Search Results (18)

Background/Objectives: The development of pharmacotherapy, particularly in antiangiogenic drugs, has led to the emergence of MRONJ as a significant side effect. With the increasing incidence of cancer, the management of MRONJ poses a growing challenge for clinicians. The aim of the study is to evaluate the effectiveness of photobiomodulation (PBM) in treating patients with stage I, II, and III medication-related osteonecrosis of the jaw (MRONJ). Methods: A total of 31 patients were divided into two groups: Group 1 (n = 14 patients), with Stage 1 MRONJ; and Group 2 (n = 17 patients), with Stage II and III MRONJ. In total, 10 patients had osteoporosis and 21 underwent cancer treatment. The sole variable under investigation was the stage of MRONJ, as all patients underwent the same photobiomodulation (PBM) procedure. For treatment protocol, PBM with a diode laser was used (Lasotronix Smart M Pro, Piaseczno, Poland) with the following parameters: 100 mW; continuous wave; 635 nm; 4 J/cm² for 20 s; irradiance for one point: 0.398 W/cm²; fluency for one point: 7.96 J/cm², and for four points, which was one appointment: 31.83 J/cm²; and tip diameter 8 mm (three points from buccal surface, perpendicular for the lesion and one point on the floor of the mouth) during each session. The protocol assumed 10 sessions at 3 days intervals. Antibiotic therapy (amoxicillin with clavulanic acid 875 mg + 125 mg or clindamycin 600 mg every 12 h) was started 3 days before PBM and continued for 14 days. Antibiotics were taken for 14 days in total. Pain was measured with VAS scale. Follow-up was after 3 and 6 months. Results: Among the 14 patients in Group 1, none exhibited any clinical signs or symptoms of MRONJ during the 3 months follow-up, and complete cure was achieved. While PBM resolved inflammation and pain in stage II MRONJ, further surgical intervention was necessary to fully address the condition. Conclusions: PBM is an effective treatment for achieving complete recovery in patients with Stage 1 MRONJ. However, in Stages II and III MRONJ, PBM significantly alleviates symptoms but requires complementary surgical intervention to achieve full resolution. A beneficial aspect is the reduction in pain symptoms and the extent of surgical intervention. Full article

Background: This study aimed to evaluate the efficacy of pentoxifylline and tocopherol therapy in patients with medication-related osteonecrosis of the jaw (MRONJ). Methods: During this study, 43 patients participated, including 21 women and 22 men with a mean age of 66.8 years, who showed 63 areas of osteitis altogether. The diagnosis was made based on X-ray imaging and histopathological findings. All the subjects received pharmacological treatment with pentoxifylline 400 mg and tocopherol 400 IU. The study scheme consisted of initial observation and two follow-up examinations every 5–6 months. MRONJ severity, peripheral blood parameters, and CRP levels were evaluated. The obtained results were statistically analyzed. Results: Complete remission occurred in 46% of the subjects, with a higher rate among those taking bisphosphonates intravenously compared to oral administration. The efficacy of pentoxifylline and tocopherol treatment was not influenced by gender or lesion location. Moreover, the worst response to treatment was observed in the group with the highest disease stage, as determined in the initial study. Conclusions: Pentoxifylline and tocopherol therapy in MRONJ was effective in patients taking oral and intravenous bisphosphonates, in patients with osteoporosis, and undergoing oncological treatment. This treatment approach allows surgery to be avoided or significantly reduced. The good response to pharmacotherapy observed in patients with early stages of MRONJ shows an urgent need to monitor the patients treated with bisphosphonates carefully to diagnose MRONJ at the initial phase. Full article

Background: Teriparatide (TPT) acts against severe primary (postmenopausal) osteoporosis (MOP), and it requires continuation with another anti-resorptive drug to conserve or enhance the effects on fracture risk reduction. Objective: To analyse the sequential pharmacotherapy in MOP who were treated upon a 24-month daily 20 µg TPT protocol (24-mo-TPT) followed by another 12 months of anti-resorptive drugs (12-mo-AR) amid real-life settings. Hypotheses: 1. TPT candidates had a more severe fracture risk profile versus those who did not fulfil the TPT criteria according to the national protocol of TPT initiation; 2. Patients treated with TPT improved their DXA profile after 24 mo; 3. After 1 year of therapy since the last TPT injection, the improved bone profile and fracture risk at the end of the TPT protocol were conserved; 4. The mineral metabolism assays and fracture risk status were similar at TPT initiation between those who finished the 24 mo protocol and those who prematurely stopped it. Methods: This was a longitudinal, retrospective, multicentre study in MOP. The entire cohort (group A) included the TPT group (B) versus the non-TPT group (non-B). Group B included subjects who finished 24-mo-TPT (group P) and early droppers (ED), and then both continued 12-mo-AR. Results: Group B (40.5%) from cohort A (N = 79) vs. non-B had lower T-scores, increased age and years since menopause. A similar profile of demographic features, BTM, and prevalent fractures (73%, respectively, 57%) was found in group P (72%) vs. ED (21.8%). Group P: osteocalcin was statistically significantly higher at 12 mo (+308.39%), respectively, at 24 mo (+171.65%) vs. baseline (p < 0.001 for each), while at 12-mo-AR became similar to baseline (p = 0.615). The cumulative probability of transient hypercalcemia-free follow-up of protocol had the highest value of 0.97 at 6 mo. An incidental fracture (1/32) was confirmed under 24-mo-TPT. BMD had a mean percent increase at the lumbar spine of +8.21% (p < 0.001), of +12.22% (p < 0.001), respectively, of +11.39% (p < 0.001). The pharmacologic sequence for 12-mo-AR included bisphosphonates (24.24% were oral BP) or denosumab (13%). BTM showed a suppression at 12-mo-AR (p < 0.05), while all BMD/T-scores were stationary. No incidental fracture was registered during 12-mo-AR. Conclusions: All research hypotheses were confirmed. This study in high-risk MOP highlighted an effective sequential pharmacotherapy in reducing the fracture risk as pinpointed by BMD/T-score measurements and analysing the incidental fractures profile. Full article

Osteoporosis, a metabolic bone disorder characterized by decreased bone mass per unit volume, poses a significant global health burden due to its association with heightened fracture risk and adverse impacts on patients’ quality of life. This review synthesizes the current understanding of the pathophysiological mechanisms underlying osteoporosis, with a focus on key regulatory pathways governing osteoblast and osteoclast activities. These pathways include RANK/RANKL/OPG, Wingless-int (Wnt)/β-catenin, and Jagged1/Notch1 signaling, alongside the involvement of parathyroid hormone (PTH) signaling, cytokine networks, and kynurenine in bone remodeling. Pharmacotherapeutic interventions targeting these pathways play a pivotal role in osteoporosis management. Anti-resorptive agents, such as bisphosphonates, estrogen replacement therapy/hormone replacement therapy (ERT/HRT), selective estrogen receptor modulators (SERMs), calcitonin, anti-RANKL antibodies, and cathepsin K inhibitors, aim to mitigate bone resorption. Conversely, anabolic agents, including PTH and anti-sclerostin drugs, stimulate bone formation. In addition to pharmacotherapy, nutritional supplementation with calcium, vitamin D, and vitamin K2 holds promise for osteoporosis prevention. However, despite the availability of therapeutic options, a substantial proportion of osteoporotic patients remain untreated, highlighting the need for improved clinical management strategies. This comprehensive review aims to provide clinicians and researchers with a mechanistic understanding of osteoporosis pathogenesis and the therapeutic mechanisms of existing medications. By elucidating these insights, this review seeks to inform evidence-based decision-making and optimize therapeutic outcomes for patients with osteoporosis. Full article

Obesity, type 2 diabetes mellitus (T2DM) and osteoporosis are serious diseases with an ever-increasing incidence that quite often coexist, especially in the elderly. Individuals with obesity and T2DM have impaired bone quality and an elevated risk of fragility fractures, despite higher and/or unchanged bone mineral density (BMD). The effect of obesity on fracture risk is site-specific, with reduced risk for several fractures (e.g., hip, pelvis, and wrist) and increased risk for others (e.g., humerus, ankle, upper leg, elbow, vertebrae, and rib). Patients with T2DM have a greater risk of hip, upper leg, foot, humerus, and total fractures. A chronic pro-inflammatory state, increased risk of falls, secondary complications, and pharmacotherapy can contribute to the pathophysiology of aforementioned fractures. Bisphosphonates and denosumab significantly reduced the risk of vertebral fractures in patients with both obesity and T2DM. Teriparatide significantly lowered non-vertebral fracture risk in T2DM subjects. It is important to recognize elevated fracture risk and osteoporosis in obese and T2DM patients, as they are currently considered low risk and tend to be underdiagnosed and undertreated. The implementation of better diagnostic tools, including trabecular bone score, lumbar spine BMD/body mass index (BMI) ratio, and microRNAs to predict bone fragility, could improve fracture prevention in this patient group. Full article

Post-traumatic osteoporosis (PTO) presents a significant challenge in clinical practice, characterized by demineralization and decreased skeletal integrity following severe traumatic injuries. This literature review manuscript addresses the knowledge gaps surrounding PTO, encompassing its epidemiology, pathophysiology, risk factors, diagnosis, treatment, prognosis, and future directions. This review emphasizes the complexity of the etiology of PTO, highlighting the dysregulation of biomineralization processes, inflammatory cytokine involvement, hormonal imbalances, glucocorticoid effects, vitamin D deficiency, and disuse osteoporosis. Moreover, it underscores the importance of multidisciplinary approaches for risk mitigation and advocates for improved diagnostic strategies to differentiate PTO from other musculoskeletal pathologies. This manuscript discusses various treatment modalities, including pharmacotherapy, dietary management, and physical rehabilitation, while also acknowledging the limited evidence on their long-term effectiveness and outcomes in PTO patients. Future directions in research are outlined, emphasizing the need for a deeper understanding of the molecular mechanisms underlying PTO and the evaluation of treatment strategies’ efficacy. Overall, this review provides a comprehensive overview of PTO and highlights avenues for future investigation to enhance clinical management and patient outcomes. Full article

Sacral insufficiency fractures commonly affect elderly women with osteoporosis and can cause debilitating lower back pain. First line management is often with conservative measures such as early mobilization, multimodal pain management, and osteoporosis management. If non-operative management fails, sacroplasty is a minimally invasive intervention that may be pursued. Candidates for sacroplasty are patients with persistent pain, inability to tolerate immobilization, or patients with low bone mineral density. Before undergoing sacroplasty, patients’ bone health should be optimized with pharmacotherapy. Anabolic agents prior to or in conjunction with sacroplasty have been shown to improve patient outcomes. Sacroplasty can be safely performed through a number of techniques: short-axis, long-axis, coaxial, transiliac, interpedicular, and balloon-assisted. The procedure has been demonstrated to rapidly and durably reduce pain and improve mobility, with little risk of complications. This article aims to provide a narrative literature review of sacroplasty including, patient selection and optimization, the various technical approaches, and short and long-term outcomes. Full article

Background/Objectives: 25-hydroxy vitamin D (25-OH-D) is a fat-soluble compound that plays many essential functions, including bone formation, neuromuscular functions, and prevention of osteoporosis and inflammation. Recent data indicate that its metabolites are associated with rheumatoid arthritis (RA) progression and neuropathic pain in RA patients. We aimed to assess the effect of RA pharmacotherapy and seasonal variation on serum levels of 25-OH-D in RA patients who received treatment with methotrexate (MTX) or leflunomide (LEF) for at least one year. Methods: This study is a retrospective analysis of data collected from 101 patients with RA who received treatment for at least one year. All of them have supplemented 25-OH-D (2000 IU daily) for at least one year. Results: We observed a significant seasonal variation in 25-OH-D concentration (p = 0.004). Moreover, there were significant differences (p = 0.03) between LEF (50.63 ± 17.73 ng/mL) and MTX (34.73 ± 14.04 ng/mL) treatment groups, but only for the summer population. A correlation was observed between 25-OH-D and RA duration—once again, in the summer population (the whole group—r = −0.64; treatment subgroups—r = −0.82 for LEF and −0.61 for MTX). Deficiency of 25-OH-D (below 20 ng/mL) was confirmed in 28.7% of patients, while 18.8% had suboptimal 25-OH-D levels (20–30 ng/mL). Conclusions: Our results showed that both RA pharmacotherapy and seasonal variation affect the serum levels of 25-OH-D in patients with active RA. Full article

This study evaluated whether osteoporosis pharmacotherapy (OPT) affected functional outcomes in acute ischemic stroke patients with osteoporosis. Using a single-center registry database, we consecutively registered acute ischemic stroke patients between May 2016 and December 2020. All patients older than 55 years underwent routine bone densitometry within 7 days of stroke onset. OPT prescription was confirmed by reviewing medical records. We classified the patients into OPT and no OPT groups. We performed propensity score matching (PSM) to overcome the imbalance in multiple covariates between the two groups. We investigated whether OPT affected 1-year functional outcomes by multivariate analysis using a PSM cohort. Among 1307 consecutively registered acute ischemic stroke patients, 381 patients were enrolled in this study, of whom 134 (35.2%) were prescribed OPT at discharge, which was maintained for 1 year. In a multivariate analysis using a PSM cohort, the OPT group had a lower risk of dependency (odds ratio [OR], 0.52; 95% confidence interval [CI], 0.27–0.996) and poor functional outcome at 1 year (OR, 0.24; 95% CI, 0.10–0.57). The OPT group also had increased chance of late functional improvement (OR, 6.16; 95% CI, 1.12–33.79). This study showed that OPT could reduce dependency and poor functional outcomes and increase the chance of improving functional outcomes at 3 months and 1 year after ischemic stroke onset, and these findings could be helpful for improving functional outcomes and bone health after ischemic stroke. Full article

The present study analyzed the effect of vitamin D receptor (VDR) gene polymorphisms (ApaI, TaqI, BsmI, FokI, and Cdx2) on bone mineral density (BMD), biochemical parameters and bone turnover markers, fracture prevalence, and response to three types of antiresorptive therapy (estrogen-progesterone, raloxifene, and ibandronate) in 356 postmenopausal women from Slovakia. Association analysis revealed a significant effect of BsmI polymorphism on lumbar spine BMD, serum osteocalcin (OC), and β-CrossLaps levels. While ApaI and Cdx2 polymorphisms were associated with OC and alkaline phosphatase, TaqI polymorphism affected all turnover markers. ApaI, TaqI, and BsmI genotypes increased the risk of spinal, radial, or total fractures with odds ratios ranging from 2.03 to 3.17. Each of therapy types evaluated had a beneficial effect on all osteoporosis-related traits; however, the VDR gene affected only ibandronate and raloxifene treatment. ApaI/aa, TaqI/TT, and BsmI/bb genotypes showed a weaker or no response to ibandronate therapy in femoral and spinal BMD. The impact of aforementioned polymorphisms on turnover markers was also genotype dependent. On the contrary, only TaqI and BsmI polymorphisms influenced raloxifene therapy, even only in lumbar spine BMD. These results point to the potential of using the VDR gene in personalized pharmacotherapy of osteoporosis. Full article

Cordyceps spp. (belonging to the Ascomycota group) are entomopathogenic mushrooms that have traditionally been used in ethnomedicine in Asian countries such as China, Japan, Korea, and India. They are unique parasites of larvae of selected species of moths. Cordyceps militaris is one of the best sources of cordycepin. Worldwide, osteoporosis is one of the most common bone diseases, whose pharmacotherapy includes various medical interventions; however, the research and development of new molecules and new drugs is required. The impact of adenosine receptors (ARs) on the purinergic signaling pathway may regulate proliferation, differentiate dental pulp stem cells and bone marrow, and modulate osteogenesis and bone repair. The aim of the review was to collect and analyze the available data on the effects of Cordyceps spp. or cordycepin on bone function and related processes. To the best of our knowledge, this is the first systematic review in this perspective, not necessarily using mushroom raw material or even the isolated parent compound cordycepin, but new molecules that are analogs of nucleosides, such as those from C. militaris. This review found that Cordyceps spp. or isolated cordycepin interacts via the AR, 5′ adenosine monophosphate-activated protein kinase (AMPK), and adenosine-5′-triphosphate (ATP) signaling pathway and evaluated their impact on bones, teeth, and dental pulp. Cordyceps spp. was found to have the potential to develop regenerative medicines, thus providing an opportunity to expand the treatment or intervention methods in the recovery after traumatic injuries, convalescence, and terminal-stage or devastating diseases. Full article

The multifaceted activity of vitamin D in patients with inflammatory bowel disease (IBD) presents a challenge for further research in this area. Vitamin D is involved in the regulation of bone mineral metabolism, it participates in the regulation of the immune system, and it is an underlying factor in the pathogenesis of IBD. Additionally, vitamin D affects Th1 and Th2 lymphocytes, influencing the release of cytokines and inhibiting tumor necrosis factor (TNF) expression and the wnt/β-catenin pathway. As far as IBDs are concerned, they are associated with microbiota dysbiosis, abnormal inflammatory response, and micronutrient deficiency, including vitamin D hypovitaminosis. In turn, the biological activity of active vitamin D is regulated by the vitamin D receptor (VDR) which is associated with several processes related to IBD. Therefore, in terms of research on vitamin D supplementation in IBD patients, it is essential to understand the metabolic pathways and genetic determinants of vitamin D, as well as to identify the environmental factors they are subject to, not only in view of osteoporosis prevention and therapy, but primarily concerning modulating the course and supplementation of IBD pharmacotherapy. Full article

Diabetes mellitus is a metabolic and systematic disorder that requires individualized therapy. The disease leads to various consequences, resulting in the destruction of tissues and organs. The aforementioned outcomes also include bone mineral disorders, caused by medications as well as diet therapy and physical activity. Some drugs may have a beneficial effect on both bone mineral density and the risk of fractures. Nevertheless, the impact of other medications remains unknown. Focusing on pharmacotherapy in diabetes may prevent bone mineral disorders and influence both the treatment and quality of life in patients suffering from diabetes mellitus. On the other hand, anti-osteoporosis drugs, such as antiresorptive or anabolic drugs, as well as drugs with a mixed mechanism of action, may affect carbohydrate metabolism, particularly in patients with diabetes. Therefore, the treatment of diabetes as well as osteoporosis prevention are vital for this group of patients. Full article

Osteoporosis is considered an age-related disorder of the skeletal system, characterized primarily by decreased bone mineral density (BMD), microstructural quality and an elevated risk of fragility fractures. This silent disease is increasingly becoming a global epidemic due to an aging population and longer life expectancy. It is known that nutrition and physical activity play an important role in skeletal health, both in achieving the highest BMD and in maintaining bone health. In this review, the role of macronutrients (proteins, lipids, carbohydrates), micronutrients (minerals—calcium, phosphorus, magnesium, as well as vitamins—D, C, K) and flavonoid polyphenols (quercetin, rutin, luteolin, kaempferol, naringin) which appear to be essential for the prevention and treatment of osteoporosis, are characterized. Moreover, the importance of various naturally available nutrients, whether in the diet or in food supplements, is emphasized. In addition to pharmacotherapy, the basis of osteoporosis prevention is a healthy diet rich mainly in fruits, vegetables, seafood and fish oil supplements, specific dairy products, containing a sufficient amount of all aforementioned nutritional substances along with regular physical activity. The effect of diet alone in this context may depend on an individual’s genotype, gene-diet interactions or the composition and function of the gut microbiota. Full article

The calcitonin and amylin receptors (CTR and AMY receptors) are the drug targets for osteoporosis and diabetes treatment, respectively. Salmon calcitonin (sCT) and pramlintide were developed as peptide drugs that activate these receptors. However, next-generation drugs with improved receptor binding profiles are desirable for more effective pharmacotherapy. The extracellular domain (ECD) of CTR was reported as the critical binding site for the C-terminal half of sCT. For the screening of high-affinity sCT analog fragments, purified CTR ECD was used for fluorescence polarization/anisotropy peptide binding assay. When three mutations (N26D, S29P, and P32HYP) were introduced to the sCT(22–32) fragment, sCT(22–32) affinity for the CTR ECD was increased by 21-fold. CTR was reported to form a complex with receptor activity-modifying protein (RAMP), and the CTR:RAMP complexes function as amylin receptors with increased binding for the peptide hormone amylin. All three types of functional AMY receptor ECDs were prepared and tested for the binding of the mutated sCT(22–32). Interestingly, the mutated sCT(22–32) also retained its high affinity for all three types of the AMY receptor ECDs. In summary, the mutated sCT(22–32) showing high affinity for CTR and AMY receptor ECDs could be considered for developing the next-generation peptide agonists. Full article