The Hounds Had Weak Bones.....

Beware this is total full frontal nerdity...thoughts opinions only. Good conversation with the bro--

http://www.ti.ubc.ca/letter78.   

Ever since the introduction of bisphosphonates there have been scientists and clinicians who have hypothesized that these compounds may be harmful to bone when used long-term; although not widely acknowledged, since there was no clinical data to support the hypothesis, it is not a new concept.  Their concerns were based on the fact that bone is continually remodeled for a reason, and that reason is that over-time bone is susceptible to the development of microfractures, in a similar manner that a bridge deteriorates over-time from wear and tear and has to be fixed.  Osteocytes within the bone are believed to be able to sense the increases in stress caused by propagation of microfractures and these cells send signals to osteoblast/osteoclast to direct bone remodeling in a very specific manner to repair bone that has been “damaged”.  Bisphosphonates bind permanently to bone, and work by inhibiting bone resorption in these areas.  Although this mechanism of action effectively prevents the bone loss that occurs with osteoporosis, it acts to circumvent the natural healing process that takes place in bone.  I think there are actually some early studies in dogs, where reduced bone strength was reported in the animals administered bisphosphonates for two years, but the clinical implications were never appreciated; at the time, bisphosphonates were widely prescribed for about 10 to 15 years and no evidence of stress fractures was seen, so clinicians dismissed the findings in animals.  I suspect we are now seeing these side-effects of fractures for two reasons:

1)      Pharmaceutical companies have developed more potent bisphosphonate products, combined with the increased use of these products within the aging population.

2)      Increased clinical monitoring at an early age has probably resulted in large numbers of women using bisphosphonates at an early age to prevent osteoporosis. 

 Microfactures take time, so the early use of these products may now be manifesting as weakened bone. It is interesting that the results of the analysis revealed increased risk of atypical fractures affecting the subtrochanter and diaphysis of the femur.  Although many people intuitively think that stress fractures occurring in bone result from the physical “pounding on pavement” from walking/running, this is not true.  The greatest stresses that are exerted on bones occurs from muscle contraction; therefore it is perhaps not surprising that the stress fractures are localized to the bone supporting the large muscles of the thigh and occur in the subtrochanter and diaphysis, which experience a lot of stress from muscle contraction in a focal area.