Adverse bone effects of medications used to treat non-skeletal disorders

Watts, Nelson B.

doi:10.1007/s00198-017-4171-4

Cited by 26 publications

(13 citation statements)

References 92 publications

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“…Speculation that long-term warfarin use might increase fracture risk stems from warfarin's role as a vitamin K antagonist. 29 Vitamin K is important in posttranslational glutamination of osteocalcin, the major noncollagenous bone matrix protein. Warfarin interferes with this process and conse-quently inhibits the activation of bone matrix proteins.…”

Section: Discussionmentioning

confidence: 99%

Association of Anticoagulant Therapy With Risk of Fracture Among Patients With Atrial Fibrillation

et al. 2020

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IMPORTANCE Warfarin is prescribed to patients with atrial fibrillation (AF) for the prevention of cardioembolic complications. Whether warfarin adversely affects bone health is controversial. The availability of alternate direct oral anticoagulant (DOAC) options now make it possible to evaluate the comparative safety of warfarin in association with fracture risk.OBJECTIVE To test the hypothesis that, among patients with nonvalvular AF, use of DOACs vs warfarin is associated with lower risk of incident fracture. DESIGN, SETTING, AND PARTICIPANTS This comparative effectiveness cohort study used the MarketScan administrative claims databases to identify patients with nonvalvular AF and who were prescribed oral anticoagulants from January 1, 2010, through September 30, 2015. To reduce confounding, patients were matched on age, sex, CHA 2 DS 2 -VASc (congestive heart failure, hypertension, age [>65 years = 1 point; >75 years = 2 points], diabetes, and previous stroke/transient ischemic attack [2 points], vascular disease) score, and high-dimensional propensity scores. The final analysis included 167 275 patients with AF. Data were analyzed from February 27, 2019 to September 18, 2019. EXPOSURES Warfarin and DOACs (dabigatran etexilate, rivaroxaban, and apixaban). MAIN OUTCOMES AND MEASURES Incident hip fracture, fracture requiring hospitalization, and all clinical fractures (identified using inpatient or outpatient claims) defined by International Classification of Diseases, Ninth Revision, Clinical Modification codes. RESULTSIn the study population of 167 275 patients with AF (38.0% women and 62.0% men; mean [SD] age, 68.9 [12.5] years), a total of 817 hip fractures, 2013 hospitalized fractures, and 7294 total fractures occurred during a mean (SD) follow-up of 16.9 (13.7) months. In multivariable-adjusted, propensity score-matched Cox proportional hazards regression models, relative to new users of warfarin, new users of DOACs tended to be at lower risk of fractures requiring hospitalization (hazard ratio [HR], 0.87; 95% CI, 0.79-0.96) and all clinical fractures (HR, 0.93; 95% CI, 0.88-0.98), whereas the association with hip fractures (HR, 0.91; 95% CI, 0.78-1.07) was not statistically significant. When comparing individual DOACs with warfarin, the strongest findings were for apixaban (HR for hip fracture, 0.67 [95% CI, 0.45-0.98]; HR for fractures requiring hospitalization, 0.60 [95% CI, 0.47-0.78]; and HR for all clinical fractures, 0.86 [95% CI, 0.75-0.98]). In subgroup analyses, DOACs appeared more beneficial among patients with AF who also had a diagnosis of osteoporosis than among those without a diagnosis of osteoporosis. CONCLUSIONS AND RELEVANCEIn this real-world population of 167 275 patients with AF, use of DOACs-particularly apixaban-compared with warfarin use was associated with lower fracture risk. These associations were more pronounced among patients with a diagnosis of osteoporosis. Given the potential adverse effects of warfarin on bone health, these findings suggest that caution should be used when...

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Section: Discussionmentioning

confidence: 99%

Association of Anticoagulant Therapy With Risk of Fracture Among Patients With Atrial Fibrillation

et al. 2020

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“…Also, the notion of a greater risk for men than women is borne out by some reports on hip fracture incidence ( Pouwels et al, 2011 ; Yu et al, 2011 ) but finds itself at odds with others ( Zhou et al, 2016 ; Yu et al, 2008 ). In the present study, we did not have access to information on medications other than anti-osteoporotic drugs, and on co-morbidities which often exert adverse effects on bone and predispose to fractures, encompassing drugs such as glucocorticoids, loop diuretics, and anti-depressants, as well as disorders like diabetes, chronic obstructive pulmonary disease, cerebrovascular disease, dementia, renal failure, HIV infection, and rheumatoid arthritis ( Watts, 2017 ; Kanis et al, 2005 ; Reyes et al, 2014 ). Since PPIs are often prescribed alongside such medications and diseases, confounding must be considered a major factor underlying our results.…”

Section: Discussionmentioning

confidence: 99%

Higher dose but not low dose proton pump inhibitors are associated with increased risk of subsequent hip fractures after first hip fracture: A nationwide observational cohort study

Brozek¹,

Reichardt

Zwerina³

et al. 2019

Bone Reports

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Aim To examine the association of proton pump inhibitor (PPI) use with subsequent hip fracture incidence in hip fracture patients, accounting for gender, age, PPI doses, PPI initiation before or after first fracture, and year from first fracture in which the first subsequent fracture occurred. Methods Data from 31,668 Austrian patients ≥50 years with the first hip fracture between July 2008 and December 2010 were analyzed retrospectively. After exclusion of patients on anti-osteoporotic medication, incidence of subsequent hip fractures was compared between users and non-users of PPIs using regression models. Results In general, use of PPIs among hip fracture patients was associated with increased risk for subsequent hip fracture (OR 1.58, 95%-CI 1.25–2.00), in particular in men, in the age group of 70–84 years, and when PPIs were initiated before the first fracture. Low PPI doses of ≤90 cumulative DDDs and ≤0.25 DDDs/day, however, were not linked to elevated subsequent fracture risk, especially among female patients. Subsequent hip fracture incidence was elevated within the first year after first fracture in female and male PPI users (OR 1.75, 95%-CI 1.28–2.38) and dropped in women but not in men in the second year. Conclusions Low-dose PPI use is not associated with increased risk of subsequent hip fractures, especially in women. Patients thus get most benefit of short-term PPI use after a hip fracture that has previously been linked to lowered mortality if low doses are not exceeded. Varying risk profiles for the time of subsequent hip fracture could have implications for risk group-specific follow-up care.

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“…This observation can be explained by the high doses of glucocorticoids administered during the first 6 months after transplantation, inducing accelerated bone remodeling [26]. Although glucocorticoids are essential for normal osteoblasts development, at non-physiological doses, osteoblasts and osteocytes are glucocorticoid targets [27]. Notably, the studies with the highest reported rate of BMD loss are those using high doses of glucocorticoids, up to 5 -6 grams of cumulative dose in the first year after transplantation [3,4,18].…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Maintenance low dose systemic glucocorticoids have limited impact on bone strength and mineral density among incident renal allograft recipients: A pilot prospective cohort study

Pérez‐Sáez

Herrera

Prieto‐Alhambra

et al. 2018

Bone

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Soon after kidney transplant (KT), a decrease in parathormone and bone mineral density (BMD) occur, but little is known on the impact of KT on novel bone quality parameters including trabecular bone score (TBS) and bone material strength index (BMSi). We aimed to study BMD, TBS and BMSi in the first year after KT, in patients not treated with any bone therapy. A cohort including 36 patients underwent KT on a low-glucocorticoid-dose protocol (5 mg daily-prednisone from post-operative-day 42 onwards) and was observed for 12 months prospectively. At 3 months, phosphorus and parathormone decreased, while calcium increased. We also observed at 3 months a transient mild 2.9% bone loss at femoral neck (BMD change 0.752 ± 0.15 vs 0.730 ± 0.15; p = 0.004), but no change at either spine or total hip. Both TBS and BMSi remained stable. At 12 months, lumbar (but not total hip or femoral neck) BMD slightly decreased by 2.1% vs baseline (0.950 ± 0.15 vs 0.930 ± 0.5; p = 0.046), while TBS and BMSi remained unmodified. In KT patients on low-dose glucocorticoids and no bone therapy, there were small BMD decreases at femoral neck (at 3 months) and lumbar spine (at 12 months), but no change in either TBS or BMSi. Low-dose post-KT glucocorticoid treatment shows limited impact on bone, supporting steroid-restrictive protocols.

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Adverse bone effects of medications used to treat non-skeletal disorders

Cited by 26 publications

References 92 publications

Association of Anticoagulant Therapy With Risk of Fracture Among Patients With Atrial Fibrillation

Association of Anticoagulant Therapy With Risk of Fracture Among Patients With Atrial Fibrillation

Higher dose but not low dose proton pump inhibitors are associated with increased risk of subsequent hip fractures after first hip fracture: A nationwide observational cohort study

Maintenance low dose systemic glucocorticoids have limited impact on bone strength and mineral density among incident renal allograft recipients: A pilot prospective cohort study

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