Reduced Bone Volume Research Articles

Scopolamine mitigates oophorectomy-induced osteoporosis: potential mechanisms and direct effects on bone structure

The aim of our research is to investigate the therapeutic effects of scopolamine (SCO) on osteoporosis and to explore the underlying mechanism. To study osteoporosis, we established an ovariectomy (OVX) model. The rats were divided into four groups: sham operation, OVX, OVX+SCO, and OVX+SCO+ML385 (Nrf2 inhibitor). ELISA, Realtime PCR, Western blot, and kits were utilised to assess the expression of related proteins and substances. The OVX rats exhibited significant weight gain, reduced bone volume, destruction of trabecular and cortical bone microstructure, decreased expression of ALP, OCN, OPN, COL1A1, Runx2, Nrf2 proteins, and CAT, SOD, GST, GPX levels while increased expression of TRAP protein and ROS levels. SCO was able to restore these indices in OVX rats, while ML385 blocked the effects of SCO. In conclusion, SCO inhibits oxidative stress response to exert therapeutic effects on osteoporosis by activating the Nrf2 signalling pathway.

Pharmacologic or genetic targeting of peripheral nerves prevents peri-articular traumatic heterotopic ossification

Heterotopic ossification (HO) is a pathological process that commonly arises following severe polytrauma, characterized by the anomalous differentiation of mesenchymal progenitor cells and resulting in the formation of ectopic bone in non-skeletal tissues. This abnormal bone growth contributes to pain and reduced mobility, especially when adjacent to a joint. Our prior observations suggested an essential role of NGF (Nerve Growth Factor)-responsive TrkA (Tropomyosin Receptor Kinase A)-expressing peripheral nerves in regulating abnormal osteochondral differentiation following tendon injury. Here, we utilized a recently developed mouse model of hip arthroplasty-induced HO to further validate the role of peripheral nerve regulation of traumatic HO. Nerve ingrowth was either modulated using a knockin transgenic animals with point mutation in TrkA, or local treatment with an FDA-approved formulation of long acting Bupivacaine which prevents peripheral nerve growth. Results demonstrate exuberant sensory and sympathetic nerve growth within the peri-articular HO site, and that both methods to reduce local innervation significantly reduced heterotopic bone formation. TrkA inhibition led to a 34% reduction in bone volume, while bupivacaine treatment resulted in a 50% decrease. Mechanistically, alterations in TGFβ and FGF signaling activation accompanied both methods of local denervation, and a shift in macrophages from M1 to M2 phenotypes was observed. In sum, these studies reinforce the observations that peripheral nerves play a role in the etiopathogenesis of HO, and that targeting local nerves represents a potential therapeutic approach for disease prevention.

Targeting CDC42 reduces skeletal degeneration after hematopoietic stem cell transplantation

AbstractOsteopenia and osteoporosis are common long-term complications of the cytotoxic conditioning regimen for hematopoietic stem cell transplantation (HSCT). We examined mesenchymal stem and progenitor cells (MSPCs), which include skeletal progenitors, from mice undergoing HSCT. Such MSPCs showed reduced fibroblastic colony-forming units frequency, increased DNA damage, and enhanced occurrence of cellular senescence, whereas there was a reduced bone volume in animals that underwent HSCT. This reduced MSPC function correlated with elevated activation of the small Rho guanosine triphosphate hydrolase CDC42, disorganized F-actin distribution, mitochondrial abnormalities, and impaired mitophagy in MSPCs. Changes and defects similar to those in mice were also observed in MSPCs from humans undergoing HSCT. A pharmacological treatment that attenuated the elevated activation of CDC42 restored F-actin fiber alignment, mitochondrial function, and mitophagy in MSPCs in vitro. Finally, targeting CDC42 activity in vivo in animals undergoing transplants improved MSPC quality to increase both bone volume and trabecular bone thickness. Our study shows that attenuation of CDC42 activity is sufficient to attenuate reduced function of MSPCs in a BM transplant setting.

Bone volume and height changes for lateral window sinus floor elevation using two types of deproteinized bovine bone mineral: A retrospective cohort study of 1-4 years.

To compare bone volume and height changes of two types of deproteinized bovine bone mineral (DBBM) for lateral window sinus floor elevation (LSFE) with simultaneous implant placement. This retrospective cohort study involved 72 patients who underwent LSFE using low-temperature sintered cancellous bone-derived DBBM (C-DBBM) or high-temperature two-step sintered epiphyseal-derived DBBM (E-DBBM). Cone-beam computed tomography (CBCT) was acquired preoperatively, immediately postoperatively, 6 months and 1-4 years post-surgery. Bone volume (BV), apical bone height (ABH), endo-sinus bone gain (ESBG), and crestal bone level (CBL) were evaluated through three-dimensional fitting and superimposition. Linear mixed models (LMM) were employed to analyze factors influencing the reduction of BV (ΔBV) and ESBG (ΔESBG). The E-DBBM group showed no significant change in BV 1-4 years post-surgery, while the C-DBBM group demonstrated a significant reduction (p = .006) with volume stability of 85.86%. Bone height in the E-DBBM group increased at 6 months and subsequently decreased at 1-4 years (p = .003). In the C-DBBM group, it decreased at 6 months (p = .014), then further decreased at 1-4 years (p = .001). ΔESBG was lower in the E-DBBM group than the C-DBBM group from immediate postoperative to 1-4 years (p = .009). LMM showed graft material type was the primary factor influencing ΔBV (p = .026) and ΔESBG (p = .003). Within the limitations of this study, both types of DBBM could achieve favorable clinical outcomes. E-DBBM demonstrated enhanced stability in maintaining bone volume and height.

Estradiol induces bone osteolysis in triple-negative breast cancer via its membrane-associated receptor ERα36.

Triple-negative breast cancer (TNBC) is thought to be an estradiol-independent, hormone therapy-resistant cancer because of lack of estrogen receptor alpha 66 (ERα66). We identified a membrane-bound splice variant, ERα36, in TNBC cells that responds to estrogen (E2) and may contribute to bone osteolysis. We demonstrated that the MDA-MB-231 TNBC cell line, which expresses ERα36 similarly to MCF7 cells, is responsive to E2, forming osteolytic tumors in vivo. MDA-MB-231 cells activate osteoclasts in a paracrine manner. Conditioned media (CM) from MDA-MB-231 cells treated with bovine serum albumin-bound E2 (E2-BSA) increased activation of human osteoclast precursor cells; this was blocked by addition of anti-ERα36 antibody to the MDA-MB-231 cultures. Osteoclast activation and bone resorption genes were elevated in RAW 264.7 murine macrophages following treatment with E2-BSA-stimulated MDA-MB-231 CM. E2 and E2-BSA increased phospholipase C (PLC) and protein kinase C (PKC) activity in MDA-MB-231 cells. To examine the role of ERα36 signaling in bone osteolysis in TNBC, we used our bone-cancer interface mouse model in female athymic homozygous Foxn1nu mice. Mice with MDA-MB-231 tumors and treated with tamoxifen (TAM), E2, or TAM/E2 exhibited increased osteolysis, cortical bone breakdown, pathologic fracture, and tumor volume; the combined E2/TAM group also had reduced bone volume. These results suggest that E2 increased osteolytic lesions in TNBC through a membrane-mediated PLC/PKC pathway involving ERα36, which was enhanced by TAM, demonstrating the role of ERα36 and its membrane-associated signaling pathway in bone tumors. This work suggests that ERα36 may be a potential therapeutic target in patients with TNBC.

Pannexin 3 deletion in mice results in knee osteoarthritis and intervertebral disc degeneration after forced treadmill running.

Pannexin 3 (Panx3) is a glycoprotein that forms mechanosensitive channels expressed in chondrocytes and annulus fibrosus cells of the intervertebral disc (IVD). Evidence suggests Panx3 plays contrasting roles in traumatic versus aging osteoarthritis (OA) and intervertebral disc degeneration (IDD). However, whether its deletion influences the response of joint tissue to forced useis unknown. The purpose of this study was to determine if Panx3 deletion in mice causes increased knee joint OA and IDD after forced treadmill running. Male and female wildtype (WT) and Panx3 knockout (KO) mice were randomized to either a no-exercise group (sedentary; SED) or daily forced treadmill running (forced exercise; FEX) from 24 to 30 weeks of age. Knee cartilage and IVD histopathology were evaluated by histology, while tibial secondary ossification centers were analyzed using microcomputed tomography (µCT). Both male and female Panx3 KO mice developed larger superficial defects of the tibial cartilage after forced treadmill running compared with SED WT mice. Additionally, Panx3 KO mice developed reduced bone volume, and female PANX3 KO mice had lengthening of the lateral tubercle at the intercondylar eminence. In the lower lumbar spine, both male and female Panx3 KO mice developed histopathological features of IDD after running compared to SED WT mice. These findings suggest that the combination of deleting Panx3 and forced treadmill running induces OA and causes histopathological changes associated with the degeneration of the IVDs in mice.

Does Chronic Pancreatitis in Growing Pigs Lead to Articular Cartilage Degradation and Alterations in Subchondral Bone?

Chronic pancreatitis (CP), a progressive inflammatory disease, poses diagnostic challenges due to its initially asymptomatic nature. While CP's impact on exocrine and endocrine functions is well-recognized, its potential influence on other body systems, particularly in young individuals, remains underexplored. This study investigates the hypothesis that CP in growing pigs leads to alterations in articular cartilage and subchondral bone, potentially contributing to osteoarthritis (OA) development. Utilizing a pig model of cerulein-induced CP, we examined the structural and compositional changes in subchondral bone, articular cartilage, and synovial fluid. Histological analyses, including Picrosirius Red and Safranin-O staining, were employed alongside immuno-histochemistry and Western blotting techniques. Our findings reveal significant changes in the subchondral bone, including reduced bone volume and alterations in collagen fiber composition. Articular cartilage in CP pigs exhibited decreased proteoglycan content and alterations in key proteins such as MMP-13 and TGF-β1, indicative of early cartilage degradation. These changes suggest a link between CP and musculoskeletal alterations, underscoring the need for further research into CP's systemic effects. Our study provides foundational insights into the relationship between CP and skeletal health, potentially guiding future pediatric healthcare strategies for early CP diagnosis and management.

High-throughput micro-CT analysis identifies sex-dependent biomarkers of erosive arthritis in TNF-Tg mice and differential response to anti-TNF therapy.

Development of reliable disease activity biomarkers is critical for diagnostics, prognostics, and novel drug development. Although computed tomography (CT) is the gold-standard for quantification of bone erosions, there are no consensus approaches or rationales for utilization of specific outcome measures of erosive arthritis in complex joints. In the case of preclinical models, such as sexually dimorphic tumor necrosis factor transgenic (TNF-Tg) mice, disease severity is routinely quantified in the ankle through manual segmentation of the talus or small regions of adjacent bones primarily due to the ease in measurement. Herein, we sought to determine the particular hindpaw bones that represent reliable biomarkers of sex-dependent disease progression to guide future investigation and analysis. Hindpaw micro-CT was performed on wild-type (n = 4 male, n = 4 female) and TNF-Tg (n = 4 male, n = 7 female) mice at monthly intervals from 2-5 (females) and 2-8-months (males) of age, since female TNF-Tg mice exhibit early mortality from cardiopulmonary disease at approximately 5-6-months. Further, 8-month-old WT (n = 4) and TNF-Tg males treated with anti-TNF monoclonal antibodies (n = 5) or IgG placebo isotype controls (n = 6) for 6-weeks were imaged with micro-CT every 3-weeks. For image analysis, we utilized our recently developed high-throughput and semi-automated segmentation strategy in Amira software. Synovial and osteoclast histology of ankle joints was quantified using Visiopharm. First, we demonstrated that the accuracy of automated segmentation, determined through analysis of ~9000 individual bones by a single user, was comparable in wild-type and TNF-Tg hindpaws before correction (79.2±8.9% vs 80.1±5.1%, p = 0.52). Compared to other bone compartments, the tarsal region demonstrated a sudden, specific, and significant bone volume reduction in female TNF-Tg mice, but not in males, by 5-months (4-months 4.3± 0.22 vs 5-months 3.4± 0.62 mm3, p<0.05). Specifically, the cuboid showed significantly reduced bone volumes at early timepoints compared to other tarsals (i.e., 4-months: Cuboid -24.1±7.2% vs Talus -9.0±5.9% of 2-month baseline). Additional bones localized to the anterolateral region of the ankle also exhibited dramatic erosions in the tarsal region of females, coinciding with increased synovitis and osteoclasts. In TNF-Tg male mice with severe arthritis, the talus and calcaneus exhibited the most sensitive response to anti-TNF therapy measured by effect size of bone volume change over treatment period. We demonstrated that sexually dimorphic changes in arthritic hindpaws of TNF-Tg mice are bone-specific, where the cuboid serves as a reliable early biomarker of erosive arthritis in female mice. Adoption of automated segmentation approaches in pre-clinical or clinical models has potential to translate quantitative biomarkers to monitor bone erosions in disease and evaluate therapeutic efficacy.

Neutrophils are involved in early bone formation during midpalatal expansion.

Midpalatal expansion (MPE) is routinely employed to treat transverse maxillary arch deficiency. Neutrophils are indispensable for recruiting bone marrow stromal cells (BMSCs) at the initial stage of bone regeneration. This study aimed to explore whether neutrophils participate in MPE and how they function during bone formation under mechanical stretching. The presence and phenotype of neutrophils in the midpalatal suture during expansion were detected by flow cytometry and immunofluorescence staining. The possible mechanism of neutrophil recruitment and polarization was explored invitro by exposing vascular endothelial cells (VECs) to cyclic tensile strain. The number of neutrophils in the distracted suture peaked on Day 3, and N2-type neutrophils significantly increased on Day 5 after force application. The depletion of circulatory neutrophils reduced bone volume by 43.6% after 7-day expansion. The stretched VECs recruited neutrophils via a CXCR2 mechanism invitro, which then promoted BMSC osteogenic differentiation through the VEGFA/VEGFR2 axis. Consistently, these neutrophils showed higher expression of canonical N2 phenotype genes, including CD206 and Arg1. These results suggested that neutrophils participated in early bone formation during MPE. Based on these findings, we propose that stretched VECs recruited and polarized neutrophils, which, in turn, induced BMSC osteogenic differentiation.

Changes in Volume and Bone Density of Calvarial Grafts After Two Years of Orbital Reconstruction.

One of the greatest challenges in orbital reconstruction is to obtain adequate orbital volume and globe projection after traumatic injury. Autologous bone graft has been considered the gold standard for orbital floor reconstruction, but the harvesting yields many possible complications, such as donor site morbidity. Bone resorption is a frequent problem that can lead to insufficient volume after graft placement. There is a theoretically lower resorption rate of skull bone grafts, even though the exact amount is not known yet. This study is the first to evaluate bone volume and density changes of calvarial split bone grafts after orbital floor reconstruction with a 2-year follow-up. Bone volume and density of calvarial split grafts were determined using computed tomography scans and the software program RadiAnt Dicom Viewer in a total of 10 patients with orbital floor fracture reconstruction. Computed tomography scans taken immediately after surgery (T0) and after a postoperative period of 2 years (T1) were evaluated. The authors found a mean bone volume reduction of 34.25% after 2 years. Bone density was still high after 2 years (over 850 HU), with a mean reduction of 8%. Based on these findings, calvarial split bone grafts represent the ideal reconstruction material for orbital floor fractures.

Socket regeneration after immediate loading implants with tissue and bone graft

Evaluation of ridge alteration after 1 year follow up after immediate loading implant placement. Methods: Ten patients were included in the study, in whom the ridge volume, height, and thickness were evaluated from region of interest (ROI) of tomographic images of the operated areas (test group) and compared to the opposite tooth (control group). Results: After one year, there was no implant loss and all patients were satisfied with the treatment. In the test group there was a statistically significant increase in ridge height (2.89±1.05 mm) when compared to the control group. No significant difference in relation to ridge volume and thickness was observed. In the intragroup evaluation, a significant gain in ridge height (2.65±3.08 mm) was observed when compared to baseline. Conclusion: The placement of an immediate implant, temporary crown, and tissue regeneration in sockets with buccal defects promotes the regeneration of the buccal wall while preventing the reduction of bone volume and thickness.

Effects of Systemic Peroxisome Proliferator-Activated Receptor Gamma Inhibition on Bone and Immune Cells in Aged Female Mice.

This study investigates the effects of peroxisome proliferator-activated receptor gamma (PPARγ) inhibition on bone and immune cell profiles in aged female mice, as well as in vitro stromal stem cell osteogenic differentiation and inflammation gene expression. The hypothesis was that inhibition of PPARγ would increase bone mass and alter immune and other cellular functions. Our results showed that treatment with PPARγ antagonist GW9662 for 6 weeks reduced bone volume and trabecular number and increased trabecular spacing. However, inhibition of PPARγ had no significant effect on marrow and spleen immune cell composition in aged female mice. In vitro experiments indicated that GW9662 treatment increased the expression of osteogenic genes but did not affect adipogenic genes. Additionally, GW9662 treatment decreased the expression of several inflammation-related genes. Overall, these findings suggest that PPARγ inhibition may have adverse effects on bone in aged female mice.

An in vivo study to investigate an original intramedullary bone graft harvesting technology

BackgroundHarvesting bone graft (BG) from the intramedullary canal to treat bone defects is largely conducted using the Reamer–Irrigator–Aspirator (RIA) system. The RIA system uses irrigation fluid during harvesting, which may result in washout of osteoinductive factors. Here, we propose a new harvesting technology dedicated to improving BG collection without the potential washout effect of osteoinductive factors associated with irrigation fluid. This novel technology involves the conceptual approach of first aspirating the bone marrow (BM) with a novel aspirator prototype, followed by reaming with standard reamers and collecting the bone chips with the aspirator (reaming–aspiration method, R–A method). The aim of this study was to assess the harvesting efficacy and osteoinductive profile of the BG harvested with RIA 2 system (RIA 2 group) compared to the novel harvesting concept (aspirator + R–A method, ARA group).MethodsPre-planning computed tomography (CT) imaging was conducted on 16 sheep to determine the femoral isthmus canal diameter. In this non-recovery study, sheep were divided into two groups: RIA 2 group (n = 8) and ARA group (n = 8). We measured BG weight collected from left femur and determined femoral cortical bone volume reduction in postoperative CT imaging. Growth factor and inflammatory cytokine amounts of the BGs were quantified using enzyme-linked immunosorbent assay (ELISA) methods.ResultsThe use of the stand-alone novel aspirator in BM collection, and in harvesting BG when the aspirator is used in conjunction with sequential reaming (R–A method) was proven feasible. ELISA results showed that the collected BG contained relevant amounts of growth factors and inflammatory cytokines in both the RIA 2 and the ARA group.ConclusionsHere, we present the first results of an innovative concept for harvesting intramedullary BG. It is a prototype of a novel aspirator technology that enables the stepwise harvesting of first BM and subsequent bone chips from the intramedullary canal of long bones. Both the BG collected with the RIA 2 system and the aspirator prototype had the capacity to preserve the BG’s osteoinductive microenvironment. Future in vivo studies are required to confirm the bone regenerative capacity of BG harvested with the innovative harvesting technology.

Bone structure and composition in a hyperglycemic, obese, and leptin receptor-deficient rat: Microscale characterization of femur and calvarium.

Metabolic abnormalities, such as diabetes mellitus and obesity, can impact bone quantity and/or bone quality. In this work, we characterize bone material properties, in terms of structure and composition, in a novel rat model with congenic leptin receptor (LepR) deficiency, severe obesity, and hyperglycemia (type 2 diabetes-like condition). Femurs and calvaria (parietal region) from 20-week-old male rats are examined to probe bones formed both by endochondral and intramembranous ossification. Compared to the healthy controls, the LepR-deficient animals display significant alterations in femur microarchitecture and in calvarium morphology when analyzed by micro-computed X-ray tomography (micro-CT). In particular, shorter femurs with reduced bone volume, combined with thinner parietal bones and shorter sagittal suture, point towards a delay in the skeletal development of the LepR-deficient rodents. On the other hand, LepR-deficient animals and healthy controls display analogous bone matrix composition, which is assessed in terms of tissue mineral density by micro-CT, degree of mineralization by quantitative backscattered electron imaging, and various metrics extrapolated from Raman hyperspectral images. Some specific microstructural features, i.e., mineralized cartilage islands in the femurs and hyper-mineralized areas in the parietal bones, also show comparable distribution and characteristics in both groups. Overall, the altered bone microarchitecture in the LepR-deficient animals indicates compromised bone quality, despite the normal bone matrix composition. The delayed development is also consistent with observations in humans with congenic Lep/LepR deficiency, making this animal model a suitable candidate for translational research.

Reduced angiogenesis and delayed endochondral ossification in CD163-/- mice highlights a role of M2 macrophages during bone fracture repair.

While recent studies showed that macrophages are critical for bone fracture healing, and lack of M2 macrophages have been implicated in models of delayed union, functional roles for specific M2 receptors have yet to be defined. Moreover, the M2 scavenger receptor CD163 has been identified as a target to inhibit sepsis following implant-associated osteomyelitis, but potential adverse effects on bone healing during blockage therapy have yet to be explored. Thus, we investigated fracture healing in C57BL/6 versus CD163-/- mice using a well-established closed, stabilized, mid-diaphyseal femur fracture model. While gross fracture healing in CD163-/- mice was similar to that of C57BL/6, plain radiographs revealed persistent fracture gaps in the mutant mice on Day 14, which resolved by Day 21. Consistently, 3D vascular micro-CT demonstrated delayed union on Day 21, with reduced bone volume (74%, 61%, and 49%) and vasculature (40%, 40%, and 18%) compared to C57BL/6 on Days 10, 14, and 21 postfracture, respectively (p < 0.01). Histology confirmed large amounts of persistent cartilage in CD163-/- versus C57BL/6 fracture callus on Days 7 and 10 that resolves over time, and immunohistochemistry demonstrated deficiencies in CD206+ M2 macrophages. Torsion testing of the fractures confirmed the delayed early union in CD163-/- femurs, which display decreased yield torque on Day 21, and a decreased rigidity with a commensurate increase in rotation at yield on Day 28 (p < 0.01). Collectively, these results demonstrate that CD163 is required for normal angiogenesis, callus formation, and bone remodeling during fracture healing, and raise potential concerns about CD163 blockade therapy.

Patterns and function of pneumaticity in the vertebrae, ribs, and ilium of a titanosaur (Dinosauria, Sauropoda) from the Upper Cretaceous of Texas

ABSTRACT Many sauropod dinosaurs exhibit extensive postcranial skeletal pneumaticity that may have facilitated the evolution of extreme body sizes. Among titanosauriforms, complex, irregularly branching camellate chambers are found throughout the presacral vertebral column, often invading the ribs and ilium as well. To explore the function of these camellae, including reduction in bone volume, pneumaticity was examined in a titanosaur sauropod from the Upper Cretaceous Black Peaks Formation of Big Bend National Park, Texas, that includes pneumatic dorsal ribs and ilia. Using natural breaks to non-destructively observe the internal structure, patterns of camellate pneumaticity are described for the dorsal vertebrae, ribs, and ilium. The space occupied by camellae is quantified as the airspace proportion, which is reported here in a sauropod ilium for the first time. Airspace proportions exceed 70% in parts of the dorsal vertebrae and ilium, with lower values near the cotyles of the vertebral centra and the acetabulum. Values in the ribs decrease distally. These values are not appreciably different from those of sauropods with simpler camerate pneumaticity. If camellae did not offer greater weight reduction than camerae, they may have enhanced structural strength, as the chambers appear to align with stress in the vertebral centra and ilium. Apneumatic trabecular bone around the acetabulum, preacetabular process, and postzygapophyses, however, may indicate stresses too great for camellate bone to bear, although an ontogenetic influence cannot be ruled out.

Role of hormones in bone remodeling in the craniofacial complex: A review.

Diseases such as periodontitis and osteoporosis are expected to rise tremendously by 2050. Bone formation and remodeling are complex processes that are disturbed in a variety of diseases influenced by various hormones. This study aimed to review and present the roles of various hormones that regulate bone remodeling of the craniofacial complex. A literature search was conducted on PubMed and Google Scholar for studies related to hormones and jawbone. Search strategies included the combinations ("name of hormone"+"dental term") of the following terms: "hormones", "oxytocin", "estrogen", "adiponectin", "parathyroid hormone", "testosterone", "insulin", "angiotensin", "cortisol", and "erythropoietin", combined with a dental term "jaw bone", "alveolar bone", "dental implant", "jaw+bone regeneration, healing or repair", "dentistry", "periodontitis", "dry socket", "osteoporosis" or "alveolitis". The papers were screened according to the inclusion criteria from January 1, 2000 to March 31, 2021 in English. Publications included reviews, book chapters, and original research papers; in vitro studies, in vivo animal, or human studies, including clinical studies, and meta-analyses. Bone formation and remodeling is a complex continuous process involving many hormones. Bone volume reduction following tooth extractions and bone diseases, such as periodontitis and osteoporosis, cause serious problems and require a great understanding of the process. Hormones are with us all the time, shape our development and regulate homeostasis. Newly discovered effects of hormones influencing bone healing open the possibilities of using hormones as therapeutics to combat bone-related diseases.

Effect of periodontal phenotype characteristics on post-extraction dimensional changes of the alveolar ridge: A prospective case series.

This study was primarily aimed at assessing the effect that specific periodontal phenotypical characteristics have on alveolar ridge remodelling after tooth extraction. Patients in need of extraction of a non-molar maxillary tooth were enrolled. Baseline phenotypical characteristics (i.e., mid-facial and mid-palatal soft tissue and bone thickness, and supracrestal soft tissue height [STH]) were recorded upon extraction. A set of clinical, digital imaging (linear and volumetric), and patient-reported outcomes were assessed over a 14-week healing period. A total of 78 subjects were screened. Forty-two subjects completed the study. Linear and volumetric bone changes, as well as vertical linear soft tissue and alveolar ridge volume (soft tissue contour) variations, were indicative of a marked dimensional reduction of the alveolar ridge over time. Horizontal facial and palatal soft tissue thickness gain was observed. Thin facial bone (≤1 mm) upon extraction, compared with thick facial bone (>1 mm), was associated with greater linear horizontal (-4.57 ± 2.31 mm vs. -2.17 ± 1.65 mm, p=.003) and vertical mid-facial (-0.95 ± 0.67 mm vs. -4.08 ± 3.52 mm, p < 0.001) and mid-palatal (-2.03 ± 2.08 mm vs. -1.12 ± 0.99 mm, p=0.027) bone loss, as well as greater total (-34% ± 10% vs. 15% ± 6%, p < 0.001), facial (-51% ± 19% vs. 28% ± 18%, p=0.040), and palatal bone volume reduction (-26% ± 14% vs. -8% ± 10%, p < 0.001). Aside from alveolar bone thickness, STH was also found to be a predictor of alveolar ridge resorption since this variable was directly correlated with bone volume reduction. Patient-reported discomfort scores progressively decreased over time, and the mean satisfaction upon study completion was 94.5 ± 0.83 out of 100. Alveolar ridge remodelling is a physiological phenomenon that occurs after tooth extraction. Post-extraction alveolar ridge atrophy is more marked on the facio-coronal aspect. These dimensional changes are more pronounced in sites exhibiting a thin facial bone phenotype (Clinicaltrials.gov NCT02668289).

Influence of a resorbable collagen membrane for alveolar bone graft on clinical outcomes and ridge volume stability in cleft alveolus

This study compared the clinical outcomes, graft quality, and graft quantity after alveolar bone grafting with and without a resorbable collagen membrane. Twenty unilateral cleft patients undergoing defect repair with cancellous iliac bone were assigned to either the collagen membrane group (Mb group) or standard group without a membrane (St group). Postoperative pain and swelling, bone density, and bone volume and quality were assessed. The Mb group showed significantly lower postoperative pain than the St group (P < 0.001) and significantly less swelling (P < 0.01) on day 3 postoperative. The reduction in bone density was significantly greater in the St group than in the Mb group at 1 and 3 months postoperative (P ≤ 0.001), but not at 6 months. The reduction in bone volume in the St group was significantly greater than that in the Mb group at 3 months (29.11 ± 6.26% vs 17.67 ± 11.89%, P = 0.016) and 6 months postoperative (40.95 ± 6.81% vs 25.67 ± 11.51%, P = 0.002). Nine cases in the Mb group versus six in the St group showed good bone quality. In conclusion, the collagen membrane facilitated predictable clinical outcomes in bone maturation, bone volume preservation, and bone bridging in the alveolar bone graft.

Simvastatin therapy in higher dosages deteriorates bone quality: Consistent evidence from population-wide patient data and interventional mouse studies

BackgroundCombining mouse experiments with big data analysis of the Austrian population, we investigated the association between high-dose statin treatment and bone quality. MethodsThe bone microarchitecture of the femur and vertebral body L4 was measured in male and ovariectomized female mice on a high-fat diet containing simvastatin (1.2 g/kg). A sex-specific matched big data analysis of Austrian health insurance claims using multiple logistic regression models was conducted (simvastatin 60–80 mg/day vs. controls; males: n = 138,666; females: n = 155,055). ResultsHigh-dose simvastatin impaired bone quality in male and ovariectomized mice. In the trabecular femur, simvastatin reduced bone volume (µm3: ♂, 213 ± 15 vs. 131 ± 7, p < 0.0001; ♀, 66 ± 7 vs. 44 ± 5, p = 0.02) and trabecular number (1/mm: ♂, 1.88 ± 0.09 vs. 1.27 ± 0.06, p < 0.0001; ♀, 0.60 ± 0.05 vs. 0.43 ± 0.04, p = 0.01). In the cortical femur, bone volume (mm3: ♂, 1.44 ± 0.03 vs. 1.34 ± 0.03, p = 0.009; ♀, 1.33 ± 0.03 vs. 1.12 ± 0.03, p = 0.0002) and cortical thickness were impaired (µm: ♂, 211 ± 4 vs. 189 ± 4, p = 0.0004; ♀, 193 ± 3 vs. 169 ± 3, p < 0.0001). Similar impairments were found in vertebral body L4. Simvastatin-induced changes in weight or glucose metabolism were excluded as mediators of deteriorations in bone quality. Results from mice were supported by a matched cohort analysis showing an association between high-dose simvastatin and increased risk of osteoporosis in patients (♂, OR: 5.91, CI: 3.17–10.99, p < 0.001; ♀, OR: 4.16, CI: 2.92–5.92, p < 0.001). ConclusionHigh-dose simvastatin dramatically reduces bone quality in obese male and ovariectomized female mice, suggesting that direct drug action accounts for the association between high dosage and increased risk of osteoporosis as observed in comparable human cohorts. The underlying pathophysiological mechanisms behind this relationship are presently unknown and require further investigation.