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Osteoporosis in Men

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					                            Chapter III.
                              Osteoporosis in Men




La Lettre du Rhumatologue                 ASBMR 2007
             Osteoporosis in Men                                                                                 28


      Endogenous Sex Hormones and Incident Fracture Risk in Older Men
                         The DUBBO Study (1)

           Data on the relationship between serum testosterone and estradiol level
            and the risk of osteoporotic fractures in elderly men remain controversial
           Prospective cohort: 1990-2006, community dwelling men > 60 years

           Baseline: for all patients
            – risk factors, serum samples
            – measurements: serum testosterone, estradiol by mass spectrometry
                                   SHBG by immuno-assay
            – spine and femoral BMD (DPX, Lunar)

           Incidence of low trauma fractures assessed by X-ray
            609 men, mean age 73 years, mean follow up 5.8 years (1-12 years)
            – 113 men with 149 incident fractures
            – 496 non fracture controls


La Lettre du Rhumatologue               ASBMR 2007 – From Meier CH et al., Basel, Switzerland, abstract 0358, updated
             Osteoporosis in Men                                                                                         29


      Endogenous Sex Hormones and Incident Fracture Risk in Older Men
                         The DUBBO Study (2)
                  Sex hormones and fracture risk: unadjusted and adjusted analysis
                                                                          HR (95% CI)                    P-value
     Serum testosterone
     Unadjusted                                                         1.33 (1.09-1.62)                 0.004
     Adjusted for SHBG                                                  1.48 (1.22-1.78)                < 0.0001
     Adjusted for SHBG, age                                             1.31 (1.06-1.58)                 0.005
     Adjusted for SHBG, age, weight                                     1.26 (1.03-1.55)                 0.022
     Adjusted for SHBG, age, femoral neck BMD                           1.20 (0.98-1.47)                 0.074
     Serum estradiol
     Unadjusted                                                         1.16 (0.95-1.40)                  0.140
     Adjusted for SHBG                                                  1.21 (1.00-1.47)                  0.046
     Adjusted for SHBG, age                                             1.18 (0.98-1.43)                  0.087
     Adjusted for SHBG, age, weight                                     1.17 (0.96-1.43)                  0.110
     Adjusted for SHBG, age, femoral neck BMD                           1.12 (0.92-1.37)                  0.270

           Serum testosterone, but not estradiol, was an independent predictor
            of fracture risk in elderly men
           Measurements of testosterone may provide incremental prognosis
            value for assessment of fracture risk

La Lettre du Rhumatologue                       ASBMR 2007 – From Meier CH et al., Basel, Switzerland, abstract 0358, updated
             Osteoporosis in Men                                                                                        30


Serum DHEA is Independently of Sex Hormones Related to Incident Fractures
               in Elderly Men – The MrOS SWEDEN Study
                            Yearly incidence of fractures in relation to serum DHEA
                     after adjustment for free estradiol and free testosterone serum levels

                                     0.12

                                     0.10
                 Yearly incidence
                  of all fractures




                                     0.08

                                     0.06

                                     0.04

                                     0.02

                                       0
                                        0.1       1                        10 DHEA (ng/ml)

     Elderly men with low free estradiol or low free testosterone have an increased risk of fracture
     Serum DHEA levels are an independent predictor of fracture risk in elderly men
            Aged-adjusted model including free estradiol and free testosterone
            All incident fracture: DHEA (HR per SD decrease) = 1.25 (1.09-1.44)
            Non-vertebral osteoporotic fractures: DHEA (HR per SD decrease) = 1.32 (1.07-1.63)

La Lettre du Rhumatologue                     ASBMR 2007 – From Ohlsson C et al., Gothenburg, Sweden, abstract 1200, updated
              Osteoporosis in Men                                                                                       31


      Biochemical Markers of Bone Turnover and the Risk of Non-Vertebral
                          Fractures in Older Men (1)
            Nested case-control study within the Osteoporotic Fractures in Men (MrOS) study
         –       406 men with ≥ 1 incident non-vertebral fracture (NVF) during a mean follow-up
                 of 4.2 yrs (± 1.6)
         –       922 randomly selected controls among the 5,995 MrOS subjects
         –       outcomes
                • fasting baseline serum for PINP, CTX and TRACP5b measurements
                • hip BMD measured by DXA (Hologic QDR 4500) at baseline and follow-up
         –       multivariate models adjusted for age and clinic for fracture outcomes and bone loss
            Results
         –        compared to men without fracture, those with ≥ 1 incident NVF were older
                  (75.4 ± 6.4 versus 73.6 ± 5.9 yrs, p < 0.05) and had lower baseline hip BMD
         –        baseline hip BMD was lower and hip bone loss was greater among men
                  in the highest quartile of PINP, CTX or TRACP5b




La Lettre du Rhumatologue                      ASBMR 2007 - From Bauer DC et al., San Francisco, USA, abstract 1074, updated
             Osteoporosis in Men                                                                                      32


       Biochemical Markers of Bone Turnover and the Risk of Non-Vertebral
                           Fractures in Older Men (2)

   –     In multivariate analyses adjusted for age and baseline hip BMD, markers of bone turnover
         were neither associated with the risk of incident NVF nor with that of hip fracture
                Turnover and fracture risk, BMD adjusted (highest quartile versus other 3)
                                                                                     Relative Hazard (95% CI)*
              Fracture                  PINP                         sCTX                        TRACP5b
                                         1.1                          0.9                            1.0
             Non-spine
                                      (0.9-1.5)                    (0.7-1.2)                      (0.7-1.3)
                                         1.1                          0.9                            0.7
                 Hip
                                      (0.6-2.0)                    (0.5-1.6)                      (0.4-1.2)

       *Age, clinic and hip BMD adjusted
       Separate model for each marker and fracture type

    Although higher levels of bone turnover were associated with greater hip bone loss,
     increased turnover was not independently associated with the risk of hip or NVF


La Lettre du Rhumatologue                    ASBMR 2007 - From Bauer DC et al., San Francisco, USA, abstract 1074, updated
             Osteoporosis in Men                                                                                           33


                          Diabetes and Fracture Risk in Older Men
                       The Osteoporotic Fractures in Men (MrOS) Study
                 Risk of any non-spine fracture (compared with non-Diabetic Men [DM])
Adjusted for…
           Age, race, clinic site, total hip                                       2.2          Insulin
           BMD, BMI, grip strength,                                    1.9                      Oral DM med*
           walking speed, use arms for
           chair stand, osteoporosis                               0.83                         Non-DM med
           drug use, stroke, eGFR                                1.0                            Non-DM

           All of the above and                                                   2.0
           fall in previous year                                       1.0
                                                                   0.82
                                                                                     * DM med: diabetic men medication
                                                                 1.0
                            0.1                           1.0                                 10.0
                                                      RR (95% CI)

    Compared with non-DM, fracture risk was increased in older diabetic men
     on insulin therapy but not among others with diabetes, even after adjusting
     for more frequent falls

La Lettre du Rhumatologue                      ASBMR 2007 – From Schwartz AV et al., San Francisco, USA, abstract 1161, updated
             Osteoporosis in Men                                                                                                              34


          Aortic Calcification Correlate with Volumetric Bone Mineral Density
             and Bone Microstructure in Men: a Population-Based Study
       Relationship of vertebral vBMD and aortic calcifications in Rochester, Minnesota Men
                                              250
                                                                                               p < 0.001
                Vert trabecular vBMD mg/cm3




                                              200


                                              150                                                                * Age < 50 years
                                                                                                                 * Age 50+ years
                                              100


                                              50

                                                    0   1        2       3        4        5        6
                                                            Log (Agatston per CT Slice)

          vBMD is inversely correlated with aortic calcification (AC) in men
           This correlation seems to disappear with age adjustment
          Specific changes in bone microstructure correlate with AC in older men
           They could result from common mechanisms regulating bone structure and vascular
           calcification
La Lettre du Rhumatologue                                                 ASBMR 2007 – From Chow JT et al., Rochester, USA, abstract 1160, updated
             Osteoporosis in Men                                                                                                35


      Asymmetry in Leg Power Increases Non-Spine and Hip Fracture Risk
         in Older Men: the Osteoporotic Fractures in Men (MrOS) Study

                                 Risk of hip fracture hazard ratio (95% CI)
       Model 1: Adjusted for        1.00
       age and clinical center      1.74*                                                  Similar leg power
                                    3.32*
                                                                                           Asymmetrical leg power
       Model 2: Multivariate        1.00
       adjustment*                  1.66*                                                  Unable leg power
                                    3.19*

       Model 3: Multivariate        1.00
       adjustment plus leg BMD      1.65*                                                  *p < 0.05
                                    4.85*
                                                                                           *Adjusted for age, clinical center
       Model 4: Multivariate        1.00                                                   and history of stroke
       adjustment plus              1.66*
       history of falls             3.19*

                                            0                                10

      Asymmetry in leg power is associated with an increased risk of non-spine or hip fracture
      Inability to complete leg power measure in one leg is associated with increased likelihood
       of falls and risk of fracture, especially hip fracture

La Lettre du Rhumatologue                       ASBMR 2007 – From Cawthon PM et al., San Francisco, USA, abstract 1158, updated
                                      Osteoporosis in Men                                                                                               36



                                    Arterial Oxygen Saturation During Sleep and the Risk of Fractures,
                                                     Falls and Mortality in Older Men

                                        Age-adjusted rates of fracture and mortality by oxygen saturation during sleep

                                       Non-spine fracture (n = 126 fx)                                                Mortality rate (n = 140 deaths)
                               40                                                                                40




                                                                                 Mortality rate (per 1,000 py)
Fracture rate (per 1,000 py)




                               35                                                                                35
                               30                                                                                30
                               25                                                                                25
                               20                                                                                20
                               15                                                                                15
                               10                                                                                10
                                5                                                                                 5
                                0                                                                                 0
                                      <1     1-3.5 3.5 < 10 10+                                                        <1     1-3.5 3.5 < 10 10+
                                           % time SaO2 < 90%                                                                % time SaO2 < 90%
                                Greater time spent at nocturnal saturation levels below 90% increases risk
                                 of fractures, falls and mortality

 La Lettre du Rhumatologue                                               ASBMR 2007 – From Cauley JA et al., Pittsburgh, USA, abstract 1157, updated
                               Osteoporosis in Men                                                                                           37


               SSRI Use is Associated with Increased Risk of Fracture Among Older Men

                         Medication use and fracture rate                     Multivariate analyses for SSRI use and fracture

                                                            SSRI users
                                                                                                                        Non-spine fracture
                         50           31                    Non-users          Adjusted model
                                                                                 Marker                                   HR (95% CI)
                                                                                                                             OR*
                                                                                             Marker                            OR*
per 1,000 person years
Age-adjusted fractures




                         40
                                                                               Age, hip BMD
                                                                                OC                                          2.3 (1.6-3.3)
                                                                                                OC                             1.44
                         30
                                                                               Age, hip BMD, fall history
                                                                                BAP
                         20                                 15                            BAP                                 1.61
                                                                                                                            2.1 (1.5-3.0)
                                                                               and SF-12 mental score
                         10                                                      P1NP      P1NP                                1.56
                                                                                                                              1.56
                                                                               Final adjusted model*                        1.9 (1.3-2.8)
                          0
                                       Non-spine fracture                        *Included adjustment for age, hip BMD, BMI, non-traumatic
                                                                                 fracture after age 50, falls in past 12 months, height change
                          95% CI: SSRI users: 17.0-45.4                          since age 25, SF-12 mental summary score, IADL impairment,
                                  Non-users: 13.1-15.9                           SF-12 physical summary score

                             Selective serotonin reuptake inhibitors (SSRI) use is associated
                              with increased risk of fracture in elderly men

    La Lettre du Rhumatologue                                            ASBMR 2007 – From Haney EM et al., Portland, USA, abstract 1159, updated
              Osteoporosis in Men                                                                                          38


         High Cardiovascular Risk in Men with Increased Bone Resorption
                               or Low Bone Mass

   Risk of major cardiovascular event in men with high BTM levels (> 1 SD above the mean)
                                  [n = 628], 8 years follow-up
        Marker                                                  OR*               95% CI                    p

        OC                                                      1.44            0.66-2.08                 < 0.28

        BAP                                                     1.61            0.56-2.68                 < 0.23

        P1NP                                                    1.56            0.38-2.65                 < 0.32

        Total DPD                                               2.90            1.41-5.98                < 0.005

        Free DPD                                                2.24            1.13-4.44                 < 0.03

        ßCTX-I                                                  2.37            1.09-5.16                 < 0.03

        * Adjusted for age, co-morbidity, aortic calcification score, season and creatinine concentration



            This study shows, for the first time, that increased bone resorption
             is associated with an increased cardiovascular risk in elderly men


La Lettre du Rhumatologue                                ASBMR 2007 - From Szulc P et al., Lyon, France, abstract S468, updated

				
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