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Journal of Functional Biomaterials Sep 2023Hypertension and estrogen deficiency can affect bone metabolism and therefore increase the risk of osseointegration. Antihypertensive drugs such as losartan not only...
Hypertension and estrogen deficiency can affect bone metabolism and therefore increase the risk of osseointegration. Antihypertensive drugs such as losartan not only control blood pressure but also enhance bone healing. In addition, alendronate sodium is widely used to treat postmenopausal osteoporosis. Hence, we evaluated the effect of systemic antihypertensive and local alendronate coted on implants on osseointegration under hypertensive and estrogen-deficiency conditions. A total of 64 spontaneously hypertensive rats (SHRs) treated with losartan were randomly divided according to the estrogen-deficiency induction by ovariectomy (OVX) or not (SHAM), and whether the implant surface was coated with sodium alendronate (ALE) or not, resulting in four groups: SHR SHAM, SHR SHAM ALE, SHR OVX, and SHR OVX ALE. The removal torque, microcomputed tomography, and epifluorescence microscopy were the adopted analyses. The hypertensive and estrogen-deficiency animals presented a lower removal torque even when treated with alendronate on implant surface. The microcomputed tomography revealed a higher bone volume and bone-to-implant contact in the SHRs than the SHR OVX rats. Epifluorescence showed a decreased mineral apposition ratio in the SHR OVX ALE group. The data presented indicate that estrogen deficiency impairs osseointegration in hypertensive rats; in addition, alendronate coated on the implant surface does not fully reverse this impaired condition caused by estrogen deficiency.
PubMed: 37754885
DOI: 10.3390/jfb14090471 -
Neurospine May 2024We investigated the clinical efficacy of anabolic agents compared with bisphosphonates (BPs) for the incidence of new osteoporotic vertebral fracture (OVF) and fracture...
Comparison of the Clinical Efficacy of Anabolic Agents and Bisphosphonates in the Patients With Osteoporotic Vertebral Fracture: Systematic Review and Meta-analysis of Randomized Controlled Trials.
OBJECTIVE
We investigated the clinical efficacy of anabolic agents compared with bisphosphonates (BPs) for the incidence of new osteoporotic vertebral fracture (OVF) and fracture healing of OVF in the patients with OVF via meta-analyses of randomized controlled trials (RCTs).
METHODS
Electronic databases, including PubMed, Embase, and Cochrane Library were searched for published RCTs till December 2022. The RCTs that recruited participants with osteoporosis at high-/very high-risk of fracture (a history of osteoporotic vertebral or hip fracture) or fresh OVF were included in this study. We assessed the risk of bias on every included RCTs, estimated relative risk (RR) for the incidence of new OVF and fracture healing of OVF, and overall certainty of evidence. Meta-analyses were performed by Cochrane review manager (RevMan) version 5.3. Cochrane risk of bias 2.0 and GRADEpro/GDT were applied for evaluating methodological quality and overall certainty of evidence, respectively.
RESULTS
Five hundred eighteen studies were screened, and finally 6 eligible RCTs were included in the analysis. In the patients with prevalent OVF, anabolic agents significantly reduced the incidence of new OVF (teriparatide and romosozumab vs alendronate and risedronate [RR = 0.57, 95% CI 0.45 - 0.71; p < 0.00001; high-certainty of evidence]; teriparatide vs risedronate [RR = 0.50, 95% CI 0.37 - 0.68; p < 0.0001; high-certainty of evidence]. However, there was no evidence of teriparatide compared to alendronate in fracture healing of OVF (RR = 1.23, 95% CI 0.95 - 1.60; p = 0.12; low-certainty of evidence).
CONCLUSION
In the patients with prevalent OVF, anabolic agents showed a significant superiority for preventing new OVF than BPs, with no significant evidence for promoting fracture healing of OVF. However, considering small number of RCTs in this study, additional studies with large-scale data are required to obtain more robust evidences.
PubMed: 38697911
DOI: 10.14245/ns.2347256.628 -
Journal of Pharmacy & Bioallied Sciences Jul 2023Class II mandibular furcation defect is a periodontal condition characterized by a cul-de-sac lesion, a definite parallel constituent with only a portion of alveolar...
Class II mandibular furcation defect is a periodontal condition characterized by a cul-de-sac lesion, a definite parallel constituent with only a portion of alveolar bone remaining intact. There may be involvement of vertical bone loss. Local drug deliveries such as Boric acid, alendronate gel, and other drugs exhibited anti-inflammatory, antibacterial & osteoblastic differentiation activity. The present systematic review compares the drugs based on their outcomes and pharmacological action. To analzse & compare various forms of local drug delivery systems on a class II furcation. A search was conducted using PubMed, Google scholar, science direct, and Pub Med central using MeSH terms - local drug delivery in periodontics, boric acid in the management of class II mandibular furcation, simvastatin in the treatment of furcation. A total of 560 articles were screened; 58 out of 560 were full-text articles accessed for eligibility, and five articles were included in the systematic review. PRISMA guidelines were used for reporting this review. In addition, five randomized controlled trials were enclosed and used in this systematic review. The various local drugs used in treating class II mandibular furcation defects are effective in the prevention of bleeding on probing, bone resorption, gingival bleeding index and increase in the bone fill, and microbial deposit removal. The managing of class II mandibular furcation defect with the drugs mentioned in this review can be effective by reducing several clinical parameters such as bleeding on probing, gingival indices, osteoblastic differentiation, bone fill, etc., Considering the results of the studies, it can be concluded that it can be used as a therapeutic therapy against class II furcation defects with positive outcomes.
PubMed: 37654351
DOI: 10.4103/jpbs.jpbs_572_22 -
Journal of Bone and Mineral Metabolism May 2024The 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... (Randomized Controlled Trial)
Randomized Controlled Trial
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.
Topics: Humans; Alendronate; Female; Teriparatide; Bone Density; Aged; Middle Aged; Bone Density Conservation Agents; Japan; Osteoporosis; Osteoporosis, Postmenopausal; Spinal Fractures; Lumbar Vertebrae; East Asian People
PubMed: 38755328
DOI: 10.1007/s00774-024-01515-5 -
European Journal of Dentistry May 2024Osteoporosis is a disease characterized by disruption of the bone microarchitecture. It is observed in both sexes, but to a greater extent in women. It affects the whole...
Osteoporosis is a disease characterized by disruption of the bone microarchitecture. It is observed in both sexes, but to a greater extent in women. It affects the whole body, including the jaws. The main indicator of the presence of osteoporosis accepted by the World Health Organization is bone mineral density. The aim of this article is to find data on the influence of osteoporosis on apical periodontitis, to investigate how the intake of osteoporosis drugs affects apical periodontitis, and to establish various data that may be of benefit to the dental practitioner when treating patients with osteoporosis and apical periodontitis. Open-access publications are included. The presence of osteoporosis is important to the dentist. Apical periodontitis in these patients has a faster progression. They are characterized by inflammation and destruction of the tissues located around the tooth root. Osteoporosis has a destructive effect on bone tissue through different mechanisms: nuclear factor-κβ ligand and NLRP3/Caspase-1/IL-1β cascade. It is also associated with low estrogen levels. Various medications such as corticosteroids, bisphosphonates (alendronate, zoledronate (Zoledronic acid), calcitonin, raloxifene, and strontium used to treat osteoporosis can affect the course of apical periodontitis. When treating patients with periapical lesions, the dentist must take a proper medical history and general medical history. In cases of osteoporosis or taking bisphosphonates and other medications, consideration should be given to whether consultation with a specialist is necessary, what treatment approach would be most appropriate, and what the prognosis will be. Chronic diseases affect both the general state of the body and dental health. It has been found that in patients with osteoporosis, inflammation of the apical periodontium develops with faster bone resorption. Before starting dental treatment, it is important to specify the etiology of osteoporosis, the bone density of each patient, as well as the medications they are taking.
PubMed: 38759999
DOI: 10.1055/s-0044-1785533 -
Experimental Biology and Medicine... Dec 2023With the aging population and the popularity of implant prostheses, an increasing number of postmenopausal osteoporosis (PMOP) patients require implant restorations;...
With the aging population and the popularity of implant prostheses, an increasing number of postmenopausal osteoporosis (PMOP) patients require implant restorations; however, poor bone condition affects the long-term stability of implant prostheses. This study aimed to investigate the therapeutic effect of quercetin (QR) compared with alendronate (ALN), the primary treatment for PMOP, on mandibular osteoporosis (OP) induced by ovariectomy (OVX) in female rats. Adult female rats were treated with QR (50 mg/kg/day), ALN (6.25 mg/kg/week) by gavage for 8 weeks, chloroquine (CQ, 10 mg/kg/twice a week), and cytokine release inhibitory drug 3 (MCC950, 10 mg/kg/three times a week) by intraperitoneal injection for 8 weeks after bilateral OVX. Blood samples were collected prior to euthanasia; the mandibles were harvested and subjected to micro-computed tomography (micro-CT) and pathological analysis. QR administration controlled weight gain and significantly improved the bone microstructure in OVX rats, increasing bone mass, and bone mineral density (BMD), reducing bone trabecular spacing, and decreasing osteoclast numbers. Western blotting, real-time quantitative PCR (RT-qPCR), and serum markers confirmed that QR inhibited interleukin- 1β (IL-1β) and interleukin-18 (IL-18) on the nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) protein 3 (NLRP3) pathway thereby inhibiting osteoclast differentiation, immunofluorescence and western blotting also confirmed that QR inhibited autophagy in OVX rats and suppressed the number of tartrate-resistant acid phosphatase (TRAP)-stained positive osteoclasts. The findings suggest that QR may protect the bone structure and prevent bone loss in osteoporotic rats by inhibiting the NLRP3 pathway and autophagy in osteoclasts with comparable effects to ALN, thus QR may have the potential to be a promising alternative supplement for the preventive and therapeutic treatment of PMOP.
Topics: Animals; Female; Rats; Alendronate; Autophagy; Bone Density; Bone Density Conservation Agents; NLR Family, Pyrin Domain-Containing 3 Protein; Osteoporosis; Osteoporosis, Postmenopausal; Ovariectomy; Quercetin; X-Ray Microtomography
PubMed: 38240215
DOI: 10.1177/15353702231211977 -
International Journal of Clinical... Apr 2024Ibandronate is effective in reducing the risk of vertebral fractures, but experimental evidence offers conflicting results regarding nonvertebral fractures. Real-world... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Ibandronate is effective in reducing the risk of vertebral fractures, but experimental evidence offers conflicting results regarding nonvertebral fractures. Real-world evidence has been published evaluating the anti-nonvertebral fracture effect of ibandronate.
AIM
This meta-analysis of observational studies assessed the effectiveness of ibandronate in reducing the risk of nonvertebral fractures in women with osteoporosis.
METHOD
Pubmed/Embase databases were searched for observational studies. Risks of nonvertebral fractures and hip fractures were the outcomes. Meta-analyses were performed pooling rate ratios (RRs), using random-effects models. Data were reanalysed in sensitivity analyses considering Knapp-Hartung method and Bayesian random-effects.
RESULTS
Six cohort studies were included. Overall, once-monthly 150 mg oral ibandronate reduced the risk of nonvertebral fractures (RR 0.84; 95% CI 0.76-0.94). Similar results were obtained when the comparison was restricted to once-monthly 150 mg risedronate, but no differences were found when the comparator was other oral bisphosphonates (weekly alendronate/risedronate). Ibandronate didn't significantly change the risk of hip fractures (RR 1.25; 95% CI 0.89-1.76). The risk of hip fracture was comparable between once monthly, 150 mg oral ibandronate and other oral bisphosphonates. Intravenous ibandronate was not effective in reducing hip fractures comparing to intravenous zoledronate. The low number of studies diminished the robustness of sensitivity analyses.
CONCLUSION
Results suggest that once-monthly 150 mg oral ibandronate may be as effective as other oral bisphosphonates in reducing the risk of nonvertebral fractures. However, uncertainty associated to the small number of included studies, which are characterized by heterogeneous demographics and methodologies, precluded definitive conclusions.
Topics: Female; Humans; Ibandronic Acid; Risedronic Acid; Bone Density Conservation Agents; Diphosphonates; Bayes Theorem; Osteoporosis; Hip Fractures; Osteoporosis, Postmenopausal; Observational Studies as Topic
PubMed: 38112890
DOI: 10.1007/s11096-023-01666-x -
Annals of Hematology Jan 2024Myeloid malignancies are a group of blood disorders characterized by the proliferation of one or more haematopoietic myeloid cell lineages, predominantly in the bone...
Myeloid malignancies are a group of blood disorders characterized by the proliferation of one or more haematopoietic myeloid cell lineages, predominantly in the bone marrow, and are often caused by aberrant protein tyrosine kinase activity. The protein tyrosine phosphatase CD45 is a trans-membrane molecule expressed on all haemopoietic blood cells except that of platelets and red cells. CD45 regulates various cellular physiological processes including proliferation, apoptosis, and lymphocyte activation. However, its role in chemotherapy response is still unknown; therefore, the aim of this study was to investigate the role of CD45 in myeloid malignancies in terms of cellular growth, apoptosis, and response to chemotherapy. The expression of CD45 on myeloid leukaemia primary cells and cell lines was heterogeneous with HEL and OCI-AML3 cells showing the highest level. Inhibition of CD45 resulted in increased cellular sensitivity to cytarabine and ruxolitinib, the two main therapies for AML and MPN. Bioinformatics analysis identified genes whose expression was correlated with CD45 expression such as JAK2, ACTR2, THAP3 Serglycin, and PBX-1 genes, as well as licensed drugs (alendronate, allopurinol, and balsalazide), which could be repurposed as CD45 inhibitors which effectively increases sensitivity to cytarabine and ruxolitinib at low doses. Therefore, CD45 inhibition could be explored as a potential therapeutic partner for treatment of myeloid malignancies in combination with chemotherapy such as cytarabine especially for elderly patients and those showing chemotherapy resistance.
Topics: Humans; Aged; Leukemia, Myeloid; Pyrazoles; Nitriles; Cytarabine; Myeloproliferative Disorders; Leukemia, Myeloid, Acute
PubMed: 37917373
DOI: 10.1007/s00277-023-05520-y -
Biomedicine & Pharmacotherapy =... May 2024Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility. The aim of this study was to investigate the therapeutic potential of vitamin C,...
Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility. The aim of this study was to investigate the therapeutic potential of vitamin C, glutamine, mesalazine, hydralazine, and alendronate as new drug candidates for the treatment of letrozole-induced PCOS in female Wistar rats. PCOS was induced in rats by intramuscular injection of estradiol valerate (2 mg/kg body weight for 28 days). The rats then received normal saline (PCOS group), letrozole (0.5 mg/kg), vitamin C (100 mg/kg), glutamine (1000 mg/kg), mesalazine (200 mg/kg), hydralazine (30 mg/kg), and alendronate (17.5 mg/kg). Serum testosterone, LH, FSH, estradiol and progesterone levels were determined by ELISA method. H&E staining was used for histological analysis in the ovarian tissues. The groups treated with hydralazine and alendronate, show a significant decrease in testosterone, LH hormone, cystic and atretic follicles, and a significant increase in the number of single layer, multilayer, antral, graafian follicles and the volume of corpus luteum as compared to the PCOS group. Hydrolazine and alendronate appear to be effective in restoring folliculogenesis and increasing ovulation in PCOS rat. So that the natural process of ovulation and the improvement of the histology of polycystic ovaries and its shift towards healthy and active ovaries were observed. This finding supports the potential beneficial effect of hydrolazine and alendronate on improving PCOS complication.
Topics: Animals; Female; Rats; Alendronate; Aromatase Inhibitors; Disease Models, Animal; Estradiol; Hydralazine; Letrozole; Luteinizing Hormone; Ovary; Polycystic Ovary Syndrome; Rats, Wistar; Testosterone
PubMed: 38552442
DOI: 10.1016/j.biopha.2024.116504 -
JFMS Open Reports 2023A 10-year-old spayed female domestic medium hair cat presented after sustaining atraumatic insufficiency fractures of the right calcaneus and the left tibia...
CASE SUMMARY
A 10-year-old spayed female domestic medium hair cat presented after sustaining atraumatic insufficiency fractures of the right calcaneus and the left tibia approximately 6 weeks apart. Chronic alendronate therapy had been ongoing for 9 years for the management of previously diagnosed idiopathic hypercalcemia. The right calcaneal fracture was managed non-operatively due to minimal functional impairment. The left tibial fracture was managed via open reduction and internal fixation with orthogonal plating. Alendronate therapy was discontinued at the time of the fracture repair with prednisolone being used to manage the hypercalcemia. Despite rapid clinical improvement, the tibial fracture had a protracted healing course, with clinical union only being achieved 22 weeks postoperatively. At 17 months postoperatively, the idiopathic hypercalcemia remained well controlled. Gait assessment, orthopedic examination and orthogonal radiographs performed at this time revealed resolution of left pelvic limb lameness, a normal orthopedic examination of the left pelvic limb and no evidence of implant-associated complications. Monitoring is ongoing but at the time of publication, no further fractures have occurred.
RELEVANCE AND NOVEL INFORMATION
As reported in humans, this case report gathers evidence of associations between bisphosphonate treatment and the occurrence of insufficiency fractures in cats, and provides evidence that stress reactions may precede their development. If bisphosphonate therapy is utilized in the long term, serial radiographic monitoring for signs of impending fracture may be warranted. Fracture repair can be successful in cats that have received long-term bisphosphonate therapy, but delayed healing should be anticipated and implant choices made accordingly.
PubMed: 37581124
DOI: 10.1177/20551169231183752