Long-term effect of statins on the risk of new-onset osteoporosis: A nationwide population-based cohort study

Abstract

BackgroundSeveral observational cohort and meta-analytical studies in humans have shown that statin users have a lower risk of fractures or greater bone mineral densities (BMD) than nonusers. However, some studies including randomized clinical trials have the opposite results, particularly in Asian populations.ObjectiveThis study investigates the impacts of statins on new-onset osteoporosis in Taiwan.MethodsIn a nationwide retrospective population-based cohort study, 45,342 subjects aged between 50–90 years having received statin therapy (statin-users) since January 1 2001, and observed through December 31 2013 were selected from the National Health Insurance Research Database of Taiwan. Likewise, 115,594 patients had no statin therapy (statin-non-users) were included as controls in this study. Multivariable Cox proportional hazards analysis for drug exposures was employed to evaluate the association between statin treatment and new-onset of osteoporosis risk. We also used the long-rank test to evaluate the difference of probability of osteoporosis-free survival.ResultsDuring the 13-year follow-up period, 16,146 of all enrolled subjects (10.03%) developed osteoporosis, including 3097 statin-users (6.83%) and 13,049 statin-non-users (11.29%). Overall, statin therapy reduced the risk of new-onset osteoporosis by 48% (adjusted hazard ratio [HR] 0.52; 95% CI 0.50 to 0.54). A dose-response relationship between statin treatment and the risk of new-onset osteoporosis was observed. The adjusted hazard ratios for new-onset osteoporosis were 0.84 (95% CI, 0.78 to 0.90), 0.56 (95% CI, 0.52 to 0.60) and 0.23 (95% CI, 0.21 to 0.25) when cumulative defined daily doses (cDDDs) ranged from 28 to 90, 91 to 365, and more than 365, respectively, relative to nonusers. Otherwise, high-potency statins (rosuvastatin and atorvastatin) and moderate-potency statin (simvastatin) seemed to have a potential protective effect for osteoporosis.ConclusionsIn this population-based cohort study, we found that statin use is associated with a decreased risk of osteoporosis in both genders. The osteoprotective effect of statins seemed to be more prominent with a dependency on the cumulative dosage and statin intensity.

Statins as potential agents for the prevention and treatment of osteoporosis

“…If Shahrezaee and coworkers had utilized a wider dose range, they would have been able to efficiently compare the anti-osteoporotic effects of statins in OVX rats. In line with our experimental data, a recent population-based cohort study reported that high (rosuvastatin and atorvastatin) and moderate potency (simvastatin) statins more effectively reduced the risk of newonset osteoporosis [3].…”

Diagnosis of osteoporosis in statin-treated patients is dose-dependent

“…A recent meta-analysis concluded that statin treatment had a tendency towards a positive effect on the reduction of fracture risk and marked improvement of BMD in statin-treated patients 3. A large meta-analysis conducted in Taiwan, including 45 342 patients in the statin cohort and 115 594 patients in the control cohort, stated that statin therapy correlates with a decreased risk of osteoporosis when taken daily over a longer period of time, however, also not accounting for the different types of statins and their dosages 7. In the present study, there was an increased risk of being diagnosed with osteoporosis in the general study population of statin-treated patients when compared with controls.…”

“…Due to the elevated fracture risk, osteoporosis can have detrimental effects on a patient’s quality of life and is associated with a higher mortality and morbidity as well as being an economic burden 2. By now, numerous studies about osteoporosis and its treatment have been conducted—many of which revolve around the question whether statins affect bone metabolism 3–10. Statins play a crucial role in the management of hypercholesterolemia, which makes them a commonly used drug 11.…”

New applications of statin in therapy

“…W publikowanych później badaniach wykazywano kolejne korzystne działania statyn na metabolizm kostny, m.in. ich wpływ na proliferację osteoblastów oraz hamowanie działania osteoklastów [7]. W kilku badaniach na ludziach potwierdzono związek między przyjmowaniem statyn a wzrostem gęstości mineralnej kości (BMD) i zmniejszeniem ryzyka złamań [8,9].…”

“…Większe korzyści ze stosowania statyn obserwowano w populacji męskiej [10]. W opublikowanym w maju 2018 r. retrospektywnym badaniu kohortowym przeprowadzonym na 45 342 uczestnikach potwierdzono, iż długotrwałe przyjmowanie statyn o silnym działaniu (rosuwastatyna i atorwastatyna) wiąże się ze zmniejszonym o 48% ryzykiem wystąpienia nowych przypadków osteoporozy u obu płci [7]. Mimo to w niektórych pracach badacze wykazywali negatywną korelację między przyjmowaniem statyn a BMD [11,12].…”