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Chap ter III.

Chap ter III. Osteoporosis in Men. 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

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Chap ter III.

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  1. Chapter III. Osteoporosis in Men

  2. Osteoporosis in Men 28 Endogenous Sex Hormones and Incident Fracture Risk in Older MenThe 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

  3. Osteoporosis in Men 29 Endogenous Sex Hormones and Incident Fracture Risk in Older MenThe DUBBO Study (2) Sex hormones and fracture risk: unadjusted and adjusted analysis • 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

  4. 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 DHEAafter adjustment for free estradiol and free testosterone serum levels 0.12 0.10 0.08 Yearly incidence of all fractures 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

  5. 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

  6. 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)* *Age, clinic and hip BMD adjustedSeparate 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

  7. Osteoporosis in Men 33 Diabetes and Fracture Risk in Older MenThe 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 hipBMD, BMI, grip strength,walking speed, use arms forchair stand, osteoporosisdrug use, stroke, eGFR 2.2 Insulin 1.9 Oral DM med* Non-DM med 0.83 1.0 Non-DM All of the above andfall in previous year 2.0 1.0 0.82 * DM med: diabetic men medication 1.0 0.1 1.0RR (95% CI) 10.0 • 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

  8. Osteoporosis in Men 250 p < 0.001 200 Vert trabecular vBMD mg/cm3 * Age < 50 years* Age 50+ years 150 100 50 0 1 2 3 4 5 6 Log (Agatston per CT Slice) 34 Aortic Calcification Correlate with Volumetric Bone Mineral Densityand Bone Microstructure in Men: a Population-Based Study Relationship of vertebral vBMD and aortic calcifications in Rochester, Minnesota Men • vBMD is inversely correlated with aortic calcification (AC) in menThis 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

  9. Osteoporosis in Men Similar leg power Asymmetrical leg power Unable leg power 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 forage and clinical center 1.00 1.74* 3.32* Model 2: Multivariateadjustment* 1.00 1.66* 3.19* Model 3: Multivariateadjustment plus leg BMD 1.00 1.65* *p < 0.05 4.85* *Adjusted for age, clinical center and history of stroke Model 4: Multivariateadjustment plushistory of falls 1.00 1.66* 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

  10. 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 35 35 30 30 25 25 20 20 Mortality rate (per 1,000 py) Fracture rate (per 1,000 py) 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

  11. Osteoporosis in Men 37 SSRI Use is Associated with Increased Risk of Fracture Among Older Men Medicationuse and fracture rate Multivariate analyses for SSRI use and fracture • Selective serotonin reuptake inhibitors (SSRI) use is associated with increased risk of fracture in elderly men SSRI users Non-users 50 31 40 30 Age-adjusted fracturesper 1,000 person years 15 20 10 0 Non-spine fracture *Included adjustment for age, hip BMD, BMI, non-traumatic fracture after age 50, falls in past 12 months, height change since age 25, SF-12 mental summary score, IADL impairment, SF-12 physical summary score 95% CI: SSRI users: 17.0-45.4Non-users: 13.1-15.9 La Lettre du Rhumatologue ASBMR 2007 – From Haney EM et al., Portland, USA, abstract 1159, updated

  12. This study shows, for the first time, that increased bone resorption is associated with an increased cardiovascular risk in elderly men Osteoporosis in Men 38 High Cardiovascular Risk in Men with Increased Bone Resorptionor 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 ASBMR 2007 - From Szulc P et al., Lyon, France, abstract S468, updated La Lettre du Rhumatologue

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