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Introduction: This retrospective study highlights the salient aspects of a series of feline patients affected with bisphosphonate related osteonecrosis of the jaw. Though more commonly published in human literature, this presentation is rare in cats. The authors hope that this study will assist in making this a more globally known entity with subsequent improved prognosis. Methods: Data was retrospectively obtained from the medical records between 2015 and 2021 of 20 cats with Medication Related Osteonecrosis of the Jaw. Data included patient information, clinical history, presenting complaint, systemic diseases, details referable to hypercalcemia and treatment thereof, bisphosphonate specifics (dose and duration), clinical presentation of the lesion, diagnostic testing including radiographic and histopathologic descriptions, treatment, and outcome. Results: Pertinent results include that all 20 cats who developed Medication Related Osteonecrosis of the Jaw had been treated for idiopathic hypercalcemia with the bisphosphonate medication alendronate. Eighty-five percent of the cases had prior dental extractions at the site of MRONJ lesion. Ninety-five percent of the affected cats required a surgical procedure to control the disease. Thirty-five percent of cases required at least one revision surgery after the initial procedure was performed. Diagnosis of MRONJ was made by a correlation of diagnostic findings and patient history. No single diagnostic, or combination was pathognomonic for lesion diagnosis. As well, there were no statistically significant associations between patient variables assessed and the overall patient outcome. Discussion: The case series reveals that cats with feline idiopathic hypercalcemia treated with alendronate may be at a risk for development of MRONJ, a serious oral condition with significant morbidity. Prior dental extraction sites in patients concurrently treated with bisphosphonate medications were often associated with MRONJ lesions. Therefore, any needed dental surgery should be performed prior to the use of bisphosphonates where possible. The authors have also included a relevant comparative literature review. [ABSTRACT FROM AUTHOR]

Systemic administration of alendronate is associated with various adverse reactions in clinical settings. To mitigate these side effects, poloxamer 407 (P-407) modified with cellulose was chosen to encapsulate alendronate. This drug-loaded system was then incorporated into a collagen/β-tricalcium phosphate (β-TCP) scaffold to create a localized drug delivery system. Nuclear magnetic resonance spectrum and rheological studies revealed hydrogen bonding between P-407 and cellulose as well as a competitive interaction with water that contributed to the delayed release of alendronate (ALN). Analysis of the degradation kinetics of P-407 and release kinetics of ALN indicated zero-order kinetics for the former and Fickian or quasi-Fickian diffusion for the latter. The addition of cellulose, particularly carboxymethyl cellulose (CMC), inhibited the degradation of P-407 and prolonged the release of ALN. The scaffold's structure increased the contact area of P-407 with the PBS buffer, thereby, influencing the release rate of ALN. Finally, biocompatibility testing demonstrated that the drug delivery system exhibited favorable cytocompatibility and hemocompatibility. Collectively, these findings suggest that the drug delivery system holds promise for implantation and bone healing applications. [ABSTRACT FROM AUTHOR]

BACKGROUND: Some studies have found that local application of alendronate can promote osteogenesis, but less is reported on the process of distraction osteogenesis. OBJECTIVE: To observe the promoting effect of alendronate on rapid mandibular distraction in a rabbit model and explore its possible mechanism. METHODS: Thirty-six male New Zealand white rabbits were randomly divided into groups A, B and C (n=12 per group) after operation and rapid distraction (3- day delay period followed by 3-day distraction at 1.5 mm/12 hours). At the 1st, 3rd and 7th days of the consolidation period, animal were injected with 200 μg/kg alendronate in group A and 100 μg/kg alendronate in group B, while those in group C were treated as controls. CT scanning and dual energy X-ray bone mineral density measurement were performed at 4 and 8 weeks of the consolidation period. After the radionuclide scanning was completed at the 4th week, several animals were sacrificed and the samples were collected for western blot assay and tartrate resistant acid phosphatase staining. A three-point bending test was performed after the animals were sacrificed at the 8th week. RESULTS AND CONCLUSION: CT results showed that bone formation in the distraction space of group B was significantly better than that in groups A and C. At the 4th week, the bone mineral density in group B was (0.092±0.010) g/cm², which was 1.26 times higher than that in group A (P < 0.001) and 1.28 times higher than that in group C (P < 0.001). At the 8th week, the bone mineral density in group B was (0.175±0.029) g/cm², which was 1.38 times higher than that in group A (P < 0.001) and 1.45 times higher than that in group C (P < 0.001). Tartrate resistant acid phosphatase staining showed that the number of osteoclast-like cells in group C were 2.83 times more than that in group A (P < 0.001) and 2.21 times more than that in group B (P < 0.001). The radionuclide intensity was higher in group C than in groups A and B. Western blot assay results showed that the expression of Runx2 was significantly stronger in group B than in groups A and C. The maximum biomechanical load in group B was (158.48 ± 23.21) N, which was 1.26 times higher than that in group A (P=0.007) and 1.31 times higher than that in group C (P=0.003). To conclude, the low concentration of alendronate may promote rapid distraction osteogenesis of the rabbit mandible by inhibiting osteoclast signals. [ABSTRACT FROM AUTHOR]

Denosumab and bisphosphonates for primary osteoporosis are generally well-tolerated, but their comparative safety remains unclear. We aimed to explore the comparative safety of denosumab and bisphosphonates in primary osteoporosis. Databases such as PubMed and Google Scholar were searched for relevant peer-reviewed randomized controlled trials published in English (as of December 2023). Trials comparing adverse events (AE) between denosumab and bisphosphonates in patients with primary osteoporosis were investigated. Data were pooled using a fixed- or random-effects model to determine the risk ratios (RR) and 95% confidence intervals (CIs) for various AEs in patients treated with denosumab in comparison to patients treated with bisphosphonates. Eleven trials (5,545 patients; follow-up period: 12–24 months) were included in this meta-analysis. All trials had a risk of bias (e.g., reporting bias linked to secondary endpoints and selection bias linked to random allocation). In comparison to bisphosphonates, denosumab was significantly associated with less withdrawal due to AEs (RR = 0.49; 95% CI 0.34–0.71), more five-point major adverse cardiovascular events (RR = 2.05; 95% CI 1.03–4.09), more cardiovascular AEs (RR = 1.61; 95% CI 1.07–2.41), more infections (RR = 1.14; 95% CI 1.02–1.27), more upper respiratory tract infections (RR = 1.56; 95% CI 1.08–2.25), less vertebral fractures (RR = 0.54; 95% CI 0.31–0.93), and less abdominal pain (RR = 0.44;95% CI 0.22–0.87). We explored the comparative safety of denosumab and bisphosphonates for primary osteoporosis, some of which could be attributed to their beneficial effects. However, all trials had a risk of bias. Further investigations are required to confirm our results. [ABSTRACT FROM AUTHOR]

Bone is one of the most prevalent sites of metastases in various epithelial malignancies, including breast cancer and this metastasis to bone often leads to severe skeletal complications in women due to its osteolytic nature. To address this, we devised a novel drug delivery approach using an Alendronate (ALN) functionalized self-assembled porous crystalsomes for concurrent targeting of Oleanolic acid (OA) and ALN (ALN + OA@NCs) to bone metastasis. Initially, the conjugation of both PEG-OA and OA-PEG-ALN with ALN and OA was achieved, and this conjugation was then self-assembled into porous crystalsomes (ALN + OA@NCs) by nanoemulsion crystallization. The reconstruction of a 3D single particle using transmission electron microscopy ensured the crystalline porous structure of ALN + OA@NCs, was well aligned with characteristic nanoparticle attributes including size distribution, polydispersity, and zeta potential. Further, ALN + OA@NCs showed enhanced efficacy in comparison to OA@NCs suggesting the cytotoxic roles of ALN towards cancer cells, followed by augmentation ROS generation (40.81%), mitochondrial membrane depolarization (57.20%), and induction of apoptosis (40.43%). We found that ALN + OA@NCs facilitated inhibiting osteoclastogenesis and bone resorption followed by inhibited osteolysis. In vivo activity of ALN + OA@NCs in the 4 T1 cell-induced tibia model rendered a reduced bone loss in the treated mice followed by restoring bone morphometric markers which were further corroborated bone–targeting effects of ALN + OA@NCs to reduce RANKL-stimulated osteoclastogenesis. Further, In vivo intravenous pharmacokinetics showed the improved therapeutic profile of the ALN + OA@NCs in comparison to the free drug, prolonging the levels of the drug in the systemic compartment by reducing the clearance culminating the higher accumulation at the tumor site. Our finding proposed that ALN + OA@NCs can effectively target and treat breast cancer metastasis to bone and its associated complications. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Dental pulp stem cells (DPSCs) possess mesenchymal stem cell characteristics and have potential for cell-based therapy. Cell expansion is essential to achieve sufficient cell numbers. However, continuous cell replication causes cell aging in vitro, which usually accompanies and potentially affect DPSC characteristics and activities. Continuous passaging could alter susceptibility to external factors such as drug treatment. Therefore, this study sought to investigate potential outcome of in vitro passaging on DPSC morphology and activities in the absence or presence of external factor. Methods: Human DPSCs were subcultured until reaching early passages (P5), extended passages (P10), and late passages (P15). Cells were evaluated and compared for cell and nuclear morphologies, cell adhesion, proliferative capacity, alkaline phosphatase (ALP) activity, and gene expressions in the absence or presence of external factor. Alendronate (ALN) drug treatment was used as an external factor. Results: Continuous passaging of DPSCs gradually lost their normal spindle shape and increased in cell and nuclear sizes. DPSCs were vulnerable to ALN. The size and shape were altered, leading to morphological abnormality and inhomogeneity. Long-term culture and ALN interfered with cell adhesion. DPSCs were able to proliferate irrespective of cell passages but the rate of cell proliferation in late passages was slower. ALN at moderate dose inhibited cell growth. ALN caused reduction of ALP activity in early passage. In contrast, extended passage responded differently to ALN by increasing ALP activity. Late passage showed higher collagen but lower osteocalcin gene expressions compared with early passage in the presence of ALN. Conclusion: An increase in passage number played critical role in cell morphology and activities as well as responses to the addition of an external factor. The effects of cell passage should be considered when used in basic science research and clinical applications. [ABSTRACT FROM AUTHOR]

Background: Osteogenesis imperfecta (OI) is a genetic disorder of connective tissue caused by mutations associated with type I collagen, which results in defective extracellular matrix in temporomandibular joint (TMJ) cartilage and subchondral bone. TMJ is a fibrocartilaginous joint expressing type I collagen both in the cartilage and the subchondral bone. In the present study the effects of alendronate and altered loading of the TMJ was analyzed both in male and female OI mice. Materials and methods: Forty-eight, 10-weeks-old male and female OI mice were divided into 3 groups: (1) Control group: unloaded group, (2) Saline + Loaded: Saline was injected for 2 weeks and then TMJ of mice was loaded for 5 days, (3) alendronate + loaded: alendronate was injected for 2 weeks and then TMJ of mice was loaded for 5 days. Mice in all the groups were euthanized 24-h after the final loading. Results: Alendronate pretreatment led to significant increase in bone volume and tissue density. Histomorphometrically, alendronate treatment led to increase in mineralization, cartilage thickness and proteoglycan distribution. Increased mineralization paralleled decreased osteoclastic activity. Our immunohistochemistry revealed decreased expression of matrix metallopeptidase 13 and ADAM metallopeptidase with thrombospondin type 1 motif 5. Conclusion: The findings of this research support that alendronate prevented the detrimental effects of loading on the extracellular matrix of the TMJ cartilage and subchondral bone. [ABSTRACT FROM AUTHOR]

PCSK9 inhibitors have been shown to lower serum low density lipoprotein cholesterol (LDL-C) levels and are considered integral in the treatment of cardiovascular diseases. However, the potential association between PCSK9 inhibitors and osteoporosis is unclear now. In this study, drug-targeted mendelian randomization (MR) was utilized in conjunction with mediation analysis including bone mineral density (BMD), total 25-hydroxyvitamin D (T25(OH)D) levels and calcium supplementation to investigate the causal relationship between PCSK9 inhibitors and osteoporosis. The LDL-C level was chosen as the exposure variable in a sample size of 173,082 individuals. We conducted a MR analysis on the relationship between PCSK9 inhibitors and osteoporosis, elucidating the mediators involved. Utilizing the inverse variance weighted (IVW) method, we found the risk of osteoporosis was reduced by 0.6% in those who used PCSK9 inhibitors compared with non-users (OR: 0.994, 95%CI: 0.991–0.998, P < 0.001). In people aged 30–45 years, the risk of low BMD was 1.176 times higher among PCSK9 inhibitor users compared to non-users (OR: 1.176, 95%CI: 1.017–1.336, P = 0.045). Conversely, people aged 45–60 years who used PCSK9 inhibitors had a 14.9% lower risk of low BMD compared to non-users (OR: 0.851, 95%CI: 0.732–0.968, P = 0.007). Mediation analysis revealed that 43.33% of the impact of PCSK9 inhibitors on osteoporosis was mediated through BMD levels, with the remaining 56.67% being a direct effect. Effects of PCSK9 inhibitors on BMD levels varied in different ages. In addition, the risk of high serum T25(OH)D levels were 1.091 times among PCSK9 inhibitor users compared to non-users (OR: 1.091, 95%CI: 1.065–1.112, P < 0.001), providing valuable insights for clinicians. [ABSTRACT FROM AUTHOR]

Summary: Post hoc analysis of FRAME and ARCH revealed that on-study nonvertebral and vertebral fractures by Month 12 were less common in women initially treated with romosozumab versus placebo or alendronate. Recurrent fracture risk was also lower in romosozumab‑treated patients, and there were no fracture‑related complications. Results support continuing romosozumab treatment post‑fracture. Purpose: Post hoc analysis evaluating efficacy and safety of romosozumab, administered in the immediate post‑fracture period, in the FRAME and ARCH phase 3 trials. Methods: In FRAME (NCT01575834) and ARCH (NCT01631214), postmenopausal women with osteoporosis were randomized 1:1 to romosozumab 210 mg monthly or comparator (FRAME, placebo; ARCH, alendronate 70 mg weekly) for 12 months, followed by antiresorptive therapy (FRAME, denosumab; ARCH, alendronate). In patients who experienced on-study nonvertebral or new/worsening vertebral fracture by Month 12, we report the following: fracture and treatment‑emergent adverse event (TEAE) incidence through 36 months, bone mineral density changes (BMD), and romosozumab timing. Due to the sample sizes employed, meaningful statistical comparisons between treatments were not possible. Results: Incidence of on-study nonvertebral and vertebral fractures by Month 12 was numerically lower in romosozumab- versus comparator-treated patients (FRAME, 1.6% and 0.5% versus 2.1% and 1.6%; ARCH, 3.4% and 3.3% versus 4.6% and 4.9%, respectively). In those who experienced on-study nonvertebral fracture by Month 12, recurrent nonvertebral and subsequent vertebral fracture incidences were numerically lower in patients initially treated with romosozumab versus comparator (FRAME, 3.6% [2/56] and 1.8% [1/56] versus 9.2% [7/76] and 3.9% [3/76]; ARCH, 10.0% [7/70] and 5.7% [4/70] versus 12.6% [12/95] and 8.4% [8/95], respectively). Among those with on-study vertebral fracture by Month 12, recurrent vertebral and subsequent nonvertebral fracture incidences were numerically lower with romosozumab versus comparator (FRAME, 0.0% [0/17] and 0.0% [0/17] versus 11.9% [7/59] and 8.5% [5/59]; ARCH, 9.0% [6/67] and 7.5% [5/67] versus 15.0% [15/100] and 16.0% [16/100], respectively). In patients with fracture by Month 12, no fracture‑related complications were reported in romosozumab-treated patients. BMD gains were numerically greater with romosozumab than comparators. Conclusion: Data suggest support for the efficacy and safety of continuing romosozumab treatment following fracture. Trial registrations: NCT01575834; NCT01631214. [ABSTRACT FROM AUTHOR]

Summary: This study evaluated the cost-effectiveness of sequential treatment with romosozumab-to-alendronate compared to alendronate monotherapy and teriparatide-to-alendronate, in postmenopausal osteoporotic women from a Belgian healthcare perspective. Romosozumab-to-alendronate was found to be cost-effective compared to alendronate monotherapy and dominant compared to teriparatide-to-alendronate for osteoporotic women at high risk of fracture in Belgium. Purpose: This study aimed to evaluate the cost-effectiveness of sequential treatment with romosozumab followed by alendronate compared to alendronate monotherapy and teriparatide followed by alendronate, in postmenopausal osteoporotic women at high risk of fracture, from a Belgian healthcare perspective. Romosozumab is reimbursed in Belgium since December 2021. Methods: A Markov microsimulation model was used to evaluate the cost-effectiveness of romosozumab-to-alendronate compared to alendronate monotherapy and to teriparatide-to-alendronate over a lifetime horizon. Patients transition between five different health states every 6 months based on fracture risks or death. The model was populated with Belgium-specific epidemiological and cost data, where available. The fracture risk reduction of romosozumab treatment was collated from the ARCH study, and from a published network meta-analysis. Costs were included from a healthcare perspective (NIHDI). Cost-effectiveness was reported in terms of costs per quality-adjusted life year (QALY), reported in Euro (€) 2022. Deterministic (DSA) and probabilistic sensitivity analyses (PSA) were performed. Results: Romosozumab-to-alendronate was associated with 0.12 additional QALYs at an additional cost of €2314 compared to alendronate monotherapy, resulting in an ICER of €19,978. Compared to teriparatide-to-alendronate, romosozumab-to-alendronate was found to be dominant, with higher QALYs and lower costs. The base-case results were robust to uncertainty in the input parameters when conducting the sensitivity analysis. Conclusion: Sequential treatment with romosozumab followed by alendronate was found to be cost-effective compared to alendronate monotherapy and dominant compared to teriparatide followed by alendronate for postmenopausal women with osteoporosis at high risk of fracture in Belgium. [ABSTRACT FROM AUTHOR]

The objective of this review is to examine the connection between osteoporosis and diabetes, compare the underlying causes of osteoporosis in various forms of diabetes, and suggest optimal methods for diagnosing and assessing fracture risk in diabetic patients. This narrative review discusses the key factors contributing to the heightened risk of fractures in individuals with diabetes, as well as the shared elements impacting the treatment of both diabetes mellitus and osteoporosis. Understanding the close link between diabetes and a heightened risk of fractures is crucial in effectively managing both conditions. There are several review articles of meta-analysis regarding diaporosis. Nevertheless, no review articles showed collected and well-organized medications of antidiabetics and made for inconvenient reading for those who were interested in details of drug mechanisms. In this article, we presented collected and comprehensive charts of every antidiabetic medication which was linked to fracture risk and indicated plausible descriptions according to research articles. [ABSTRACT FROM AUTHOR]

Bone metastasis secondary to breast cancer negatively impacts patient quality of life and survival. The treatment of bone metastases is challenging since many anticancer drugs are not effectively delivered to the bone to exert a therapeutic effect. To improve the treatment efficacy, we developed Pluronic P123 (P123)-based polymeric micelles dually decorated with alendronate (ALN) and cancer-specific phage protein DMPGTVLP (DP-8) for targeted drug delivery to breast cancer bone metastases. Doxorubicin (DOX) was selected as the anticancer drug and was encapsulated into the hydrophobic core of the micelles with a high drug loading capacity (3.44%). The DOX-loaded polymeric micelles were spherical, 123 nm in diameter on average, and exhibited a narrow size distribution. The in vitro experiments demonstrated that a pH decrease from 7.4 to 5.0 markedly accelerated DOX release. The micelles were well internalized by cultured breast cancer cells and the cell death rate of micelle-treated breast cancer cells was increased compared to that of free DOX-treated cells. Rapid binding of the micelles to hydroxyapatite (HA) microparticles indicated their high affinity for bone. P123-ALN/DP-8@DOX inhibited tumor growth and reduced bone resorption in a 3D cancer bone metastasis model. In vivo experiments using a breast cancer bone metastasis nude model demonstrated increased accumulation of the micelles in the tumor region and considerable antitumor activity with no organ-specific histological damage and minimal systemic toxicity. In conclusion, our study provided strong evidence that these pH-sensitive dual ligand-targeted polymeric micelles may be a successful treatment strategy for breast cancer bone metastasis. [ABSTRACT FROM AUTHOR]

Abstract Background Osteogenesis imperfecta (OI) is a genetic disorder of connective tissue caused by mutations associated with type I collagen, which results in defective extracellular matrix in temporomandibular joint (TMJ) cartilage and subchondral bone. TMJ is a fibrocartilaginous joint expressing type I collagen both in the cartilage and the subchondral bone. In the present study the effects of alendronate and altered loading of the TMJ was analyzed both in male and female OI mice. Materials and methods Forty-eight, 10-weeks-old male and female OI mice were divided into 3 groups: (1) Control group: unloaded group, (2) Saline + Loaded: Saline was injected for 2 weeks and then TMJ of mice was loaded for 5 days, (3) alendronate + loaded: alendronate was injected for 2 weeks and then TMJ of mice was loaded for 5 days. Mice in all the groups were euthanized 24-h after the final loading. Results Alendronate pretreatment led to significant increase in bone volume and tissue density. Histomorphometrically, alendronate treatment led to increase in mineralization, cartilage thickness and proteoglycan distribution. Increased mineralization paralleled decreased osteoclastic activity. Our immunohistochemistry revealed decreased expression of matrix metallopeptidase 13 and ADAM metallopeptidase with thrombospondin type 1 motif 5. Conclusion The findings of this research support that alendronate prevented the detrimental effects of loading on the extracellular matrix of the TMJ cartilage and subchondral bone.

Sodium alendronate (ALN) is a very hydrosoluble and poorly permeable molecule used as an antiresorptive agent and with vascular anticalcifying capacity. Loaded into targeted nanovesicles, its anti-inflammatory activity may be amplified towards extra-osseous and noncalcified target cells, such as severely irritated vascular endothelium. Here cytotoxicity, mitochondrial membrane potential, ATP content, and membrane fluidity of human endothelial venous cells (HUVECs) were determined after endocytosis of ALN-loaded nanoarchaeosomes (nanoARC-Chol(ALN), made of polar lipids from Halorubrum tebenquichense: cholesterol 7:3 w/w, 166 ± 5 nm, 0.16 ± 0.02 PDI, −40.8 ± 5.4 mV potential, 84.7 ± 21 µg/mg ALN/total lipids, TL). The effect of nanoARC-Chol(ALN) was further assessed on severely inflamed HUVECs. To that aim, HUVECs were grown on a porous barrier on top of a basal compartment seeded either with macrophages or human foam cells. One lighter and one more pronounced inflammatory context was modelled by adding lipopolysaccharide (LPS) to the apical or the apical and basal compartments. The endocytosis of nanoARC-Chol(ALN), was observed to partly reduce the endothelial-mesenchymal transition of HUVECs. Besides, while 10 mg/mL dexamethasone, 7.6 mM free ALN and ALN-loaded liposomes failed, 50 μg/mL TL + 2.5 μg/mL ALN (i.e., nanoARC-Chol(ALN)) reduced the IL-6 and IL-8 levels by, respectively, 75% and 65% in the mild and by, respectively, 60% and 40% in the pronounced inflammation model. This is the first report showing that the endocytosis of nanoARC-Chol(ALN) by HUVECs magnifies the anti-inflammatory activity of ALN even under conditions of intense irritation, not only surpassing that of free ALN but also that of dexamethasone.

Abstract Background Antiresorptive therapy (AR) disrupts osseous homeostasis and can induce direct irritation over the gastrointestinal mucosa; however, its possible erosive effects on the oral epithelium have not been totally described. Among the most frequent oral erosive lesions, oral lichen planus (OLP) frequently presents as painful mucosal ulcerations, arising from basal membrane inflammatory damage. Thus, the aim of this retrospective study was to describe the association between AR and the incidence of OLP. Methods This case-control study included data from 148 patients (17 patients undergoing AR therapy (AR group) / 131 without AR therapy (Control group)). Each patient record was systematically processed and the association between AR drugs and OLP clinical characteristics within both groups was assessed. Results The erosive form of OLP was significantly more frequent in the AR group than in the Control group (p = 0.029). Indeed, the AR treatment using alendronic acid (41.2%) was the most frequently reported. Additionally, the erosive form of OLP showed the strongest association with pain and burning sensation among the OLP types (p

Context: Anterior cruciate ligament (ACL) reconstruction often faces challenges due to poor integration of the tendon with bone. Aims: To evaluate the potential benefits of alendronate and platelet-rich plasma (PRP) in enhancing tendon-to-bone osteointegration in ACL surgery. Methods: This was a post-test only control group experimental study with Ovis aries Linnaeus sheep as experimental animals. The sample was divided into four groups: the control group ACL reconstruction with calcaneal tendons given NaCl, the group given PRP, alendronate, and PRP and alendronate. Bone healing biomarkers (NF-kB, TNF-α, MMP-9, TGF-β1, and COL1A1) were examined through immunohistochemical analysis and histological studies to assess osteoblast counts and inflammatory tissue. Results: There was a statistically significant (p0.05). The intervention did not affect NF-kB and TGF-β1 (p> 0.05). Conclusions: These results show that the administration of alendronate and PRP improves the healing of tendon-calcaneal ACL reconstruction surgery in sheep.

Objective To analyze the effectiveness and safety of bisphosphonates in the treatment of patients with calcification defense. Methods PubMed, Embase databases, CNKI and Wanfang were searched to collect the case reports and clinical studies of bisphosphonates for calcification defense. Then, the relevant information of patients was extracted for statistical analysis. Results A total of 18 case reports were selected involving 20 patients. Thirteen patients (65.0%) were treated with pamidronate, four (20.0%) were treated with etidronate, two (10.0%) were treated with alendronate, and one (5.0%) was treated with zoledronic acid. Thirteen patients (65.0%) recovered completely, the recovery time of whom ranged from half month to nine months. The tolerance of bisphosphonates in most patients(90.0%)was good, while one patient who did not tolerate pamidronate recovered after the frequency of administration was adjusted and one patient with high dosage of etidronate returned to normal after the discontinuation of the usage. Conclusions Bisphosphonates, an inhibitor of bone resorption, is effective and safe in the treatment of patients with calcification defense.

Abstract Osteoporosis is a highly prevalent metabolic disease characterized by low systemic bone mass and deterioration of bone microarchitecture, resulting in reduced bone strength and increased fracture risk. Current treatment options for osteoporosis are limited by factors such as efficacy, cost, availability, side effects, and acceptability to patients. Gold nanoparticles show promise as an emerging osteoporosis therapy due to their osteogenic effects and ability to allow therapeutic delivery but have inherent constraints, such as low specificity and the potential for heavy metal accumulation in the body. This study reports the synthesis of ultrasmall gold particles almost reaching the Ångstrom (Ång) dimension. The antioxidant alpha-lipoic acid (LA) is used as a dispersant and stabilizer to coat Ångstrom-scale gold particles (AuÅPs). Alendronate (AL), an amino-bisphosphonate commonly used in drug therapy for osteoporosis, is conjugated through LA to the surface of AuÅPs, allowing targeted delivery to bone and enhancing antiresorptive therapeutic effects. In this study, alendronate-loaded Ångstrom-scale gold particles (AuÅPs-AL) were used for the first time to promote osteogenesis and alleviate bone loss through regulation of the WNT signaling pathway, as shown through in vitro tests. The in vivo therapeutic effects of AuÅPs-AL were demonstrated in an established osteoporosis mouse model. The results of Micro-computed Tomography, histology, and tartrate-resistant acid phosphatase staining indicated that AuÅPs-AL significantly improved bone density and prevented bone loss, with no evidence of nanoparticle-associated toxicity. These findings suggest the possible future application of AuÅPs-AL in osteoporosis therapy and point to the potential of developing new approaches for treating metabolic bone diseases using Ångstrom-scale gold particles.

Osteoporosis is a commonly observed systemic metabolic disease characterized by a decrease in bone mineral density and an increased risk of fractures worldwide. Bisphosphonates are commonly preferred for its prevention and treatment. Among the side effects of bisphosphonates used orally and parenterally are gastrointestinal symptoms, musculoskeletal pains, flu-like syndrome, and an increase in acute-phase reactants. In this case report, a rare side effect observed during alendronate treatment, polyarticular synovitis, will be presented.

BACKGROUND: The mechanisms and targets of alendronate in the treatment of osteoporosis still need to be investigated in depth. OBJECTIVE: To investigate the mechanism by which alendronate regulates bone metabolism in rats with osteoporosis and to perform a bioinformatics analysis of differentially expressed proteins. METHODS: Female Sprague-Dawley rats were randomly divided into three groups (n=12 per group): model group, alendronate group and sham-operated group. Animal models of osteoporosis were prepared using ovariectomy in the model and alendronate groups. At 4 weeks after modeling, rats in the alendronate group were gavaged with alendronate; the other two groups were given the equal volume of normal saline. After 12 weeks of continuous gavage, the bone mineral density of the tibia was measured and the lumbar spine of the rats was taken for proteomic analysis using Tandem mass tag-liquid chromatography-tandem mass spectrometry technique to identify differentially expressed proteins for gene ontology, Kyoto Encyclopedia of Genes and Genomes pathway and protein-protein interaction analysis. RESULTS AND CONCLUSION: There were 32 up-regulated proteins and 51 down-regulated proteins identified between the alendronate group and model group. Gene ontology enrichment analysis showed that the differentially expressed proteins were mainly involved in molecular functions, such as binding and catalytic activity, and in biological processes, such as cellular process and metabolic process. Kyoto Encylopedia of Genes and Genomes enrichment analysis showed that the differentially expressed proteins in the alendronate group and model group were mainly involved in the biosynthesis of pantothenate and coenzyme A. Protein-protein interaction analysis indicated that among the differentially expressed proteins in the alendronate group and model group, Hspa1l, Enpp3, Unc45a, Myh9 and Cant1 were located at the nodes of the protein-protein interaction network and were closely related to bone metabolism. Overall, these findings indicate that alendronate may regulate bone metabolism in the rat model of osteoporosis by regulating the expression of differentially expressed proteins and biosynthesis of pantothenate and coenzyme A. [ABSTRACT FROM AUTHOR]

The surface modification of dental implants plays an important role in establishing a successful interaction of the implant with the surrounding tissue, as the bioactivity and osseointegration properties are strongly dependent on the physicochemical properties of the implant surface. A surface coating with bioactive molecules that stimulate the formation of a mineral calcium phosphate (CaP) layer has a positive effect on the bone bonding process, as biomineralization is crucial for improving the osseointegration process and rapid bone ingrowth. In this work, the spontaneous deposition of calcium phosphate on the titanium surface covered with chemically stable and covalently bound alendronate molecules was investigated using an integrated experimental and theoretical approach. The initial nucleation of CaP was investigated using quantum chemical calculations at the density functional theory (DFT) level. Negative Gibbs free energies show a spontaneous nucleation of CaP on the biomolecule-covered titanium oxide surface. The deposition of calcium and phosphate ions on the alendronate-modified titanium oxide surface is governed by Ca2+–phosphonate (-PO3H) interactions and supported by hydrogen bonding between the phosphate group of CaP and the amino group of the alendronate molecule. The morphological and structural properties of CaP deposit were investigated using scanning electron microscopy, energy dispersive X-ray spectroscopy, X-ray diffraction and attenuated total reflectance Fourier transform infrared spectroscopy. This integrated experimental–theoretical study highlights the spontaneous formation of CaP on the alendronate-coated titanium surface, confirming the bioactivity ability of the alendronate coating. The results provide valuable guidance for the promising forthcoming advancements in the development of biomaterials and surface modification of dental implants. [ABSTRACT FROM AUTHOR]

Purpose: To determine the effect of alendronate sodium combined with radial shock wave on hemorheology and degree of pain in patients with femoral head necrosis. Methods: The study comprised 188 patients with femoral head necrosis treated in Taizhou People's Hospital, China from June 2020 to June 2022. They were divided into control group (CG, n = 96) and study group (SG, n = 92). Control group was given radial shock wave therapy once in 30 days, while the study group was given alendronate sodium orally (10 mg/daily) for 3 months, as well as radial shock wave therapy. Hemorheology indices (plasma viscosity (PV), low-cut reduced viscosity (LRV), high-cut reduced viscosity (HRV)); degree of pain (McGill Pain Questionnaire (MPQ)), joint muscle strength, and clinical efficacy in both groups were compared. Results: The SG had significantly lower levels of PV, LRV and HRV, and lesser MPQ scores at 1 month (T1) and 2 months post-treatment (T2) than CG (p < 0.05). The post-treatment levels of PV, LRV, HRV, and MPQ scores at T1 stage in the two groups were significantly lower than the pre-treatment (T0) scores (p < 0.001). The scores of PV, LRV, HRV, and MPQ at T2 in both groups were significantly lower than the corresponding T1 scores (p < 0.05). Higher numbers of cases with grade 4 and grade 5 joint muscle strength were seen in SG than in CG at T2. Treatment efficacy/effectiveness in SG was significantly higher than in CG (p < 0.05). Conclusion: Alendronate sodium combination with radial shock wave, produces significant improvement in femoral head necrosis, mitigates symptoms and enhances joint muscle strength of patients. Future studies with larger sample sizes will be necessary to validate the outcome of this study. [ABSTRACT FROM AUTHOR]

Aminobisphosphonates (NBPs) are the first-choice medication for osteoporosis (OP); NBP treatment aims at increasing bone mineral density (BMD) by inhibiting the activity of farnesyl diphosphate synthase (FDPS) enzyme in osteoclasts. Despite its efficacy, inadequate response to the drug and side effects have been reported. The A allele of the rs2297480 (A > C) SNP, found in the regulatory region of the FDPS gene, is associated with reduced gene transcription. This study evaluates the FDPS variant rs2297480 (A > C) association with OP patients' response to alendronate sodium treatment. A total of 304 OP patients and 112 controls were enrolled; patients treated with alendronate sodium for two years were classified, according to BMD variations at specific regions (lumbar spine (L1-L4), femoral neck (FN) and total hip (TH), as responders (OP-R) (n = 20) and non-responders (OP-NR) (n = 40). We observed an association of CC genotype with treatment failure (p = 0.045), followed by a BMD decrease in the regions L1-L4 (CC = −2.21% ± 2.56; p = 0.026) and TH (CC = −2.06% ± 1.84; p = 0.015) after two years of alendronate sodium treatment. Relative expression of the FDPS gene was also evaluated in OP-R and OP-NR patients. Higher expression of the FDPS gene was also observed in OP-NR group (FC = 1.84 ± 0.77; p = 0.006) when compared to OP-R. In conclusion, the influence observed of FDPS expression and the rs2897480 variant on alendronate treatment highlights the importance of a genetic approach to improve the efficacy of treatment for primary osteoporosis. [ABSTRACT FROM AUTHOR]

Background: In traditional Chinese medicine, You-Gui-Wan (YGW) is typically used to treat osteoporosis associated with kidney-yang deficiency. However, there have been few mechanistic studies on the effectiveness of kidney-yang deficiency-type osteoporosis with YGW. To further clarify the role of YGW in the effect of osteoporosis with kidney-yang deficiency, the study analyzed the therapeutic advantages of YGW by comparing the therapeutic effects of YGW and alendronate (ALN) on osteoporosis with kidney-yang deficiency. Methods: SPF female SD rats were randomly divided into control, osteoporosis, osteoporosis with kidney-yang deficiency, osteoporosis with kidney-yang deficiency + YGW and osteoporosis with kidney-yang deficiency + ALN groups. Except for the control group, osteoporosis was induced by the removal of bilateral ovaries. After 12 weeks, rats with osteoporosis in the kidney-yang deficiency group had kidney-yang deficiency syndrome triggered by hydrocortisone for 14 days. Rats were treated with YGW or ALN for 12 weeks. The weights of rats were recorded. Hematoxylin-eosin staining staining was used to observe pathological changes in bone trabeculae, liver, spleen, and kidneys of rats. Depletion of the growth plate cartilage of rats in different groups was observed by safranine-O staining. The expression of osteoclast key indices (ACP) and osteoblast key indices (ALP) in the bone tissue of rats in the different groups was observed by immunohistochemical staining. The expression of bone resorption-related indicators (TRAP and NXT-1), bone formation-related indicators (BALP, BGP, and P1NP), and major indicators of kidney-yang deficiency (ACTH, T3, T4, cAMP, and cGMP) were observed using an ELISA detection kit. The expression levels of the main indices of liver function (ALT and AST) were detected in different groups. Results: The differences between the osteoporosis with kidney-yang deficiency group and osteoporosis group were that the weight of rats and the expression of ACTH, T3, T4, and cAMP decreased significantly, and the expression of cGMP increased in the osteoporosis with kidney-yang deficiency group. Moreover, both YGW and ALN effectively improved the symptoms of osteoporosis, including the injury of bone trabeculae and growth plates, as well as the expression of bone metabolism-related indicators. However, unlike ALN, YGW simultaneously ameliorated the expression of key indicators of kidney-yang deficiency and prevented weight loss in rats. In addition, YGW caused no obvious damage to the liver, spleen, or kidney, whereas ALN led to liver cirrhosis. Conclusion: The results reveal that YGW plays a crucial part in osteoporosis with kidney-yang deficiency, increases bone mineral density, and improves bone metabolism indicators, and is safe and efficient for the efficacy of osteoporosis with kidney-yang deficiency. YGW might have a better therapeutic effect on osteoporosis in patients with kidney-yang deficiency. Therefore, alendronate should be used cautiously in patients with osteoporosis and poor liver function. [ABSTRACT FROM AUTHOR]

Bioactive scaffolds based on the 14.6Li 2 O⋅8.6ZrO 2 ⋅67.3SiO 2 ⋅9.5Al 2 O 3 glass-ceramic for use in drug delivery is presented. Powders of the parent glass (212 mm > particle size >38 mm) were heat-treated at 725 °C for 3 h for surface crystallization. They were subjected to a chemical attack with 6 vol% of hydrofluoric acid for 40 s for partial dissolution of the residual glass, and washed with deionised water and calcium carbonate. Structural and microstructural analyses were performed to identify the formed crystalline phases and porosity. Mesopores with 2.05 nm-radius were detected. The immersion method was used to insert alendronate sodium into the scaffolds. The drug delivering capability was evaluated by infrared spectroscopy and thermogravimetric analysis (TG). The FTIR spectra showed the typical functional groups existing in the alendronate sodium, confirming their impregnation into the scaffold's pores. Moreover, the TG thermograms showed loss weights of ∼2% indicating the effective inoculation of the drug into the scaffold. The bioactivity of the material was evaluated through calcium phosphate layer formation after incubation in a simulated body fluid for up to 28 days (37 ± 1 °C) and then analysed by infrared spectroscopy (FTIR). Calcium phosphates were identified after 24 h of immersion indicating the bioactivity of the glass-ceramic. The cytotoxicity and hemocompatibility tests showed that the LZSA glass-ceramic scaffold is not considered toxic to the human body at concentrations below 40 μg/mL and does not show hemolytic effects at all tested concentrations. Thus, the obtained microstructure renders the material promising for use as a drug delivery agent for bone regeneration. [ABSTRACT FROM AUTHOR]

Toll-like receptors (TLRs) recognize whole cells or components of microorganisms. Alendronate (ALN) is an anti-bone-resorptive drug that has inflammatory side effects. The aim in this study was to examine whether ALN augments TLR2 ligand-induced proinflammatory cytokine production using mouse macrophage-like RAW264.7 cells transfected with murine apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) gene (hereafter, referred to as "RAW-ASC cells"). RAW-ASC cells were pretreated with or without ALN and then incubated with or without TLR2 ligands. The levels of secreted mouse IL-1α, IL-1β, IL-6, and tumor necrosis factor-α (TNF-α) in culture supernatants and the activation of activator protein-1 (AP-1) or nuclear factor-κB (NF-κB) were measured using enzyme-linked immunosorbent assay (ELISA). The expressions of myeloid differentiation factor 88 (MyD88), caspase-11, nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3), ASC, NF-κB p65, and actin were analyzed via Western blotting. TLR2 expression was analyzed using flow cytometry. ALN substantially upregulated the Pam 3 CSK 4 -induced release of IL-1α, IL-1β, IL-6, and TNF-α and MyD88 expression in RAW-ASC cells. ST-2825, a MyD88 inhibitor, inhibited the ALN-augmented release of these cytokines. Pretreatment with ALN augmented Pam 3 CSK 4 -induced NF-κB activation in RAW-ASC cells and upregulated AP-1 activation. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) S protein and ALN synergically upregulated the release of IL-1α, IL-1β, IL-6 and TNF-α in RAW-ASC cells. Our findings suggest that ALN augments TLR2 ligand-induced proinflammatory cytokine production via the upregulation of MyD88 expression, and this augmentation is accompanied by the activation of NF-κB and AP-1 in RAW-ASC cells. • ALN augmented TLR2 ligand-induced proinflammatory cytokine production by RAW-ASC cells. • ALN upregulated the expression of MyD88 and caspase-11, but not TLR2 in RAW-ASC cells. • ST-2825, a MyD88 inhibitor, inhibited ALN-augmented proinflammatory cytokine production. • ALN also upregulated the activation of NF-κB and AP-1 in RAW-ASC cells. [ABSTRACT FROM AUTHOR]

Background: Alendronate is used to treat Paget's bone disease, glucocorticoid‐induced osteoporosis, and postmenopausal osteoporosis because it suppresses osteoclast activity to stop bone resorption. Case report: We present an exceptional case of esophagitis caused by alendronate. Blood tests and other data were normal when the patient was taken to the hospital, but an endoscopic examination revealed significant esophageal redness, erosion, and ulceration, along with pseudomembrane. The patient was given medicine after receiving a diagnosis of alendronate pill‐induced esophagitis based on the pathological findings. Conclusion: This case report is a timely reminder of the importance of thorough pharmacovigilance, patient education, and smart therapeutic decision‐making in the context of alendronate use. To properly treat and prevent problems with the esophagus caused by alendronate, additional research is required. [ABSTRACT FROM AUTHOR]

Background: The amyloid-β (Aβ) enhances the number and activity of blood monocyte-derived osteoclasts (OCs). Individuals with osteoporosis (OP) face an increased risk of developing dementia or Alzheimer's disease (AD). Despite this association, the contribution of bone-resorbing OCs to the progression of AD pathology remains unclear. Objective: Our objective was to investigate the potential impacts of OCs on the development of AD pathology. Methods: We conducted targeted analysis of publicly available whole blood transcriptomes from patients with AD to characterize the blood molecular signatures and pathways associated with hyperactive OCs. In addition, we used APP23 transgenic (APP23 TG) AD mouse model to assess the effects of OCs pharmacological blockade on AD pathology and behavior. Results: Patients with AD exhibited increased osteoclastogenesis signature in their blood cells, which appears to be positively correlated with dysfunction of peripheral clearance of Aβ mediated by immune cells. Long-term anti-resorptive intervention with Alendronate inhibited OC activity in APP23 mice, leading to improvements in peripheral monocyte Aβ-degrading enzyme expression, Aβ-deposition, and memory decline. Conclusions: Our findings suggest that OCs have a disease-promoting role in the development and progression of AD, possibly linked to their modulation of peripheral immunity. These findings guide future research to further elucidate the connection between OP and AD pathogenesis, highlighting the potential benefits of preventing OP in alleviating cognitive burden. [ABSTRACT FROM AUTHOR]

Vitamin D, an essential micronutrient crucial for skeletal integrity and various non-skeletal physiological functions, exhibits limited bioavailability and stability in vivo. This study is focused on the development of polyethylene glycol (PEG)-grafted phospholipid micellar nanostructures co-encapsulating vitamin D3 and conjugated with alendronic acid, aimed at active bone targeting. Furthermore, these nanostructures are rendered optically traceable in the UV–visible region of the electromagnetic spectrum via the simultaneous encapsulation of vitamin D3 with carbon dots, a newly emerging class of fluorescents, biocompatible nanoparticles characterized by their resistance to photobleaching and environmental friendliness, which hold promise for future in vitro bioimaging studies. A systematic investigation is conducted to optimize experimental parameters for the preparation of micellar nanostructures with an average hydrodynamic diameter below 200 nm, ensuring colloidal stability in physiological media while preserving the optical luminescent properties of the encapsulated carbon dots. Comprehensive chemical-physical characterization of these micellar nanostructures is performed employing optical and morphological techniques. Furthermore, their binding affinity for the principal inorganic constituent of bone tissue is assessed through a binding assay with hydroxyapatite nanoparticles, indicating significant potential for active bone-targeting. These formulated nanostructures hold promise for novel therapeutic interventions to address skeletal-related complications in cancer affected patients in the future. [ABSTRACT FROM AUTHOR]

Introduction: The purpose of this study was to evaluate whether bone mineral density (BMD) ≥ −2.5 SD could be used as the treat-to-target (T2T) goal when treating osteoporosis with teriparatide (TPTD) and alendronate (ALN), and to investigate the relationship with incident vertebral fracture by re-analyzing data from a randomized, controlled trial (JOINT-05) involving postmenopausal Japanese women at high fracture risk. Materials and methods: Participants received sequential therapy with once-weekly TPTD for 72 weeks, followed by ALN for 48 weeks (TPTD-ALN group) or ALN monotherapy for 120 weeks (ALN group). BMDs were measured at the lumbar spine (L2-4), total hip, and femoral neck at 0, 24, 48, 72, and 120 weeks by dual-energy X-ray absorptiometry. The T2T goal was BMD ≥ −2.5 SD, and the endpoint was the proportion of participants with baseline BMD < −2.5 SD in three measurement sites achieving BMD ≥ −2.5 SD. Results: A total of 559 participants were selected. BMD ≥ −2.5 SD at 120 weeks in the L2-4, total hip, and femoral neck sites was achieved in 20.5%, 23.1%, and 5.9%, respectively, in the TPTD-ALN group and 22.2%, 11.7%, and 7.3%, respectively, in the ALN group. Incident vertebral fractures occurred in areas of both lower and high BMD. Conclusion: During the 1.5-year treatment period, more than 20% of participants achieved BMD ≥ −2.5 SD as a T2T goal at L2-4. Since the achievement level differed depending on the BMD measurement site, the appropriate site should be selected according to the baseline BMD level. [ABSTRACT FROM AUTHOR]

Bone mineral density (BMD) loss in people living with HIV occurs with the initiation of combined antiretroviral therapy (cART), particularly with tenofovir disoproxil fumarate (TDF) containing cART. Switching from TDF to abacavir (ABC) or dolutegravir (DTG) leads to increased BMD. Whether BMD gains are due to cessation of TDF or anabolic effects of ABC or DTG is unclear. We investigated the effects of ABC and DTG on osteoblast lineage cells in vitro and in vivo. Primary human osteoblasts and male C57BL/6 mice were treated with individual antiretrovirals (ARVs) or a combination of ABC/DTG/lamivudine (3TC). Nearly all ARVs and cART inhibited osteogenic activity in vitro. Due to the importance of Wnt/β-catenin in bone formation, we further investigated ARV effects on the Wnt/β-catenin pathway. ABC, alone and as part of ABC/DTG/3TC, increased osteoblastic β-catenin activity as indicated by increased TOPFlash activity, hypo-phosphorylated (active) β-catenin staining, and β-catenin targeted gene expression. Mice treated with TDF had decreased lumbar spine BMD and trabecular connectivity density in the vertebrae, while those treated with ABC/DTG/3TC reduced cortical area and thickness in the femur. Mice treated with ABC alone had no bone structural changes, increased circulating levels of the bone formation marker, P1NP, and elevated expression of the Wnt/β-catenin target gene, Lef1, in osteocyte enriched samples. Further, bones from ARV-treated mice were isolated to evaluate ARV distribution. All ARVs were detected in the bone tissue, which was inclusive of bone marrow, but when bone marrow was removed, only TDF, ABC, and DTG were detected at ~0.1% of the circulating levels. Overall, our findings demonstrate that ABC activates Wnt/β-catenin signaling, but whether this leads to increased bone formation requires further study. Assessing the impact of ARVs on bone is critical to informing ARV selection and/or discovery of regimens that do not negatively impact the skeleton. [ABSTRACT FROM AUTHOR]

Osteoporosis is a highly prevalent metabolic disease characterized by low systemic bone mass and deterioration of bone microarchitecture, resulting in reduced bone strength and increased fracture risk. Current treatment options for osteoporosis are limited by factors such as efficacy, cost, availability, side effects, and acceptability to patients. Gold nanoparticles show promise as an emerging osteoporosis therapy due to their osteogenic effects and ability to allow therapeutic delivery but have inherent constraints, such as low specificity and the potential for heavy metal accumulation in the body. This study reports the synthesis of ultrasmall gold particles almost reaching the Ångstrom (Ång) dimension. The antioxidant alpha-lipoic acid (LA) is used as a dispersant and stabilizer to coat Ångstrom-scale gold particles (AuÅPs). Alendronate (AL), an amino-bisphosphonate commonly used in drug therapy for osteoporosis, is conjugated through LA to the surface of AuÅPs, allowing targeted delivery to bone and enhancing antiresorptive therapeutic effects. In this study, alendronate-loaded Ångstrom-scale gold particles (AuÅPs-AL) were used for the first time to promote osteogenesis and alleviate bone loss through regulation of the WNT signaling pathway, as shown through in vitro tests. The in vivo therapeutic effects of AuÅPs-AL were demonstrated in an established osteoporosis mouse model. The results of Micro-computed Tomography, histology, and tartrate-resistant acid phosphatase staining indicated that AuÅPs-AL significantly improved bone density and prevented bone loss, with no evidence of nanoparticle-associated toxicity. These findings suggest the possible future application of AuÅPs-AL in osteoporosis therapy and point to the potential of developing new approaches for treating metabolic bone diseases using Ångstrom-scale gold particles. [ABSTRACT FROM AUTHOR]