). Over 4 years, there was no significant change in mean lumbar spine BMD for the entire cohort, but there was a statistically significant decline in the femoral neck BMD at year 2 (−0.0084 ± 0.03 gm/cm2). ConclusionThe current practice of initiating BP holidays needs further evaluation, particularly in the real-world setting. Elderly patients and those with very low BMD warrant close follow-up during a drug holiday. A fracture, early significant rise in bone turnover markers, and/or a decline in BMD should warrant resumption of osteoporosis therapy. (Endocr Pract. 2013;19:989-994)

Bisphosphonate drug holiday: who, when and how long

Bisphosphonates have been widely used in the treatment of osteoporosis with robust data from numerous placebo-controlled trials demonstrating efficacy in fracture risk reduction over 3-5 years of treatment. Although bisphosphonates are generally safe and well tolerated, concerns have emerged about adverse effects related to long-term use. For most patients with osteoporosis, the benefits of treatment outweigh the risks. Because these agents accumulate in bone with some persistent antifracture efficacy after therapy is stopped, it is reasonable to consider a 'drug holiday.' There is considerable controversy regarding the optimal duration of therapy and the length of the holiday, both of which should be based on individual assessments of risk and benefit.

Bisphosphonate Drug Holiday: Choosing Appropriate Candidates

Osteoporosis related fractures contribute to morbidity and mortality in U.S. patients, placing a heavy financial burden on society. Randomized clinical trials involving over 30,000 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.

Risk of hip fracture after bisphosphonate discontinuation: implications for a drug holiday

Based upon interest in a bisphosphonate drug holiday, we evaluate the risk for hip fracture after bisphosphonate discontinuation. Among women compliant with bisphosphonates for > or = 2 years, the risk of hip fracture was increased after discontinuation, although with higher compliance and a longer duration of preceding bisphosphonate therapy, this risk was attenuated. Recent data suggest that hip fracture risk was not significantly increased among women receiving 5 years of bisphosphonate therapy who were subsequently randomized to placebo. We studied older women compliant with bisphosphonates > or = 2 years to evaluate the risk of hip fracture after bisphosphonate discontinuation. Using administrative databases from a large U.S. healthcare organization, we identified women initiating bisphosphonate therapy compliant (Medication Possession Ratio, MPR > or = 66%) for 2 years. We examined the rate of hip fracture among women who discontinued bisphosphonates versus those who remained on therapy. At 2 years, 9,063 women were eligible for analysis. Hip fracture incidence among women who discontinued bisphosphonates versus those who did not was 8.43 versus 4.67 per 1000 person years (p = 0.016). The adjusted hazard ratio of hip fracture per 90 days following discontinuation was 1.2 (1.1-1.3). For women with higher compliance at 2 years (MPR > or = 80%) or compliant for 3 years, there were no significant differences in risk associated with discontinuation. The rate of hip fracture was increased among women compliant with bisphosphonate therapy for 2 years who subsequently discontinued, suggesting that discontinuation is not advisable under these conditions. This association was attenuated with higher compliance and a longer duration of previous bisphosphonate therapy.