Am 10.45 lindsay bone health

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  • With the strength data and the various architectural measures quantified we then use logistic regression models to examine the relative contribution of each of the elements to overall bone strength. Shown here are some of the results. If we use a simple one variable model, bone volume can explain about 76% of the observed strength. Used singly the various trabecular elements account formore than 60% of the strength. Trabecular thickness is shown here. Other single elements also show comparable results. IF we begin to use multiple variable models we can account for a larger and larger fraction of the observed strength. Trabecular separation and thickness together can account for about 80% of observed bone strength. And the combination of bone volume, the standard deviation of trabecular separation and trabecular number (which is essentially a way to describe how many trabeculae there are and how they are spaced) can explain over 90% of the observed strength.
  • I’ve talked about a lot different things in the last 30 minutes
  • Am 10.45 lindsay bone health

    1. 1. Bone Health in theReproductive Years Robert Lindsay Helen Hayes Hospital & Columbia University New York
    2. 2. Competing Interests• Consultant - Eli Lilly, Amgen, Azelon• Speaker – Eli Lilly, Amgen, Warner-Chilcott• Institutional Research Grants – Eli Lilly, Amgen, Pfizer This talk will not discuss specific therapeutic agents
    3. 3. Bone Mass by Age
    4. 4. Outline• Determinants of peak skeletal mass• Bone mass and its control during premenopausal years• Interpretation of bone density in young women• Commonly seen intercurrent problems affecting skeletal status in young women
    5. 5. Outline• Determinants of peak skeletal mass
    6. 6. Bone growth and peak skeletal mass• Heredity – 80% of variability in peak bone mass thought to be under genetic control• 241 SNP’s from 9 genes identified as significantly associated with BMD or fracture – Wnt signaling (LRP5, LRP4, SOST) – RANK, RANK-L, OPG Richards Annals Internal Medicine 2009
    7. 7. Discovery of the HBM Phenotype • Proband was 18-yr-old woman referred to Creighton ORC due to “unusually dense” femur • Hip and spine density 5 standard deviations above normal population (Z-score) • All bones were of normal shape • No history of any type of bone fracture and no indication of adverse effects on health Proband Normal • 17 out of 37 members of the family exhibited the HBMJohnson ML, et al. Am J Hum Genet. 1997;60:1326-32. phenotype
    8. 8. Peak Bone Mass Bone mass reaches a peak at between 18 and 25 years of age Genetics  Allelic variation in several different genes influences peak bone mass Endocrine status  Age of menarche  Use of birth control  Altered menstruation status  Altered levels of testosterone
    9. 9. Peak Bone Mass Load bearing physical activity can help increase bone mass  Childhood Exercise  Adult Exercise  Sport Specific Exercise Body Composition Nutritional Status  Calcium  Vitamin D  Protein  Other factors
    10. 10. Protein and Bone Health• Relatively high protein intake favors bone growth accrual during childhood1• In adult women there is a positive association reported between protein intake and BMD 1-3 although several studies report no association 4-7 and excessive intake was related to lower BMD 8.• Diets moderate in protein (1 to 1.5 g protein/kg) are associated with normal calcium metabolism10. 1. Chevally 2002 2. Hirota 1992 6. Mazess 1991 3. Cooper 1996 7. New 1997 4. Teegarden 1998 8. Nieves 1995 5. Henderson 1995 9. Anderson 1995 10. Kerstetter 2003
    11. 11. Bone growth and peak skeletal mass• Nutrition – In utero and early life* – Growth (protein calcium and vitamin D) • Micronutrients• Physical Activity (may be maintained into adulthood**) *Cooper OI 2011; **Erlandson et al JBMR 2012
    12. 12. Higher Fruit and Vegetable Intake Relates to Greater Estimated % Change BMD 8 7 6 5 boys 4 girls 3 2 spine BMD (% difference) 1 0 fruit fruit & vegetablesMedian=250 gm Prynne et al, Am J Clin Nutr, 2006WHO 2005; 400 gm
    13. 13. Physical Activity• Impact loading increases skeletal strength especially during growth• These effects are continued into adulthood• Total body BMC at 11yrs of age 1400g vs 1100g for non-gymnasts and at 25 (retired for 6-14yrs) TB-BMC was 2400g vs 2200 in non-athletes Corrected for height, weight, Erlandson et al JBMR 2012 menarchal age
    14. 14. Milk and CheeseSupplementation Cadogan et al, BMJ 1997 Cheng 2007
    15. 15. Milk Intake Versus Soda Intake
    16. 16. Bone Turnover Responses to 10-dayIntervention with 2.5 Liters of Milk or Cola Respectively in Young Men Parameter and Baseline After 10 days Treatment Treatment PTH, pmol/l Milk 4.9 + 1.2 5.3 + 1.5 P =0.046 Cola 5.1 + 1.2 5.9 + 0.9 Osteocalcin, µg/l Milk 45.3 + 13.7 36.8 + 11.8 P =<0.001 Cola 44.5 + 19.6 50.6 + 17.1 CTX, µg/l Milk 0.8 + 0.3 0.6 + 0.2 P =<0.001 Cola 0.8 + 0.4 0.9 + 0.3 NTX, nmol BCE/mmol creatinine Milk 62.1 + 19.2 47.3 + 15.5 P = <0.001 Cola 61.8 + 22.8 66.3 + 17.1 Kristensen et al, Osteoporos Int 2005
    17. 17. Lumbar spine L2–L4BMC and BMD in 192adolescent girls. BMCand BMD values (zscore)Esterle L, OI 2009
    18. 18. Vitamin D Intake and Bone Mass in Children:• Vitamin D Supplementation in Infancy (400 IU/d) for median 12 months vs. BMD age 7-9 1• In 168 Finnish girls age 14-16, those with 25(OH)D <25nmol/L had lower radial BMD.2• A cross sectional study in young Finnish men age 18-20 found approximately 4% difference in BMD between high vs low serum 25(OH)D3. 1. Zamoraa 1999. 2. Cheng 2003. 3. Valimaki 2004
    19. 19. Impact of MenstrualFunction On Bone Mass and Size
    20. 20. Contraception in teenagers• May impede final skeletal growth perhaps by suppressing IGF-1 Soyka et al. JCEM 1999
    21. 21. Impact of OC on Bone Size and Mass
    22. 22. Contraception in adults• Bone remodeling is controlled by estrogen (in both genders)• At any age loss of ovarian estrogen production increases bone remodeling and eventually loss of architecture and mass• In adults in combination OC products there is usually sufficient synthetic estrogen to protect the skeleton
    23. 23. Contraception in adults• OC use does not seem to change BMD in women 20-40yrs• OC use after 40 may retard the pre and perimenopausal acceleration of bone loss
    24. 24. Progestin Contraception• Depot MPA – most studies suggest some deterioration in BMD in young women• But positive effects on BMD suggested for norethisterone, L-norgestrel, and oral MPA
    25. 25. Correlations Between Nutrients and BMD and BMD Change FN BMD FN BMD (adjusted) change (adjusted) Calcium Diet only (mg) 0.172 0.229 Total calcium (mg) 0.164 0.203 Phosphorous (mg) 0.160 0.244 Potassium (mg) 0.182 0.160 Magnesium (mg) 0.167 0.199 Zinc (mg) 0.081 0.057 Folate (mg) 0.095 0.131 Vitamin C (mg) 0.195 0.199 n=146 perimenopausal McDonald et al, Am J Clin Nutr 2004
    26. 26. Vitamin D Intake and Bone Mass in ChildrenIn a 3-year longitudinalstudy of 171 peripubertalgirls, there was asignificant associationbetween the baselineconcentration of 25(OH)Dand 3-year change in BMDof the lumbar spine andfemoral neck. Lehtonen-Veromaa, et al Am J Clin Nutr 2002
    27. 27. Engage in Regular Physical ActivityInteraction Between Exercise and Calciumon gain in Tibia-Fibula BMC (g/ 8.5 months) Bass et al, JBMR, 2007
    28. 28. Interaction Between Calcium and Exercise Cortical Thickness for Each Level of Exercise and Milk Intake 7.0 7.0 6.5 6.5 H M H Cortical H M Cortical M L LOW <1 milk (glasses/day) L L (glasses/day)Thickness 6.0Thickness 6.0 L M (mm) (mm) M 1 to 2 MEDIUM 1 to 2 milk (glasses/day) H milk L 5.5 5.5 H HIGHmilk > 3 milk (glasses/day) >=3 5.0 5.0 0.0 0.0 1 to 3 4 to 6 7 to 10 > 11 Hours of Exercise/Week Hours of Exercise/Week
    29. 29. Interaction Between Calcium,Vitamin D Intake and ExerciseRecker 1992Lohman 1995Prince 1995Specker 1996Stear 2003Jones 1998Rowlands 2004Lloyd 2004Courteix, 2005Cussler 2005Ianc 2006Bass 2007
    30. 30. Lifestyle Variables forMale Cadets prior to entry
    31. 31. Milk ExerciseInteraction- Males
    32. 32. PEAK BONE MASS GRAPH Healy et al, Peak Bone Mass Osteoporisis International (2000) 11:985-1009
    33. 33. Effect of Pregnancy on Bone Remodeling Bone Resorption Bone Formation Weeks of Gestation Black et al, 2000
    34. 34. The Bone Strength Framework BONE STRENGTH BONE STRUCTURE BONE MATERIALSTATIC e.g. Architecture e.g. crystal size Shape collagen quality BMD BMDDYNAMIC OPTIMAL LEVEL OF BONE REMODELING
    35. 35. Metabolically vs Mechanically Driven Remodeling Bone Turnover Rate Metabolically driven remodeling (Excess) ? Optimum Mechanically driven remodeling (Essential)
    36. 36. Outline• Interpretation of bone density in young women
    37. 37. Bone Density by DXA• Measures absorption or deflection of x-rays divided by the perceived area of tissue• Does not measure “density” (gms/cc)• Small people have small bones interpreted by DXA as low bone density!• In healthy premenopausal women results in the low BMD range should be considered to be normal (i.e. within the range for 25 year olds)• The presence of a co-morbidity changes that conclusion and may require further patient assessment
    38. 38. PLEASE – PLEASE - PLEASECAN WE KILL OSTEOPENIA! When talking about young women!
    39. 39. For premenopausal women a negative T- score usually means you are below the population average value!Being 61 inches means you are below average height – not that you have inchopenia (feetopenia or centimopenia)
    40. 40. BMD Testing in Premenopausal Women• Generally not necessary or clinically relevant• May be useful when comorbidities known to affect the skeleton are present (MS, AN Steroid Rx etc)• May be useful when fractures occur in unusual circumstances i.e. modest trauma
    41. 41. Thank you for referring Ms Smith for bone density evaluation. Her T-score is -2 which increases her risk of fracture by 4 times.
    42. 42. Thank you for referring Ms Smith for bone density evaluation. Her T-score is -2 which increases her risk of fracture by 4 times.What think you if Ms Smith is 60 inches and 100lbs?
    43. 43. Thank you for referring Ms Smith for bone density evaluation. Her T-score is -2 which increases her risk of fracture by 4 times.What think you if Ms Smith is 70 inches and 200lbs?
    44. 44. Thank you for referring Ms Smith for bone density evaluation. Her T-score is -2 which increases her risk of fracture by 4 times.What if she is 70 yrs old?
    45. 45. Predicting Bone Strength From ArchitectureParameter R2Bone Volume (BV/TV) .76Trabecular Thickness .63Tb. Separation + Tb. Thickness .83Volume+ SD- Tb Separation + Tb .92Number
    46. 46. Bone Quality Is Maximized When Turnover Is Within the Physiological Window Physiological Bone Quality Window Bone TurnoverToo little turnover: Aging bone, unrepaired Too much turnover:micro-cracks, hyper-mineralized Under-mineralized, stress risers
    47. 47. Functions of Bone Remodeling Repair of Microdamage (Bone 28:524-531, 2001)
    48. 48. FATIGUE CRACKS :MECHANICAL STRESS RISERS www.tam.uiuc.edu
    49. 49. Co-Morbidities• Any chronic disease that interferes with activity, nutrition or ovarian function can negatively impact on the skeleton
    50. 50. Co-Morbidities• Any chronic disease that interferes with activity, nutrition or ovarian function can negatively impact on the skeleton• The classic example is anorexia nervosa
    51. 51. Drugs that affect the skeleton• Steroids• Psychotropic Medications• Diabetes treatment• PPI’s• Anticonvulsants• Aromatase Inhibitors• GnRH agonists• Chemotherapeutic agents• Etc, etc,
    52. 52. General Recommendations for Osteoporosis• Maintain Physical Activity – do something you like and make it a social experience• Eat a good diet – modest amounts of red meat (acid load), but high in fruits and vegetables• Try to get 1000-1500mg calcium per day (on average) from diet.• Supplement vitamin D intake• Avoid cigarettes and keep alcohol intake modest
    53. 53. Conclusions• Try to avoid the overuse of BMD measurements in young persons• Do not ever tell someone they have osteopenia• Avoid using osteoporosis medications whenever possible, at least until after menopause• If fractures are present evaluate and treat

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