Thiazides and Osteoporotic Spinal Fractures: A Suspected Linkage Investigated by Means of a Two-Center, Case-Control Study

Vecchis, Renato De; Ariano, Carmelina; Biase, Giuseppina Di; Noutsias, Michel

doi:10.14740/jocmr3193w

Cited by 6 publications

(4 citation statements)

References 31 publications

(28 reference statements)

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“…Chow et al and De Vecchis et al reported that TAH was associated with fracture in a univariate analysis but not in a multivariate analysis [26,27]. However, in both retrospective studies thiazide could have been stopped after a symptomatic hyponatremic episode; in such cases, the duration of hyponatremia would have been too short to increase fracture risk.…”

Section: Discussionmentioning

confidence: 99%

Thiazide-associated hyponatremia attenuates the fracture-protective effect of thiazide: A population-based study

Yang

Huang

et al. 2018

PLoS ONE

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BackgroundThiazide, a first-line therapy for hypertension, lowers blood pressure, increases bone mineral density, and reduces the risk of fractures. However, hyponatremia, an adverse effect of thiazide, is associated with increased risk of osteoporosis and fractures. It is currently unclear whether thiazide-associated hyponatremia (TAH) outweighs the protective effects of thiazide.MethodsUsing data from Taiwan’s National Health Insurance Research Database, we identified patients who were prescribed thiazide between 1998 and 2010. Those diagnosed with hyponatremia within three years after initiation of thiazide were selected for the TAH group. Thiazide users without hyponatremia were selected for the control group. The association between TAH and fracture risk was further evaluated using multivariable Cox regression models adjusted for comorbidities and medications. Subjects were followed up from the index date until the appearance of a fracture, death, or the end of a 3-year period.ResultsA total of 1212 patients were included in the TAH group, matched with 4848 patients in the control group. The incidence rate of fracture was higher in the TAH group than in the control group (31.4 versus 20.6 per 1000 person-years). TAH was associated with a higher risk of total fractures (adjusted hazard ratio [aHR]: 1.47, 95% confidence interval [CI] = 1.15–1.88), vertebra fractures (aHR: 1.84, 95% CI = 1.12–3.01), and hip fractures (aHR: 1.66, 95% CI = 1.12–2.46) after controlling for comorbidities and other medications.ConclusionsThiazide users with hyponatremia have a higher risk of fracture than thiazide users without hyponatremia. The fracture-protective effect of thiazide is attenuated by TAH.

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Section: Discussionmentioning

confidence: 99%

Thiazide-associated hyponatremia attenuates the fracture-protective effect of thiazide: A population-based study

Yang

Huang

et al. 2018

PLoS ONE

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Section: Cardiovascular Medications and Their Effects On Bone Healthmentioning

confidence: 99%

“…46 The observed increase in fracture risk with thiazide-induced hyponatremia was only found in univariate analysis, but was no longer evident after controlling for age and BMI in two retrospective studies in the elderly. 47,48 In summary, thiazide diuretics have been shown to reduce the risk of fractures while slightly increasing bone density. Thiazide-associated hyponatremia, however, was found to attenuate this benefit, which is concerning for the risk of falls and fractures.…”

Section: Thiazide Diureticsmentioning

confidence: 99%

The interplay between bone and heart health as reflected in medication effects: A narrative review

Trost

Tesfaye

Harindhanavudhi

2023

Womens Health (Lond Engl)

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There is mounting evidence of an association between osteoporosis and cardiovascular disease that extends beyond shared risk factors for these conditions. In turn, the medications used to treat each of these conditions can have effects that impact the other organ system: medications used in heart disease have the potential to affect bone health, while osteoporosis medications may modify cardiovascular health. While data in this subject area are limited by the paucity of large randomized controlled trials with bone mineral density or fracture risk as primary outcomes, this review explores the data available that can provide some insight into these reciprocal effects of medications on bone and heart health. Data on bone health effects of the loop and thiazide diuretics, beta blockers, calcium channel blockers, statins, warfarin, sodium-glucose cotransporter 2 inhibitors, metformin, and medications impacting the renin–angiotensin–aldosterone system are examined; the cardiovascular effects of osteoporosis therapies and vitamin D are also discussed. Importantly, while most data in this realm are inconclusive, recognizing the parallels between cardiovascular and bone disorders and how this is reflected in medication effects might prompt the clinician to consider the indirect impact of drug regimens when making therapeutic choices for patients with osteoporosis and heart disease.

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“…Association between thiazides and low-energy fractures has been studied less [16–18], and to our knowledge there are no prior studies on the association of thiazide use among persons with Alzheimer’s disease, the most common form of dementia [19]. These data are important because persons with AD are particularly prone to falls and fractures [20, 21].…”

Section: Introductionmentioning

confidence: 99%

Long-term thiazide use and risk of low-energy fractures among persons with Alzheimer’s disease—nested case-control study

et al. 2019

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Summary We investigated the association between thiazide use and the risk of low-energy fractures among community dwellers with Alzheimer’s disease. Longer use was associated with a decreased risk of low-energy fractures. This study extends the previous knowledge of reduced fracture risk of thiazides to persons with Alzheimer’s disease. Introduction To investigate the association between thiazide use and the risk of low-energy fractures (LEF), and hip fracture among community dwellers with Alzheimer’s disease (AD). No prior study has evaluated the effect of thiazides on LEF risk of AD patients. Methods LEF cases were identified from the MEDALZ study, including all community-dwelling persons diagnosed with AD in Finland 2005–2011. During the follow-up from AD diagnoses until the end of 2015, cases with LEF ( N = 10,416) and hip fracture ( N = 5578) were identified. LEF cases were matched with up to three controls without LEF, according to time since AD diagnosis, age and gender. Thiazide use identified from the Prescription register data was modeled with PRE2DUP method. Current use was defined in 0–30 days’ time window before the fracture/matching date, and duration of current use was assessed. The association between thiazide exposure and LEFs was assessed with conditional logistic regression. Results Current thiazide use was observed in 10.5% of LEF cases and 12.5% of controls. Current thiazide use was associated with a decreased risk of LEF (adjusted OR [aOR] 0.83, 95% CI 0.77–0.88). In terms of the duration of use, no association was observed with short-term use (< 1 year or 1–3 years), while longer use (> 3 years) was associated with a reduced risk of LEF (aOR 0.77, 95% CI 0.71–0.83) and hip fracture (aOR 0.68, 95% CI 0.60–0.78). Conclusions Our study extends the previous knowledge of reduced fracture risk of thiazides to persons with AD, a population with significantly increased background risk of fractures. Electronic supplementary material The online version of this article (10.1007/s00198-019-04957-0) contains supplementary material, which is available to authorized users.

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Thiazides and Osteoporotic Spinal Fractures: A Suspected Linkage Investigated by Means of a Two-Center, Case-Control Study

Cited by 6 publications

References 31 publications

Thiazide-associated hyponatremia attenuates the fracture-protective effect of thiazide: A population-based study

Thiazide-associated hyponatremia attenuates the fracture-protective effect of thiazide: A population-based study

The interplay between bone and heart health as reflected in medication effects: A narrative review

Long-term thiazide use and risk of low-energy fractures among persons with Alzheimer’s disease—nested case-control study

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