Search Results (503)

Background: The long-term success of total knee arthroplasty (TKA) is often compromised by stress shielding, which can lead to bone resorption and even implant loosening. This study employs finite element analysis (FEA) to compare the stress-shielding effects of a knee prosthesis made from polyether ether ketone (PEEK) with a traditional titanium Ti6Al4V implant on an osteoporotic tibial bone model. Methods: Stress distribution and the stress-shielding factor (SSF) were evaluated at seven critical points in the proximal tibia under physiological loading conditions. Results: Results indicate that the PEEK prosthesis yields a more uniform stress transmission, with von Mises stress levels within the optimal 2–3 MPa range for bone maintenance and consistently negative or near-zero SSF values, implying minimal stress shielding. Conversely, titanium implants exhibited significant stress shielding with high positive SSF values across all points. Additionally, stress concentrations on the polyethylene liner were lower and more evenly distributed in the PEEK model, suggesting reduced wear potential. Conclusions: These findings highlight the biomechanical advantages of PEEK in reducing stress shielding and preserving bone integrity, supporting its potential use to improve implant longevity in TKA. Further experimental and clinical validation are warranted. Full article

Background: Type 2 diabetes (T2D) has been placed among the risk factors for fragility (osteoporotic) fractures, particularly in menopausal women amid modern clinical practice. Objective: We aimed to analyze the bone status in terms of mineral metabolism assays, blood bone turnover markers (BTM), and bone mineral density (DXA-BMD), respectively, to assess the 10-year fracture probability of major osteoporotic fractures (MOF) and hip fracture (HF) upon using conventional FRAX without/with femoral neck BMD (MOF-FN/HF-FN and MOF+FN/HF+FN) and the novel model (FRAXplus) with adjustments for T2D (MOF+T2D/HF+T2D) and lumbar spine BMD (MOF+LS/HF+LS). Methods: This retrospective, cross-sectional, pilot study, from January 2023 until January 2024, in menopausal women (aged: 50–80 years) with/without T2D (group DM/nonDM). Inclusion criteria (group DM): prior T2D under diet ± oral medication or novel T2D (OGTT diagnostic). Exclusion criteria: previous anti-osteoporotic medication, prediabetes, insulin therapy, non-T2D. Results: The cohort (N = 136; mean age: 61.36 ± 8.2y) included T2D (22.06%). Groups DM vs. non-DM were age- and years since menopause (YSM)-matched; they had a similar osteoporosis rate (16.67% vs. 23.58%) and fracture prevalence (6.66% vs. 9.43%). In T2D, body mass index (BMI) was higher (31.80 ± 5.31 vs. 26.54 ± 4.87 kg/m²; p < 0.001), while osteocalcin and CrossLaps were lower (18.09 ± 8.35 vs. 25.62 ± 12.78 ng/mL, p = 0.002; 0.39 ± 0.18 vs. 0.48 ± 0.22 ng/mL, p = 0.048), as well as 25-hydroxyvitamin D (16.96 ± 6.76 vs. 21.29 ± 9.84, p = 0.013). FN-BMD and TH-BMD were increased in T2D (p = 0.007, p = 0.002). MOF+LS/HF+LS were statistically significant lower than MOF-FN/HF-FN, respectively, MOF+FN/HF+FN (N = 136). In T2D: MOF+T2D was higher (p < 0.05) than MOF-FN, respectively, MOF+FN [median(IQR) of 3.7(2.5, 5.6) vs. 3.4(2.1, 5.8), respectively, 3.1(2.3, 4.39)], but MOF+LS was lower [2.75(1.9, 3.25)]. HF+T2D was higher (p < 0.05) than HF-FN, respectively, HF+FN [0.8(0.2, 2.4) vs. 0.5(0.2, 1.5), respectively, 0.35(0.13, 0.8)] but HF+LS was lower [0.2(0.1, 0.45)]. Conclusion: Type 2 diabetic menopausal women when compared to age- and YSM-match controls had a lower 25OHD and BTM (osteocalcin, CrossLaps), increased TH-BMD and FN-BMD (with loss of significance upon BMI adjustment). When applying novel FRAX model, LS-BMD adjustment showed lower MOF and HF as estimated by the conventional FRAX (in either subgroup or entire cohort) or as found by T2D adjustment using FRAXplus (in diabetic subgroup). To date, all four types of 10-year fracture probabilities displayed a strong correlation, but taking into consideration the presence of T2D, statistically significant higher risks than calculated by the traditional FRAX were found, hence, the current model might underestimate the condition-related fracture risk. Addressing the practical aspects of fracture risk assessment in diabetic menopausal women might improve the bone health and further offers a prompt tailored strategy to reduce the fracture risk, thus, reducing the overall disease burden. Full article

Adjuvant endocrine therapy for early breast cancer significantly reduces recurrence but increases bone fragility. Given limited data on denosumab (60 mg every 6 months) in premenopausal patients receiving endocrine therapy for early breast cancer, we conducted a retrospective real-world study at the Gemelli Hospital (September 2018–January 2025). A descriptive analysis was performed. The primary endpoint was to assess efficacy, evaluated by changes in bone mineral density via dual-energy X-ray absorptiometry and by monitoring bone turnover markers, particularly serum C-terminal telopeptide of type I collagen. Safety was evaluated based on adverse endocrine therapy events (osteoporotic fractures) and adverse denosumab events (osteonecrosis of the jaw). Sixty-nine patients were eligible for the study. Endocrine therapy included ovarian function suppression with exemestane (89.8%) or tamoxifen (10.1%). Baseline spinal osteoporosis decreased from 20.3% to 5.8%, osteopenia from 39.1% to 34.8%, with normal T-scores rising from 17.4% to 34.8%. Femoral improvements were similar. Serum C-terminal telopeptide of type I collagen levels (evaluated in 35.8%) showed stable reduction in 97%. Denosumab adherence was 89.9%. One osteonecrosis of the jaw case occurred (1.4%); no fractures were reported. Denosumab demonstrated efficacy in improving bone density and reducing bone turnover, with excellent adherence and favorable safety. Longer follow-up is needed to assess post-discontinuation effects. Full article

Three-dimensional cell culture systems are relevant in vitro models for studying cellular behavior. In this regard, this present study investigates the interaction between human osteoblast-like cells and 3D-printed scaffolds mimicking physiological and osteoporotic bone structures under simulated microgravity conditions. The objective is to assess the effects of scaffold architecture and dynamic culture conditions on cell adhesion, proliferation, and metabolic activity, with implications for osteoporosis research. Polylactic acid scaffolds with physiological (P) and osteoporotic-like (O) trabecular architectures were 3D-printed by means of fused deposition modeling technology. Morphometric characterization was performed using micro-computed tomography. Human osteoblast-like SAOS-2 and U2OS cells were cultured on the scaffolds under static and dynamic simulated microgravity conditions using a rotary cell culture system (RCCS). Scaffold biocompatibility, cell viability, adhesion, and metabolic activity were evaluated through Bromodeoxyuridine incorporation assays, a water-soluble tetrazolium salt assay, and an enzyme-linked immunosorbent assay of tumor necrosis factor-α secretion. Both scaffold models supported osteoblast-like cell adhesion and growth, with an approximately threefold increase in colonization observed on the high-porosity O scaffolds under dynamic conditions. The dynamic environment facilitated increased surface interaction, amplifying the effects of scaffold architecture on cell behavior. Overall, sustained cell growth and metabolic activity, together with the absence of detectable inflammatory responses, confirmed the biocompatibility of the system. Scaffold microstructure and dynamic culture conditions significantly influence osteoblast-like cell behavior. The combination of 3D-printed scaffolds and a RCCS bioreactor provides a promising platform for studying bone remodeling in osteoporosis and microgravity-induced bone loss. These findings may contribute to the development of advanced in vitro models for biomedical research and potential countermeasures for bone degeneration. Full article

Senescent cells secrete pro-inflammatory cytokines, collectively referred to as the senescence-associated secretory phenotype (SASP). Certain pro-inflammatory SASP factors are known to inhibit the differentiation of bone-forming osteoblast while promoting the differentiation of bone-resorbing osteoclasts, thereby causing osteoporosis. In this study, we screened cabozantinib, a tyrosine kinase inhibitor used to treat medullary thyroid cancer, for its ability to reduce doxorubicin-induced cellular senescence in both osteoblast and osteoclast progenitors. This non-cytotoxic agent suppressed the secretion of SASP factors (e.g., TNFα, IL1α, IL1β, IL6, and CCL2) from senescent osteoblast and osteoclast progenitors, resulting in enhanced osteoblast differentiation and reduced osteoclast differentiation. Furthermore, intraperitoneal administration of cabozantinib to age-related estrogen-deficient mice subjected to ovariectomy prevented bone loss without apparent side effects, increasing osteoblast numbers and reducing osteoclast numbers along the surface of the trabecular bone. In summary, our findings suggest that anti-aging cabozantinib has potential as a preventive anti-osteoporotic agent by promoting osteogenesis and inhibiting osteoclastogenesis through the repression of SASP. Full article

A new, simple machine was developed to address a long-standing challenge in biomedical and mechanical engineering: how to enhance the primary stability and long-term integration of screws and implants in low-density or heterogeneous materials, such as bone or composite substrates. Traditional screws often rely solely on external threading for fixation, leading to limited cohesion, poor integration, or early loosening under cyclic loading. In response to this problem, we designed and built a novel device that leverages a unique mechanical principle to simultaneously perforate, collect, and compact the substrate material during insertion. This mechanism results in an internal material interlock, enhancing cohesion and stability. Drawing upon principles from physics, chemistry, engineering, and biology, we evaluated its biomechanical behavior in synthetic bone analogs. The maximum insertion (MIT) and removal torques (MRT) were measured on synthetic osteoporotic bones using a digital torquemeter, and the values were compared directly. Experimental results demonstrated that removal torque (mean of 21.2 Ncm) consistently exceeded insertion torque (mean of 20.2 Ncm), indicating effective material interlocking and cohesive stabilization. This paper reviews the relevant literature, presents new data, and discusses potential applications in civil infrastructure, aerospace, and energy systems where substrate cohesion is critical. The findings suggest that this new simple machine offers a transformative approach to improving fixation and integration across multiple domains. Full article

Osteoporosis is a chronic disease associated with significant morbidity and mortality and requires long-term therapy. Efficacious and well-tolerated treatments are available, but their effect is either short-lived or lost following their discontinuation. The exception is bisphosphonates that reduce bone resorption and turnover, can be administered in regimens ranging from once-daily to once-yearly, and have been shown in randomized clinical trials to reduce the incidence of all osteoporotic fractures, but their effect persists following their discontinuation. This is due to their property of being taken-up selectively by the skeleton and being slowly released following treatment arrest. This property allows the discontinuation of bisphosphonate treatment for different periods of time, the so-called drug holiday, which reduces the risk of rare adverse events while maintaining the effect; an action particularly important for patients at very high risk of fractures for whom sequential therapy with different agents is currently advised. Thus, bisphosphonates, apart from being the treatment of choice for certain groups of patients, are also indispensable for the consolidation and maintenance of the gains of all other treatments, providing, in addition, the opportunity of temporary treatment arrest. Most patients with postmenopausal osteoporosis will, therefore, receive bisphosphonate at some stage during therapy of their disease, regardless of their initial fracture risk. Full article

Fragility fractures of the pelvis (FFPs) are common in elderly patients, particularly those with osteoporosis. FFPs can be associated with high mortality, morbidity, and functional decline. Known risk factors include being over 80 years old and delays in surgical intervention when this is required. While the role of surgery in FFPs remains less defined than in proximal femoral fractures in the elderly, studies indicate that surgical fixation offers improved survival and functional outcomes. Similarly, the choice of fixation method, whether posterior or anterior, and their combinations, vary between clinicians. It depends on the fracture type and patient-specific factors, such as bone quality and comorbidities, as well as the surgeon’s experience and the availability of resources. Additionally, orthobiologic adjuncts such as cement augmentation and sacroplasty can enhance the stability of an osteoporotic fracture during surgical intervention. Furthermore, medical treatments for osteoporosis, especially the use of teriparatide, have demonstrated beneficial effects in reducing fractures and promoting healing of the FFPs. Return to pre-injury activities is often limited, with independence rates remaining low at mid-term follow-up. Factors that influence clinical outcomes include fracture type, with Type III and IV fractures generally leading to poorer outcomes, and patient age, functional reserve, and comorbidities. The present tutorial aims to summarise the relevant evidence on all aspects of FFPs, inform an updated management strategy, and provide a template of the reconstruction ladder referring to the most available surgical techniques and treatment methods. Further research, based on large-scale studies, is needed to address the open questions described in this manuscript and refine surgical techniques, as well as determine optimal treatment pathways for this vulnerable patient population. Full article

The aim of this study was to evaluate structural and micro-architectural changes in the mandible, parietal bone, femur, and tibia in OVX rats at different time periods after ovariectomy. Forty-two 11-month-old female Wistar rats were used. Six rats without surgery were euthanized to serve as a baseline. Eighteen rats were ovariectomized and fed with a calcium-deficient diet, and eighteen animals were used as controls (Ctrls) and fed with a standard diet. Six OVX rats and six Ctrls were euthanized at 3, 6, and 9 months. Qualitative histology and dual-energy X-ray absorptiometry (DXA) were performed. Histological evaluation of bones harvested from the OVX groups revealed trabecular bone reduction, while no significant differences in the cortical bone of OVX and Ctrls were observed. DXA measurements of (1) femoral diaphysis showed a significant decrease in the OVX group compared to the Ctrl groups at 3 (p = 0.041), 6 (p < 0.001), and 9 months (p < 0.001); (2) the proximal tibia showed a significant decrease in the OVX group compared to the Ctrl groups (p < 0.001); (3) parietal bone showed a significant difference between OVX and Ctrls at 6 months (p = 0.012); and (4) the mandible showed no significant differences between the OVX and Ctrl groups. OVX aged rats might present reductions in the density of the femoral diaphysis, proximal tibia, parietal bone, and mandible at different time points. These findings contribute to the field of biomimetics by providing more details for the understanding of age- and hormone-related bone changes in the osteoporotic-like rat model. Such data are critical for the development of biomimetic materials and structures that attempt to simulate natural bone adaptation and deterioration, especially in the context of postmenopausal or osteoporotic conditions. Full article

This study investigated the effects of local fibroblast growth factor (FGF)-2 application on periodontal healing in an osteoporotic model, both in vivo and in vitro. Wistar rats were divided into the ovariectomy (OVX) and Control groups. Periodontal defects were created 8 weeks post-OVX and treated with hydroxypropylcellulose (HPC) or FGF-2 + HPC. Healing was evaluated through micro-computed tomography and histological analyses at 2 and 4 weeks. In vitro, bone marrow mesenchymal stromal cells (BMSCs) were cultured with/without FGF-2 and assessed for cell morphology, viability/proliferation, and osteoblastic marker expression. Alkaline phosphatase (ALP) staining was also performed. FGF-2-treated defects in both groups showed significantly greater bone volume fraction, trabecular number, and thickness compared to HPC only. Histologically, FGF-2 enhanced new bone formation, with the greatest levels in the Control group. In vitro, OVX BMSCs showed reduced actin staining versus controls. FGF-2 increased cell viability/proliferation and protrusions in both groups while downregulating Alpl and Bglap expression levels and reducing ALP-positive cells. FGF-2 increased new bone formation in the OVX group, stimulated proliferation of OVX BMSCs, and modulated their differentiation. FGF-2 could enhance periodontal healing even under osteoporotic conditions, albeit to a lesser extent. Full article

Tanshinones are a class of lipophilic diterpenoid quinones extracted from Salvia miltiorrhiza (Dan shen), a widely used herb in traditional Chinese medicine. These compounds, particularly tanshinone IIA (T-IIA) and sodium tanshinone sulfonate (STS), have been acknowledged for their broad spectrum of biological activities, including anti-inflammatory, antioxidant, anti-tumor, antiresorptive, and antimicrobial effects. Recent studies have highlighted the potential of tanshinones in the treatment of osteolytic diseases, characterized by excessive bone resorption, such as osteoporosis, rheumatoid arthritis, and periodontitis. The therapeutic effects of tanshinones in these diseases are primarily attributed to their ability to inhibit osteoclast differentiation and activity, suppress inflammatory cytokine production (e.g., tumor necrosis factor alpha (TNF-α), interleukin (IL)-1β, and IL-6), and modulate critical signaling pathways, including NF-kB, MAPK, PI3K/Akt, and the RANKL/RANK/OPG axis. Additionally, tanshinones promote osteoblast differentiation and mineralization by enhancing the expression of osteogenic markers such as Runx2, ALP, and OCN. Preclinical models have demonstrated that T-IIA and STS can significantly reduce bone destruction and inflammatory cell infiltration in arthritic joints and periodontal tissues while also enhancing bone microarchitecture in osteoporotic conditions. This review aims to provide a comprehensive overview of the pharmacological actions of tanshinones in osteolytic diseases, summarizing current experimental findings, elucidating underlying molecular mechanisms, and discussing the challenges and future directions for their clinical application as novel therapeutic agents in bone-related disorders, especially periodontitis. Despite promising in vitro and in vivo findings, clinical evidence remains limited, and further investigations are necessary to validate the efficacy, safety, and pharmacokinetics of tanshinones in human populations. Full article

Open reduction and internal fixation (ORIF) is widely regarded as the primary treatment for acetabular fractures, but limitations arise in complex cases, leading to non-anatomical reductions and increased risk of post-traumatic osteoarthritis. Given the high incidence of secondary arthritis (12–57%) following ORIF, total hip arthroplasty (THA) is often necessitated, particularly in scenarios unsuitable for ORIF, such as extensive comminution or combined femoral head and neck fractures. The surgical landscape has shifted from a traditional “fix or replace” to a more integrated “fix and replace” approach, especially beneficial in managing elderly patients with osteoporotic bones. THA is applied across various timelines, including acute (0–3 weeks), delayed (3 weeks to 3 months), and late (beyond 3 months), each presenting distinct challenges and requiring specific strategies to optimize outcomes. The importance of precise bone defect classifications and the role of dual mobility cups in reducing dislocation risks are highlighted, alongside the use of modern surgical and fixation techniques to improve stability and patient outcomes. Enhanced recovery protocols and meticulous postoperative management are critical to addressing complications, such as infections and hardware interference, tailoring treatment approaches to each patient’s needs, and advancing care for complex acetabular fractures. Full article

The increasing incidence of osteoporotic fractures determines ongoing research on new methods and strategies for improving the difficult healing process of this type of fracture. Osteoporotic patients suffer from the intense side effects of accustomed drug treatment and its systemic distribution in the body. To overcome these drawbacks, besides searching for new drugs, 3D-printed scaffolds and drug delivery systems have started to be increasingly seen as the main strategy employed against osteoporosis. Three-dimensionally printed scaffolds can be tailored in intricate designs and make use of nanoscale topographical and biochemical cues able to enhance bone tissue regeneration. Research regarding drug delivery systems is exploring bold new ways of targeting bone tissue, making use of designs involving nanoparticles and intricate encapsulation and support methods. The local administration of treatment with the help of a scaffold-based drug delivery system looks like the best option through its use of the advantages of both structures. Biomimetic systems are considered the future norm in the field, while stimuli-responsiveness opens the door for the next level of efficiency, patient compliance, and a drastic reduction in side effects. The successful approval of these products still requires numerous challenges throughout the development and regulatory processes, but the interest and effort in this direction are high. This review explored various strategies for managing osteoporosis, emphasizing the use of scaffolds for targeted drug delivery to bone tissue. Instead of covering the whole subject, we focused on the most important aspects, with the intention to provide an up-to-date and useful introduction to the management of osteoporosis. Full article

Background: Patients awaiting total hip arthroplasty (THA), particularly those with hip osteoarthritis (OA), face an elevated risk of osteoporosis due to age and gender-related factors. Osteoporosis, indicated by low bone mineral density (BMD), can affect implant osteointegration, long-term stability, and increase the likelihood of periprosthetic fractures. Despite these risks, osteoporosis is often underdiagnosed and undertreated in THA candidates. While several studies have addressed this issue in Northern populations, data on Southern European cohorts, particularly Italian patients, remain limited. This study aims to evaluate the prevalence of osteoporosis and vitamin D deficiency, as well as the rates of related treatments, in patients with hip osteoarthritis scheduled for THA. Methods: This single-center, retrospective study was conducted at Policlinico Universitario di TorVergata, Italy, involving 66 hip OA patients (35 men, 31 women; mean age 67.5 years). BMD was assessed at the femoral neck, total femur, and lumbar spine via DEXA, alongside vitamin D and PTH levels. Demographic data, ongoing anti-osteoporotic therapies, Harris Hip Score (HHS), and handgrip strength were recorded. Statistical analysis included t-tests and Pearson’s correlation. Osteoporosis was defined per WHO criteria, with significance set at p < 0.05. Results: In this study of 66 patients with hip osteoarthritis (35 men, 31 women; mean age 67.5 years), women exhibited significantly lower bone mineral density (BMD) at the total femur (−0.98 ± 1.42 vs. −0.08 ± 1.04; p < 0.05) and lumbar spine (−0.66 ± 1.74 vs. 0.67 ± 1.59; p < 0.05) compared to men. Handgrip strength was also significantly reduced in females (17.1 ± 8.2 kg) versus males (27.3 ± 10.3 kg; p < 0.05). Vitamin D levels were below 30 ng/mL in 89.4% of patients, and 63.6% had levels below 20 ng/mL; PTH levels were elevated (>65 pg/mL) in 54.5% of cases, indicating frequent secondary hyperparathyroidism. Only 9 patients were receiving vitamin D supplementation and none were on anti-osteoporotic treatment. Conclusions: These findings highlight the frequent coexistence of low BMD, vitamin D deficiency, and reduced muscle strength in THA candidates, suggesting a pattern of musculoskeletal vulnerability that warrants clinical attention. Full article

Background and Objectives: Bisphosphonates (BP) like zoledronic acid (ZA) and alendronic acid (AA) are used for osteoporosis (OP) or other bone-related conditions as well as to prevent the spread of metastases and in rheumatoid arthritis treatment. However, they have been associated with an increased risk of osteonecrosis of the jaw (ONJ). This systematic review aimed to assess the incidence and risk of ONJ in osteoporotic patients treated with ZA or AA and evaluate the impact of treatment duration. Material and Methods: The systematic literature review was conducted following PRISMA guidelines. The keywords “Zoledronic acid,” “Alendronic acid,” “Osteoporosis,” and “Osteonecrosis” were searched in PubMed and ScienceDirect databases. Selection criteria included studies on humans written in English, published from 2014. The systematic review protocol was registered in the PROSPERO register under the following number: CRD42024587046. Results: A total of 7 studies with 98,717 osteoporotic patients met the criteria, showing a higher ONJ incidence with ZA than AA. Six studies linked longer BP use to increased ONJ risk, which quadrupled after 5 years of AA use. A positive correlation was found between BP use (≥3 years) and ONJ in OP patients, primarily affecting females over 60. ONJ appeared after 1 year with AA, increasing over time, while ZA-related ONJ emerged as early as 5 months with a higher overall incidence. Conclusions: ZA poses a higher ONJ risk and incidence and earlier onset than AA, occurring within 5 months versus 1 year for AA. These findings emphasize the need for careful monitoring, especially in long-term BP therapy with additional risk factors. Full article