Abstract
Current approved medical treatments for osteoporosis reduce fracture risk to a greater degree than predicted from change in BMD in women with postmenopausal osteoporosis. We hypothesize that bone active agents improve bone strength in osteoporotic bone by altering different material properties of the bone. Eighteen-month-old female Fischer rats were ovariectomized (OVX) or sham-operated and left untreated for 60 days to induce osteopenia before they were treated with single doses of either risedronate (500 μg/kg, IV), zoledronic acid (100 μg/kg, IV), raloxifene (2 mg/kg, PO, three times per week), hPTH(1-34) (25 μg/kg, SC, three times per week), or vehicle (NS; 1 ml/kg, three times per week). Groups of animals were killed after days 60 and 180 of treatment, and either the proximal tibial metaphysis or lumbar vertebral body were studied. Bone volume and architecture were assessed by μCT and histomorphometry. Measurements of bone quality included the degree of bone mineralization (DBM), localized elastic modulus, bone turnover by histomorphometry, compression testing of the LVB, and three-point bending testing of the femur. The trabecular bone volume, DBM, elastic modulus, and compressive bone strength were all significantly lower at day 60 post-OVX (pretreatment, day 0 study) than at baseline. After 60 days of all of the bone active treatments, bone mass and material measurements agent were restored. However, after 180 days of treatment, the OVX + PTH group further increased BV/TV (+30% from day 60, p < 0.05 within group and between groups). In addition, after 180 days of treatment, there was more highly mineralized cortical and trabecular bone and increased cortical bone size and whole bone strength in OVX + PTH compared with other OVX + antiresorptives. Treatment of estrogen-deficient aged rats with either antiresorptive agents or PTH rapidly improved many aspects of bone quality including microarchitecture, bone mineralization, turnover, and bone strength. However, prolonged treatment for 180 days with PTH resulted in additional gains in bone quality and bone strength, suggesting that the maximal gains in bone strength in cortical and trabecular bone sites may require a longer treatment period with PTH.
Highlights
OSTEOPOROSIS IS A disease that results from the deterioration of the material properties of such that the bone fractures with very little stress
The determinants of bone fragility in osteoporosis and how currently approved treatments for osteoporosis augment bone strength independent of changes in BMD are still being defined.[35,36,37] we evaluated the effects of antiresorptive agents and PTH on other properties of bone quality including bone microarchitecture, surfacebased and biochemical markers of turnover, mineralization, crystal size, and whole bone material properties in aged estrogen deficiency OVX rats for 60 and 180 days
Antiresorptive agents and PTH are prescribed for individuals with low bone mass or osteoporotic fractures and both seem to reduce the risk of new incident vertebral fractures by a similar magnitude[4,5,38,39,40,41,42,43,44]; risedronate seems to have a more rapid action, with significant vertebral fracture reduction after 6 mo of therapy.[3]. The bone strengthening properties of bisphosphonates result from a reduction in the initiation of bone remodeling
Summary
OSTEOPOROSIS IS A disease that results from the deterioration of the material properties of such that the bone fractures with very little stress. Types of medications are approved for the treatment of osteoporosis These medications include antiresorptive agents that reduce bone turnover and prolong the secondary mineralization phase of bone, which results in a rapid improvement in bone strength because vertebral fracture risk reduction is observed within 6 mo of initiating the therapy.[2,3] Bisphosphonates in general increase lumbar spine BMD ;3–4% after 1–2 yr of treatment.[4,5]. Treatment of postmenopausal women with PTH injections for 18 mo results in nearly 65% reduction in new vertebral fractures and a gain in lumbar spine BMD of nearly 9%.(8) The improved bone strength after PTH treatment is not associated with the gain in bone mass or the magnitude of the bone turnover changes.[8,9] because the initial effects of PTH are directed to the trabecular bone surface, less is known about the effect of PTH on cortical bone. The association of cortical bone mass changes and bone strength with PTH has not been carefully evaluated
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