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Despite its invasive character, bone biopsy followed by histomorphometry remains the gold standard for diagnosing and classifying many metabolic bone diseases. However, the interpretation of histomorphometric parameters requires comparison with average values obtained from a proper control group, which are only available for some populations, and reference standards still need to be published. Therefore, our objective was to estimate average values for bone histomorphometric parameters overall, by age, gender, and race (White and Black) categories of healthy adult individuals, based on a systematic review and meta-analysis of clinical studies. Relevant studies published in English with available results until December 2020 were identified by PubMed (Medline) search and consulting experts in the field. Out of 447 potentially relevant studies, 37 met the inclusion criteria. Meta-analysis using fixed-effects models was used to pool mean estimates and 95% confidence intervals (CI) for 16 bone histomorphometry parameters. An age-by-gender trend was observed in most histomorphometry parameters. The mean estimates of bone volume/tissue volume (BV/TV), trabecular thickness (Tb.Th), and trabecular number (Tb.N) decreased. In contrast, trabecular separation (Tb.Sp) increased from the youngest to the oldest age categories in both genders. Osteoblast surface (Ob.S/BS) and osteoclast surface (Oc.S/BS) decreased across all age categories in males. Mineralizing surface (MS/BS) increased from the youngest to the oldest age categories in females, while mineralization lag time (Mlt) increased in both genders. Furthermore, gender and race had a significant effect on several histomorphometry parameters. In conclusion, this meta-analysis provided mean estimates for normal values of histomorphometric parameters that clinicians may use when evaluating bone biopsies in patients. This enables the direct comparison of patients' histomorphometric values with the suitable reference group regarding age, gender, and race., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Aníbal Ferreira reports statistical analysis and writing assistance were provided by Center for Research and Development in the Nephrology Area (NIDAN). The remaining authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Secondary hyperparathyroidism is a complication of chronic kidney disease that compromises skeletal integrity. In patients with secondary hyperparathyroidism undergoing parathyroidectomy, parathyroid hormone levels dramatically decrease. The effects of parathyroidectomy on bone tissue are poorly understood, especially regarding the proteins expressed by osteocytes, such as fibroblast growth factor 23, dentin matrix protein 1, matrix extracellular phosphoglycoprotein, sclerostin, receptor activator of nuclear factor kappa B ligand (RANKL) and osteoprotegerin, which regulate bone turnover. The objective of this study was to characterize the bone expression of these proteins by immunohistochemistry and correlate these results with those of bone histomorphometry before and after parathyroidectomy. We studied bone biopsies that were obtained from 23 patients before and 12 months after parathyroidectomy. We observed an improvement in bone microarchitecture, but impaired mineralization after parathyroidectomy. We found significant increases in sclerostin and osteoprotegerin expression and a decrease in the RANKL/osteoprotegerin ratio after parathyroidectomy, suggesting that their expression is regulated by parathormone. These proteins correlated with structural and bone formation parameters. We conclude that after parathyroidectomy, significant changes occur in the bone expression of osteocyte proteins and that these proteins potentially regulate bone remodeling., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Chronic kidney disease (CKD) is associated with disorders of mineral and bone metabolism (MBD) which include renal osteodystrophy and vascular calcifications. This is of clinical concern because the high risk of cardiovascular (CVD) complications observed in uremic patients may be linked with bone disease. In this context, our aim was to characterize the bone lesions in CKD-apolipoprotein E-deficient mice (apoE(-/-)) and analyze their relationships with the vascular calcifications which these animals develop rapidly in this model. With ApoE being also involved in bone metabolism, we compared the effects of CRF on the bone of apoE(-/-) mice to those observed in wild type mice (WT) of the same genetic background, C57/BL6., Methods: After CRF creation or sham surgery, 10 week-old female apoE(-/-) and WT mice were randomized to 4 groups (n=10-14/group) and fed with standard diet. Eight weeks later, animals were euthanized. Serum, aorta and femur were sampled. Femurs were imaged with 3-dimensional microtomography (microCT) and processed for bone histomorphometry (BHM). Additional quantitative histology was performed on atherosclerotic and calcified lesions in the aortas of apoE(-/-) mice., Results: First, apoE(-/-) mice exhibited higher cortical (10%) and trabecular (31%) bone mass than WT. CRF led to a further increase in trabecular BV/TV in WT and in apoE(-/-) mice (10.2% and 77.2%, respectively). We observed a similar increase in osteoid surface and osteoblastic parameters in CRF mice of both genotypes while resorption parameters were less augmented by CRF in apoE(-/-) mice. Finally, based on either BHM or microCT we found positive correlations between the extent of atherosclerotic lesions and bone volume parameters, and between the size of plaque calcification and osteoclast parameters in apoE(-/-) mice., Conclusion: ApoE deficiency is associated with an increase in bone mass and volumetric mineral density in 20 week-old female mice. Bone mass is further increased, whereas bone mineral density is decreased, in response to CRF in association with histological features of osteitis fibrosa. Finally, our findings of correlations between changes in bone and aortic lesions in apoE(-/-) mice, are compatible with the hypothesis of a link between bone and vascular disease and require further study., (2010 Elsevier Inc. All rights reserved.)