The relationship between long-term proton pump inhibitor therapy and skeletal frailty

Lau, Arthur; Tomizza, Michael; Wong-Pack, Matthew; Παπαϊωάννου, Αλεξάνδρα; Adachi, Jonathan D.

doi:10.1007/s12020-015-0576-z

Cited by 23 publications

(13 citation statements)

References 32 publications

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“…Accordingly, key observations on the impact of each class on BMD and fracture risk are indicated in table 6, primarily in accordance with the findings of Panday et al in their 2014 review on medication-induced osteoporosis [81]. Recent literature reviews specific to each drug class are also cited to provide the reader with a source of more detailed current information [82][83][84][85][86][87][88][89][90][91]. A focus on three commonly used classes -glucocorticoids, androgen deprivation therapy and aromatase inhibitors -serves to illustrate the potential benefits of strategies to prevent osteoporosis induced by medicines.…”

Section: Osteoporosis Induced By Medicinessupporting

confidence: 67%

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Mind the (treatment) gap: a global perspective on current and future strategies for prevention of fragility fractures

et al. 2017

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-none for this submission. EVM -none for this submission. JAK and PJM have undertaken consultancy for governments, national osteoporosis societies, healthcare professional organisations and private sector companies relating to systematic approaches to fragility fracture care and prevention. JYR has no disclosures related to this work, and has received consultancy, lecture fees and grant support from Amgen, Analis, Asahi Kasei, Boehringer, Bristol Myers Squibb, Chiltern, Danone, Ebewee Pharma, Endocyte, Galapagos, GlaxoSmithKline, IBSAGenevrier, Lilly, Merck Sharp and Dohme, Merckle, Negma, Novartis, NovoNordisk, NPS, Nycomed-Takeda, Organon, Pfizer, PharmEvo, Radius Health, Roche, Rottapharm, Servier, Teijin, Teva, Theramex, Therabel, UCB, Will Pharma, Wyeth, Zodiac. NCWH has no disclosures related to this work, and has received consultancy, lecture fees and honoraria from Alliance for Better Bone Health, AMGEN, MSD, Eli Lilly, Servier, Shire, Consilient Healthcare and Internis Pharma. PJM serves as a consultant to the International Osteoporosis Foundation and received remuneration for his contribution to this manuscript. RR has received honoraria for participation in Advisory boards or speaker bureau fees from Danone, Labatec, Nestlé, and ObsEva. Introduction-This narrative review considers the key challenges facing healthcare professionals and policymakers responsible for providing care to populations in relation to bone health. These challenges broadly fall into 4 distinct themes: Europe PMC Funders Group

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Section: Osteoporosis Induced By Medicinessupporting

confidence: 67%

“…Lau et al [89] Selective serotonin reuptake inhibitors Small studies have found an association between SSRI use and bone loss. However, meta-analysis has reported SSRI-related fractures in the absence of bone loss.…”

Section: Fls Model Proportion Investigated With Bmd Testing Proportiomentioning

confidence: 99%

Mind the (treatment) gap: a global perspective on current and future strategies for prevention of fragility fractures

et al. 2017

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“…In addition, peripheral neuropathy is also a consequence of vitamin B12 deficiency, increasing the risk of falls and, consequently, of bone fractures. The association between PPI use and increased risk of falls has been clearly demonstrated . Moreover, a direct PPI action on bone is also a possibility .…”

Section: Discussionmentioning

confidence: 99%

“…The association between PPI use and increased risk of falls has been clearly demonstrated. (24) Moreover, a direct PPI action on bone is also a possibility. (25) Osteoclast function is dependent on proton pumps, which may be directly inhibited by PPIs, reducing bone resorption and turnover.…”

Section: Discussionmentioning

confidence: 99%

Increased Risk of Bone Fractures in Hemodialysis Patients Treated with Proton Pump Inhibitors in Real World: Results from the Dialysis Outcomes and Practice Patterns Study (DOPPS)

Fusaro

D’Arrigo

Pitino

et al. 2019

Journal of Bone and Mineral Research

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Long‐term treatment with proton pump inhibitors (PPIs) is associated with an increased risk of fractures in the general population. PPIs are widely prescribed to dialysis patients but to date no study has specifically tested, by state‐of‐art statistical methods, the relationship between use of PPIs and fractures in this patient population. This study aimed to assess whether use of PPIs is associated with bone fractures (ie, hip fractures and fractures other than hip fractures) in a large international cohort of hemodialysis patients. We considered an observational prospective cohort of 27,097 hemodialysis patients from the Dialysis Outcomes and Practice Patterns Study (DOPPS). Data analysis was performed by the Fine and Gray method, considering the competitive risk of mortality, as well as by a cause‐specific hazards Cox model with death as a censoring event and matching patients according to the prescription time. Of 27,097 hemodialysis patients, 13,283 patients (49%) were on PPI treatment. Across the follow‐up period (median, 19 months), 3.8 bone fractures × 100 person‐years and 1.2 hip fractures × 100 person‐years occurred. In multiple Cox models, considering the competitive risk of mortality, the incidence rate of bone (subdistribution hazard ratio [SHR] 1.22; 95% CI, 1.10 to 1.36; p < 0.001) and hip fractures (SHR 1.35; 95% CI, 1.13 to 1.62; p = 0.001) was significantly higher in PPI‐treated than in PPI‐untreated patients. These findings also held true in multiple, cause‐specific, hazards Cox models matching patients according to the prescription time (bone fractures: HR 1.47; 95% CI, 1.23 to 1.76; p < 0.001; hip fractures: HR 1.85; 95% CI, 1.37 to 2.50; p < 0.001). The use of PPIs requires caution and a careful evaluation of risks/benefits ratio in hemodialysis patients. © 2019 American Society for Bone and Mineral Research.

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“…Potential mechanisms have been recently reviewed and there is evidence implying an increased risk of falling by PPIs [20]. Future research is required to clarify the mechanisms for the prevention of fractures in elderly patients with PPI therapy.…”

Section: Dear Editormentioning

confidence: 99%

Calcium, proton pump inhibitors, and fracture risk

et al. 2015

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Dear Editor,The latest meta-analysis of observational studies regarding the association between proton pump inhibitors (PPIs) and fracture risk by Zhou and colleagues [1] showed that PPI therapy was linked to an increased incidence of hip fracture (15 studies; relative risk 1.26, 95 % confidence interval 1.16 to 1.36), vertebral fracture (4 studies; 1.58, 1.38 to 1.82), and total fracture (10 studies; 1.33, 1.15 to 1.54). This is an important update because a PPI is one of the most frequently prescribed drugs in older people. Although the mechanisms by which use of PPIs increases fracture risk remain unclear, the authors did not support a long-standing explanation that the major cause would be the impairment of calcium absorption by PPIs [1]. On the basis of the latest research, we would like to discuss this topic further from a different point of view.There is no doubt that appropriate calcium as well as vitamin D is essential for bone health. In agreement with the earlier suggestion by Kanis and Passmore [2, 3], however, the latest systematic review and meta-analyses concluded that the effects of increasing calcium intake on areal bone mineral density (BMD) and fracture risk are limited [4][5][6][7]. Of note, this is compatible with accumulating data indicating no significant relation between PPI therapy and areal BMD [8] despite its possible inhibitory effect on intestinal calcium absorption.In contrast to PPIs, vitamin D is expected to increase calcium absorption in the gut. However, recent meta-analyses have consistently shown that its effects on areal BMD and fracture risk are also limited [9-13]. Furthermore, the latest randomized, double-blind, placebo-controlled clinical trial in postmenopausal women younger than 75 years with vitamin D insufficiency but not osteoporosis found that neither lowdose (800 IU daily) nor high-dose (50,000 IU twice monthly) vitamin D treatment for one year significantly changed areal BMD; the mean levels of serum 25-hydroxyvitamin D in the placebo, low-dose, and high-dose groups were 19, 28, and 56 ng/mL, respectively [14].We have suggested that the effect of osteoporosis therapy is limited by skeletal adaptation to mechanical environment, because bone normally responds to mechanical loading to maintain resultant elastic deformation (strain) while an increase in bone strength by nutrients or drugs results in a decrease in bone strain from physical activity [15,16]. This natural homeostatic system can explain that a small gain in areal BMD resulting from increasing calcium intake was observed during the first year but there was no further increase later [4] and is likely to work against "mild" mineral-related changes in bone material stiffness associated with PPIs as well as vitamin D [17][18][19].In conclusion, we agree with the suggestion by the authors [1] that calcium malabsorption would not be a major cause of the association between PPI use and an increased risk of fractures. Potential mechanisms have been recently reviewed and there is evidence implying an increased risk...

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The relationship between long-term proton pump inhibitor therapy and skeletal frailty

Cited by 23 publications

References 32 publications

Mind the (treatment) gap: a global perspective on current and future strategies for prevention of fragility fractures

Mind the (treatment) gap: a global perspective on current and future strategies for prevention of fragility fractures

Increased Risk of Bone Fractures in Hemodialysis Patients Treated with Proton Pump Inhibitors in Real World: Results from the Dialysis Outcomes and Practice Patterns Study (DOPPS)

Calcium, proton pump inhibitors, and fracture risk

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