Bisphosphonates and PTH for Preventing Fractures - Skeletal Aging and Osteoporosis: Biomechanics and Mechanobiology - page 151

Fig. 2 Higher bone strength with bisphosphonate treatment is explained by the drugs' effect on
bone density. Following 1, 2, or 3 years of treatment with daily oral alendronate in dogs (total
n = 84), the ultimate load of the lumbar vertebrae is significantly increased. This higher bone
strength is almost entirely explained by the higher areal bone mineral density (aBMD) as the
relationship between ultimate load and aBMD is not different from vehicle-treated animals (total
n = 36)
reduces the loss of bone that occurs through remodeling and allows sites that are
actively remodeling to refill. This latter effect is responsible for the initial increase
in bone mass that is usually observed with BP treatment. In addition to reducing
the number of BMUs BPs also have recently been shown to decrease the size of
those few BMUs that are initiated [ 15 ]. As BPs have minimal effects on osteoblast
activity, this reduction in BMU size means that even those sites that do undergo
remodeling in the presence of BP treatment lose less bone than would normally
occur.
Reductions of remodeling and preservation (or small increases) in bone mass
translate into improved whole bone mechanical properties—the ultimate goal of
any bone treatment. Virtually all of the effects of the BPs on bone strength, and
presumably fracture resistance, can be attributed to increased BMD achieved
through maintenance of the amount of bone and increases in its mineralization
(Fig. 2 ) [ 16 ]. Following 1-3 years of treatment with clinical doses of BPs, the
relationship between vertebral ultimate load, a measure of strength, and areal
BMD was nearly identical in animals treated with BP or with saline vehicle. That
is, the increased compressive strength in BP-treated animals was entirely
accounted for by increased BMD, and at a given BMD, BP and control treated
animals had similar bone strength. Clinical data corroborate this relationship, at
least to a point, showing that those BPs that increase BMD the most, reduce
fracture to the greatest degree (Table 1 ). This is important as some individuals
treated with BPs do not see large increases in BMD—therefore these patients may
have reduced fracture protection.