Mineral Density and Bone Strength Are Dissociated in Long Bones of Rat Osteopetrotic Mutations

Tuukkanen, Juha; Koivukangas, Antti; Jämsä, Timo; Sundquist, K.; MacKay, Carole A.; Marks, Sandy C.

doi:10.1359/jbmr.2000.15.10.1905

Cited by 44 publications

(24 citation statements)

References 43 publications

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“…No metaphyseal scan was taken in the metatarsal for technical reasons because of the small size of the bone and very short metaphysis. For identifying trabecular bone we selected the area protocol which is a standard in the CT software and a convention applied by others (Tuukkanen et al 2000, McHugh et al 2003. The cutoff of inner 45% of the bone cross-section has a high correlation to trabecular bone volume/tissue volume as measured by conventional histomorphometry.…”

Section: Methodsmentioning

confidence: 99%

Skeletal changes in type-2 diabetic Goto-Kakizaki rats

Ahmad¹,

Ohlsson²,

Sääf³

et al. 2003

Journal of Endocrinology

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We characterized appendicular and axial bones in rats with type-2 diabetes in five female Goto-Kakizaki (GK) rats, a strain developed from the Wistar rat showing spontaneous type-2 diabetes, and five age-and sex-matched nondiabetic Wistar rats. The humerus, tibia, metatarsals and vertebral bodies were analysed by peripheral quantitative computerized tomography (pQCT). In diabetic rats, the height of the vertebral bodies and length of the humerus were decreased while the length of the metatarsals was increased. A decreased cross-sectional area was found in the vertebral end-plate region and the tibial metaphysis. Notably, the diaphysis in all long bones showed expansion of periosteal and endosteal circumference. In tibia this resulted in increased cortical thickness, whereas in humerus and metatarsal it was unchanged. Areal moment of inertia was increased in all diaphyses suggesting greater bending strength. The most conspicuous finding in diabetic rats pertained to trabecular osteopenia. Thus, trabecular bone mineral density was significantly reduced in all bones examined, by 33-53%. Our pQCT study of axial and appendicular bones suggests that the typical feature of diabetic osteopathy in the GK rat is loss of trabecular bone and expansion of the diaphysis. The loss of metaphyseal trabecular bone if also present in diabetic patients may prove to underlie the susceptibility to periarticular fracture and Charcot arthropathy. The findings suggest that the risk of fracture in diabetes varies according to the specific sub-regions of a bone. The approach described may prove to be useful in the early detection of osteopathy in diabetic patients who may be amenable to preventive treatment.

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Section: Methodsmentioning

confidence: 99%

Skeletal changes in type-2 diabetic Goto-Kakizaki rats

Ahmad¹,

Ohlsson²,

Sääf³

et al. 2003

Journal of Endocrinology

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“…These results clearly suggest that BMD alone is insufficient for determining bone strength. Many studies have indicated the limited capability of BMD alone for the determination of bone mechanical properties [78][79][80]. Correlation and multiple regression analyses revealed that the degree of BAp c-axis orientation had a more significant contribution to Young's modulus than BMD [21].…”

Section: Contribution Of the Bap C-axis Orientation To Bone Mechanicamentioning

confidence: 99%

A paradigm shift for bone quality in dentistry: A literature review

Kuroshima

Kaku

Ishimoto

et al. 2017

Journal of Prosthodontic Research

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A B S T R A C TPurpose: The aim of this study was to present the current concept of bone quality based on the proposal by the National Institutes of Health (NIH) and some of the cellular and molecular factors that affect bone quality. Study selection: This is a literature review which focuses on collagen, biological apatite (BAp), and bone cells such as osteoblasts and osteocytes. Results: In dentistry, the term "bone quality" has long been considered to be synonymous with bone mineral density (BMD) based on radiographic and sensible evaluations. In 2000, the NIH proposed the concept of bone quality as "the sum of all characteristics of bone that influence the bone's resistance to fracture," which is completely independent of BMD. The NIH defines bone quality as comprising bone architecture, bone turnover, bone mineralization, and micro-damage accumulation. Moreover, our investigations have demonstrated that BAp, collagen, and bone cells such as osteoblasts and osteocytes play essential roles in controlling the current concept of bone quality in bone around hip and dental implants. Conclusion: The current concept of bone quality is crucial for understanding bone mechanical functions. BAp, collagen and osteocytes are the main factors affecting bone quality. Moreover, mechanical loading dynamically adapts bone quality. Understanding the current concept of bone quality is required in dentistry.

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“…Likewise, in humans who have one of their genes encoding the chloride-7 channel inactivated, osteoclasts are present, but there is inhibition of bone resorption with no reduction in bone formation (84)(85)(86). These data are in sharp contrast to mouse models that result in defective osteoclastogenesis, such as mice lacking c-fos or M-CSF, which have no osteoclasts and also exhibit defective bone formation (87)(88)(89). Thus, it seems that the presence of osteoclasts, whether or not they are resorbing bone, is needed for normal bone formation and that the release of bone-bound factors might not be required to couple osteoclasts to the bone formation phase of bone turnover.…”

Section: Figurementioning

confidence: 99%

Building bone to reverse osteoporosis and repair fractures

2008

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An important, unfilled clinical need is the development of new approaches to improve fracture healing and to treat osteoporosis by increasing bone mass. Recombinant forms of bone morphogenetic protein 2 (BMP2) and BMP7 are FDA approved to promote spinal fusion and fracture healing, respectively, and the first FDA-approved anabolic drug for osteoporosis, parathyroid hormone, increases bone mass when administered intermittently but can only be given to patients in the US for two years. As we discuss here, the tremendous explosion over the last two decades in our fundamental understanding of the mechanisms of bone remodeling has led to the prospect of mechanismbased anabolic therapies for bone disorders.There are currently a number of FDA-approved drugs for the prevention and treatment of osteoporosis that work by inhibiting bone resorption (i.e., they are anticatabolic). However, these compounds, which include bisphosphonates, calcitonin, and selective estrogen receptor modulators, only prevent further loss of bone; they do not stimulate new bone formation. The only FDAapproved compound capable of stimulating new bone formation (and thus reversing bone loss) is parathyroid hormone (PTH). However, PTH is a protein that needs to be administered subcutaneously, and patients generally prefer taking an oral medication; there are potential side effects (e.g., hypercalcemia and hypercalciuria) associated with its use; and the duration of treatment with this drug is limited to 18 months in Europe and 24 months in the US, because rodents administered high doses of PTH were shown to develop osteosarcomas (1). Thus, there is a clear clinical need to develop new bone anabolic agents (particularly small molecules that can be used orally), and understanding the molecular details of the pathways that control bone formation is critical for the development of novel approaches to reverse osteoporosis.It might be possible to modulate these pathways not only for the treatment osteoporosis, but also to accelerate the healing of fractures and to treat the 5%-10% of fractures that fail to heal satisfactorily (2, 3). This Review focuses on current approaches, as well as those on the horizon, that have the potential to achieve these goals. Although the osteoblast, as the bone-forming cell, is the obvious target for agents that aim to mediate bone anabolism, other cells are now also being considered as therapeutic targets. For example, osteocytes, cells that have historically largely been ignored because they lie entombed in the bone matrix, and osteoclasts, the boneresorbing cells that have long been a target for agents that are anticatabolic, are now also potential targets for drugs that stimulate bone anabolism. The development of agents that target more than one of these cell types might be the most effective therapy, as there is some evidence to suggest that PTH utilizes all of the above cell types in achieving its anabolic effects on bone. Bone remodeling: evolving conceptsAlthough macroscopically the skeleton seems to be a static or...

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Mineral Density and Bone Strength Are Dissociated in Long Bones of Rat Osteopetrotic Mutations

Cited by 44 publications

References 43 publications

Skeletal changes in type-2 diabetic Goto-Kakizaki rats

Skeletal changes in type-2 diabetic Goto-Kakizaki rats

A paradigm shift for bone quality in dentistry: A literature review

Building bone to reverse osteoporosis and repair fractures

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