1. MRC Human Nutrition Research, Cambridge, UK.
Moderate Alcohol Ingestion and Bone Quality: Old Associations but New Mechanisms
Jonathan J Powell
MRC Human Nutrition Research, Cambridge, UK.

2. Normal Bone
Osteoporotic Bone
UK Osteoporosis costs: 2 billion US dollars per annum.

3. Determinants of Skeletal Homeostasis and Bone Mass.
(Taken from Harada & Rodan Nature 2003.)

4. Alcohol and Bone Moderate alcohol intake and bone
Ethanol effects on bone
Non-ethanol effects on bone

5. Mortality
Risk of Death
Moderation
Excess
Abuse

6. Moderate Alcohol Consumption and Bone Mineral Density:
Measurement and Study Errors in Assessing Associations
Lack of Validated Alcohol Intake Methodology.
Lack of consumer recognition of alcohol intake.
(2) Fidelity of self-reported intakes.
General measurement error.
Lack of parity between studies
(1) Assessment of alcohol intakes.
(2) Linear investigations of non-linear associations.
(3) General sample size issues
Proc. Nut. Soc. (2006), 65,

8. BMD & FRACTURE RISK WHO Criteria:
Osteoprosis: BMD  2.5 SD below mean peak bone mass
of young, normal adult
or T score:  -2.5
Osteopenia: T score: < -1 but  -2.5
Normal: T score: 0 or  -1
For each SD decline in BMD there is a 2-fold increase
in fracture risk compared with a normal BMD.
(Taken from Cummings et al., JAMA 2002.)

9. Moderate Alcohol Consumption and Bone Health: Summary of Associations
Study Types.
EtOH and Fracture: Few studies & equivocal findings (but not –ve).
EtOH and BMD: Most cross sectional plus some longitudinal.
EtOH and BMD: Mainly post-menopausal women (Circumstantial).
Study Results.
(1) EtOH and BMD: Few and poor data show no association.
(2) EtOH and BMD: g/day- peak association.
(3) EtOH and BMD: Marked association c.f. nutrient effects
Proc. Nut. Soc. (2006), 65,

10. Am J Clin Nutr. 2000; 72(5):

11. Alcohol Intake and FN BMD Change
Mean ± 2 SEM
0.00
-0.20
-0.40
FN BMD CHANGE %/YR
-0.60
-0.80
-1.00
-1.20
QUARTILES OF ALCOHOL INTAKE
MacDonald et al Am J Clin Nutr Jan;79(1):155-65

12. Framingham Cohort

13. Alcohol and Bone Moderate alcohol intake and bone
Ethanol effects on bone
Non-ethanol effects on bone

14. Moderate Alcohol Consumption Bone Health: Potential Ethanol Effects
Estrogenic Effects of Ethanol
Stimulate ER activity (v. high dose).
Increase Androgen aromatisation (v. high dose)
Inhibit Estradiol Catabolism (No HRT-EtOH interactions)
Stimulate Calcitonin (high dose).
Inhibit Parathyroid Hormone (high dose).
Red wine and beer contain numerous compounds which may be bioactive.
They include…..
Resveratrol – a stilbene – although probably the most well-known polyphenol in red wine, anthocyanidins, catechins, and other flavonols, including quercetin, kaempferol, are present in higher concentrations
Several prenylflavonoids in beer – derived from hops and derivatives from the brewing process
XH – principal prenylflavonoid in hops
IXH – principal prenylflavonoid in diet
8-PN (8-prenylnaringenin) – most potent phytoestrogen of all those found in diet, including genistein and daidzein
Concentrations of polyphenols vary widely with source, type, type of processing etc
Proc. Nut. Soc. (2006), 65,

15. Moderate Alcohol Consumption Bone Health: Potential Ethanol Effects
Estrogenic Effects of Ethanol
Stimulate ER activity (v. high dose).
Increase Androgen aromatisation (v. high dose)
Inhibit Estradiol Catabolism (No HRT-EtOH interactions)
Stimulate Calcitonin (high dose).
Inhibit Parathyroid Hormone (high dose).
Red wine and beer contain numerous compounds which may be bioactive.
They include…..
Resveratrol – a stilbene – although probably the most well-known polyphenol in red wine, anthocyanidins, catechins, and other flavonols, including quercetin, kaempferol, are present in higher concentrations
Several prenylflavonoids in beer – derived from hops and derivatives from the brewing process
XH – principal prenylflavonoid in hops
IXH – principal prenylflavonoid in diet
8-PN (8-prenylnaringenin) – most potent phytoestrogen of all those found in diet, including genistein and daidzein
Concentrations of polyphenols vary widely with source, type, type of processing etc
Proc. Nut. Soc. (2006), 65,

16. Serum CTx following Ca ingestion
Osteoporosis Int (sup 4): S31

17. Serum CTx following Ca or Alcohol ingestion
Osteoporosis Int (sup 4): S31

18. Serum iPTH following Ca ingestion
Osteoporosis Int (sup 4): S31
Time (hr)

19. Serum iPTH following Ca or Alcohol ingestion
Osteoporosis Int (sup 4): S31

20. Serum Calcitonin following Alcohol ingestion
Osteoporosis Int (sup 4): S31

21. Alcohol and Bone Moderate alcohol intake and bone
Ethanol effects on bone
Non-ethanol effects on bone

22. Orthosilic acid (silicon)
Moderate Alcohol Consumption Bone Health: Potential Non-ethanol Effects
Phenolic Compounds
Flavonols and related glycosides.
Flavanols
Anthocyanins
Prenylflavonoids and related compounds.
Hydroxycinnamates and phenolic acids
Stilbenes
Micronutrients
Orthosilic acid (silicon)
Red wine and beer contain numerous compounds which may be bioactive.
They include…..
Resveratrol – a stilbene – although probably the most well-known polyphenol in red wine, anthocyanidins, catechins, and other flavonols, including quercetin, kaempferol, are present in higher concentrations
Several prenylflavonoids in beer – derived from hops and derivatives from the brewing process
XH – principal prenylflavonoid in hops
IXH – principal prenylflavonoid in diet
8-PN (8-prenylnaringenin) – most potent phytoestrogen of all those found in diet, including genistein and daidzein
Concentrations of polyphenols vary widely with source, type, type of processing etc
Proc. Nut. Soc. (2006), 65,

23. Epidemiological Study
Jugdaohsingh et al JBMR 2004

24. Aberdeen Prospective Osteoporosis Screening Study (APOSS)
3198 women from total of 3883 (age 49  2 y)
Dietary intakes using 7-day validated FFQ
BMD by DEXA ( , repeated 6-7 y later)
Adjusted for all potential confounders of BMD and nutrient intake.
(Macdonald et al., ASBMR 2005; Nashville, USA)

25. Aberdeen Prospective Osteoporosis Screening Study (APOSS)
Silicon Intake & BMD: separate menopausal status, HRT use
FN BMD LS BMD
Menopausal Group r P r P
Pre-menopausal (n=109)
Pre- & Peri-menopausal (n=333)
Post-menopausal
no-HRT (n=1018)
past-HRT (n=664)
current-HRT (n=1170) <
(Macdonald et al., ASBMR 2005; Nashville, USA)

26. Conclusions
Excessive alcohol consumption is associated with abnormal bone loss.
Moderate Alcohol intake is associated with acute suppression of bone Resorption.
The anti-resorptive effects are in part associated with an early simple energy effect (? GLP-2) but also in part due to a late novel ethanol-specific effect
Orthosilicic acid (a major nutrient of beer) is involved in bone Formation.
Mathematical models may allow us to integrate mechanisms, both qualitatively and quantitatively, with epidemiological observations.

27. Acknowledgements Collaborators - Dr Ravin Jugdaohsingh (STH)
- Dr Supannee Sripanyakorn (STH)
- Sir Richard Thompson (STH)
- Drs Doug Kiel (Harvard) and Katie Tucker (Tufts)
- Dr Helen MacDonald (STH)
Funding
- MRC
- Newman Foundation
- IBD and BBPA