Comparative effectiveness of denosumab, teriparatide, and zoledronic acid among frail older adults: a retrospective cohort study

Zullo, Andrew R.; Lee, Y.; Lary, Christine W.; Daiello, Lori A.; Kiel, Douglas P.; Berry, Sarah D.

doi:10.1007/s00198-020-05732-2

Cited by 16 publications

(10 citation statements)

References 41 publications

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“…Our results support the notion of total hip BMD T ‐score as an operational surrogate for fracture risk. Our findings, in combination with existing real‐world evidence demonstrating the benefits of osteoporosis treatments on BMD and fracture risk, ( 24 , 25 , 26 , 27 ) also support total hip BMD T ‐score as a potentially useful treatment target in the management of patients in a clinical setting. ( 6 ) Although several studies have shown that change in BMD from baseline provides useful context for treatment decisions, its use in a treat‐to‐target or goal‐oriented treatment strategy is problematic.…”

Section: Discussionsupporting

confidence: 80%

Total Hip Bone Mineral Density as an Indicator of Fracture Risk in Bisphosphonate-Treated Patients in a Real-World Setting

Banefelt

Timoshanko

Söreskog

et al. 2020

Journal of Bone and Mineral Research

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Bone mineral density (BMD) is an established measure used to diagnose patients with osteoporosis. In clinical trials, change in BMD has been shown to provide a reliable estimate of fracture risk reduction, and achieved BMD T-score has been shown to reflect the near-term risk of fracture. We aimed to test the association between BMD T-score and fracture risk in patients treated for osteoporosis in a real-world setting. This retrospective, observational cohort study included Swedish females aged ≥55 years who had a total hip BMD measurement at one of three participating clinics. Patients were separated into two cohorts: bisphosphonate-treated and bisphosphonate-naïve prior to BMD measurement, stratified by age and prior nonvertebral fracture status. The primary outcome was cumulative incidence of clinical fractures within 24 months of BMD measurement, with other fracture types included as secondary outcomes. Associations between T-score and fracture risk were estimated using proportional hazards regression and restricted cubic splines. A total of 15,395 patients were analyzed: 11,973 bisphosphonate-naïve and 3422 bisphosphonate-treated. In the 24 months following BMD measurement, 6.3% (95% confidence interval [CI], 5.9-6.7) of bisphosphonate-naïve and 8.4% (95% CI, 7.5-9.4) of bisphosphonate-treated patients experienced a clinical fracture. Strong inverse relationships between BMD T-score and fracture incidence were observed in both cohorts. Among bisphosphonate-naïve patients, this relationship appeared to plateau around T-score À1.5, indicating smaller marginal reductions in fracture risk above this value; bisphosphonate-treated patients showed a more consistent marginal change in fracture risk across the evaluated T-scores (À3.0 to -0.5). Trends remained robust regardless of age and prior fracture status. This real-world demonstration of a BMD-fracture risk association in both bisphosphonate-naïve and bisphosphonate-treated patients extends evidence from clinical trials and recent meta-regressions supporting the suitability of total hip BMD as a meaningful outcome for the clinical management of patients with osteoporosis.

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Section: Discussionsupporting

confidence: 80%

Total Hip Bone Mineral Density as an Indicator of Fracture Risk in Bisphosphonate-Treated Patients in a Real-World Setting

Banefelt

Timoshanko

Söreskog

et al. 2020

Journal of Bone and Mineral Research

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“…Skeletal-related events (SREs) occur frequently in cancer bone metastases, and in some studies of zoledronic acid and SREs, ZA has been found to be effective in preventing SRE, reducing pain, and improving quality of life ( Mhaskar and Djulbegovic, 2018 ; Miller et al, 2018 ; Finianos and Aragon-Ching, 2019 ; Sun et al, 2019 ; Hu et al, 2020 ). The link between ZA and osteoclasts was originally studied for the treatment of osteoporosis, now many monoclonal antibodies have been developed to treat osteoporosis, which can replace ZA ( Anagnostis et al, 2017 ; Raje et al, 2018 ; Makras et al, 2021 ; Zullo et al, 2021 ). However, ZA, the longest used and most effective anti-osteoporosis drug, will still be used clinically and studied by researchers and clinicians for a long time in the future.…”

Section: New Directions and Hot Spots In Research Of Zoledronic Acidmentioning

confidence: 99%

How zoledronic acid improves osteoporosis by acting on osteoclasts

et al. 2022

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Osteoporosis is called a silent disease, because it is difficult to detect until comprehensive examinations for osteoporosis are performed or osteoporotic fractures occur. Zoledronic acid is currently the first-line anti-osteoporotic drug, with good efficacy and treatment compliance. A major advantage of zoledronic acid is that intravenous zoledronic acid often guarantees a therapeutic effect for up to 1 year after infusion. The reasons why zoledronic acid is effective in improving osteoporosis are that it can inhibit osteoclast differentiation and induce osteoclast apoptosis, thus suppressing bone resorption and increasing bone density. The story between zoledronic acid and osteoclasts has been written long time ago. Both the canonical receptor activator of the receptor activator of nuclear factor-κB ligand (RANKL) pathway and the non-canonical Wnt pathway are the main pathways by which zoledronic acid inhibits osteoclast differentiation. Farnesyl pyrophosphate synthase (FPPS), reactive oxygen species (ROS), and ferroptosis that was first proposed in 2012, are all considered to be closely associated with zoledronic acid-induced osteoclast apoptosis. Here, we provide a brief review of the recent progress on the study of zoledronic acid and osteoclasts, and hope to elaborate how zoledronic acid improves osteoporosis by acting on osteoclasts.

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“…Such programs to optimize medication management are particularly important for SNF residents since polypharmacy is common and an estimated 40% of individuals in SNFs take ≥ 9 medications. [4][5][6][7][8] The types of SNFs each LTC pharmacy chain serves and the clinical services provided to each facility (beyond medication dispensing) are currently unknown. In the absence of data on how SNFs differ by LTC pharmacy provider, including facility characteristics (e.g., SNF size) and quality ratings, researchers and policymakers are limited in their ability to design collaborative interventions or policies that improve medication management in SNFs.…”

Section: Introductionmentioning

confidence: 99%

Differences in Skilled Nursing Facility Characteristics and Quality Ratings by Long-Term Care Pharmacy Provider

Zullo

Riester

Goldberg

et al. 2021

Preprint

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Objectives: Limited data exist on the U.S. long-term care (LTC) pharmacy market and how skilled nursing facilities (SNFs) may differ by LTC pharmacy provider. We estimated the market shares of two major LTC pharmacies (Omnicare and PharMerica) and assessed if SNF characteristics differ by pharmacy. Design: Cross-sectional. Setting and Participants: Seventy-five Rhode Island (RI) SNFs that provided post-acute care (PAC) services in 2019. Methods: SNF location, structure, staffing measures, and quality ratings were ascertained from publicly available data sources. The LTC pharmacy used by each SNF was compiled by case managers at a RI health system. Results: Among 75 SNFs, 32 (43%) were served by Omnicare and 36 (48%) by PharMerica. LASSO logistic regression and random forest models identified 5 key predictors of SNFs selecting PharMerica over Omnicare: number of skilled beds, total number of beds, nursing hours per resident per day, five-star health inspection rating, and average number of residents per day. In a multivariable regression model including 4 predictors (total number of beds excluded due to collinearity), SNFs had a 6% higher prevalence of using Omnicare over PharMerica for every additional 10 skilled beds (Prevalence Ratio 1.06, 95% CI 1.02-1.10). Conclusions and Implications: Omnicare and PharMerica comprised over 90% of the SNF PAC market in RI, with Omnicare covering larger facilities. Understanding if these companies serve a similar proportion of SNFs in other U.S. states is necessary to advance future research initiatives and examine how collaborations between SNFs and LTC pharmacy chains may improve medication management in SNFs.

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Comparative effectiveness of denosumab, teriparatide, and zoledronic acid among frail older adults: a retrospective cohort study

Cited by 16 publications

References 41 publications

Total Hip Bone Mineral Density as an Indicator of Fracture Risk in Bisphosphonate-Treated Patients in a Real-World Setting

Total Hip Bone Mineral Density as an Indicator of Fracture Risk in Bisphosphonate-Treated Patients in a Real-World Setting

How zoledronic acid improves osteoporosis by acting on osteoclasts

Differences in Skilled Nursing Facility Characteristics and Quality Ratings by Long-Term Care Pharmacy Provider

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