ORIGINAL ARTICLE

Risk of fractures associated with treatment for benignprostate hyperplasia in men

P. Vestergaard & L. Rejnmark & L. Mosekilde

Received: 10 March 2010 /Accepted: 1 June 2010 /Published online: 15 June 2010# International Osteoporosis Foundation and National Osteoporosis Foundation 2010

AbstractSummary Treatment of benign prostate hyperplasia with α-blockers may affect blood pressure while treatment with 5-α-reductase inhibitors may affect conversion of testosteronepotentially leading to osteoporosis. In our study, neither 5-α-reductase inhibitors nor α-blockers were associated withnegative effects on fractures, α-blockers perhaps beingassociated with a limited decrease in fractures.Introduction The objective is to study fracture risk associatedwith drugs for benign prostate hyperplasia. The hypotheseswere that (1) α-blockers may elevate fracture risk by causingpresyncope/falls and (2) 5-α-reductase inhibitors may elevatefracture risk by lowering dihydrotestosterone.Methods This is a nationwide case-control study using all9,719 male fracture patients aged ≥60 years in the year 2000as cases and drawing 29,156 age- and gender-matchedcontrols. The main exposure was the use of the drugsmentioned above for benign prostate hyperplasia. Confoundercontrol included social variables, contacts to hospitals andgeneral practitioners, alcoholism and other variables.Results For the 5-α-reductase inhibitors, no change inoverall risk of fractures was seen. No change in risk ofhip, spine and forearm fractures was present. For the α-blockers, a decrease in overall risk of fractures was seen, aswell as a decrease in the risk of hip and spine fractures, butonly at average doses >0.5 defined daily doses per day. No

decrease was seen for forearm fractures. A decreasing riskof any fracture, hip fractures and spine fractures were seenwith increasing dose of α-blockers, while no such associ-ation was seen for the forearm fractures.Conclusion Neither the 5-α-reductase inhibitors nor α-blockers were associated with negative effects on fracturerisk. A small trend towards a decrease in fracture risk maybe present for the α-blockers. However, more research isneeded to confirm if this trend is real.

Keywords 5-α-reductase inhibitors . Benign prostatehyperplasia . Fracture .α-blockers

Introduction

Benign prostate hyperplasia (BPH) is a frequent condi-tion in elderly men [1]. Little is known on the effects ofdrugs to treat BPH on the skeleton. Treatment with 5-α-reductase inhibitors (finasteride, dutasteride) may intheory reduce the conversion of testosterone to dihydro-testosterone [2] but apparently does not increase the risk ofsexual dysfunction or gynecomastia compared to controls[3]. However, it is not clear if such treatment may beassociated with an increase in the risk of fractures. Oneprior study failed to show an excess risk of hip fractures inusers of finasteride [4]. However, the number of menexposed to finasteride was limited (109 and 141 in thecase and control group, respectively) [4]. Three rando-mised controlled trial of finasteride and dutasteride failedto show any effect of 5-α-reductase inhibition on bonemineral density (BMD) [5–7], even after 4 years of follow-up [7]. Also, no detrimental effects of dutasteride onbiochemical markers of bone turnover have been demon-strated [2, 8].

P. Vestergaard : L. Rejnmark : L. MosekildeDepartment of Endocrinology and Internal Medicine,Aarhus University Hospital,Aarhus, Denmark

P. Vestergaard (*)The Osteoporosis Clinic, Aarhus University Hospital,Tage Hansens Gade 2,8000 Aarhus C, Denmarke-mail: p-vest@post4.tele.dk

Osteoporos Int (2011) 22:731–737DOI 10.1007/s00198-010-1320-4

However, besides the 5-α-reductase inhibitors, adrenergicα-receptor blockers are also widely used to alleviate thesymptoms of BPH. The α-receptor blockers have theadded effect that they may lower blood pressure [9],which could lead to dizziness [10] and thus an increasedrisk of falls and fractures. One prior study failed to showany association between α-blocker exposure and risk offractures [11], while another reported an increased risk offractures [12]. A further study showed that the fracture riskassociated with α-receptor blockers seemed limited tothose who used them for cardiovascular disease [13]. Ameta-analysis of drugs used for hypertension failed toshow an association between use of α-receptor blockersand risk of fractures [14]. Besides the effects on bloodpressure, no evidence exists for an effect of the α-blockerson bone turnover and BMD. Only indirect evidence existsfor an effect of α agonists on the osteoclast differentiation,and thus a potential effect of the α-blockers [15].

Thus, only one prior study on 5-α-reductase inhibitorsexists, covering only hip fractures [4]. The study addressedthe cumulative dose of drugs and not measures of dailydose. Also, the study was limited in size.

For the α-blockers, one study addressed both α-blockersused for hypertension and for BPH [13]. It did thus notspecifically address the α-blockers used for BPH. Onefurther study used a composite end point of falls, fracturesand hypotension related events, i.e. not looking at fracturesper se [9]. The meta-analysis did mainly look at α-blockersused for hypertension [14].

The current study thus aimed at assessing the associationof 5-α-reductase inhibitors and α-blockers used specificallyfor BPH and their effect on:

1. the overall risk of fractures, the risk of hip, spine andforearm fractures,

2. the average daily dose on risk of fractures and3. the duration of treatment on risk of fractures.

Material and methods

Study design

The study was designed as a case-control study. All malesubjects aged 60 years or above sustaining a fractureduring the year 2000 in Denmark were included as cases(n=9,719), and for each case, three subjects of the sameage (same birth year) and gender were randomly selectedfrom the background population as controls (n=29,156).Fracture risk increases with age especially after the age of60 in men [16] and also the prevalence of BPH, and thus,the use of drugs against this is rare below the age of 60. Acut-off value of 60 years was thus chosen.

End points

The study end points were occurrence of any fracture (ICD10codes: S02.0–S02.9, S07.0–S07.9, S12.0–S12.9, S22.0–S22.9, S32.0–S32.8, S42.0–S42.9, S52.0–S52.9, S62.0–S62.9, S72.0–S72.9, S82.0–S82.9, S92.0–S92.9) betweenJanuary 1 2000 and December 31, 2000. In Denmark, almostall patients with fractures are managed in the hospital system(also including the emergency rooms) [17], even fracturessustained abroad are registered upon return for insurancereasons. The capture of fractures is thus high [18, 19]. Thevertebral fractures included were clinical fractures collectedfrom hospital records of patients referred to emergencyrooms or other departments and patients who had a vertebralfracture diagnosed.

Exposure variables

The primary exposure variables were use of either 5-α-reductase inhibitors (finasteride or dutasteride) or α-blockers(alfuzosin, doxazosin, tamsulosin, terazosin). In Denmark,these drugs are only licensed to use for BPH. The α-blockersmentioned are not licensed to treat say hypertension, andprescription is thus limited to benign hypertension.

The exposure was defined as ever use of these drugsor not. Duration was calculated from the first use afterJanuary 1, 1996 and the occurrence of a fracture duringthe year 2000 among the fracture patients or thecorresponding dummy date among the controls. The totaldose was calculated as the total number of redeemeddaily doses of the drug in question from the first day ofuse to the date of fracture or corresponding dummy dateamong the control subjects. Average daily dose wascalculated as total dose divided by time from first use tothe date of fracture or corresponding dummy date amongthe controls. Regarding recency, this was defined as thelast date where a prescription of the drug in question wasmade.

The other exposure variables were occurrence of (1) theuse of drugs known to be associated with fracture risk(corticosteroids, anti-epileptic drugs, LHRH agonists), (2)the number of contacts to the health service (hospitals,general practitioners or specialists) as a proxy variable fordisease severity [20], and the Charlson index, which is anindex of 19 comorbid conditions [21], and (3) socialvariables [22]. These factors were chosen as they wereknown to potentially affect fracture risk, and were regardedas important potential confounders in a setting where manyvariables besides the main factor may influence the risk offractures (confounding by indication). The variables wereentered into the statistical analysis, and analyses forinteraction were performed. Other important disease con-founders included (1) alcoholism [23], (2) occurrence of a

732 Osteoporos Int (2011) 22:731–737

prior fracture or not [24], (3) prostate cancer and (4)orchiectomy.

The social variables were: (1) working or not, (2) incomein the year of the fracture (dichotomised by averageincome) and (3) living alone or together with anotherperson. These factors were included as prior studies haveindicated that living in a relationship rather than livingalone may be associated with a decreased risk of fractures,and that having a job may be associated with fewerfractures than being retired or out of a job, and that incomein some settings may be a predictor of fracture risk [22].

Registers used

The information on fracture occurrence and occurrence ofother diseases, prior fractures, alcoholism came from tworegisters: (1) The National Hospital Discharge Register [18]and (2) The Psychiatric Central Register [25].

The National Hospital Discharge Register was foundedin 1977 [18]. It covers all in-patient contacts from 1977 to1994, and also from 1995, all outpatient visits to hospitals,outpatient clinics and emergency rooms [18]. Upondischarge, the physician codes the reason for the contactusing the ICD system. The code used is at the discretion ofthe individual physician. The register has a nationwidecoverage and an almost 100% capture of contacts [18]. Ingeneral, the validity of registrations is high [19] especiallyfor fractures where a precision of 97% has been reportedboth for fractures treated on an in-patients basis and forfractures treated on an outpatient basis via emergencyrooms (say a forearm fracture) [26]. The cases occurredonly once in the analyses with the first occurrence of anincident fracture during the year 2000.

The National Health Service keeps a register of allcontacts to general practitioners for reimbursement purpo-ses. The register does not contain ICD codes for thecontacts but codes for the nature of the contact (regularcheck-up visit, routine vaccination in children).

The number of bed days in the year 1999 was counted asthe number of days the patient spent on an in-patient basisin any hospital in 1999. The number of contacts to generalpractitioner or specialist was counted as the total number ofreimbursement codes issued by the general practitioner orspecialist in the year 1999 for each patient.

The Danish Medicines Agency keeps a nationwideregister of all drugs sold at pharmacies throughout thecountry from 1996 and onwards (The National Pharmaco-logical Database run by the Danish Medicines Agency,http://www.dkma.dk). Any drug bought is registered withATC code, dosage sold and date of sale for the periodJanuary 1 1996 to December 31, 2000. As all sales areregistered to the individual who redeemed the prescription,the capture and validity is high.

The psychiatric central register along with the NationalHospital Discharge Register and the database on drugs soldformed the basis of classification as having a diagnosis ofalcoholism or using drugs against alcoholism.

Information on income was obtained from the Taxauthorities, and information on working status and maritalstatus from the National Bureau of Statistics (Statistics,Denmark).

It is possible to link these sources of information throughthe Central Person Register Number, which is a uniqueregistration code given to every inhabitant—to some degreesimilar to the American social security number—thatallows registration on an individual basis.

The project was approved and controlled by the NationalBoard of Health, the Danish Data Protection Agency andthe Directory Board of the Psychiatric Central Register.

Statistical analyses

Mean and standard deviation were used as descriptivestatistics. Crude and adjusted odds ratios (ORs), and 95%confidence intervals were calculated. A conditional logisticregression analysis was used to assess the associationbetween any fracture and the exposure variable. Crudeand multiply adjusted ORs were calculated. Analyses wereperformed using STATA 8.2 (STATA Corp., CollegeStation, TX) and SPSS 14.0 (SPSS Inc., Chicago, IL), bothin the UNIX version.

Results

Table 1 shows baseline characteristics of the patients andcontrols. The patients and controls were well matchedconcerning age and gender. Fracture cases more often thancontrols had comorbid conditions, had a diagnosis ofalcoholism and had prior fractures. The frequency of useof 5-α-reductase inhibitors or use of α-blockers was higheramong fracture cases than among controls.

Table 2 shows the crude risk of any fracture associatedwith 5-α-reductase inhibitors and α-blockers. There was asmall excess risk of any fracture with both the 5-α-reductase inhibitors and the α-blockers. No dose–responserelationship was present for the 5-α-reductase inhibitors,while for the α-blockers a decreasing risk of fractures waspresent with increasing average daily dose (for trend,p<0.01).

Table 3 shows the adjusted risk of any fractureassociated with the 5-α-reductase inhibitors and α-blockers. After adjustment, no significant decrease in therisk of any fracture was present for the 5-α-reductaseinhibitors, while a significant decrease was seen for the α-blockers. At average doses larger than 0.5 defined daily

Osteoporos Int (2011) 22:731–737 733

doses (DDD) per day, a statistically significant decreasewas seen for both 5-α-reductase inhibitors and α-blockers.No trend with dose was seen for the 5-α-reductaseinhibitors, while a decreasing trend with increasing dosewas seen for the α-blockers (for trend, p<0.01).

Table 4 shows the results for hip, forearm and spinefractures. For the hip fractures, no reduction in overall riskwas seen for the 5-α-reductase inhibitors, while a decreasewas seen for the α-blockers. For the α-blockers, a smallreduction in risk of hip fractures was present for the highestdoses, while for the 5-α-reductase inhibitors, a reduction wasseen for the lowest doses. For the hip fractures, a significantdecrease in fracture risk was present with dose for the α-blockers, but not for the 5-α-reductase inhibitors. For theforearm fractures, no significant change in fracture risk waspresent.For the spine fractures, a pattern similar to the hipfractures was present with a decrease at the highest doses ofthe α-blockers and a decrease with increasing dose. For the

Variable Cases (n=9,719) Controls (n=29,156) P

Age (years) 74.5±9.6 74.5±9.6 –

Annual income (DKR) 169.209±156.137 180.818±309.360 <0.01

Previous fracture 3,192 (32.8%) 3,185 (10.9%) <0.01

Number of bed days in hospital in 1999 7.8±29.3 20.2±43.2

Charlson indexa <0.01

0 4,588 (47.2%) 18,122 (62.2%)

1–2 3,210 (33.0%) 8,169 (28.0%)

3–4 1,261 (13.0%) 2,098 (7.2%)

≥5 660 (6.8%) 767 (2.6%)

No. of contacts to GP or specialists in 1999 37.6±56.9 25.8±40.2 <0.01

Living with someone 5,548 (57.5%) 19,246 (66.4%) <0.01

Working 1,204 (12.5%) 4,401 (15.2%) <0.01

Duration of follow-up before the index date 43,250 years 129,744 years –

Alcoholism 1,004 (10.3%) 957 (3.3%) <0.01

Ever use of anti-epileptic drugs 941 (9.7%) 1,363 (4.7%) <0.01

Ever use of any glucocorticoid 6,243 (64.2%) 17,063 (58.5%) <0.01

Loop diuretics 2,925 (30.1%) 5,555 (19.1%) <0.01

Thiazide diuretics 2,286 (23.5%) 6,262 (21.5%) <0.01

Potassium-sparing diuretics 615 (6.3%) 1,005 (3.4%) <0.01

Other diuretics 643 (6.6%) 1,918 (6.6%) 0.90

ACE inhibitors/ARB 1,800 (18.5%) 5,016 (17.2%) <0.01

α-blocking agents for hypertension 138 (1.4%) 418 (1.4%) 0.92

Beta blockers 1,372 (14.1%) 4,219 (14.5%) 0.39

Calcium channel blockers 2,020 (20.8%) 5,608 (19.2%) <0.01

Weak analgesics 7,694 (79.2%) 17,941 (61.5%) <0.01

Strong analgesics 5,208 (53.6%) 7,506 (25.7%) <0.01

Ever use of 5-α-reductase inhibitors 663 (6.8%) 1,806 (6.2%) 0.03

Ever use of α-blocking agents for BPH 1,356 (14.0%) 3,663 (12.6%) <0.01

Prior prostate cancer 395 (4.1%) 613 (2.1%) <0.01

LHRH agonists 26 (0.3%) 25 (0.1%) <0.01

Orchiectomy 230 (2.4%) 377 (1.3%) <0.01

Table 1 Baseline characteristicsof fracture cases and controls—only men ≥60 years

GP general practitioner, DKRDanish crowns (5.5 DKR∼US$1), ACE angiotensin-converting enzyme, ARB An-giotensin II receptor blockersa A composite index of 19 comor-bid conditions (see text)

Table 2 Crude OR for any fracture among users of 5-α-reductaseinhibitors or α-blockers

Drug OR (95% CI)

α-blockers 1.13 (1.06–1.21)*

Average daily dose of α-blocker

≤0.1 DDD per day (532/1268) 1.28 (1.15–1.42)*

0.11–0.5 DDD per day (408/1069) 1.16 (1.04–1.31)*

>0.5 DDD per day (416/1326) 0.96 (0.85–1.07)

5-α-reductase inhibitors 1.11 (1.01–1.22)*

Average daily dose of 5-α-reductase inhibitors

≤0.1 DDD per day (203/559) 1.10 (0.93–1.29)

0.11–0.5 DDD per day (242/558) 1.31 (1.12–1.53)*

>0.5 DDD per day (218/689) 0.96 (0.82–1.11)

*: 2p<0.05

734 Osteoporos Int (2011) 22:731–737

5-α-reductase inhibitors, an increase was present at thelowest doses, and no dose–response was present.

Table 5 shows the effect of treatment duration on risk ofany fracture. For the 5-α-reductase inhibitors, no trend withduration was present. For the α-blockers, the time interval1–3 years of treatment was associated with a decrease in therisk of fractures.

Table 6 shows the effects of age. No trend with age waspresent for the 5-α-reductase inhibitors while for the α-blockers, the effect tended to be more pronounced in thoseolder than 80 years than in younger men but only for theaverage doses >0.5 DDD per day.

The effect of α-blockers on overall risk of fracturesdisappeared more than 3 month after last use (for anyfracture: for ≤3 months, adjusted OR=0.76, 95% confidenceof intervals (CI): 0.67–0.86; for 3 months–2 years after lastuse, crude OR=1.05, 95% CI: 0.93–1.18; >2 years since lastuse, crude OR=1.03, 95% CI: 0.91–1.16). For the 5-α-

Table 3 Adjusted OR for any fracture among users of 5-α-reductaseinhibitors or α-blockers

Drug OR (95% CI)

α-blockers 0.93 (0.86–1.00)

Average daily dose of α-blocker(DDD per day)≤0.1 1.05 (0.93–1.17)

0.11–0.5 0.91 (0.80–1.04)

>0.5 0.83 (0.74–0.94)*

5-α-reductase inhibitors 0.93 (0.84–1.03)

Average daily dose of 5-α-reductaseinhibitors (DDD per day)≤0.1 0.88 (0.74–1.05)

0.11–0.5 1.08 (0.91–1.28)

>0.5 0.84 (0.71–0.99)*

Adjusted for prior fracture, ever use of corticosteroids, ever use ofdrugs against epilepsy, ever use of strong analgesics, ever use of weakanalgesics, Charlson index, number of bed days in 1999, number ofcontacts to GP or specialist in 1999, alcoholism, income, working ornot, living with someone or living alone, use of beta blockers, use ofcalcium channel blockers, use of ACE inhibitors/angiotensin IIreceptor blockers, α-blockers as antihypertensives, loop diuretics,thiazide diuretics, potassium-sparing and other types of diuretics,prostate cancer, orchiectomy and use of LHRH agonists

*: 2p<0.05

Table 4 Adjusted OR for hip, forearm and spine fractures

Drug Hip Forearm Spine

α-blockers 0.86 (0.74–0.99)* 0.89 (0.68–1.16) 0.99 (0.71–1.39)

Average daily dose of α-blocker (DDD per day)

≤0.1 0.99 (0.80–1.22) 1.17 (0.81–1.69) 1.52 (0.93–2.48)

0.11–0.5 0.89 (0.70–1.12) 0.71 (0.44–1.16) 1.10 (0.62–1.95)

>0.5 0.71 (0.57–0.90)* 0.73 (0.46–1.15) 0.56 (0.32–0.97)*

5-α-reductase inhibitors 0.92 (0.77–1.11) 1.21 (0.85–1.72) 1.15 (0.74–1.77)

Average daily dose of 5-α-reductase inhibitors (DDD per day)

≤0.1 0.57 (0.40–0.82)* 1.14 (0.64–2.04) 2.48 (1.15–5.32)*

0.11–0.5 1.25 (0.93–1.68) 1.13 (0.63–2.04) 0.97 (0.47–1.98)

>0.5 0.99 (0.74–1.32) 1.39 (0.77–2.50) 0.79 (0.40–1.56)

Adjusted for prior fracture, ever use of corticosteroids, ever use of drugs against epilepsy, ever use of strong analgesics, ever use of weakanalgesics, Charlson index, number of bed days in 1999, number of contacts to GP or specialist in 1999, alcoholism, income, working or not,living with someone or living alone, use of beta blockers, use of calcium channel blockers, use of ACE inhibitors/angiotensin II receptor blockers,α-blockers as antihypertensives, loop diuretics, thiazide diuretics, potassium-sparing and other types of diuretics, prostate cancer, orchiectomy anduse of LHRH agonists

*: 2p<0.05

Table 5 Effect of duration of treatment on risk of any fracture

Duration (years) OR (95% CI)

α-blocker

≤1 0.93 (0.83–1.05)

1.1–3 0.86 (0.75–0.98)*

>3 0.98 (0.87–1.11)

5-α-reductase inhibitors

≤3 0.91 (0.76–1.09)

3.1–5 1.01 (0.85–1.19)

>5 0.88 (0.75–1.03)

Adjusted for prior fracture, ever use of corticosteroids, ever use ofdrugs against epilepsy, ever use of strong analgesics, ever use of weakanalgesics, Charlson Index, number of bed days in 1999, number ofcontacts to GP or specialist in 1999, alcoholism, income, working ornot, living with someone or living alone, use of beta blockers, use ofcalcium channel blockers, use of ACE inhibitors/angiotensin IIreceptor blockers, α-blockers as antihypertensives, loop diuretics,thiazide diuretics, potassium-sparing and other types of diuretics,prostate cancer, orchiectomy, and use of LHRH agonists.

*: 2p<0.05

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reductase inhibitors, any effects were also only seen with usewithin the last 6 months: adjusted OR=0.80, 95% CI: 0.67–0.95; 6 month–3 years, OR=1.01, 95% CI: 0.85–1.21;>3 years since last use OR=0.99, 95% CI: 0.85–1.16).

Discussion

In this large-scale population-based case-control study, noincrease in the risk of fractures at any of the sites studied wasseen for the 5-α-reductase inhibitors. Also, no dose–responserelationship was present for the 5-α-reductase inhibitors. Thefew significant findings for the 5-α-reductase inhibitors didnot show any pattern and may be due to chance findings. Forthe α-blockers, a trend towards fewer fractures was seen bothfor overall risk of fractures, hip fractures and spine fractures,while no trend was present for the forearm fractures. In theinterpretation of the results, it should be noted that only a fewsubgroup analyses showed statistical significance and chancefindings are a possibility.

None of the prior studies have specifically addressed theα-blockers used for BPH, but the study by Souverein et al.[13] which addressed all α-blockers, both those forcardiovascular disease and those for BPH, failed to show adecreasing trend in hip fracture risk with cumulated dose.The study observed an excess hip fracture risk for the α-blockers used for cardiovascular disease early after treatmentinitiation. This may signal that the α-blockers used for BPHmay have a particular effect, which may differ from thoseused against hypertension. However, a selection bias mayalso be a possibility—those with a high risk of falls are nottreated with the α-blockers of fear from falls [9]. This is thefirst major study on α-blockers used specifically for BPHwith fractures as end point. The dose dependent decrease inrisk of fractures for several fracture types with α-blockers

may indicate that the relationship may be causal. If therelationship was spurious, those falling would terminate thedrugs and thus those with low exposures should have anexcess risk of fractures, and those who tolerate the drugsshould not have any decrease in the risk of fractures. Onlyfor the spine fracture was an excess risk of fractures seenwith low doses, while a decrease was seen for hip fractures.This speaks against a spurious relationship. However, morestudies are needed to confirm the effect. The blood pressure-lowering effect of the α-blockers used for BPH maydecrease urine calcium loss [27], and the effect on fracturerisk may thus be the same as seen for other drugs usedagainst hypertension [28]. If this truly is the mechanism, theeffect should be limited to patients with high blood pressure.More research is needed to determine the limits above whichblood pressure lowering may prevent fractures as well asestablish the limits below which blood pressure should notbe lowered. Analyses of secondary end points from the largerandomised controlled trials on antihypertensives may provea good source for such studies.

It also needs to be established if the fracture preventionis solely limited to a blood pressure effect or whether adirect effect on the α-receptors may also play a role.Treatment with epinephrine, an α-receptor agonist, hasshown to increase osteoclast differentiation factor [15]. Itmay thus be that inhibition of this signal may decreaseosteoclast activity, bone remodelling and bone loss.However, more work is needed to confirm this hypothesis.

The absence of a decrease in risk of any fracture less than1 year after the start of the α-blockers followed by a decrease1–3 years after the start and a reversal to no increase ordecrease in risk of any fracture more than 3 years after start ofthe α-blocker may signal a double effect. First of all, it maytake some time for the blood pressure to decrease and urinecalcium excretion to adapt, therefore an effect is first seen after

Table 6 Effects of age group on risk of any fracture

Average daily drug dose 60–69years 70–79years ≥80years

α-blockers (DDD per day)

≤0.1 1.05 (0.81–1.35) 1.17 (0.96–1.42) 1.01 (0.85–1.20)

0.11–0.5 0.84 (0.64–1.12) 0.91 (0.73–1.13) 0.99 (0.81–1.20)

>0.5 0.85 (0.64–1.11) 1.02 (0.83–1.24) 0.72 (0.60–0.88)*

5-α-reductase inhibitors (DDD per day)

≤0.1 0.88 (0.57–1.36) 0.84 (0.63–1.13) 0.94 (0.73–1.22)

0.11–0.5 0.69 (0.44–1.07) 0.98 (0.75–1.30) 1.41 (1.10–1.80)*

>0.5 0.66 (0.41–1.08) 0.85 (0.64–1.12) 0.93 (0.74–1.18)

Adjusted for prior fracture, ever use of corticosteroids, ever use of drugs against epilepsy, ever use of strong analgesics, ever use of weakanalgesics, Charlson index, number of bed days in 1999, number of contacts to GP or specialist in 1999, alcoholism, income, working or not,living with someone or living alone, use of beta blockers, use of calcium channel blockers, use of ACE inhibitors/angiotensin II receptor blockers,α-blockers as antihypertensives, loop diuretics, thiazide diuretics, potassium-sparing and other types of diuretics, prostate cancer, orchiectomy anduse of LHRH agonists.

*: 2p<0.05

736 Osteoporos Int (2011) 22:731–737

some time. However, this time dependency could also signalan effect mediated over BMD, which takes some time to setin. Secondly, the lack of an effect with more than 3 years oftreatment may be the effect of lack of adherence or anadaption to the effects of the α-blockers, so that some of theinitial effect is lost. The age effect with a more pronouncedeffect in older menmay be due to a higher risk of hypertensionwith age [29], and perhaps also a higher risk of osteoporosisand fractures with age [16].

The main advantage of the study is the large study size,the long duration of follow-up and the completeness andquality of diagnoses during follow-up. The major draw-backs are lack of information on individual parameters suchas weight, height, blood pressure, and smoking.

In conclusion, neither the 5-α-reductase inhibitors nor α-blockers were associated with negative effects on fracturerisk. A small trend towards a decrease in fracture risk maybe present for the α-blockers. However, more research isneeded to confirm if this trend is real.

Conflicts of interest None.

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