Risedronate preserves bone architecture in postmenopausal women with osteoporosis as measured by three-dimensional microcomputed tomography

Borah, Babul; Dufresne, Thomas E.; Chmielewski, Paula A.; Johnson, Troy D.; Chines, Arkadi; Manhart, Michael D.

doi:10.1016/j.bone.2003.12.013

Cited by 169 publications

(89 citation statements)

References 46 publications

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“…(43) In a clinical study of risedronate, CT analysis of biopsies have shown that risedronate preserves trabecular architecture in postmenopausal women with osteoporosis. (44) Taken together, these studies suggest that antiresorptives preserve both microarchitecture, tissue material properties, and biomechanical strength and do not fundamentally alter any structure-function relations of the bone. Similarly, preclinical studies of teriparatide have not shown any alterations of the strength-density relation of bone, (45,46) nor are we aware of any other preclinical studies that have shown the contrary for contemporary treatments.…”

Section: Discussionmentioning

confidence: 73%

Effects of Teriparatide and Alendronate on Vertebral Strength as Assessed by Finite Element Modeling of QCT Scans in Women With Osteoporosis

Keaveny

Donley

Hoffmann

et al. 2007

Journal of Bone and Mineral Research

234

137

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FE modeling was used to estimate the biomechanical effects of teriparatide and alendronate on lumbar vertebrae. Both treatments enhanced predicted vertebral strength by increasing average density. This effect was more pronounced for teriparatide, which further increased predicted vertebral strength by altering the distribution of density within the vertebra, preferentially increasing the strength of the trabecular compartment.Introduction: Teriparatide 20 g/day (TPTD) and alendronate 10 mg/day (ALN) increase areal, measured by DXA, and volumetric, measured by QCT, lumbar spine BMD through opposite effects on bone remodeling. Using finite element (FE) modeling of QCT scans, we sought to compare the vertebral strength characteristics in TPTD-and ALN-treated patients. Materials and Methods: A subset of patients (N ‫ס‬ 28 TPTD; N ‫ס‬ 25 ALN) from the Forteo Alendronate Comparator Trial who had QCT scans of the spine at baseline and postbaseline were analyzed. The QCT scans were analyzed for compressive strength of the L 3 vertebra using FE modeling. In addition, using controlled parameter studies of the FE models, the effects of changes in density, density distribution, and geometry on strength were calculated, a strength:density ratio was determined, and a response to bending was also quantified. Results: Both treatments had positive effects on predicted vertebral strength characteristics. At least 75% of the patients in each treatment group had increased strength of the vertebra at 6 months compared with baseline. Patients in both treatment groups had increased average volumetric density and increased strength in the trabecular bone, but the median percentage increases for these parameters were 5-to 12-fold greater for TPTD. Larger increases in the strength:density ratio were also observed for TPTD, and these were primarily attributed to preferential increases in trabecular strength. Conclusions: These results provide new insight into the effects of these treatments on estimated biomechanical properties of the vertebra. Both treatments positively affected predicted vertebral strength through their effects on average BMD, but the magnitudes of the effects were quite different. Teriparatide also affected vertebral strength by altering the distribution of density within the vertebra, so that overall, teriparatide had a 5-fold greater percentage increase in the strength:density ratio.

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Section: Discussionmentioning

confidence: 73%

Effects of Teriparatide and Alendronate on Vertebral Strength as Assessed by Finite Element Modeling of QCT Scans in Women With Osteoporosis

Keaveny

Donley

Hoffmann

et al. 2007

Journal of Bone and Mineral Research

234

137

View full text Add to dashboard Cite

show abstract

“…[129][130][131][132][133] However, there have been concerns about whether the use of prolonged high doses of bisphosphonates may impair bone turnover to such an extent that bone strength is impaired. High doses in animals are associated with increased microdamage 134,135 and even fractures.…”

Section: Some Current Issues With Bisphosphonates: Bone Architecturementioning

confidence: 99%

Bisphosphonates: Mode of Action and Pharmacology

2007

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The profound effects of the bisphosphonates on calcium metabolism were discovered over 30 years ago, and they are now well established as the major drugs used for the treatment of bone diseases associated with excessive resorption. Their principal uses are for Paget disease of bone, myeloma, bone metastases, and osteoporosis in adults, but there has been increasing and successful application in pediatric bone diseases, notably osteogenesis imperfecta. Bisphosphonates are structural analogues of inorganic pyrophosphate but are resistant to enzymatic and chemical breakdown. Bisphosphonates inhibit bone resorption by selective adsorption to mineral surfaces and subsequent internalization by bone-resorbing osteoclasts where they interfere with various biochemical processes. The simpler, non-nitrogen-containing bisphosphonates (eg, clodronate and etidronate) can be metabolically incorporated into nonhydrolysable analogues of adenosine triphosphate (ATP) that may inhibit ATP-dependent intracellular enzymes. In contrast, the more potent, nitrogen-containing bisphosphonates (eg, pamidronate, alendronate, risedronate, ibandronate, and zoledronate) inhibit a key enzyme, farnesyl pyrophosphate synthase, in the mevalonate pathway, thereby preventing the biosynthesis of isoprenoid compounds that are essential for the posttranslational modification of small guanosine triphosphate (GTP)-binding proteins (which are also GTPases) such as Rab, Rho, and Rac. The inhibition of protein prenylation and the disruption of the function of these key regulatory proteins explains the loss of osteoclast activity. The recently elucidated crystal structure of farnesyl diphosphate reveals how bisphosphonates bind to and inhibit at the active site via their critical nitrogen atoms. Although bisphosphonates are now established as an important class of drugs for the treatment of many bone diseases, there is new knowledge about how they work and the subtle but potentially important differences that exist between individual bisphosphonates. Understanding these may help to explain differences in potency, onset and duration of action, and clinical effectiveness.www.pediatrics.org/cgi

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“…118 This unique improvement of bone microarchitecture illustrates the bone forming properties of teriparatide and distinguishes it from the maintenance observed with bisphosphonates. 119 Because of its cost and its unique anabolic property, teriparatide is usually reserved for patients with severe osteoporosis.…”

Section: Parathyroid Hormonementioning

confidence: 99%

Canadian Consensus Conference on Osteoporosis, 2006 Update

Brown¹,

Fortier²,

Frame

et al. 2006

Journal of Obstetrics and Gynaecology Canada

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Objective-To provide guidelines for the health care provider on the diagnosis and clinical management of postmenopausal osteoporosis.Outcomes-Strategies for identifying and evaluating high-risk individuals, the use of bone mineral density (BMD) and bone turnover markers in assessing diagnosis and response to management, and recommendations regarding nutrition, physical activity, and the selection of pharmacologic therapy to prevent and manage osteoporosis. Values-The quality of evidence is rated using the criteria described in the report of the Canadian Task Force on the Periodic Health Examination. Recommendations for practice are ranked according to the method described in this report.

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Risedronate preserves bone architecture in postmenopausal women with osteoporosis as measured by three-dimensional microcomputed tomography

Cited by 169 publications

References 46 publications

Effects of Teriparatide and Alendronate on Vertebral Strength as Assessed by Finite Element Modeling of QCT Scans in Women With Osteoporosis

Effects of Teriparatide and Alendronate on Vertebral Strength as Assessed by Finite Element Modeling of QCT Scans in Women With Osteoporosis

Bisphosphonates: Mode of Action and Pharmacology

Canadian Consensus Conference on Osteoporosis, 2006 Update

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