Persistence at 12 months with denosumab in postmenopausal women with osteoporosis: interim results from a prospective observational study

Silverman, Stuart L.; Siris, Ethel S.; Kendler, David L.; Belazi, Dalila; Brown, Jacques P.; Gold, Deborah T.; Lewiecki, E. Michael; Παπαϊωάννου, Αλεξάνδρα; Simonelli, Christine; Ferreira, Irene; Balasubramanian, Akhila; Dakin, Paula; Ho, Pei-Ran; Siddhanti, Suresh; Stolshek, Bradley S.; Recknor, Chris

doi:10.1007/s00198-014-2871-6

Cited by 54 publications

(64 citation statements)

References 33 publications

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“…Notably, 1-year persistence of 70 % was reported for the one injectable therapy included in the SARA study (parathyroid hormone). Furthermore, two large observational studies of women with PMO treated in routine practice in North America and Europe have reported 1-year persistence with 6-monthly subcutaneous denosumab of 82 and 87-95 %, respectively [25,26]. These data support the high 1-year persistence observed in this study for parenteral treatments (74 %), particularly for the less frequently administered parenteral therapies, such as those administered half-yearly (81 %).…”

Section: Discussionsupporting

confidence: 82%

“…Research into the relationship between such factors and clinical outcomes is becoming increasingly important. Long dosing intervals and injectable formulations are thought to contribute to better persistence and compliance, which may in turn lead to improved clinical outcomes [12,14,[23][24][25][26]. To date, few studies have followed patients longitudinally to assess the impact of persistence, compliance and other known risk factors on clinical outcomes such as fracture, hospitalization and death.…”

Section: Introductionmentioning

confidence: 99%

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A Retrospective Longitudinal Database Study of Persistence and Compliance with Treatment of Osteoporosis in Hungary

Lakatos

Takács

Marton³

et al. 2015

Calcif Tissue Int

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This study assessed persistence and compliance with anti-osteoporosis therapies, and associations between compliance and clinical outcomes (fracture, fracture-related hospitalization and death), in Hungarian women with postmenopausal osteoporosis. The study used the Hungarian National Health Insurance Fund Administration database and included women with PMO aged at least 50 years, for whom a prescription for anti-osteoporosis medication had been filled between 1 January 2004 and 31 December 2013 (index event). Persistence (prescription refilled within 8 weeks of the end of the previous supply) was evaluated over 2 years; good compliance (medication possession ratio ≥ 80 %) was evaluated at 1 year. Associations between compliance and clinical outcomes (data collected for up to 6 years) were assessed with adjustment for baseline covariates. A total of 296,300 women met the inclusion criteria (524,798 index events). Persistence and compliance were higher for less frequent and parenteral therapies (1- and 2-year persistence: half-yearly [parenteral] vs. daily/weekly/monthly [oral and parenteral], 81 and 38 % vs. 21-34 and 10-18 %, respectively; parenteral vs. oral, 75 and 36 % vs. 32 and 16 %; good compliance: half-yearly vs. daily/weekly/monthly, 70 vs. 24-39 %; parenteral vs. oral 78 vs. 36 %). Good compliance significantly reduced the risks of fracture, fracture-related hospitalization and death (relative risk vs. non-compliance [95 % confidence interval]: 0.77 [0.70-0.84], 0.72 [0.62-0.85] and 0.57 [0.51-0.64], respectively; P < 0.01). Improving compliance through long-interval parenteral therapies may result in clinical benefits for patients.

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Section: Discussionsupporting

confidence: 82%

Section: Introductionmentioning

confidence: 99%

A Retrospective Longitudinal Database Study of Persistence and Compliance with Treatment of Osteoporosis in Hungary

Lakatos

Takács

Marton³

et al. 2015

Calcif Tissue Int

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“…Postmenopausal osteoporosis affects women and is characterized by increased bone loss associated with both the loss of bone-protective role of estrogens and the increased levels of systemic and local pro-inflammatory and pro-resorptive cytokines [136]. Indeed, increased levels of IL-6, IL-1 and TNF-a characterize a subclinical systemic chronic inflammatory state during aging named “inflamm-aging”, which has been linked with postmenopausal bone loss [137–139].…”

Section: Opportunities For Enhancing Bone Repair By Modulating Infmentioning

confidence: 99%

“…Indeed, increased levels of IL-6, IL-1 and TNF-a characterize a subclinical systemic chronic inflammatory state during aging named “inflamm-aging”, which has been linked with postmenopausal bone loss [137–139]. Likewise, increased serum levels of the bone remodeling cytokines RANKL and the ratio RANKL/OPG have been associated with postmenopausal osteoporosis [136, 137]. Interestingly, in postmenopausal osteoporosis, the osteogenic capacity remains unaltered [135].…”

Section: Opportunities For Enhancing Bone Repair By Modulating Infmentioning

confidence: 99%

Inflammation, fracture and bone repair

Loi

Córdova

Pajarinen

et al. 2016

Bone

969

883

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The reconstitution of lost bone is a subject that is germane to many orthopaedic conditions including fractures and non-unions, infection, inflammatory arthritis, osteoporosis, osteonecrosis, metabolic bone disease, tumors, and periprosthetic particle-associated osteolysis. In this regard, the processes of acute and chronic inflammation play an integral role. Acute inflammation is initiated by endogenous or exogenous adverse stimuli, and can become chronic in nature if not resolved by normal homeostatic mechanisms. Dysregulated inflammation leads to increased bone resorption and suppressed bone formation. Crosstalk amongst inflammatory cells (polymorphonuclear leukocytes and cells of the monocyte-macrophage-osteoclast lineage) and cells related to bone healing (cells of the mesenchymal stem cell-osteoblast lineage and vascular lineage) is essential to the formation, repair and remodeling of bone. In this review, the authors provide a comprehensive summary of the literature related to inflammation and bone repair. Special emphasis is placed on the underlying cellular and molecular mechanisms, and potential interventions that can favorably modulate the outcome of clinical conditions that involve bone repair.

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“…However, despite the favorable benefit risk profile, many-perhaps most-patients will discontinue therapy. In observational studies, persistence of 83-95 % after one year of denosumab therapy (meaning the patient received a second dose six months after their initial dose) and 68 % at 24 months has been described [17][18][19][20]. Data regarding longer-term treatment or outside a clinical trial setting are not yet available.…”

mentioning

confidence: 99%

Cancel the denosumab holiday

McClung

2016

Osteoporos Int

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Denosumab, a fully human IgG2 anti-RANK ligand antibody, quickly and substantially inhibits bone remodeling [1]. As expected by the pharmacology of denosumab, this inhibition of remodeling is completely reversible upon stopping treatment [2]. In clinical trials, discontinuing therapy after 2 years results in a rapid rebound in bone turnover markers, raising concern about whether that high remodeling rate and consequent rapid bone loss that occurs has clinical relevance beyond a simple waning of the treatment benefit [3,4]. Despite these concerns, many patients stop denosumab therapy, sometimes upon the advice of their physicians, especially in preparation for invasive dental procedures [5][6][7]. Three recent reports have described five patients in whom denosumab treatment was stopped because substantial gains on bone mineral density (BMD) had been achieved and who then experienced vertebral fractures within the first several months after discontinuing therapy. These cases re-focus our attention on the concern about a rebound in fracture risk and make it clear that a Bholiday^from denosumab therapy is not justified in patients with osteoporosis [8][9][10].It is well established that denosumab treatment of postmenopausal women with osteoporosis and of men and women receiving hormone ablation therapy for the management of prostate and breast cancer is associated with substantial (about 70 %) reduction in the risk of vertebral fracture [11][12][13]. In women with osteoporosis, hip fracture risk is reduced by 40 % and non-vertebral fracture risk by 20 %, and efficacy may be sustained with long-term therapy [11,14]. Progressive increases in bone mineral density (BMD) are observed with long-term therapy with increments from baseline of 18 and 8 % observed in the lumbar spine and total hip region, respectively, after 8 years, and emerging evidence suggests that the proximal femur BMD achieved on therapy is a good indicator of an individual patient's risk of non-vertebral fracture [14,15].There are few reasons to stop denosumab therapy. Refractoriness to therapy has not been demonstrated. Intolerance is uncommon. Although rare cases of atypical femoral fracture have been described in patients who have received denosumab (most often in patients with a history of previous bisphosphonate use), there is no clear signal of any risk associated with the duration of therapy [16]. However, despite the favorable benefit risk profile, many-perhaps most-patients will discontinue therapy. In observational studies, persistence of 83-95 % after one year of denosumab therapy (meaning the patient received a second dose six months after their initial dose) and 68 % at 24 months has been described [17][18][19][20]. Data regarding longer-term treatment or outside a clinical trial setting are not yet available. The usual reasons for discontinuing treatment exist (perceived intolerance or ineffectiveness, concerns about rare side effects, cost, etc.). In addition, physicians themselves may recommend that treatment be stopped after several ye...

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Persistence at 12 months with denosumab in postmenopausal women with osteoporosis: interim results from a prospective observational study

Cited by 54 publications

References 33 publications

A Retrospective Longitudinal Database Study of Persistence and Compliance with Treatment of Osteoporosis in Hungary

A Retrospective Longitudinal Database Study of Persistence and Compliance with Treatment of Osteoporosis in Hungary

Inflammation, fracture and bone repair

Cancel the denosumab holiday

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