A new semiautomatic method for quantitative static and dynamic bone histology

Malluche, Hartmut H.; Sherman, David; Meyer, Wolfang; Massry, Shaul G.

doi:10.1007/bf02411282

Cited by 147 publications

(67 citation statements)

References 8 publications

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“…Static and dynamic parameters of bone structure, formation, and resorption were measured using a semi-automatic method (Osteoplan II, Kontron, Munich, Germany) (18,28). In 6-week-old mice, measurements were confined to the secondary spongiosa of the distal femur to ensure that only remodeling sites were analyzed.…”

Section: Methodsmentioning

confidence: 99%

Osteoblast-specific Knockout of the Insulin-like Growth Factor (IGF) Receptor Gene Reveals an Essential Role of IGF Signaling in Bone Matrix Mineralization

Zhang

Xuan

Bouxsein

et al. 2002

Journal of Biological Chemistry

641

561

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To examine the local actions of IGF signaling in skeletal tissue in a physiological context, we have used Cremediated recombination to disrupt selectively in mouse osteoblasts the gene encoding the type 1 IGF receptor (Igf1r). Mice carrying this bone-specific mutation were of normal size and weight but, in comparison with normal siblings, demonstrated a striking decrease in cancellous bone volume, connectivity, and trabecular number, and an increase in trabecular spacing. These abnormalities correlated with a striking decrease in the rate of mineralization of osteoid that occurred despite an unexpected osteoblast and osteoclast hyperactivity, detected from the significant increments in both osteoblast and erosion surfaces. Our findings indicate that IGF1 is essential for coupling matrix biosynthesis to sustained mineralization. This action is likely to be particularly important during the pubertal growth spurt when rapid bone formation and consolidation are required.Body size and linear bone growth in mammals is affected by cellular signaling pathways controlled by growth factors and hormones (1). In this regard, a major growth-promoting signaling system consisting of the insulin-like growth factors (IGF, 1 IGF1 and IGF2) and the type 1 IGF receptor (IGF1R) regulates embryonic growth, as shown by gene knockout experiments in mice (1). IGF1 acting through IGF1R also plays central roles in postnatal growth either independently or by mediating growth hormone functions (2). Signaling through the IGF1R tyrosine kinase receptor not only promotes cell proliferation, but also mediates anti-apoptotic actions (3, 4). The IGF system includes a second receptor (IGF2R) devoid of signaling properties, but serving IGF2 turnover, and at least six IGF-binding proteins (IGFBPs) of obscure functional significance (single and also some double mouse mutations ablating IGFBPs have not revealed as yet significant consequences in growth impairment). 2 The IGFs are produced locally in various tissues, including bones, and exert autocrine/paracrine functions, but they are also present in serum, mostly associated with IGFBPs. Whether the circulating IGFs act systemically as hormones is currently controversial (5, 6).A number of in vitro and in vivo studies are progressively unraveling the significance of the IGF system for skeletal development and metabolic control (for a review see Ref. 7). IGF1, by stimulating the proliferation of chondrocytes in the growth plate, plays an essential role in longitudinal bone growth (2) and is also involved in the formation of trabecular bone. In fact, chondrocytes and bone cells produce IGFs and express IGF1R (see for example Refs. 8 and 9). Studies using osteoblast culture systems have shown that IGF1 stimulates osteoblast proliferation, accelerates their differentiation, and enhances bone matrix production (10, 11). In addition, IGF1 is being recognized as a critical factor for bone cell survival (12)(13)(14). Finally, IGF1 also appears to regulate bone resorption, either directly or through its actio...

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Section: Methodsmentioning

confidence: 99%

Osteoblast-specific Knockout of the Insulin-like Growth Factor (IGF) Receptor Gene Reveals an Essential Role of IGF Signaling in Bone Matrix Mineralization

Zhang

Xuan

Bouxsein

et al. 2002

Journal of Biological Chemistry

641

561

View full text Add to dashboard Cite

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“…This process was done using the semiautomatic method (Osteoplan II; Kontron, Munich, Germany). 32,33 All measured parameters comply with the nomenclature of the Histomorphometry Committee of the American Society of Bone and Mineral Research. 34 …”

Section: Qualitative and Quantitative Assessment Of Bonementioning

confidence: 99%

Differences in Bone Quality in Low- and High-Turnover Renal Osteodystrophy

Malluche

Porter

Monier‐Faugere

et al. 2012

Journal of the American Society of Nephrology

Self Cite

114

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Abnormal bone turnover is common in CKD, but its effects on bone quality remain unclear. We qualitatively screened iliac crest bone specimens from patients on dialysis to identify those patients with low (n=18) or high (n=17) bone turnover. In addition, we obtained control bone specimens from 12 healthy volunteers with normal kidney function. In the patient and control specimens, Fourier transform infrared spectroscopy and nanoindentation quantified the material and mechanical properties of the specimens, and we used bone histomorphometry to assess parameters of bone microstructure and bone formation and resorption. Compared with high or normal turnover, bone with low turnover had microstructural abnormalities such as lower cancellous bone volume and reduced trabecular thickness. Compared with normal or low turnover, bone with high turnover had material and nanomechanical abnormalities such as reduced mineral to matrix ratio and lower stiffness. These data suggest that turnover-related alterations in bone quality may contribute to the diminished mechanical competence of bone in CKD, albeit through different mechanisms. Therapies tailored specifically to low-or high-turnover bone may treat renal osteodystrophy more effectively. Bone turnover abnormalities are well known in patients with chronic kidney disease (CKD). 1 These abnormalities encompass a spectrum from severely suppressed to markedly elevated bone turnover. Abnormal bone turnover occurs in approximately 85% of patients with CKD stage 5 on dialysis (CKD-5D), 2 and within this patient group, there is a greater risk of bone fracture than within the general population. [3][4][5] Although turnover abnormalities are well described, 1 little information is available on whether these abnormalities are associated with changes in bone quality. Bone quality is the contemporary term used to refer to the structural and material parameters that collectively enable bone to bear load and resist fracture or excessive deformation. 6,7 The potential link between bone turnover and bone quality is an important question meriting study because of the relatively high incidence of fractures reported to occur with abnormal turnover. [8][9][10][11][12][13][14] Thus, the specific aim of this study was to advance the understanding of this potential link by quantifying how the microstructural parameters, material composition, and nanomechanical properties vary in bone with low-or high-turnover renal osteodystrophy (ROD) compared with bone with normal turnover from normal volunteers. RESULTSAmong 163 iliac crest bone biopsies sequentially screened from patients with CKD-5D on dialysis, 35

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“…In addition, histomorphometric parameters were measured using the Osteoplan System II (Kronton, Munich, Germany) as described previously (26,27). Data were also analyzed on the basis of the turnover, mineralization, and bone volume "TMV" classification system (1,6).…”

Section: Bone Biopsymentioning

confidence: 99%

Relationship between Bone Histology and Markers of Bone and Mineral Metabolism in African-American Hemodialysis Patients

Moore

Yee

Malluche

et al. 2009

Clinical Journal of the American Society of Nephrology

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Background and objectives: Racial differences in mineral metabolism exist in the chronic kidney disease population, especially as it relates to intact parathyroid hormone (iPTH) levels. Few data exist on the relationship of these markers to bone biopsy findings in African-American (AA) hemodialysis patients across the spectrum of renal osteodystrophy (ROD).Design, setting, participants, & measurements: In prevalent AA hemodialysis subjects, we prospectively evaluated subjects by performing transiliac bone biopsy and correlating biochemical and clinical data to bone histology.Results: Study patients (n ‫؍‬ 43) had an average age of 53.7 (؎11.6) yr, with dialysis vintage of 40.4 (؎24.5) mo, 30% with diabetes, and 51% male. Bone histology revealed adynamic bone disease (ABD) (16%), mild to moderate hyperparathyroidism (HPT) (72%), severe (12%) HPT, and no osteomalacia or mixed uremic osteodystrophy. At the time of biopsy, mean corrected calcium was 9.1, 8.9, and 9.4 mg/dl (P ‫؍‬ 0.344); calcium-phosphorus (Ca ؋ PO 4 ) product was 42, 55, and 62 mg 2 /dl 2 (P ‫؍‬ 0.002); phosphorus was 4.6, 6.2, and 6.7 mg/dl (P ‫؍‬ 0.005); and iPTH was 225, 566, and 975 pg/ml (P ‫؍‬ 0.006), respectively. Median values for bone-specific alkaline phosphatase (BS-AP) were 16, 34, and 64 ng/ml (P < 0.0001) among the three groups.Conclusions: These data demonstrate that across the spectrum of ROD, iPTH levels are higher than expected in AA hemodialysis subjects. iPTH, PTH peptides, and bone-specific alkaline phosphatase correlated directly with histomorphometric measurements of bone turnover and when subjects were grouped by histologic diagnosis. Only 9.5% of subjects were simultaneously within suggested Kidney Disease Outcomes Quality Initiative (K/DOQI) ranges for Ca ؋ PO 4 , phosphorus, and iPTH, of which 75% demonstrated ABD on biopsy.

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A new semiautomatic method for quantitative static and dynamic bone histology

Cited by 147 publications

References 8 publications

Osteoblast-specific Knockout of the Insulin-like Growth Factor (IGF) Receptor Gene Reveals an Essential Role of IGF Signaling in Bone Matrix Mineralization

Osteoblast-specific Knockout of the Insulin-like Growth Factor (IGF) Receptor Gene Reveals an Essential Role of IGF Signaling in Bone Matrix Mineralization

Differences in Bone Quality in Low- and High-Turnover Renal Osteodystrophy

Relationship between Bone Histology and Markers of Bone and Mineral Metabolism in African-American Hemodialysis Patients

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