Comparison of Aluminum Related with Vitamin D Related Osteomalacia by Tetracycline Based Bone Histomorphometry

Parfitt, A. M.; Rao, D. Srinivasa; Stanciu, J; Villanueva, A. R.

doi:10.1007/978-1-4684-5206-8_35

Cited by 6 publications

(7 citation statements)

References 13 publications

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“…To determine whether this osteopenic phenotype was caused by a functional or quantitative defect of osteoblasts, histomorphometrical analysis was performed with postnatal 21-day-old mice using tetracycline/tetracycline double labeling. (27) Bone formation rate/bone surface (BFR/BS) analyses of tetracycline-labeled sections of tibia showed significant differences for the rates of growth in the cortical area between the wildtype and Osr2⌬N transgenic mice (1.02 ± 0.23 mm /yr for transgenic mice, p < 0.05), indicating that the BFR/BS ratio was reduced to ∼40% in the Osr2⌬N transgenic mice (Fig. 4E).…”

Section: Impaired Bone Formation In Long Bones Of Osr2⌬n Transgenic Micementioning

confidence: 98%

“…(26) Mice in the 2-wk-old group were injected with tetracycline (Sigma-Aldrich) at 7 or 2 days before death, using a standard tetracycline double-labeling procedure. (27) After radiological analyses of the skeletons (Softex, Kanagawa, Japan), tibia specimens were dissected and fixed in 70% ethanol for 24 h at 4°C. Undecalcified bones were embedded in glycolmethylacrylate, and 5-m sections were prepared on a rotation microtome (Ultracut; ReichertJung, Heidelberg, Germany), as described previously.…”

Section: Skeletal Analysismentioning

confidence: 99%

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Zinc-Finger Transcription Factor Odd-Skipped Related 2 Is One of the Regulators in Osteoblast Proliferation and Bone Formation

Kawai

Yamauchi

Wakisaka

et al. 2007

Journal of Bone and Mineral Research

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We report that Osr2 is one of the regulators of osteoblast function, because dominant-negative Osr2 transgenic mice exhibited decreased osteoblast activity and delayed mineralization in calvarial and tibial bone tissues. Our results indicate that Osr2 functions in regulation of osteoblast proliferation.Introduction: Molecular mechanisms that control bone formation have received attention with increasing knowledge related to genetic control of osteoblast differentiation. The odd-skipped related (Osr) gene is a zinc-finger transcription factor recently suggested to be involved in bone formation, although little is known about its role. Materials and Methods: To elucidate the in vivo function of Osr2, we generated transgenic mice overexpressing dominant-negative Osr2. Results: In this study, N-terminal-deleted Osr2 was found to act as a dominant-negative mutant toward both Osr1 and Osr2. Dominant-negative Osr2 (Osr2⌬N) transgenic mice showed delayed mineralization in calvarial and cortical bone tissues. Furthermore, soft X-ray analysis of transgenic mice bones revealed distinctly increased radiolucency. Examinations of newborn Osr2⌬N transgenic mice skeletons stained with alcian blue and alizarin red showed reduced intensities in the skull and skeletal elements. Morphologically, calvariae and tibias of Osr2⌬N transgenic mice were composed of markedly thinner parietal and cortical bones and lower numbers of osteoblastic cells on bone surfaces, indicating a reduced proliferation of osteoblasts. Furthermore, calvarial osteoblasts obtained from Osr2⌬N transgenic mice showed highly attenuated osteoblast differentiation and proliferation, confirming that Osr2 is needed for osteogenesis. Finally, results of Runx2-deficient cell assays suggested that Osr2 induces alkaline phosphatase (ALP) expression, but to a lesser degree than Runx2-expressing cells. Conclusions: Our genetic observations showed that the Osr2 gene plays a key role in osteoblastic cell proliferation.

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Section: Impaired Bone Formation In Long Bones Of Osr2⌬n Transgenic Micementioning

confidence: 98%

Section: Skeletal Analysismentioning

confidence: 99%

Zinc-Finger Transcription Factor Odd-Skipped Related 2 Is One of the Regulators in Osteoblast Proliferation and Bone Formation

Kawai

Yamauchi

Wakisaka

et al. 2007

Journal of Bone and Mineral Research

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“…Current schemes for classifying renal bone disease are based largely on observations restricted to patients with renal failure (6,(46)(47)(48), but my own approach is derived from experience with all varieties of metabolic bone disease (49). This experience has indicated the central importance of osteoid thickness and adjusted apposition rate (previously termed corrected or effective apposition rate) in the definition of impaired mineralization (50,51).…”

Section: The Pathogenesis Of Aluminum-related Bone Diseasementioning

confidence: 99%

“…The latter two disorders are also included in the definition of so-called type 2 osteomalacia (47), in which osteoid maturation time, given by osteoid thickness divided by unadjusted apposition rate (19), and referred to by these workers as direct mineralization lag time, is normal. Although generalized osteomalacia is the most characteristic form of bone disease found in patients with aluminum at the bone interface (18,47,49), focal osteomalacia (56)(57)(58), atypical osteomalacia (33,47,55), hyperparathyroid bone disease without osteomalacia (57,59,60), defective osteoblast function without osteomalacia or low turnover osteopenia (54,55,58) and combinations of these disorders (6,46) can also be found.…”

Section: The Pathogenesis Of Aluminum-related Bone Diseasementioning

confidence: 99%

“…A high concentration of aluminum at the cement line/bone interface is strategically placed to inhibit mineralization and so induce the most obvious defect in severe aluminum-related bone disease. Comparison of aluminum-related with vitamin D-related osteomalacia indicates that in the former, cessation of mineralization occurs earlier in the course of the disease (49). As a result, retention of the second tetracycline label is less common and absence of any tetracycline fluorescence more common, osteoid surface is less increased and osteoid thickness relatively more increased, and the bone interface is more likely to remain at the cement line.…”

Section: The Pathogenesis Of Aluminum-related Bone Diseasementioning

confidence: 99%

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The Localization of Aluminum in Bone: Implications for the Mechanism of Fixation and for the Pathogenesis of Aluminum-Related Bone Disease

Parfitt

1988

Int J Artif Organs

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The clinical, biochemical, radiographic, histologic and prognostic features of aluminum-related bone disease, the sources and methods of removal of aluminum, the differences between epidemic and sporadic forms, and whether or not the condition should be referred to as aluminum-induced bone disease have all received a great deal of recent attention (1-8). Early reports identified three sites for aluminum deposition in bone -the junction between osteoid and mineralized bone, cement lines, and the neutral or quiescent bone surface (9-13). In the most comprehensive recent account the deposition of aluminum in bone is vaguely described as either on the bone surface or diffusely within the bone (7), but even in this era of molecular biology old fashioned anatomic precision should not be disdained. The purpose of this editorial review is to re-emphasize the importance of knowing exactly where aluminum is to be found in bone and the inferences that can be drawn from such knowledge.

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Frequency distributions of tetracycline-based measurements: Implications for the interpretation of bone formation indices in the absence of double-labeled surfaces

Foldes¹,

Shih²,

Parfitt³

1990

Journal of Bone and Mineral Research

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The frequency distributions of mineral apposition rate (MAR) and mineralizing surface (MS), measured separately on the intracortical, endocortical, and cancellous surfaces in 46 normal subjects and 79 patients with postmenopausal osteoporosis, indicated that MAR has a finite lower limit of 0.3 mu/day (uncorrected for section obliquity) but that MS has no finite lower limit. We conclude that in the absence of labels MAR, and indices derived from it, must be treated as missing values, but that MS and indices with MS in the numerator should be allowed to take values of zero. To avoid infinite values for indices with MS in the denominator, we propose that osteoid mineralization rate (the reciprocal of mineralization lag time) and osteoblast vigor (the reciprocal of formation period) be used instead. For surfaces with genuine single labels (SL) but no double labels, we propose that MS is calculated as SL/2 and that for MAR either the lower limit of 0.3 or the mean measured value from other surfaces be used for calculating derived indices.

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Comparison of Aluminum Related with Vitamin D Related Osteomalacia by Tetracycline Based Bone Histomorphometry

Cited by 6 publications

References 13 publications

Zinc-Finger Transcription Factor Odd-Skipped Related 2 Is One of the Regulators in Osteoblast Proliferation and Bone Formation

Zinc-Finger Transcription Factor Odd-Skipped Related 2 Is One of the Regulators in Osteoblast Proliferation and Bone Formation

The Localization of Aluminum in Bone: Implications for the Mechanism of Fixation and for the Pathogenesis of Aluminum-Related Bone Disease

Frequency distributions of tetracycline-based measurements: Implications for the interpretation of bone formation indices in the absence of double-labeled surfaces

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