The next step after anti-osteoporotic drug discontinuation: an up-to-date review of sequential treatment

Guañabens, Núria; Moro-Álvarez, M.J.; Casado, Enrique; Blanch-Rubiò, Josep; Gómez‐Alonso, Carlos; Díaz-Guerra, Guillermo Martínez; Pino-Montes, Javier del; Lamadrid, C. Valero Díaz de; Peris, Pilar; Muñóz-Torres, Manuel

doi:10.1007/s12020-019-01919-8

Cited by 28 publications

(12 citation statements)

References 95 publications

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“…The effect of denosumab discontinuation on fracture risk has been reviewed extensively. 21,60,61 Denosumab discontinuation is closely associated with a rebound effect, indicated increased BTM levels and the parallel loss of gained BMD within 6-24 months of discontinuation, as reported in several case reports, observational study, RCTs and post-hoc analysis of FREEDOM data. [62][63][64][65][66][67] Additionally, denosumab discontinuation also resulted in a higher risk of rebound-associated vertebral fracture, including multiple vertebral fractures.…”

Section: Discontinuation Of Denosumab and Fracture Riskmentioning

confidence: 89%

<p>A Review on the Role of Denosumab in Fracture Prevention</p>

Pang¹,

Low²,

Chin³

2020

DDDT

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Denosumab is a receptor activator of nuclear factor kappa-Β ligand inhibitor, which suppresses the bone resorption process to preserve bone mass. It is usually recommended to postmenopausal women and men with high fracture risk. With the recent publication of the results from FREEDOM study and its extension, the long-term effect of denosumab in preventing fragility fractures has been put forward. This review aims at summarising the evidence of denosumab in reducing fracture risk and its safety derived from clinical studies. Most of the evidence are derived from FREEDOM trials up to 10 years of exposure. Denosumab is reported to prevent vertebral and non-vertebral fractures. It is also proven effective in Japanese women, patients with chronic kidney diseases and breast cancer patients receiving antineoplastic therapy. Denosumab discontinuation leads to high remodeling, loss of bone mineral density and increased fracture risk. These negative effects might be preventable by bisphosphonate treatment. The safety profile of denosumab is consistent with increased years of exposure. In conclusion, denosumab is a safe and effective option for reducing fracture risk among patients with osteoporosis.

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Section: Discontinuation Of Denosumab and Fracture Riskmentioning

confidence: 89%

<p>A Review on the Role of Denosumab in Fracture Prevention</p>

Pang¹,

Low²,

Chin³

2020

DDDT

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“…The data on ON in pediatric cancer patients treated with bisphosphonates are limited. The frequency of ON in adult cancer patients treated with bisphosphonates is reported to be 0–6.7%, whereas patients without cancer treated with bisphosphonates for osteoporosis have a much lower frequency for ON of the jaw (0.01–0.025%) …”

Section: Discussionmentioning

confidence: 99%

“…The frequency of ON in adult cancer patients treated with bisphosphonates is reported to be 0-6.7%, whereas patients without cancer treated with bisphosphonates for osteoporosis have a much lower frequency for ON of the jaw (0.01-0.025%). 27,28 Several studies have reported an increased risk for osteoporosis and reduced BMD in survivors of early onset cancer. However, most of the studies concentrate on survivors of ALL or brain tumors and contain only a low number of subjects.…”

Section: Discussionmentioning

confidence: 99%

Diseases of renal function and bone metabolism after treatment for early onset cancer: A registry‐based study

Liuhto

Grönroos

Malila

et al. 2019

Intl Journal of Cancer

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Modern cancer therapy has led to a growing number of pediatric and young adult cancer survivors, who are prone to increased morbidities caused by the late effects of therapy. The aim of our study was to investigate pediatric and young adult cancer survivors' morbidity due to renal and bone metabolism diseases and especially to study bone metabolism in cancer survivors with renal disease. Patients were identified from the Finnish Cancer Registry, and the cohort consisted of 13,860, 5‐year survivors of cancer diagnosed below the age of 35 years. Healthy siblings were used as the comparison cohort. Information on the main outcomes was linked from the national Care Register for Health Care. Hazard ratios (HRs) comparing cancer survivors to siblings were calculated for various outcomes. The patient cohort was separated into two age groups, pediatric (0–19 years) and young adults (20–34 years). Significantly elevated HRs (p < 0.0001) in survivors were observed in both age groups for scoliosis (HR 1.6, 95% confidence interval [CI] 1.3–2.0), osteoporosis (HR 5.2, 95% CI 2.4–11.4), osteonecrosis (HR 12.7, 95% CI 5.4–29.7), nephritis (HR 1.9, 95% CI 1.5–2.2) and kidney failure (HR 3.6, 95% CI 2.4–5.3) for all. For cancer survivors with a renal outcome, the risk for developing any outcome of bone metabolism was increased (HR 2.3, 95% CI 1.4–3.6). These results show that pediatric and young adult cancer survivors have an elevated risk for long‐term, adverse outcomes related to renal function and bone metabolism. These results suggest follow‐up care for young cancer patients.

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“…Each reference was reviewed, and if necessary, the abstract or full text was reviewed as well to check whether the study met our inclusion criteria. Three recent reviews on this topic were also checked for relevant references [6][7][8]. With this criteria, eligible RCTs were found regarding alendronate, zoledronic acid, risedronate and teriparatide.…”

Section: Search Methodologymentioning

confidence: 99%

Bone Mineral Density Loss and Fracture Risk After Discontinuation of Anti-osteoporotic Drug Treatment: A Narrative Review

Elbers

Raterman

Lems

2021

Drugs

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The number of patients on long-term anti-osteoporotic drug therapy is rising. Unfortunately, there are few data to guide decisions about duration of pharmacologic therapy for osteoporosis. Many practitioners discontinue therapy after a period of 5 years because of the risk of rare but severe side effects that may occur in long-term users. The objective of this narrative review was to describe the effects of discontinuation of anti-osteoporotic drugs and to investigate what is not yet known on this topic. For each anti-osteoporotic agent, PubMed was searched for evidence from randomized clinical trials in patients with osteoporosis on osteoporotic drugs lasting ≥ 3 years, followed by ≥ 1 year of follow-up after discontinuation of therapy and reported at least one item of the following: changes in bone mineral density, bone turnover markers and/or the risk of vertebral and/or nonvertebral fractures after discontinuation of therapy. The% change in bone mineral density (BMD) after 1 year of discontinuation of therapy is − 0.4% or less at the hip and femoral neck in both alendronate-and zoledronic acid-treated patients. In the other reported agents (risedronate, ibandronate, raloxifene, teriparatide, denosumab and romosozumab) this percentage of bone loss at the femoral neck and total hip was at least 1%, with the largest decrease in BMD after discontinuation of denosumab and romosozumab. In all studies reporting bone turnover markers, a substantial rapid rise in these markers was observed after discontinuation of therapy, with a large rebound increase to far above baseline levels in the denosumab-treated patients. There were few data on fracture risk after discontinuation of therapy; data showed that discontinuing alendronate, zoledronic acid and especially denosumab significantly increases the risk of vertebral fractures. In conclusion, osteoporosis should be considered more as a chronic condition. Therefore, in modern fracture risk management, continuous monitoring and treatment is required, as is the case with other chronic diseases, to sustain the benefits of therapy, especially in denosumab-and romosozumab-treated patients. The exception is alendronate and zoledronic acid, in these patients a discontinuation of drug therapy of 1 year or more might be acceptable.

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The next step after anti-osteoporotic drug discontinuation: an up-to-date review of sequential treatment

Cited by 28 publications

References 95 publications

<p>A Review on the Role of Denosumab in Fracture Prevention</p>

<p>A Review on the Role of Denosumab in Fracture Prevention</p>

Diseases of renal function and bone metabolism after treatment for early onset cancer: A registry‐based study

Bone Mineral Density Loss and Fracture Risk After Discontinuation of Anti-osteoporotic Drug Treatment: A Narrative Review

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