Sunday, May 13, 2012

Mechanisms of Osteoporosis: Part 2

Exercise 

Exercise is often recommended to prevent osteoporosis and build strong bones.  Bed rest causes rapid bone loss as bones become resistant to IGF-1 and sclerostin increases (although this effect plateaus after several months).  Exercise increases bone mineral density [1] and weight bearing exercise is more effective as swimmers only have slightly more bone mineral density than sedentary people, while other athletes like gymnasts have much more [2].  Exercise may only reduce femoral neck fractures by 11% lumbar spine fractures by 10% [3], though this doesn't include hip fractures and would depend a lot on the kind of exercise.  There are many mechanisms by which exercise promotes bone health: 

  • Exercise inhibits sclerostin through mechanical stress* [4]
  • Mechanical stress** from exercise increases IGF-1, IGF-2, PGE2, and nitric oxide, which has the effect of increasing osteoblasts and their activity*** [5]
  • Bones can convert mechanical/kinetic energy to electrical energy (piezoelectricity) as a signal and energy source for protein synthesis in bone formation.  Electrical stimulation of muscle and electromagnetic fields can also protect against bone loss [6].
  • Increased muscle mass improves exercise induced bone strength [7]
  • Between 28-35% of >65 year olds fall each year, which increases with age, and 5-10% of falls result in a fracture [8].  Exercise improves a number of physical competencies that reduce falls such as strength, power, balance, flexibility and coordination. 

That being said, overtraining may lead to osteoporosis because of elevated cortisol, a reduction in sex hormones, nutrient depletion and elevated pro-inflammatory cytokines such as IL-6 (which increases during exercise) [9

* Sclerostin seems to act like a ‘mechanosensor’ or ‘mechanostat’ to communicate to the body how much bone is needed to endure anticipated mechanical stressors 

** This mechanism is like 'a response to injury’.  Bone desensitises to mechanical stress after a few repetitions and is most sensitive when there is rest every few reps, when exercise is spread throughout the day and when there are week long rest periods 

*** Inhibiting PGE2 (NSAIDs) or nitric oxide synthesis suppresses mechanically induced bone formation

Vitamin K2 

People with osteoporosis and those who have had fractures have lower levels of vitamin K1 and K2 [10].  Vitamin K2 activates osteocalcin (the mineral binding protein), stimulates protein synthesis in osteoblasts and inhibits osteoclast activity [11].  This process is quite important as high levels uncarboxylated osteocalcin are associated with a much higher risk of fracture compared to normal levels (OR: 3.1-5.9) [12].  Vitamin K2 supplementation has some very successful outcomes:

  • Vitamin K2 protects against bone loss from age-related decline, testosterone deficiency (males), estrogen deficiency (females), glucocorticoids, stress and calcium deficiency in rats [11]
  • Trials of vitamin K2 supplementation  (often megadoses of 45 mg) increase [13] or maintain [14] bone mineral density and have been found to massively reduce fracture rates.  A meta-analysis found vitamin K2 supplementation reduces fracture rates by 60% [15]

The vitamin K2 supplements were often megadoses of 45 mg.  1.5 mg supplements also result in much lower uncarboxylated osteocalcin [16], but even this is much more than what is possible from the diet.  You would be doing well to get 50 µg from the diet [17], which is 30 times lower than 1.5 mg and 900 times lower than 45 mg.  Grass-fed animal products may have much more vitamin K2, but I doubt they have 30-900 times more. 

It might be necessary to use mega-doses because vitamin K2 is a fat soluble vitamin and these trials are essentially treating vitamin K2 deficiency (after 12 months the vitamin K2 levels in the treatment group were 65.2 ng/ml compared with 0.3 ng/ml in the control group) 

* Vitamin K1 has a similar effect on osteocalcin, but to a lesser degree [18

** Maintaining bone mineral density is an interesting finding because it seems that calcium just slows down the loss of bone mineral density (drugs and hormone replacement increase bone mineral density).  The possible implication is that with adequate K2 levels one could maintain their peak bone mineral density throughout life fairly well 

*** Vitamin K2 supplements of 1.5 mg decreased 25-hydroxyvitamin D levels over 4 weeks [16].  Vitamins A, D and K2 work together so taking one increases the need for the others. 

Further Reading:
(1) On the Trail of the Elusive X-Factor: A Sixty-Two-Year-Old Mystery Finally Solved

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