Correlation of mechanical properties of vertebral trabecular bone with equivalent mineral density as measured by computed tomography.

Lang, S; Moyle, D.D.; Berg, Espen; Detorie, N.C.; Gilpin, A T; Pappas, N J; Reynolds, James C.; Tkacik, M; Waldron, Robert L.

doi:10.2106/00004623-198870100-00013

Cited by 80 publications

(32 citation statements)

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“…The elastic modulus of bone can be approximated using its mineral density (Fig. 8) (Krischak et al, 1999;Lang et al, 1988;Lotz, Gerhart & Hayes, 1990;Wachter et al, 2001;Wachter et al, 2002).…”

Section: Bone Morphometry 3d Rendering and Solid Modelling For Feamentioning

confidence: 99%

Orthodontic mechanotransduction and the role of the P2X7 receptor

Viecilli

Katona

Chen

et al. 2009

American Journal of Orthodontics and Dentofacial Orthopedics

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DEDICATIONTo my parents, who have supported my education. iv ACKNOWLEDGMENTSOne of the most important things I have learned during my PhD is the necessity of the existence of a working network of people that can help you achieve your goals. The more effectively this network functions, the higher the chance you will achieve the goals quickly.I would first like to thank my parents, who have unconditionally supported my decision to abandon a profitable private practice in Orthodontics, and return to humble student conditions while aiming for a full time academic career.I also thank my girlfriend Laura Kruter who has (almost always) been ok with my, some might say, not very sane ideas. Sometimes they do turn out fine, though (like this "PhD" one).I can hardly think of anyone else that could have complemented my work and ideas during this Program as well as Dr. Thomas Katona. While I was passionately conditioned to an idea, he was always rational and careful. While I was sometimes furious with a shortcoming, he was always temperate and humorous. When I ran into his office with some news about a project, he would always listen and almost never seem too busy to see me. While I was working and something went wrong, he would listen and wonder with me about the "whys" and "hows", instead of telling me what to do or express disappointment. He was even subject to some of my home culinary experiments. I was extremely fortunate to find someone that thought about science the same way I did, and that actually helped me with my project instead of just telling me what to do. I felt like we worked as a team, and that helped to increase my motivation during my studies. The third part of this project tested the role of the P2X7 receptor in the dentoalveolar morphology of C57B/6 mice. P2X7R KO (knockout) mice were compared to C57B/6 WT to identify differences in a maxillary molar and bone. Tooth dimensions viii were measured and 3D bone morphometry was conducted. No statistically significant differences were found between the two mouse types. P2X7R does not have a major effect on alveolar bone or tooth morphology.The final part examines the role of the P2X7 receptor in a controlled biomechanical model. Orthodontic mechanotransduction was compared in wild-type (WT) and P2X7R knock-out (KO) mice. Using Finite Element Analysis, mouse mechanics were scaled to produce typical human stress levels. Relationships between the biological responses and the calculated stresses were statistically tested and compared.There were direct relationships between certain stress magnitudes and root resorption and bone formation. Hyalinization and root and bone resorption were different in WT and KO. Orthodontic responses are related to the principal stress patterns in the PDL and the P2X7 receptor plays a significant role in their mechanotransduction.

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Section: Bone Morphometry 3d Rendering and Solid Modelling For Feamentioning

confidence: 99%

Orthodontic mechanotransduction and the role of the P2X7 receptor

Viecilli

Katona

Chen

et al. 2009

American Journal of Orthodontics and Dentofacial Orthopedics

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“…The differential efficacy of the two regimens on bone strength was parallel to their effects on all other measures tested, indicating that the bone strength assessed by resistance against bending force in long bones can be accurately predicted by the changes in BMD, changes in a bone formation marker, and changes in cortical bone structure. Although BMD has been considered to be a major determinant of bone strength in clinical studies for more than a decade, (26)(27)(28) increases in BMD do not always reflect the effects on fracture incidence. (29,30) Neer et al (4) showed that daily injection of hPTH(1-34) at a dose 40 g/day increased BMD to a greater degree than did 20 g/day, but resulted in similar reductions in both vertebral and nonvertebral fracture risk.…”

Section: Cyclic Versus Daily Pth Regimens On Mouse Bonementioning

confidence: 99%

Effects of Cyclic Versus Daily hPTH(1-34) Regimens on Bone Strength in Association With BMD, Biochemical Markers, and Bone Structure in Mice

Iida-Klein

Hughes

et al. 2006

Journal of Bone and Mineral Research

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We developed a cyclic PTH regimen with repeated cycles of 1-week on and off daily PTH injection and explored its effects on bone strength, BMD, bone markers, and bone structure in mice. Cyclic protocols produced 60-85% of the effects achieved by daily protocols with 57% of the total PTH given, indicating more economic use of PTH. The study supports further exploration of cyclic PTH regimens for the treatment of osteoporosis.Introduction: To minimize the cost and the catabolic action of hPTH(1-34), a cyclic PTH regimen with repeated 3-month cycles of on-and-off daily injection of hPTH(1-34) was developed in humans and shown to be as effective as a daily regimen in increasing vertebral BMD. However, changes in BMD may not adequately predict changes in bone strength. A murine model was developed to explore the efficacy of a cyclic PTH regimen on bone strength in association with other bone variables. Materials and Methods: Twenty-week-old, intact, female C57BL/J6 mice (n ‫ס‬ 7/group) were treated with (1) daily injection with vehicle for 7 weeks (control); (2) daily injection with hPTH(1-34) (40 g/kg/day) for 7 weeks (daily PTH); and (3) daily injection with hPTH(1-34) and vehicle alternating weekly for 7 weeks (cyclic PTH). BMD was measured weekly by DXA, and serum bone markers, bone structure, and strength were measured at 7 weeks. Results: Daily and cyclic PTH regimens increased BMD at all sites by 16-17% and 9-12%, respectively (all p < 0.01). The most dramatic effect of cyclic PTH occurred during the second week of treatment when PTH was off, with femoral and tibial BMD continuing to increase to the same extent as that produced by daily PTH. Both daily and cyclic PTH regimens significantly increased osteocalcin (daily, 330%; cyclic, 260%), mTRACP (daily, 145%; cyclic, 70%), femoral cortical width (daily, 23%; cyclic, 13%), periosteal circumference (daily, 5%; cyclic, 3.5%), and bone strength (max load: daily, 48%; cyclic, 28%; energy absorbed: daily, 103%; cyclic, 61%), respectively. Femoral bone strength was positively correlated with BMD, bone markers, and cortical structure. Neither regimen had an effect on vertebral bone strength. Although actual effects of cyclic PTH were 60-85% of those produced by daily PTH, the effects of cyclic PTH per unit amount administered were slightly greater than those of daily PTH for most measures. Conclusions: PTH-enhanced femoral bone strength is positively correlated with its effects on femoral BMD, bone markers, and bone structure. Cyclic PTH regimens represent a potential economic use of PTH and warrant further study.

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“…Thus, the drug effects are assessed not only by measuring the mechanical resistance of the vertebral bodies and the midshaft regions of long bones, but also by using information made available by both the osteodensitometric and histomorphologic evaluations at the levels of epiphyseal, metaphyseal, intertrochanteric and femoral neck cortices. At the spinal level it can also be informative to assess the mechanical properties (compressive failure load and stiffness) of both the vertebral whole body and a cancellous core of vertebral bone [176,[178][179][180]. However, preparation techniques for the vertebral body that preserve its integrity are preferred to those that result in the destruction of the proximal and distal ends.…”

Section: Measurement Of Bone Mass and Geometrymentioning

confidence: 99%

Importance of Preclinical Studies in the Development of Drugs for Treatment of Osteoporosis: A Review Related to the 1998 WHO Guidelines

Bonjour

Ammann

Rizzoli

1999

Osteoporosis International

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Osteoporosis, which is defined as a disease characterized by low bone mass and microarchitectural deterioration of bone tissue leading to enhanced bone fragility and a consequent increase in fracture risk, is a major health issue worldwide. Among the various strategies to prevent and cure this devastating ailment, an important objective is the development of new efficacious and safe drugs. This situation prompted the World Health Organization (WHO) to provide a comprehensive statement of guiding principles for the design, implementation and interpretation of both preclinical testing and clinical trials in osteoporosis. These guidelines, which are now available, underline the crucial importance of the preclinical evaluation, particularly for assessing the effect of an intervention on bone strength. This concept is heightened by the lack of a validated technique for noninvasively evaluating bone strength in humans and the multiple difficulties and heavy burden inherent in the evaluation of fracture rate in clinical trials. The WHO guidelines emphasize that a comprehensive and adequate preclinical program is expected to provide key information on the relationship between bone mass and strength and thus attenuate the burden of clinical studies. The present report provides a review of experimental evidence in support of the preclinical program as proposed in the WHO guidelines. This program is based on the recent development and refinement of animal models of osteoporosis that mimic the human condition according to the conceptual definition of the disease. Many preclinical studies carried out in appropriate animal models with agents that exert either antiresorbing or anabolic effects on bone indicate that they have been highly predictive of the drug action in humans in terms of both bone mass and remodeling, as well as of bone strength whenever fracture rate has been documented in clinical trials. Based on this evidence the WHO guidelines propose strategies according to which the results of preclinical evaluation will determine the end-points required in the different phases of the clinical development of the drug. Such a distribution of task assignment between preclinical and clinical programs should optimize the progress of research available to patients already suffering from or at risk of osteoporosis.

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Correlation of mechanical properties of vertebral trabecular bone with equivalent mineral density as measured by computed tomography.

Cited by 80 publications

References 0 publications

Orthodontic mechanotransduction and the role of the P2X7 receptor

Orthodontic mechanotransduction and the role of the P2X7 receptor

Effects of Cyclic Versus Daily hPTH(1-34) Regimens on Bone Strength in Association With BMD, Biochemical Markers, and Bone Structure in Mice

Importance of Preclinical Studies in the Development of Drugs for Treatment of Osteoporosis: A Review Related to the 1998 WHO Guidelines

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