Nitrate Medications, Fractures, and Change in Bone Mineral Density in Postmenopausal Women: Results from the Women's Health Initiative

Abstract

Nitrate medications may increase bone mineral density (BMD), although information on fracture outcomes is sparse. We examined the association of nitrate medications with fractures (hip, wrist/arm and total fractures) and changes in BMD (hip, spine and whole body) in the Women’s Health Initiative (WHI) Clinical Trials and Observational Study. A total of 139,211 postmenopausal women 50 to 79 years old without history of hip fracture were included in this prospective study. Medication use was ascertained directly from drug containers at baseline during in-person interviews in 1993-1998. Exposure measures included any use (use/non-use), type of nitrate (as-needed, maintenance) and duration of use (≤ 5 years, > 5 years). We used separate multivariable Cox proportional hazard models to analyze associations between each exposure and fracture outcome, with results presented as hazard ratios (HRs) and 95% confidence intervals (CI). Multivariable linear regression models were used to examine 3 and 6-year changes in BMD. At baseline, 1.2% (n=1647) women were using a nitrate. During the mean (SD) follow-up of 7.7 (1.5) years through 2005, women experienced 1582 hip fractures, 5156 wrist or arm fractures, and 22, 589 total fractures. After adjustment for confounders, nitrate use was not statistically associated with risk for hip (HR, 0.81; 95% CI, 0.56–1.18), wrist/arm (HR, 0.95; 95% CI, 0.74-1.23) or total fractures (HR, 0.96; 95% CI, 0.85-1.08). As-needed nitrate use, but not maintenance therapy, was associated with a lower risk of total fractures (HR, 0.77; 95% CI, 0.62–0.95) and wrist/arm fractures (HR, 0.57; 95% CI, 0.34-0.98). Nitrate use was not associated with 3 or 6-year changes in BMD at any site. We conclude that any nitrate use was not significantly associated with lower risk of fractures or higher BMD, however as-needed nitrates were associated with lower risks of total and wrist/arm fractures.

The Women's Health Initiative: A Landmark Resource for Skeletal Research Since 1992

“…In WHI, there was no association of statins, past use of oral contraceptives, loop diuretics, laxatives, anticholinergic medications and nitrates and fracture (Table ). Use of proton pump inhibitors was associated with increased risk of spine, lower arm/wrist, and all fractures but was unrelated to hip fractures.…”

Treatment of Osteoporosis: Current Scenario from a Research Perspective

“…47 Analysing data of WHI trial, postmenopausal women who took nitrates when needed were shown to have an increase in BMD and decrease the risk of total and arm/wrist fractures. 48…”

Atherosclerosis and Osteoporosis. Common Targets for the Effects of Cardiovascular and Anti-osteoporotic Drugs (Part I). The Effect of Cardiovascular Drugs on Bone Strength

“…За период наблюдения нитраты, принимаемые в интермитирующем режиме, снижали риск всех переломов на 23% и, особенно, предплечья (на 43%). Отсутствие изменений МПК на фоне лечения, возможно, связано с малым числом пациентов, использующих нитраты [58]. Таким образом, создается впечатление, что нитратсодержащие препараты оказывают благоприятное дозозависимое действие на прочность костной ткани, если используются в прерывистом режиме.…”