Search Results (128)

A total of 38% of Americans do not meet the Recommended Dietary Allowance (RDA) for calcium including those at risk for osteoporosis. To increase the percentage of patients at risk for osteoporosis who achieve goal calcium RDA intake, a collaborative specialty pharmacy-registered dietitian-nutritionist (RDN) quality improvement program was developed. Patients aged 18 to 90 years old receiving osteoporosis therapy (denosumab, teriparatide, zoledronic acid) or medications that increase bone loss (elagolix, oral prednisone) were provided with a structured assessment and educational intervention. Daily calcium intake included patient self-reported dietary intake plus supplement use. Written and verbal education on increasing dietary intake based on patient preferences was provided with 5 calcium-rich food-source store coupons. Recommendations for supplement selection (citrate vs. carbonate) and/or medication-related problem resolution were provided. Follow-up occurred at 3–6 months. Fifty patients enrolled [94% female, mean age 66.6 years (SD 15.3)] were taking denosumab (36), teriparatide (1), zoledronic acid (1), elagolix (7) and prednisone (5). The mean baseline daily dietary calcium intake was 500 mg (SD 247) with none achieving goal intake with diet alone. Average calcium supplement use in 22 (44%) patients was 686 mg daily (SD 284). At baseline, 17 (34%) met goal daily calcium intake compared to 30 (60%) at post intervention follow-up (p = 0.009). Over half of the store coupons were redeemed. A specialty pharmacy-RDN customized intervention program provides a model for aiding patients to modify calcium intake. Full article

In this study, 3D Mg scaffolds were obtained by the spark plasma sintering (SPS), and a calcium phosphate coating was then obtained on the samples by the plasma electrolytic oxidation. A hybrid coating with vancomycin, zoledronic acid, and menaquinone MK-7 was formed to improve biocompatibility. The mechanical properties of the formed specimens were studied. According to XRD, XRF, SEM, EDS, and OSP studies obtained scaffolds have developed morphology and contain hydroxyapatite as well as bioactive substances. Formation of coatings improves the wettability of samples (contact angle decreases from 123.8 ± 3.1° to 26.9 ± 4.1°) and increases the surface roughness by more than 3 times. This makes them promising for use as a new generation of implantation materials. The results are important for the development of personalized implants with improved functional characteristics. 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

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is one of the side effects of bisphosphonate (BP) administration. Despite some preventive measures having been suggested, a definitive and effective treatment strategy for BRONJ remains to be established. Recent evidence has indicated that BPs dramatically impair the function of orofacial bone marrow stromal cells (BMSCs), which may contribute to the development of osteonecrosis. Thus, we hypothesized that recovery-impaired function of BMSCs at lesion sites could be beneficial in treating BRONJ. N6-methyladenosine (m6A) modification is the most common epigenetic modification and has been demonstrated to play a vital role in the modulation of BMSCs’ function. We detected the role of m6A modification in regulating the function of orofacial BMSCs under BP stimulation, and found that BPs led to a reduction in the global m6A methylation level, SAM level, and METTL3 expression in BMSCs during the osteogenic differentiation period. Meanwhile, betaine, a methyl group donor, effectively reversed the BP-decreased global m6A methylation level and SAM level in BMSCs, as well as rescuing the differentiation ability of impaired BMSCs. In the last part, we built a BRONJ rat model and supplemented rats with betaine via drinking water. The results showed that betaine successfully attenuated bone lesions and promoted wound healing in BP-injected rats, thereby providing new insight into future clinical treatment for BRONJ. Full article

Receptor activator of nuclear factor-κB ligand (RANKL) is essential for osteoclast formation and bone resorption, in osteolytic conditions such as osteoporosis and bone metastases. However, its role in metastasis progression remains incompletely understood. Herein, we examined whether the overexpression of human RANKL in transgenic mice (TgRANKL) affects their susceptibility to breast cancer bone metastasis compared to their wild-type (WT) littermates. Bone metastasis was induced by injecting EO771 mouse mammary adenocarcinoma cells into the caudal artery of syngeneic WT and TgRANKL mice. RANKL overexpression led to an earlier onset and increased burden of bone metastasis in EO771-bearing TgRANKL mice compared to WT mice. It also exacerbated the bone destruction caused by metastasis-associated osteolysis. The prophylactic inhibition of RANKL activity with denosumab, a monoclonal antibody targeting human RANKL, prevented osteolysis and significantly reduced the incidence and progression of bone metastases in TgRANKL mice. However, the therapeutic denosumab treatment had no effect on metastasis incidence or tumor burden, although it alleviated osteolysis. The treatment with zoledronic acid, an anti-resorptive agent inhibiting osteoclast activity, yielded results similar to those of denosumab. These findings emphasize the significance of initiating early treatment with anti-resorptive agents such as denosumab or zoledronic acid to reduce the risk of bone metastasis in patients at high risk. Full article

Background: Medication-related osteonecrosis of the jaw (MRONJ) is drug-induced bone destruction that is exposed for a minimum of 6 to 8 weeks in patients who have not received head and neck radiotherapy and who have not been diagnosed with facial bone metastases. MRONJ treatment outcomes are unpredictable. Therefore, alternative treatment methods are being explored, such as blood-derived platelet-rich preparations enriched with growth factors, including advanced platelet-rich fibrin (A-PRF). The presence of growth factors may enhance healing and reduce post-procedure complications. There are no studies examining the effect of A-PRF on the healing of patients with MRONJ. The aim of this study was to retrospectively evaluate treatment outcomes of patients with MRONJ surgically treated without and with the use of A-PRF. Materials and methods: This retrospective study included 28 patients who suffered from osteomyelitis due to MRONJ and underwent surgical treatment between 2019 and 2024. The patients were divided into two groups: the first group received surgical treatment without A-PRF, and the second group received surgical treatment with the application of A-PRF. This study analyzed demographic and clinical data, as well as treatment outcomes. Results: The patients were aged from 43 to 82 years. The most common cause of MRONJ was the administration of zoledronic acid for oncological reasons (22 patients, 78.6%), given intravenously. In 20 patients (71.4%), the antiresorptive treatment lasted longer than three years. The obtained healing distribution was binomial (presence or absence of healing). Estimation of the probability of healing using the maximum likelihood method provided a result of approximately 64%. The probability of ten or more healed patients in the A-PRF group was 41%. A-PRF helps with a probability of 59%, and without A-PRF, it was lower. Concomitantly, the differences between the group with A-PRF and without A-PRF were not statistically significant. Conclusions: The patients with MRONJ should have regular check-ups with radiological examinations at least every six months to detect possible recurrence. Treatment for MRONJ is long and difficult. Treatment of non-advanced lesions, without additional risk factors (such as treatment with zoledronate intravenously for oncological purposes for 3 years), showed a better prognosis. Sometimes, in addition to surgery, it is necessary to consider alternative methods. A-PRF may enhance MRONJ healing. However, there is no evidence of a significant effect of A-PRF on the healing of MRONJ. Full article

Lizards are distinguished as the only amniotes, and closest relatives of mammals, capable of multilineage epimorphic regeneration. Tail blastemas of green anole lizards (Anolis carolinensis) consist of col3a1⁺ fibroblastic connective tissue cells enclosed in krt5⁺ wound epidermis (WE), both of which are required for regeneration. Blastema and WE formation are known to be closely associated with phagocytic cell populations, including macrophages and osteoclasts. However, it remains unclear what specific phagocytic cell types are required to stimulate regeneration. Here, we explicitly assess the roles of osteoclast activity during blastema and WE formation in regenerating lizard tails. First, probe sequencing was performed at regenerative timepoints on fibroblasts isolated based on col3a1 expression toward establishing pathways involved in stimulating blastema formation and subsequent tail regrowth. Next, treatments with osteoclast inhibitor zoledronic acid (ZA) were used to assess the roles of osteoclast activity in lizard tail regeneration and fibroblast signaling. ZA treatment stunted lizard tail regrowth, suggesting osteoclast activity was required for blastema formation and regeneration. Transcriptomic profiling of fibroblasts isolated from ZA-treated and control lizards linked inhibition of osteoclast activity with limitations in fibroblasts to form pro-regenerative extracellular matrix and support WE formation. These results suggest that crosstalk between osteoclasts and fibroblasts regulates blastema and WE formation during lizard tail regeneration. Full article

Objectives: This study aimed to assess the effects of antiresorptive drugs on mandibular trabecular bone structure in patients with osteoporosis and those receiving antiresorptive therapy for oncologic conditions using fractal dimension (FD) analysis of panoramic radiographs. Additionally, it investigated the influences of age, gender, drug type, administration route, and treatment duration on mandibular trabecular bone structure. Methods: This retrospective cross-sectional study included 73 patients categorized into the following three groups: 23 osteoporosis patients, 25 oncologic patients, and 25 systemically healthy controls. FD analysis was conducted on panoramic radiographs to assess trabecular bone complexity in the following three standardized regions of interest: the mandibular condyle, angle, and molar region. Statistical analyses compared the groups and evaluated the associations between FD values and demographic and clinical parameters. Results: Osteoporosis patients exhibited significantly lower FD values in the molar region than controls (p < 0.05). In oncologic patients, the FD values in the condyle region were significantly higher in those receiving denosumab than in those treated with intravenous zoledronic acid (p < 0.05), and in those who had undergone antiresorptive therapy for ≥6 years than in those treated for 1–5 years (p < 0.05). A significant negative correlation was found between age and the FD values of the mandibular angle in osteoporosis patients (p < 0.05); no such association was observed in oncologic patients or controls. Conclusions: Long-term antiresorptive therapy may induce structural alterations in mandibular trabecular bone structure in patients with osteoporosis and oncologic diseases. FD analysis is a non-invasive and objective tool for clinically assessing such drug-induced skeletal changes. However, further large-scale, prospective studies are necessary to confirm these findings and shed light on their clinical significance. Full article

Background/Objectives: Osteogenesis Imperfecta (OI) is a congenital disorder, in which the production of collagen, mainly type I, is altered, leading to a decrease in bone mineral density, increasing the risk of fracture with minimal trauma. Several studies have analyzed bone mineral density in osteoporotic patients based on linear measurements such as radiomorphometric indices measured with panoramic radiographs, although few studies have investigated bone trabeculation in children diagnosed with OI. Therefore, the aim of the present investigation was to analyze the dental panoramic indices in panoramic radiographs in the cortical and trabeculated bone of children with OI. Methods: Thus, 66 pediatric patients diagnosed with OI under antiresorptive treatment were compared with a sample of controls matched for sex and age. Using Image J software (version: 1.54d), three radiomorphometric indices were analyzed in orthopantomographies of the study and control groups, evaluating the influence of disease severity as well as the type of antiresorptive treatment administered. Results: Patients with OI had a higher presence of type C2 and C3 MCI (mandibular cortical index) than their matched controls (p < 0.05), although no differences were found for the visual estimation of cortical width (SVE) and mandibular cortical width (MCW). Treatment with zoledronic acid was associated with a higher number of cases of type C1 MCI, in terms of sample description, while patients treated with a combination of pamidronate and zoledronic acid had a higher rate of type C1 and C2 MCI, with no statistical differences. Conclusions: In the overall sample, most patients showed a thin SVE index (59.1%), a C2 or C1 type MCI (46.2% and 42.4%) and an MCW of 2.9 mm. Differences in bone mineral density were also observed throughout growth and the different antiresorptive treatments. Zoledronic acid has been associated with a higher percentage of C1 and C3 ICM, and pamidronate alone or in combination is associated with a C1 and C2 MCI index. Full article

Background and Objectives: Bone metastases in patients can cause significant quality-of-life declines due to skeletal-related events (SREs). SRE is defined as the occurrence of radiotherapy for bone pain, pathologic fracture, bone surgery, spinal cord compression, or hypercalcemia. Bone-modifying agents (BMAs), such as denosumab and zoledronic acid, are crucial in reducing the frequency and severity of SREs. The inhibition of cyclin-dependent kinase 4/6 (CDK4/6) inhibitors has emerged as the standard treatment for hormone receptor-positive metastatic breast cancer, demonstrating significant improvements in survival outcomes. This study aims to compare the effectiveness of denosumab and zoledronic acid in preventing SRE in patients receiving CDK4/6 inhibitors with endocrine therapy. Materials and Methods: This retrospective study included 328 patients diagnosed with bone metastatic breast cancer receiving first-line CDK4/6 inhibitor therapy (palbociclib or ribociclib). Patients were assigned to receive either subcutaneous denosumab or intravenous zoledronic acid every 4 weeks. Time to the first skeletal-related event post bone-modifying agent initiation, SRE incidence, and the safety data were evaluated. The data were analyzed using independent samples t-tests, chi-square tests, and Kaplan–Meier methods for time-to-event data. Results: In the denosumab group, the median time to the first skeletal-related event was significantly longer than in the zoledronic acid group (44.55 months and 29.16 months, respectively). Denosumab treatment was associated with a statistically significant reduction in the risk of developing the first SRE after bone-modifying agent initiation compared to zoledronic acid (HR: 0.56, p = 0.001). Additionally, ECOG PS and the number of metastatic bone sites were identified as independent prognostic factors for time to the first SRE. The safety profile was consistent with previous studies reported in the literature. Conclusions: Our study demonstrated that when used with CDK4/6 inhibitors, denosumab is associated with a delay in SREs and a lower SRE incidence than zoledronic acid in patients with bone metastases. These findings support the efficacy of denosumab in preventing SREs and suggest that CDK4/6 inhibitors may have distinct effects on the bone microenvironment, particularly when combined with denosumab. Full article

Background: This study aimed at investigating the prolonged effects of glucocorticoids and bisphosphonates on bone. Methods: Six-to-eight-month-old skeletally mature male Sprague Dawley rats were randomized to receive a cancer therapy combination of zoledronic acid (ZA = 0.13 mg/kg) and dexamethasone (DX = 3.8 mg/kg) (treatment group, n = 10) or sterile phosphate buffer saline solution (control group, n = 10). The rats received weekly intraperitoneal injections for 8 weeks, which were stopped 6 weeks before euthanasia. Mineralized bone samples were characterized by three-point bending tests, micro-CT imaging, X-ray diffraction (XRD), thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC). Bone collagen was assessed using tensile tests on the demineralized bones and attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy on mineralized and demineralized bones. Results: The samples in the treatment group showed increased tibial cortical thickness, mineral crystal size, and toughness. Analyses of demineralized tibiae revealed decreased collagen tensile strength in the experimental group. The spectroscopic and TGA/DSC analyses showed that the ZA + DX treatment increased the collagen amide I 1660/1690 cm⁻¹ area ratio and collagen denaturalization temperature, indicating a higher level of collagen cross-linking. Conclusions: Bisphosphonates and glucocorticoids led to prolonged changes in the mechanical properties of bone as a result of increased cortical thickness, increased crystal size, and the deterioration of collagen quality. Full article

Background: Metastatic bone disease (MBD) presents significant challenges in patient management, leading to skeletal-related events (SREs), compromised health-related quality of life, and heightened pain experiences. Denosumab (Dmab) and zoledronic acid (ZA) are bone-modifying agents (BMAs) commonly employed to mitigate the sequelae of MBD. Previous meta-analyses have assessed primary outcomes such as overall survival, pathological fractures, radiation to bone, and the time to SREs within studies. However, a single comprehensive analysis comparing their efficacy across multiple primary and secondary outcomes, as well as cost-effectiveness in specific cancer types, has not yet been conducted. Methods: A literature search identified relevant randomized controlled trials (RCTs), and the primary outcomes included overall survival, pathologic fractures, radiation to bone, and the time to SREs within studies. Secondary outcomes included adverse events, pain, analgesia usage, quality of life, and cost. Results: Meta-analysis revealed that Dmab effectively reduced the need for bone-targeted radiation therapy and was superior to ZA in delaying the time to SREs, except in multiple myeloma. Dmab also reduced pathological fracture incidences in breast cancer patients by 39%. Conclusions: Our analysis suggests that while both agents similarly impact overall survival and disease progression, Dmab offers advantages in SRE reduction and improved HRQoL and pain outcomes with lower rates of opioid usage, albeit with higher risks of hypocalcemia and osteonecrosis in some subgroups. The consensus on cost-effectiveness is mixed and varies based on the cancer type and healthcare system, with some studies favoring Dmab’s superior efficacy and safety, while others find ZA more cost-effective due to its lower cost. This study underscores the potential of Dmab as a preferred BMA for MBD management, especially for high-risk skeletal complications, while highlighting cancer-specific safety considerations. Further research is warranted to refine cancer-specific BMA use and optimize MBD management strategies. Full article

Multiple myeloma is an incurable hematologic malignancy arising from plasma cells. The uncontrolled growth of monoclonal plasma cells leads to an abnormal overproduction of immunoglobulins. The recommended course of treatment for MM is according to disease progression and responses to therapeutic intervention, highlighting the necessity for multiple treatment options that alleviate different parts of MM. This comprehensive review provides insights into the current treatments and how to take preventative and prognostic measures. In advanced MM, osteoporosis is a common symptom that originates from a lack of regulation in osteoclast activity and bone resorption. Bisphosphonates such as zoledronic acid and pamidronate along with monoclonal antibodies such as denosumab hinder osteoclast function and aid in reducing the risk of fractures in patients with advanced MM. For targeted therapy approaches, proteasome inhibitors impede protein degradation pathways that cause an accumulation of misfolded proteins promoting cancer cell proliferation in patients with MM. CAR-T is another targeted therapy that can utilize T cells to target and isolate MM cells. Overall, this review highlights the frontrunners of treatments for those diagnosed with MM. Full article

Objectives: This work investigated the effect of bacterial nanocellulose (BNC) alone or with chemisorbed chlorhexidine or povidone-iodine on post-tooth extraction repair in rats undergoing bisphosphonate therapy. Methods: Forty Wistar rats were treated with zoledronic acid, subjected to tooth extractions and allocated into groups according to the material inserted in the post-extraction socket: (1) BNC (n = 10); (2) BNC/Iodine (n = 10); (3) BNC/Chlorhex (n = 10); (4) Control (n = 10). Maxillae were dissected and macro- and microscopically analyzed. Results: Oral lesion frequency on macroscopic examination did not differ between the groups, whereas it was larger in the BNC/Iodine group compared to the BNC/Chlorhex and Control. BNC/Chlorhex had significantly more connective tissue than did BNC but did not differ from the BNC/Iodine and Control. Epithelium, vital bone, non-vital bone, tooth fragment and inflammatory infiltrate did not significantly differ between the groups. BNC/Iodine showed greater CD31 immunostaining compared to BNC and the Control. Myeloperoxidase staining did not differ between the groups, and scanning electron microscopy analysis showed similar characteristics in all groups. Conclusions: BNC with chemisorbed povidone-iodine is associated with increased vascularization in post-extraction wounds of rats undergoing bisphosphonate therapy, whereas BNC with chemisorbed chlorhexidine improves connective tissue formation. BNC works as an effective carrier for the antiseptics tested. Full article

Background/Objectives: In this study, HECP2k polymer, polyethylenimine2k (PEI2k)-modified hydroxyethyl cellulose (HEC) was utilized to form the nanocomplexes with receptor activator of nuclear factor k-B (RANK) siRNA and zoledronate (Zol) for osteoclast inhibition. HECP2k/(RANK siRNA + Zol) nanocomplexes prepared by simple mixing were anticipated to overcome the low transfection efficiency of siRNA and the low bioavailability of Zol. Methods: The characterization of both HECP2k/(pDNA + Zol) nanocomplexes and HECP2k/(RANK siRNA + Zol) nanocomplexes was performed. Results: The nanocomplexes were successfully formed even in the presence of Zol, showing about 200 nm sizes and about 20 mV of positive zeta potential values suitable for efficient cellular uptake. They also possessed high endosome buffering ability by PEI and Zol, suggesting the potential for efficient endosomal escape. It was found that the low cytotoxic nanocomplexes (>90% cell viability) displayed greater transfection efficiency than PEI25k and even HECP2k polyplexes. Finally, it was found by tartrate-resistant acid phosphatase (TRAP) assay and qPCR analysis that HECP2k/(RANK siRNA + Zol) nanocomplexes could inhibit the TRAP to about 50% value and another characteristic osteoclastic gene expression, increasing FAS gene expression to about 16 times higher than control and more efficiently (about 3 times and 5 times higher, respectively) than HECP2k/siRNA polyplexes and Zol only. Conclusions: HECP2k/(RANK siRNA + Zol) nanocomplexes formed by simple mixing showed great potential for inhibiting osteoclast differentiation and osteoclast activity, inducing the apoptosis via combinatorial effects of RANK siRNA and Zol. Full article