Question:

Does statin therapy reduce postmenopausal fractures in women?

Search terms:

Statin therapy and bone mineral density and women; statins and postmenopausal women and

fractures

Database/Search engines:

Academic search complete (all databases); PubMed

Rationale:

Osteoporotic fractures contribute to the burden of diseases in women. Osteoporotic fractures

and osteoporosis closely correspond, and bone mineral density is one of the main endpoints

when studying fracture risk.1 Bone mineral density can be measured with dual x-ray

absorptiometry, or a patient’s bone mineral density can be related to a reference value for a

young normal adult of the same sex by using a T-score. Although bone mineral density is a good

indicator, there are several clinical factors associated with a fracture risk that are not calculated

into a T-score. The Fracture Risk Assessment Tool (FRAX) was developed to include clinical risk

factors which include age, sex, race, height, weight, body mass index, a history of fractures, and

other secondary causes. 2

Discussion:

Observational studies and a meta-analysis have shown that the use of statins has increased

bone mineral density in subjects and promoted a positive action for bone repair. 3,4 A number of

observational studies have shown no impact in the use of statins in preventing fractures.
Helin-Salmivaara et al. presented a population-based cohort study that consisted of women,

age 45-75, that were new users of statins or hypertensive medicine from 1996 to 2001. Patients

were placed on a statin medication (n=40,254) or an antihypertensive medication (n=41,610)

once daily and were compared to a population cohort (n=62,585). The primary outcome

measures were incidence rate of low-energy hip fractures and the hazard ratio (HR) which took

a patient’s lifestyle factors into effect. In the statin cohort 199 women (0.50%) sustained a hip

fracture, and the hypertension and population cohorts were 312 (0.75%) and 212 (0.34%)

respectively. The incident rate was highest in the hypertension cohort (2.0 per 1000 person-

years), followed by the statin (1.5) and the population cohort (1.0). When computing for the

HR, good adherence to statins was associated with a 29% decreased risk (HR 0.71; 95% CI 0.58-

0.86) compared to good adherence to antihypertensive drugs. The authors concluded that long-

term statin therapy is associated with a decreased risk of low-energy hip fracture in women. 3

A meta-analysis included studies that described the effect of statin on the risk of fracture, BMD

or bone turnover markers. A total of 33 studies were included (23 observational and 10

randomized control trials). The meta-analysis showed that statins decreased the risk of overall

fractures (OR=0.81, 95% CI 0.73-0.89) and hip fractures (OR=0.75, 95% CI 0.60-0.92). However,

the results showed that there was no positive effect on vertebral fractures, upper extremity

fractures and BMD at the femoral neck.4

Peña et al. performed a randomized, double-blind, placebo-controlled study where women

received either rosuvastatin calcium 20 mg daily (n=3,426) or placebo (n=3,375). Incident of

fracture was the clinical endpoint measured. Fractures were confirmed by using radiographs,

computed tomography and bone scan. During the study, there were 227 confirmed fractures,
122 in the rosuvastatin group and 105 in the placebo group. The incidence of fracture in the

rosuvastatin and placebo groups were 1.80 and 1.58 per 100 person-years (adjusted HR, 1.16

[95% CI, 0.89-1.50]). There were no significant differences in the rate of specific fractures

between the 2 study groups. The authors concluded that rosuvastatin therapy did not reduce

the risk of fractures and showed no benefit when compared to the placebo group. 5

Population: 109,640 adults studied receiving statin therapy

Dosing studied: rosuvastatin 20 mg daily

Risk/Benefit considerations:

The studies analyzed in the meta-analysis and the other observational studies have had

consistent findings regarding the safety of statins. In the studies there were not many reported

adverse effects, but minor headaches and nausea were reported in a few patients. In addition,

the studies have shown grater efficacy of statins with men compared to women.

Response:

The use of statins for the reduction of osteoporotic fractures has shown conflicting results.

Some studies have shown an increase in subjects bone mineral density, whereas some studies

have shown no significant difference in statin groups and placebo. In one observational study,

there was a decrease risk of low energy hip fractures in women.3 In another observational

study, it was concluded that there was no significant difference when comparing the placebo

and statin groups.5 The meta-analysis of statin trials found that statins prevented some

fractures and had no impact on other fractures.4 At this time, it cannot be recommended that

statins can be used for the prevention of fractures in postmenopausal women.

References:

Facts and Statistics [Internet]. Switzerland: International Osteoporosis Foundation; c2002

[updated 2017 cited 2019 Oct 29]; [about 18 screens]. Available from:
https://www.iofbonehealth.org/facts-statistics

Rubin KH, Friis-Holmberg T, Hermann AP, Abrahamsen B, Brixen K. Risk assessment tools to
identify women with increased risk of osteoporotic fracture: Complexity or simplicity? A
systematic review. JBMR [Internet]. 2013 [cited 2019 Oct 28];28(8): [15 p.]. Available from:
https://journals-ohiolink-edu.onu.ohionet.org/pg_99?
426129440178176::NO::P99_ENTITY_ID,P99_ENTITY_TYPE:12241504,MAIN_FILE&cs=3
Rs1d9vYVCYUrRA4v7J1C66SJjK6clNDGUnLiLmLHHj4LkV-
9e8EWhjLNsWzEJ9M4Z9tcZrNfP8ahN_o606xNjQ

Helin-Salmivaara A, Korhonen MJ, Lehenkari P, et al. Statins and Hip Fracture Prevention – A
Population Based Cohort Study in Women. PLoS ONE [Internet]. 2012 [cited 2019 Oct
28];7(10): [about 9 p.]. Available from: https://content.ebscohost.com/ContentServer.asp?
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GeqK5Ssqe4TK6WxWXS&ContentCustomer=dGJyMPGutlCuqbdIuePfgeyx44Dt6fIA

An T, Hao J, Sun S, Li R, Yang M, Cheng G, et al. Efficacy of statins for osteoporosis: a

systematic review and meta-analysis. Osteoporos Int [Internet]. 2016 [cited 2019 Oct 29];28(1):
[10 p.]. Available from: https://content.ebscohost.com/ContentServer.asp?
T=P&P=AN&K=27888285&S=R&D=mnh&EbscoContent=dGJyMMvl7ESeqLY4zdnyOLCmr
1GeqK5Ssqy4SbSWxWXS&ContentCustomer=dGJyMPGutlCuqbdIuePfgeyx44Dt6fIA

Peña JM, Aspberg S, Macfadyen J, Glynn RJ, Solomon DH, Ridker PM. Statin Therapy and
Risk of Fracture. JAMA Intern Med [Internet]. 2015 Jan [cited 2019 Oct 28];175(2): [5 p.].
Available from: https://jamanetwork-
com.onu.ohionet.org/journals/jamainternalmedicine/fullarticle/1936580