Large-scale osteocyte lacunar morphological analysis of transiliac bone in normal and osteoporotic premenopausal women

Goff, Elliott; Cohen, Adi; Shane, Elizabeth; Recker, Robert R.; Kuhn, Gisela; Müller, Ralph

doi:10.1016/j.bone.2022.116424

Cited by 15 publications

(14 citation statements)

References 61 publications

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“…The osteocyte lacunar densities identified in this investigation are similar to some ( 34–36 ) but not all ( 29,30,37 ) previous reports. Akhter and colleagues ( 29 ) reported higher Lc.N/BV in trabecular bone compared with cortical bone in iliac crest biopsies, whereas we observed an almost 2× higher Lc.N/BV in cortical than in trabecular bone in our study population.…”

Section: Discussionsupporting

confidence: 91%

Microvascular Disease Associates with Larger Osteocyte Lacunae in Cortical Bone in Type 2 Diabetes Mellitus

Zanner,

Goff,

Ghatan

et al. 2023

JBMR Plus

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Clinical studies indicate that microvascular disease (MVD) affects bone microstructure and decreases bone strength in type 2 diabetes mellitus (T2D). Osteocytes are housed in small voids within the bone matrix and lacunae and act as sensors of mechanical forces in bone. These cells regulate osteoclastic bone resorption and osteoblastic bone formation as well as osteocytic perilacunar remodeling. We hypothesized that MVD changes morphometric osteocyte lacunar parameters in individuals with T2D. We collected iliac crest bone biopsies from 35 individuals (10 female, 25 male) with T2D with MVD (15%) or without MVD (21%) with a median age of 67 years (interquartile range [IQR] 62–72 years). The participants were included based on c‐peptide levels >700 pmol L−1, absence of anti‐GAD65 antibodies, and glycated hemoglobin (HbA1c) levels between 40 and 82 mmol mol−1 or 5.8% and 9.7%, respectively. We assessed osteocyte lacunar morphometric parameters in trabecular and cortical bone regions using micro‐computed tomography (micro‐CT) at a nominal resolution of 1.2 μm voxel size. The cortical osteocyte lacunar volume (Lc.V) was 7.7% larger (p = 0.05) and more spherical (Lc.Sr, p < 0.01) in the T2D + MVD group. Using linear regression, we found that lacunar density (Lc.N/BV) in trabecular but not cortical bone was associated with HbA1c (p < 0.05, R2 = 0.067) independently of MVD. Furthermore, Lc.V was larger and Lc.Sr higher in the center than in the periphery of the trabecular and cortical bone regions (p < 0.05). In conclusion, these data imply that MVD may impair skeletal integrity, possibly contributing to increased skeletal fragility in T2D complicated by MVD. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

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Section: Discussionsupporting

confidence: 91%

Microvascular Disease Associates with Larger Osteocyte Lacunae in Cortical Bone in Type 2 Diabetes Mellitus

Zanner,

Goff,

Ghatan

et al. 2023

JBMR Plus

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“…This suggests that increased sphericity indicates reduced sensitivity and lower bone quality. [58] More importantly, the fact that we found no differences in our lacunar morphometric analysis between TH with hyperglycemia and without hyperglycemia further strengthens the argument that the TH polygenic mouse model is not a proper model for diabetic bone disease because the genetic background may be responsible for the changes we observed.…”

Section: Discussionsupporting

confidence: 78%

Utility and Limitations of TALLYHO/JngJ as a Model for Type 2 Diabetes–Induced Bone Disease

Emini,

Salbach‐Hirsch,

Krug

et al. 2023

JBMR Plus

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Type 2 diabetes mellitus (T2DM) increases risk of fractures due to bone microstructural and material deficits, though the mechanisms remain unclear. Preclinical models mimicking diabetic bone disease are required to further understand its pathogenesis. The TALLYHO/JngJ (TH) mouse is a polygenic model recapitulating adolescent‐onset T2DM in humans. Due to incomplete penetrance of the phenotype ~25% of male TH mice never develop hyperglycemia, providing a strain‐matched nondiabetic control. We performed a comprehensive characterization of the metabolic and skeletal phenotype of diabetic TH mice and compared them to either their nondiabetic TH controls or the recommended SWR/J controls to evaluate their suitability to study diabetic bone disease in humans. Compared to both controls, male TH mice with T2DM exhibited higher blood glucose levels, weight along with impaired glucose tolerance and insulin sensitivity. TH mice with/without T2DM displayed higher cortical bone parameters and lower trabecular bone parameters in the femurs and vertebrae compared to SWR/J. The mechanical properties remained unchanged for all three groups except for a low‐energy failure in TH mice with T2DM only compared to SWR/J. Histomorphometry analyses only revealed higher number of osteoclasts and osteocytes for SWR/J compared to both groups of TH. Bone turnover markers procollagen type 1 N‐terminal propeptide (P1NP) and tartrate‐resistant acid phosphatase (TRAP) were low for both groups of TH mice compared to SWR/J. Silver nitrate staining of the femurs revealed low number of osteocyte lacunar and dendrites in TH mice with T2DM. Three‐dimensional assessment showed reduced lacunar parameters in trabecular and cortical bone. Notably, osteocyte morphology changed in TH mice with T2DM compared to SWR/J. In summary, our study highlights the utility of the TH mouse to study T2DM, but not necessarily T2DM‐induced bone disease, as there were no differences in bone strength and bone cell parameters between diabetic and non‐diabetic TH mice. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

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“…Micropores smaller than 20 μm 3 and larger than 3000 μm 3 were considered cracks or artifacts and excluded from the analysis. For the purpose of this study, two separate lacunar volume ranges were investigated: small lacunae 20-900 µm³ (osteocyte lacunar microporosity characteristic of healthy bone 28,29 ), and larger lacunae 900-3000 µm³ (microporosity potentially associated to bone disease).…”

Section: Segmentation Of Osteocyte Lacunaementioning

confidence: 99%

“…Two separate lacunar volume ranges were investigated: small lacunae 20-900 µm³ (Fig. 3a-c) (osteocyte lacunar microporosity characteristic of healthy bone 28,29 ), and larger lacunae 900-3000 µm³ (Fig. 3d-f) (microporosity potentially associated to bone disease).…”

Section: Analysis Of Osteocyte Lacunar Volume Distribution and Microp...mentioning

confidence: 99%

3D osteocyte lacunar morphometry of human bone biopsies with high resolution microCT: from monoclonal gammopathy to newly diagnosed multiple myeloma

Moreno-Jiménez,

Heinig,

Heras

et al. 2023

Preprint

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Osteocytes are bone-embedded cells connected via canaliculi and they regulate the bone resorption/formation balance. Osteocyte function is altered in skeletal disorders including cancer. Multiple myeloma (MM) is a hematological malignancy, whereby plasma cells disrupt the bone homeostasis and induce excessive resorption of the mineralized extracellular matrix (ECM), as evidenced by clinical computed tomography (CT). However, morphometric analyses of the mineralized ECM and bone microporosity are not yet performed in patients with MM, nor in the precursor conditions of monoclonal gammopathy of undetermined significance (MGUS) and smoldering MM (SMM). Here, we characterize changes in 3D osteocyte lacunar morphology in bone biopsy samples obtained from patients with MGUS, SMM and newly diagnosed MM, using high resolution microCT. In the small lacunae 20-900 um3 range, we found a trend for lower lacunar density and increasing 50% cutoff of the lacunar volume cumulative distribution for diseased samples. In the larger lacunae 900-3000 um3 range, we found significantly higher lacunar density and microporosity in the MM group compared to the MGUS/SMM group. Regarding the shape distribution, the MGUS/SMM group showed a trend for flatter, more elongated and anisotropic osteocyte lacunae compared to the control group, though the differences were not statistically significant. Altogether, our findings suggest that osteocytes in human MM bone disease undergo changes in their lacunae morphology, which could be an indicator for impaired bone quality. Future studies are needed to show whether these are consistent within comparable anatomical sites and could serve as a diagnostic or prognostic marker.

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Large-scale osteocyte lacunar morphological analysis of transiliac bone in normal and osteoporotic premenopausal women

Cited by 15 publications

References 61 publications

Microvascular Disease Associates with Larger Osteocyte Lacunae in Cortical Bone in Type 2 Diabetes Mellitus

Microvascular Disease Associates with Larger Osteocyte Lacunae in Cortical Bone in Type 2 Diabetes Mellitus

Utility and Limitations of TALLYHO/JngJ as a Model for Type 2 Diabetes–Induced Bone Disease

3D osteocyte lacunar morphometry of human bone biopsies with high resolution microCT: from monoclonal gammopathy to newly diagnosed multiple myeloma

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