SCREENING OF POST-MENOPAUSAL OSTEOPOROSIS BY ANTIOSTEOPOROTIC ACTIVITY

Postmenopausal osteoporosis, a quiet plague, has become a significant wellbeing danger, harassing about half of postmenopausal ladies around the world, and is accepted to be a malady that is one of the most well-known face to face who is encountering dementia achieved by mature age. It is a constant, dynamic condition, related with infinitesimal weakening of bone tissue, bringing about diminished bone mass, diminished bone quality which builds the danger of break. Ladies are bound to create osteoporosis than men because of decrease in estrogen during menopause which prompts decrease in bone-development and increment in bone-resorption action. Estrogen can stifle creation of proinflammatory cytokines like IL-1, IL-6, IL-7 and TNF-α. This is the reason these cytokines are raised in postmenopausal ladies. This paper manages the different techniques and parameters most every now and again utilized for screening of antiosteoporotic movement in post-menopausal osteoporesis. The ovariectomized creature model is the most proper model for considering the adequacy of various medications to forestall bone misfortune in postmenopausal osteoporosis. Different parameters dissected are: Biomechanical parameters as Three point bowing of tibia, Compression IV lumbar vertebra, Loading trial of femoral neck, Bone mineral thickness estimation; Biochemical parameters viz. serum calcium and inorganic phosphorus, serum basic phosphatase (ALP), Tartrate safe corrosive phosphatase (TRAP), protein profile, serum ACTH, corticosterone, IL-6, TNF-α, osteoprotegerin (OPG) and deoxypyridinoline crosslinks to creatinine proportion (DPD/Cr); Physical parameters like thickness and the length of the femur, weight of femur, Femur bone volume, bone thickness and so forth; Histopathology of femur to watch histopathological changes like size, shape and bone design; problematic and lytic changes, and fibrocartilageneous lattice with osteodystrophy; therapeutic advancement with mineralization alongside genuinely very much dispersed osteocytes; trabeculae and grid, and shaft size and so on; Histopathology of tibia to watch bone zone, bone volume per tissue volume, bone edge, outright number of dynamic osteoblasts, the proportion of indisputably the quantity of dynamic cuboid osteoblasts per bone border, the proportion of without a doubt the quantity of osteoclasts per osteoclast edge which speak to part of the trabeculae that are secured with osteoclasts, trabecular thickness, trabecular partition, trabecular number, mineralized bone volume per tissue volume, the osteoid volume per bone volume, the osteoid surface per bone surface, the osteoblast surface per bone surface, the disintegrated surface per bone surface. Different parameters as histopathology of uterus and mammary organ tissue, immunohistochemical recoloring to quantify ER level, pee examinations, body weight, organ weight, nourishment utilization, estrogen receptor ligand restricting test (ER-LBA), assurance of oxidative pressure, social test by constrained swimming test, neonatal mouse parietal bone resorption measure and so forth can likewise be completed.

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Bone Histomorphometric Findings in Ankylosing Spondylitis: A Case Report

Journal of Bone Biology and Osteoporosis ◽

10.18314/jbo.v4i1.1511 ◽

2018 ◽

Vol 4 (1) ◽

pp. 132-137 ◽

Cited By ~ 1

Author(s):

Naoki Kondo ◽

Noriaki Yamamoto ◽

Kei Watanabe ◽

Naoto Endo

Keyword(s):

Alkaline Phosphatase ◽

Ankylosing Spondylitis ◽

Bone Resorption ◽

Bone Formation ◽

Bone Turnover ◽

Reference Values ◽

Bone Volume ◽

Bone Surface ◽

Trabecular Thickness ◽

Low Bone Turnover

There is minimal information on bone Histomorphometric characteristics in ankylosing spondylitis. We here report a case of a 36-year-old Japanese male that suffered from lumbago and could not gaze in the forward direction. Ultimately, a diagnosis of ankylosing spondylitis was made, and vertebroplasty was performed to correct the third lumbar spine. Histomorphometry of the iliac bone showed reduced bone volume parameters (bone volume, and trabecular thickness and width) than reference values. In addition, bone formation parameters (osteoid thickness and osteoblast surface per bone surface) and bone resorption parameters (eroded surface per bone surface and osteoclast number per bone surface) were also lower than reference values, indicating low bone turnover. By contrast, there was not a clear trend in bone resorption markers: bone- pecific alkaline phosphatase (17 U/l) was normal, TRACP-5b (136 mU/dl) was slightly lower, urinary N-terminal telopeptide (45.3 nmol BCE/mmol Cr) was normal, and deoxypyridinoline (9.1 nM/mM Cre) was higher than reference values. However, there was deficiency in 25-hydroxy vitamin D (25-OH-D; 14.4 ng/ml). This case highlights the rare possibility of performing bone histomorphometry, and indicates that a low bone volume and low bone turnover (in both bone formation and resorption) are characteristics of ankylosing spondylitis, although bone formation markers (bone-specific alkaline phosphatase) and bone mineral density are within the normal range. The possibility of a serum 25-OH-D deficient status in ankylosing spondylitis should be further considered.

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A Delphinidin-Enriched Maqui Berry Extract Improves Bone Metabolism and Protects against Bone Loss in Osteopenic Mouse Models

Antioxidants ◽

10.3390/antiox8090386 ◽

2019 ◽

Vol 8 (9) ◽

pp. 386 ◽

Cited By ~ 2

Author(s):

Masahiro Nagaoka ◽

Toyonobu Maeda ◽

Masahiro Chatani ◽

Kazuaki Handa ◽

Tomoyuki Yamakawa ◽

...

Keyword(s):

Bone Loss ◽

Bone Formation ◽

Bone Metabolism ◽

Mouse Models ◽

Bone Morphogenetic Protein 2 ◽

Bone Surface ◽

Bone Formation Rate ◽

Trabecular Thickness ◽

Tissue Volume ◽

Maqui Berry

In our previous investigation, delphinidin, one of the most abundant anthocyanins found in vegetables and berry fruits, had been shown to inhibit osteoclasts and prevent bone loss in mouse models of osteoporosis. In the present study, we investigated whether a delphinidin glycoside-enriched maqui berry extract (MBE, Delphinol®) exhibits beneficial effects on bone metabolism both in vitro and in vivo. MBE stimulated the osteoblastic differentiation of MC3T3-E1 cells, as indicated by enhanced mineralized nodule formation, and increased alkaline phosphatase activity, through the upregulation of bone morphogenetic protein 2 (Bmp2), runt-related transcription factor 2 (Runx2), Osterix (Osx), osteocalcin (Ocn), and matrix extracellular phosphoglycoprotein (Mepe) mRNA expression. Immunostaining and immunoprecipitation assays demonstrated that MBE suppressed NF-κB transnucleation through acting as a superoxide anion/peroxynitrite scavenger in MC3T3-E1 cells. Simultaneously, MBE inhibited both osteoclastogenesis in primary bone marrow macrophages and pit formation by maturated osteoclasts on dentine slices. Microcomputed tomography (micro-CT) and bone histomorphometry analyses of femurs demonstrated that the daily ingestion of MBE significantly increased BV/TV (ratio of bone volume to tissue volume), Tb.Th (trabecular thickness), Tb.N (trabecular number), N.Nd/N.Tm (node to terminus ratio), OV/TV (ratio of osteoid volume to tissue volume), BFR/TV (bone formation rate per tissue volume), and significantly decreased Tb.Sp (trabecular separation), ES/BS (ratio of eroded surface to bone surface) and N.Oc/BS (number of osteoclast per unit of bone surface), compared to vehicle controls in osteopenic mouse models. These findings suggest that MBE can be a promising natural agent for the prevention of bone loss in osteopenic conditions by not only inhibiting bone resorption, but also stimulating bone formation.

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Keel-bone fractures are associated with bone quality differences in laying hens

Animal Welfare ◽

10.7120/09627286.30.1.071 ◽

2021 ◽

Vol 30 (1) ◽

pp. 71-80

Author(s):

HD Wei ◽

YJ Chen ◽

XY Zeng ◽

YJ Bi ◽

YN Wang ◽

...

Keyword(s):

Bone Quality ◽

Laying Hens ◽

Bone Fractures ◽

Quality Parameters ◽

Bone Volume ◽

Tartrate Resistant Acid Phosphatase ◽

Bone Surface ◽

Mineral Density ◽

Trabecular Thickness ◽

Trap Activity

This study aimed to investigate the relationship between bone quality in terms of metabolism, homeostasis of elements, bone mineral density (BMD), and microstructure and keel-bone fractures in laying hens (Gallusgallusdomesticus). One hundred and twenty 17 week old Lohmann White laying hens with normal keel bones were individually housed in furnished cages for 25 weeks. Birds were then euthanased and dissected to assess keel-bone status at 42 weeks. Serum and keel-bone samples from normal keel (NK) and fractured keel (FK) hens were collected to determine the previously mentioned bone quality parameters. The results showed FK hens to have higher levels of the components of osteocalcin, greater alkaline phosphatase activity in serum and keel bones, and greater tartrate-resistant acid phosphatase (TRAP) activity in keel bones, compared to NK hens. Additionally, FK hens also had higher concentrations of Li, B, K, Cu, As, Se, Sn, Hg, and Pb, but lower concentrations of Na, P, and Ca. Moreover, FK hens showed decreased bone microstructural parameters including bone volume/tissue volume, trabecular number, degree of anisotropy, connectivity density, and BMD, but increased trabecular separation. Meanwhile, no differences were detected in serum TRAP activity, trabecular thickness, bone surface, or bone surface/bone volume. Results showed laying hens with keel-bone fractures to have differences in bone metabolism, elements of homeostasis, bone microstructure parameters, and BMD. These results suggest that keel-bone fractures may be associated with bone quality.

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Pedicle screws with a thin hydroxyapatite coating for improving fixation at the bone-implant interface in the osteoporotic spine: experimental study in a porcine model

Journal of Neurosurgery Spine ◽

10.3171/2017.10.spine17702 ◽

2018 ◽

Vol 28 (6) ◽

pp. 679-687 ◽

Cited By ~ 9

Author(s):

Makoto Ohe ◽

Hiroshi Moridaira ◽

Satoshi Inami ◽

Daisaku Takeuchi ◽

Yutaka Nohara ◽

...

Keyword(s):

Spinal Surgery ◽

Coating Layer ◽

Pedicle Screws ◽

Bone Volume ◽

Control Group ◽

Bone Surface ◽

Implant Surface ◽

Bone Implant ◽

Tissue Volume ◽

Ha Coating

OBJECTIVEInstrumentation failure caused by the loosening of pedicle screws (PSs) in patients with osteoporosis is a serious problem after spinal surgery. The addition of a thin hydroxyapatite (HA) surface coating applied by using a sputtering process was reported recently to be a promising method for providing bone conduction around an implant without a significant risk of coating-layer breakage. In this study, the authors evaluated the biomechanical and histological features of the bone-implant interface (BII) of PSs with a thin HA coating in an in vivo porcine osteoporotic spine model.METHODSThree types of PSs (untreated/standard [STPS], sandblasted [BLPS], and HA-coated [HAPS] PSs) were implanted into the thoracic and lumbar spine (T9–L6) of 8 mature Clawn miniature pigs (6 ovariectomized [osteoporosis group] and 2 sham-operated [control group] pigs). The spines were harvested from the osteoporosis group at 0, 2, 4, 8, 12, or 24 weeks after PS placement and from the control group at 0 or 24 weeks. Their bone mineral density (BMD) was measured by peripheral quantitative CT. Histological evaluation of the BIIs was conducted by performing bone volume/tissue volume and bone surface/implant surface measurements. The strength of the BII was evaluated with extraction torque testing.RESULTSThe BMD decreased significantly in the osteoporosis group (p < 0.01). HAPSs exhibited the greatest mean extraction peak torque at 8 weeks, and HAPSs and BLPSs exhibited significantly greater mean torque than the STPSs at 12 weeks (p < 0.05). The bone surface/implant surface ratio was significantly higher for HAPSs than for STPSs after 2 weeks (p < 0.05), and bonding between bone and the implant surface was maintained until 24 weeks with no detachment of the coating layer. In contrast, the bone volume/tissue volume ratio was significantly higher for HAPSs than for BLPSs or STPSs only at 4 weeks.CONCLUSIONSUsing PSs with a thin HA coating applied using a sputtering process strengthens bonding at the BII, which might improve early implant fixation after spinal surgery for osteoporosis. However, the absence of increased bone mass around the screw remains a concern; prescribing osteoporosis treatment to improve bone quality might be necessary to prevent fractures around the screws.

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5 alpha-Dihydrotestosterone partially restores cancellous bone volume in osteopenic ovariectomized rats

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1994.267.6.e853 ◽

1994 ◽

Vol 267 (6) ◽

pp. E853-E859 ◽

Cited By ~ 6

Author(s):

J. H. Tobias ◽

A. Gallagher ◽

T. J. Chambers

Keyword(s):

Bone Resorption ◽

Bone Loss ◽

Bone Formation ◽

Cancellous Bone ◽

Bone Growth ◽

Bone Volume ◽

Ovariectomized Rats ◽

Trabecular Thickness ◽

Longitudinal Bone Growth ◽

Periosteal Bone Formation

Although androgens are thought to be important for skeletal maintenance in females and males, little is known about the mechanisms involved. To investigate this question further, we examined the effects of administering 0.01, 0.1, or 1.0 mg/kg 5 alpha-dihydrotestosterone (DHT) for 60 days on the skeleton of ovariectomized rats. Treatment was delayed until 90 days after ovariectomy to enable bone loss to stabilize. We found that ovariectomy markedly reduced cancellous bone volume of the proximal tibial metaphysis due to a combination of loss and thinning of trabeculae. Cancellous bone volume was partially restored by all doses of DHT, with trabecular thickness, but not number, returning to that of sham-operated animals. DHT also stimulated longitudinal bone growth and endosteal and periosteal bone formation and suppressed histomorphometric indexes of cancellous bone resorption. This suggests that DHT influences skeletal metabolism in osteopenic ovariectomized rats both by stimulating bone formation and suppressing resorption, although it is unclear which, if any, of these actions predominate at cancellous sites.

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Running exercise alleviates trabecular bone loss and osteopenia in hemizygous β-globin knockout thalassemic mice

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00111.2014 ◽

2014 ◽

Vol 306 (12) ◽

pp. E1406-E1417 ◽

Cited By ~ 13

Author(s):

Kanogwun Thongchote ◽

Saovaros Svasti ◽

Jarinthorn Teerapornpuntakit ◽

Nateetip Krishnamra ◽

Narattaphol Charoenphandhu

Keyword(s):

Bone Resorption ◽

Bone Loss ◽

Bone Formation ◽

Trabecular Bone ◽

Elevated Serum ◽

Bone Volume ◽

Trabecular Bone Volume ◽

Mineral Density ◽

Trabecular Thickness ◽

Running Exercise

A marked decrease in β-globin production led to β-thalassemia, a hereditary anemic disease associated with bone marrow expansion, bone erosion, and osteoporosis. Herein, we aimed to investigate changes in bone mineral density (BMD) and trabecular microstructure in hemizygous β-globin knockout thalassemic (BKO) mice and to determine whether endurance running (60 min/day, 5 days/wk for 12 wk in running wheels) could effectively alleviate bone loss in BKO mice. Both male and female BKO mice (1–2 mo old) showed growth retardation as indicated by smaller body weight and femoral length than their wild-type littermates. A decrease in BMD was more severe in female than in male BKO mice. Bone histomorphometry revealed that BKO mice had decreases in trabecular bone volume, trabecular number, and trabecular thickness, presumably due to suppression of osteoblast-mediated bone formation and activation of osteoclast-mediated bone resorption, the latter of which was consistent with elevated serum levels of osteoclastogenic cytokines IL-1α and -1β. As determined by peripheral quantitative computed tomography, running increased cortical density and thickness in the femoral and tibial diaphyses of BKO mice compared with those of sedentary BKO mice. Several histomorphometric parameters suggested an enhancement of bone formation (e.g., increased mineral apposition rate) and suppression of bone resorption (e.g., decreased osteoclast surface), which led to increases in trabecular bone volume and trabecular thickness in running BKO mice. In conclusion, BKO mice exhibited pervasive osteopenia and impaired bone microstructure, whereas running exercise appeared to be an effective intervention in alleviating bone microstructural defect in β-thalassemia.

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Petunidin, a B-ring 5′-O-Methylated Derivative of Delphinidin, Stimulates Osteoblastogenesis and Reduces sRANKL-Induced Bone Loss

International Journal of Molecular Sciences ◽

10.3390/ijms20112795 ◽

2019 ◽

Vol 20 (11) ◽

pp. 2795 ◽

Cited By ~ 7

Author(s):

Masahiro Nagaoka ◽

Toyonobu Maeda ◽

Sawako Moriwaki ◽

Atsushi Nomura ◽

Yasumasa Kato ◽

...

Keyword(s):

Oral Administration ◽

Mrna Expression ◽

Protective Effects ◽

Bone Surface ◽

Trabecular Thickness ◽

Tissue Volume ◽

Osteoid Surface ◽

Proteolytic Activities ◽

Osteoid Formation

Several lines of evidence suggest that oxidative stress is one of the key pathogenic mechanisms of osteoporosis. We aimed to elucidate the bone protective effects of petunidin, one of the most common anthocyanidins, considering its potent antioxidative activity. Petunidin (>5 μg/mL) significantly inhibited osteoclastogenesis and downregulated c-fos, Nfatc1, Mmp9, Ctsk, and Dc-stamp mRNA expression in RAW264.7 cells. Conversely, petunidin (>16 μg/mL) stimulated mineralized matrix formation and gene expression of Bmp2 and Ocn, whereas it suppressed Mmp13, Mmp2, and Mmp9 mRNA expression and proteolytic activities of MMP13 and MMP9 in MC3T3-E1 cells. Micro-CT and bone histomorphometry analyses of sRANKL-induced osteopenic C57BL/6J mice showed that daily oral administration of petunidin (7.5 mg/kg/day) increased bone volume to tissue volume (BV/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N), the ratio of osteoid volume to tissue volume (OV/TV), osteoid thickness (O.Th), the ratio of osteoid surface to bone surface (OS/BS), the ratio of osteoblast surface to bone surface (Ob.S/BS), and the number of osteoblast per unit of bone surface (N.Ob/BS), and decreased trabecular separation (Tb.Sp), the ratio of eroded surface to bone surface (ES/BS), the ratio of osteoclast surface to bone surface (Oc.S/BS), and number of osteoclast per unit of bone surface (N.Oc/BS), compared to untreated mice. Furthermore, histological sections of the femurs showed that oral administration of petunidin to sRANKL-induced osteopenic mice increased the size of osteoblasts located along the bone surface and the volume of osteoid was consistent with the in vitro osteoblast differentiation and MMP inhibition. These results suggest that petunidin is a promising natural agent to improve sRANKL-induced osteopenia in mice through increased osteoid formation, reflecting accelerated osteoblastogenesis, concomitant with suppressed bone resorption.

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Micro-Computed Tomography Analysis of Subchondral Bone Regeneration Using Osteochondral Scaffolds in an Ovine Condyle Model

Applied Sciences ◽

10.3390/app11030891 ◽

2021 ◽

Vol 11 (3) ◽

pp. 891

Author(s):

Taylor Flaherty ◽

Maryam Tamaddon ◽

Chaozong Liu

Keyword(s):

Computed Tomography ◽

Bone Regeneration ◽

Subchondral Bone ◽

Volume Ratio ◽

Bone Volume ◽

Osteochondral Defects ◽

Micro Ct ◽

Micro Computed Tomography ◽

Trabecular Thickness ◽

Osteochondral Scaffold

Osteochondral scaffold technology has emerged as a promising therapy for repairing osteochondral defects. Recent research suggests that seeding osteochondral scaffolds with bone marrow concentrate (BMC) may enhance tissue regeneration. To examine this hypothesis, this study examined subchondral bone regeneration in scaffolds with and without BMC. Ovine stifle condyle models were used for the in vivo study. Two scaffold systems (8 mm diameter and 10 mm thick) with and without BMC were implanted into the femoral condyle, and the tissues were retrieved after six months. The retrieved femoral condyles (with scaffold in) were examined using micro-computed tomography scans (micro-CT), and the micro-CT data were further analysed by ImageJ with respect to trabecular thickness, bone volume to total volume ratio (BV/TV) ratio, and degree of anisotropy of bone. Statistical analysis compared bone regeneration between scaffold groups and sub-set regions. These results were mostly insignificant (p < 0.05), with the exception of bone volume to total volume ratio when comparing scaffold composition and sub-set region. Additional trends in the data were observed. These results suggest that the scaffold composition and addition of BMC did not significantly affect bone regeneration in osteochondral defects after six months. However, this research provides data which may guide the development of future treatments.

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Granulocyte colony-stimulating factor (G-CSF) mediates bone resorption in periodontitis

BMC Oral Health ◽

10.1186/s12903-021-01658-1 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Hui Yu ◽

Tianyi Zhang ◽

Haibin Lu ◽

Qi Ma ◽

Dong Zhao ◽

...

Keyword(s):

Bone Resorption ◽

Alveolar Bone ◽

Bone Volume ◽

Granulocyte Colony Stimulating Factor ◽

Colony Stimulating Factor ◽

Periodontal Tissues ◽

Gingival Epithelial Cells ◽

Trap Staining ◽

Experimental Periodontitis ◽

Stimulating Factor

Abstract Background Granulocyte colony-stimulating factor (G-CSF) is an important immune factor that mediates bone metabolism by regulating the functions of osteoclasts and osteoblasts. Bone loss is a serious and progressive result of periodontitis. However, the mechanisms underlying the effects of G-CSF on periodontal inflammation have yet not been completely elucidated. Here, we examined whether an anti-G-CSF antibody could inhibit bone resorption in a model of experimental periodontitis and investigated the local expression of G-CSF in periodontal tissues. Methods Experimental periodontitis was induced in mice using ligatures. The levels of G-CSF in serum and bone marrow were measured; immunofluorescence was then performed to analyze the localization and expression of G-CSF in periodontal tissues. Mice with periodontitis were administered anti-G-CSF antibody by tail vein injection to assess the inhibition of bone resorption. Three-dimensional reconstruction was performed to measure bone destruction‐related parameters via micro-computed tomography analysis. Immunofluorescence staining was used to investigate the presence of osteocalcin-positive osteoblasts; tartrate-resistant acid phosphatase (TRAP) staining was used to observe osteoclast activity in alveolar bone. Results The level of G-CSF in serum was significantly elevated in mice with periodontitis. Immunofluorescence analyses showed that G-CSF was mostly expressed in the cell membrane of gingival epithelial cells; this expression was enhanced in the periodontitis group. Additionally, systemic administration of anti-G-CSF antibody significantly inhibited alveolar bone resorption, as evidenced by improvements in bone volume/total volume, bone surface area/bone volume, trabecular thickness, trabecular spacing, and trabecular pattern factor values. Immunofluorescence analysis revealed an enhanced number of osteocalcin-positive osteoblasts, while TRAP staining revealed reduction of osteoclast activity. Conclusions G-CSF expression levels were significantly up-regulated in the serum and gingival epithelial cells. Together, anti-G-CSF antibody administration could alleviates alveolar bone resorption, suggesting that G-CSF may be one of the essential immune factors that mediate the bone loss in periodontitis.

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Osseointegration of a novel dental implant in canine

Scientific Reports ◽

10.1038/s41598-021-83700-4 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Lingxiao Wang ◽

Zhenhua Gao ◽

Yucheng Su ◽

Qian Liu ◽

Yi Ge ◽

...

Keyword(s):

Volume Ratio ◽

Volume Density ◽

Scientific Basis ◽

Bone Volume ◽

Trabecular Thickness ◽

Bone Implant ◽

Further Development ◽

Trabecular Number ◽

Histological Staining

AbstractThis study aimed to compare and verify the osseointegration performance of a novel implant (NI) in vivo, which could provide a useful scientific basis for the further development of NIs. Thirty-two NIs treated with hydrofluoric acid and anodization and sixteen control implants (CIs) were placed in the mandibles of 8 beagles. Micro-CT showed that the trabecular number (Tb.N) significantly increased and trabecular separation (Tb.Sp) significantly decreased in the NIs at 2 weeks. Significant differences were found in the trabecular thickness, Tb.N, Tb.Sp, bone surface/bone volume ratio, and bone volume/total volume ratio between the two groups from the 2nd–4th weeks. However, there were no significant differences between the two groups in the bone volume density at 2, 4, 8, or 12 weeks or bone-implant contact at 2 or 4 weeks, but the BIC in the CIs was higher than that in the NIs at the 8th and 12th weeks. Meanwhile, the histological staining showed a similar osseointegration process between the two groups over time. Overall, the NIs could be used as new potential implants after further improvement.

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