Efficacy Of Bisphosphonates Research Articles

Bisphosphonates and Antibiotics Combination Therapy for Chronic Low Back Pain Associated with Modic Change: A Quasi-Experimental Study

Background: Although effective treatments are still lacking for chronic low back pain (CLBP) associated with Modic changes (MC), in recent years, the efficacy of bisphosphonate and antibiotic treatment has been tested separately with variable success. This study aimed to compare the effectiveness of combined therapy of bisphosphonate and antibiotics versus single-drug therapy in CLBP patients with MC.Methods: This quasi-experimental study was carried out from October 2019 to September 2020 according to 1964 Helsinki declaration among 60 adult CLBP patients with MC (confirmed by magnetic resonant imaging) and randomly allocated in Group-A (n=20): Zoledronic acid (ZA) only, Group-B (n=20): amoxicillin-clavulanate only, and Group-C (n=20): both ZA and amoxicillin-clavulanate. The primary outcomes were measured by the visual analog scale (VAS) and Roland Morris disability questionnaire (RMDQ) at follow-ups after 1 month, 100 days, and 6 months. Per-protocol analysis was performed using SPSS 24.Results: Out of the 60 patients, 43 patients (72%) completed all three follow-ups. The VAS score gradually decreased in all groups after treatment, wherein Group-C patients had the significantly lowest score at the 2nd and 3rd follow-ups (2.87±0.80 and 1.68±0.70, respectively) compared to Group-A (3.40±0.63 and 2.20±0.67, respectively) and Group-B (3.50±0.52 and 2.41±0.66,respectively). In addition, RMDQ also decreased significantly after 1 month compared to pretreatment (p<0.05) in all 3 groups, and this gradual decrement was continued until 6 months of treatment. However, it was reduced more in Group-C (6.26±0.70) than in group-A (6.69±1.40) and Group-B (7.75±1.21) at the end of the 3rd follow-up. Moreover, Group-C patients had the highest satisfaction level and lowest number of days with absence from work score compared to A and B (p<0.05). However, adverse effects were relatively higher in Group-C than A and B (p>0.05).Conclusion: Bisphosphonates and antibiotics combination therapy is more effective than single-drug therapy for CLBP associated with MC.

Efficacy of Bisphosphonates in Total Hip Arthroplasty Patients: Systematic Review and Meta-Analysis.

A systematic review and meta-analysis were conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A PICOS template was developed to ensure a structured approach. A search for relevant studies was performed across four databases, including Pubmed, Scopus, Embase, and Cochrane. They were all last searched on March 1st and were assessed using the Cochrane risk of bias tool for randomised studies. The final analysis included seven studies with a total of 126 study group participants and 144 control group participants. The studies looked at Bony Mass Density in terms of bone loss on Gruen's femoral zones after THA in a bisphosphonate (treatment) and control group (placebo/no treatment). The analysis revealed a statistically significant difference (p < 0.05) in favour of the bisphosphonate group in many of the included studies at 6, 12, and 24 postoperative months. This systematic review and meta-analysis, using the most recent applicable studies, showed the efficacy of bisphosphonates in limiting periprosthetic osteolysis after THA in a period between 6 and 24 postoperative months. Future studies should focus increasing group sizes and collecting results beyond the 2-year mark.

Clinical Efficacy of Bisphosphonates in Treating Osteoporosis in Diabetes Patients: A Meta-Analysis.

The aim of the study was to explore the clinical efficacy of bisphosphonates in patients with osteoporosis in diabetes patients by meta-analysis. Six databases were systematically searched from inception to January 30,2023. Studies evaluating the treatment of diabetic osteoporosis with bisphosphonates were included. Key outcome measures, such as bone mineral density (BMD), bone metabolism markers, pain improvement, and safety assessments, were extracted and analyzed. STATA MP V17.0 was used to calculate the combined effect size. After searching Chinese and English databases, 15 studies met the inclusion criteria of this study. The results of the meta-analysis showed that the BMD of patients with osteoporosis in diabetes increased significantly after bisphosphonate treatment, and the lumbar BMD increased by 0.08 g/cm² (95% CI: 0.05-0.11). Femoral neck BMD increased by 0.06 g/cm² (95% CI: 0.01-0.11); Ward's triangle BMD increased 0.07 g/cm² (95% CI: 0.04-0.09); and trochanter BMD increased by 0.06 g/cm² (95% CI: 0.04-0.08). In addition, bone alkaline phosphatase increased 1.95 μg/l (95% CI: 1.18-2.72), while serum tartrate-resistant acid phosphatase-5b decreased 1.28 U/l (95% CI: -1.81-0.75). Moreover, improvements in pain were statistically significant. The effects of bisphosphonates on osteocalcin (MD: -0.07; 95% CI: -1.12-1.25), serum calcium (MD: 0.01; 95% CI: -0.03-0.04), serum phosphorus (MD: 0.04; 95% CI: -0.03-0.10) and medication safety (OR: 1.75; 95% CI: 1.29-2.37) were not statistically significant. Bisphosphonates have a significant positive effect on bone mineral density and bone metabolism in patients with osteoporosis in diabetes and have good safety.

Preoperative prediction for periprosthetic bone loss and individual evaluation of bisphosphonate effect after total hip arthroplasty using artificial intelligence.

This study was designed to develop a model for predicting bone mineral density (BMD) loss of the femur after total hip arthroplasty (THA) using artificial intelligence (AI), and to identify factors that influence the prediction. Additionally, we virtually examined the efficacy of administration of bisphosphonate for cases with severe BMD loss based on the predictive model. The study included 538 joints that underwent primary THA. The patients were divided into groups using unsupervised time series clustering for five-year BMD loss of Gruen zone 7 postoperatively, and a machine-learning model to predict the BMD loss was developed. Additionally, the predictor for BMD loss was extracted using SHapley Additive exPlanations (SHAP). The patient-specific efficacy of bisphosphonate, which is the most important categorical predictor for BMD loss, was examined by calculating the change in predictive probability when hypothetically switching between the inclusion and exclusion of bisphosphonate. Time series clustering allowed us to divide the patients into two groups, and the predictive factors were identified including patient- and operation-related factors. The area under the receiver operating characteristic (ROC) curve (AUC) for the BMD loss prediction averaged 0.734. Virtual administration of bisphosphonate showed on average 14% efficacy in preventing BMD loss of zone 7. Additionally, stem types and preoperative triglyceride (TG), creatinine (Cr), estimated glomerular filtration rate (eGFR), and creatine kinase (CK) showed significant association with the estimated patient-specific efficacy of bisphosphonate. Periprosthetic BMD loss after THA is predictable based on patient- and operation-related factors, and optimal prescription of bisphosphonate based on the prediction may prevent BMD loss.

The efficacy of bisphosphonates for osteoporosis in young Cushing's disease patients with biochemical remission: a retrospective cohort study.

Patients with Cushing's disease (CD) often experience slow recovery of bone mineral density (BMD), and the effectiveness of anti-osteoporosis drugs in young CD patients who have achieved biochemical remission after surgery is not well understood. Therefore, we aimed to explore whether bisphosphonates could help accelerate the recovery of osteoporosis in young CD patients with remission. We retrospectively enrolled 34 young patients with CD who achieved postoperative biochemical remission. All patients suffered from osteoporosis before surgery and were divided into postoperative bisphosphonate treatment group (16 cases) and without bisphosphonate treatment group (18 cases). Clinical data, BMD (Z Value), and bone turnover markers were collected at the time of diagnosis and one year after successful tumor resection. The Z values in the lumbar spine showed slight improvement in both groups at follow-up compared to baseline, but this improvement was not statistically significant. There was no significant difference observed between the two groups at follow-up. One year after operation, bone formation markers (OC and P1NP) were significantly higher than those at baseline in both groups. However, OC and P1NP in the bisphosphonate treatment group were lower than those in control group at one year follow-up. In without bisphosphonate treatment group, β-CTX from follow-up visit was higher than that at baseline, while no significant difference was observed in the bisphosphonate treatment group before and after surgery. Young patients with Cushing's disease combined with osteoporosis might not benefit from bisphosphonate therapy for osteoporosis recovery in the first year after achieving biochemical remission.

Is Teriparatide Superior in Treating Osteoporotic Vertebral Compression Fractures in Comparison to Bisphosphonates Treatment Alone: A 2-Year Retrospective Analysis.

Retrospective cohort study. This study aimed to compare the efficacy of bisphosphonates and teriparatide in the management of osteoporotic vertebral compression fractures with regard to pain management, prevention of nonunion, and radiological as well as clinical outcomes. Osteoporosis refers to a skeletal disorder characterized by decreased bone strength caused by poor bone density and quality causing fragility, resulting in long periods of pain-related immobilization. In a 24-month follow-up retrospective study, 191 patients with osteoporotic vertebral compression fractures were randomly assigned to the bisphosphonate group (n=104) or the teriparatide group (n=87), with patients opting for their treatment between January 2016 and October 2020. Demographic data and patient-reported outcomes scores, including the Visual Analog Scale (VAS), Oswestry Disability Index (ODI), union rates, and kyphosis progression, were assessed at baseline, 6 months, 1 year, and 2 years after treatment. Both groups had a significant decrease in VAS, from 8.38±0.74 to 3.15±1.40 in the bisphosphonate group and from 8.49±0.73 to 1.11±0.31 in the teriparatide group. The ODI scores reduced significantly at 2-year follow-ups, recording 25.02±13.94 and 15.11±2.17 in the bisphosphonate and teriparatide groups, respectively. Risks of nonunion development were slightly higher at 11.53% in the bisphosphonate group and 8.63% in the teriparatide group required operative intervention. The kyphosis progression angles were also significantly lower in the teriparatide group (4.97°±0.78°) than in the bisphosphonate group (8.09°±1.25°). Over time, numerous studies have demonstrated the efficacy of bisphosphonates and teriparatide in ameliorating pain. In this study, the efficacy of teriparatide surpassed that of bisphosphonates in certain aspects, such as the initial 6-month union rates and reduction in the progression of segmental kyphosis. However, bisphosphonates and teriparatide yield similar and favorable union rates at 1 year and final follow-up.

Legg–Calvé–Perthes disease presenting with osteoarthritis: Mechanisms of the development and prospects of conservative therapy using bisphosphonates

BACKGROUND: Aseptic necrosis of the femoral head in children remains a subject of great interest among specialists, despite its long history of study. The LeggCalvPerthes disease is the most common form of aseptic necrosis of the femoral head in children. The necrotic lesion in the femoral head results from the blockage of the arterial blood supply to the epiphysis, leading to its infarction. Some children experience a more aggressive disease course, with signs of osteoarthritis, which can result in the early development of coxarthrosis. Numerous publications have demonstrated the successful use of bisphosphonates in adult patients with aseptic necrosis of the femoral head.&#x0D; AIM: To generalize data on the use of bisphosphonates in children with the LeggCalvPerthes disease presenting with signs of osteoarthritis through the analysis of contemporary global literature.&#x0D; MATERIALS AND METHODS: A literature search was conducted in the open databases of PubMed, Science Direct, and Google Scholar, and the analysis depth spanned 20 years. The search terms used included LeggCalvPerthes disease, aseptic (avascular) necrosis of the femoral head, and bisphosphonates. The review encompassed the literature on bisphosphonates, their biological action, effectiveness of their use in patients with aseptic necrosis of the femoral head, and results of our research.&#x0D; RESULTS: Studies on the efficacy of bisphosphonates in children with LeggCalvPerthes disease are limited. Currently, the effect of bisphosphonates on disease course and outcome is unknown. Despite this, mechanisms of chronic inflammation are increasingly mentioned in the literature, which may directly or indirectly influence the clinical course and outcome of the disease. The key is the hyperactivity of osteoclasts in osteonecrosis. The experience of using bisphosphonates in adult patients with aseptic necrosis of the femoral head had positive results in preventing the progression of the deformity of femoral head deformity.&#x0D; CONCLUSIONS: Bisphosphonates are specific inhibitors of osteoclast activity, which has been used in many diseases. The results and inferences of using bisphosphonates in children with LeggCalvPerthes disease will lead to the formulation of a new treatment algorithm.

Bisphosphonates attenuate age-related muscle decline in Caenorhabditis elegans.

Age-related muscle decline (sarcopenia) associates with numerous health risk factors and poor quality of life. Drugs that counter sarcopenia without harmful side effects are lacking, and repurposing existing pharmaceuticals could expedite realistic clinical options. Recent studies suggest bisphosphonates promote muscle health; however, the efficacy of bisphosphonates as an anti-sarcopenic therapy is currently unclear. Using Caenorhabditis elegans as a sarcopenia model, we treated animals with 100nM, 1, 10, 100 and 500μM zoledronic acid (ZA) and assessed lifespan and healthspan (movement rates) using a microfluidic chip device. The effects of ZA on sarcopenia were examined using GFP-tagged myofibres or mitochondria at days 0, 4 and 6 post-adulthood. Mechanisms of ZA-mediated healthspan extension were determined using combined ZA and targeted RNAi gene knockdown across the life-course. We found 100nM and 1μM ZA increased lifespan (P<0.001) and healthspan [954±53 (100nM) and 963±48 (1μM) vs. 834±59% (untreated) population activity AUC, P<0.05]. 10μM ZA shortened lifespan (P<0.0001) but not healthspan (758.9±37 vs. 834±59, P>0.05), whereas 100 and 500μM ZA were larval lethal. ZA (1μM) significantly improved myofibrillar structure on days 4 and 6 post-adulthood (83 and 71% well-organized myofibres, respectively, vs. 56 and 34% controls, P<0.0001) and increased well-networked mitochondria at day 6 (47 vs. 16% in controls, P<0.01). Genes required for ZA-mediated healthspan extension included fdps-1/FDPS-1 (278±9 vs. 894±17% population activity AUC in knockdown+1μM ZA vs. untreated controls, respectively, P<0.0001), daf-16/FOXO (680±16 vs. 894±17%, P<0.01) and agxt-2/BAIBA (531±23 vs. 552±8%, P>0.05). Life/healthspan was extended through knockdown of igdb-1/FNDC5 (635±10 vs. 523±10% population activity AUC in gene knockdown vs. untreated controls, P<0.01) and sir-2.3/SIRT-4 (586±10 vs. 523±10%, P<0.05), with no synergistic improvements in ZA co-treatment vs. knockdown alone [651±12 vs. 635±10% (igdb-1/FNDC5) and 583±9 vs. 586±10% (sir-2.3/SIRT-4), both P>0.05]. Conversely, let-756/FGF21 and sir-2.2/SIRT-4 were dispensable for ZA-induced healthspan [630±6 vs. 523±10% population activity AUC in knockdown+1μM ZA vs. untreated controls, P<0.01 (let-756/FGF21) and 568±9 vs. 523±10%, P<0.05 (sir-2.2/SIRT-4)]. Despite lacking an endoskeleton, ZA delays Caenorhabditis elegans sarcopenia, which translates to improved neuromuscular function across the life course. Bisphosphonates might, therefore, be an immediately exploitable anti-sarcopenia therapy.

Prevalence, predictors, dynamic bone change, and treatment efficacy of osteoporosis among chronic obstructive pulmonary disease patients: a prospective cohort study.

Osteoporosis is a silent chronic obstructive pulmonary disease (COPD) comorbidity that is often under-detected. We aimed to study the prevalence and potential predictors of osteoporosis in COPD. Dynamic changes in bone mass density (BMD) and treatment efficacy of bisphosphonate were also assessed. This prospective cohort study included COPD patients between January 2017 and January 2019. Demographics data, spirometric parameters, and C-reactive protein (CRP) were collected. Bone mineral density (BMD) at the lumbar spine (L2-4) and both femoral necks were measured after enrollment and the 12-month follow-up. Participants were categorized into three groups per the baseline BMD T-score: normal (≥ - 1.0), osteopenia (between -1.0 and - 2.5), and osteoporosis (≤ - 2.5). In the osteoporosis group, alendronate 70 mg/week with vitamin D and calcium was prescribed. In total, 108 COPD patients were enrolled. The prevalence of osteoporosis and osteopenia were 31.5 and 32.4%, respectively. Advanced age, lower body mass index (BMI), history of exacerbation in the previous year, and high CRP levels were significant predictors of osteoporosis. After 12 months, 35.3% in the osteoporosis group reported new vertebral and femoral fractures, compared to none in the non-osteoporosis group (p < 0.001). In the normal BMD and osteopenia groups showed a further decline in BMD after 12-month. Conversely, the osteoporosis group showed a statistically significant improvement in BMD after anti-resorptive treatment (p < 0.001). The prevalence of osteoporosis was high in Thai COPD patients. Advanced age, lower BMI, history of exacerbation, and high CRP levels were potential predictors. A rapid decline in BMD was observed in COPD patients without treatment.

Abstract #1406508: A Rare Case of Calcitriol-mediated Hypercalcemia in a Patient with Pneumocystis Jiroveci Pneumonia and the Role of Steroids in its Management

Calcitriol-mediated hypercalcemia is an uncommon complication of Pneumocystis jiroveci pneumonia (PJP). Some cases of PJP have been reported in patients with solid organ transplants and AIDS. Here we present a case of calcitriol-mediated hypercalcemia due to granulomatous Pneumocystis jiroveci pneumonia in a patient with a history of multiple sclerosis. A 45-year-old man with a medical history of multiple sclerosis, spondyloarthritis, smoking, and bipolar disorder was admitted for the evaluation of fever, fatigue, constipation, confusion, and weight loss of 10 Lbs over three months. His medications include rituximab, methotrexate, vitamin D-4000 IU, lithium, and calcium carbonate-600 mg. Laboratory evaluation showed elevated serum calcium (15 mg/dl) with a suppressed parathyroid hormone (9 pg/mL). Other pertinent findings include mildly elevated 25-hydroxyvitamin D (87 ng/ml), significantly elevated 1,25-dihydroxyvitamin D (381 pg/ml), and normal PTHrP (<2 pmol/L), vitamin A (0.82 mg/L) and TSH (1.31 mU/L). Extensive workup including AFB smear for tuberculosis, ACE level for sarcoidosis, SPEP for multiple myeloma, leukemia-lymphoma flow cytometry, and CT chest and PET-CT for malignancy were unremarkable. Treatment with large-volume intravenous fluids, calcitonin, and zoledronic acid followed by denosumab showed a transient reduction in serum calcium level to 10.5 mg/dl in 2 days and a rebound to a peak of 15.4 mg/dl in a week. Bronchoscopy with bronchoalveolar lavage which was done for persistent fever and new onset hypoxia revealed PJP confirmed by PCR. With this new finding, the diagnosis of PJP-induced calcitriol-mediated hypercalcemia was considered. He was then treated with Bactrim and prednisone 60 mg daily. Due to the severity of hypercalcemia, he required a hemodialysis session while waiting for the medications to take effect. His calcium normalized a week after the initiation of steroids and antibiotics and he was discharged on a slow prednisone taper. Clinic follow-up 4 weeks after discharge showed normal calcium, 1,25-dihydroxyvitamin D, and 25-hydroxyvitamin D levels. Discontinuation of prednisone was attempted but resulted in rebound elevation of 1,25-dihydroxyvitamin D requiring continuation of low-dose prednisone 5 mg. Our immunocompromised patient developed hypercalcemia induced by PJP infection due to granulomatous production of 1α-hydroxylase resulting in increased calcitriol formation. Steroids unsurprisingly appear to have the best impact on PJP-induced hypercalcemia because of their anti-inflammatory property. In this clinical entity, it inhibits inflammation and granuloma formation leading to a reduction in the release of 1α-hydroxylase and 1,25-dihydroxyvitamin D levels. It is essential to consider PJP as an etiology of hypercalcemia, especially in immunosuppressed patients. Steroid appears to be effective medical therapy in this setting. The timing and duration of treatment, and the efficacy of bisphosphonates and denosumab, require further studies.

The Efficacy of Bisphosphonate in the Treatment of Giant Cell Tumour of the Bone: A Systematic Review and Meta-Analysis.

Anti-osteoclastic mechanism of Bisphosphonate (BP) is crucial to treat Giant Cell Tumour of the Bone (GCTB), however no established guidelines of its use have been published. This systematic review and meta-analysis is the first to summarise recent clinical studies on the subject. A systematic search was performed based on PRISMA guidelines for clinical trials of BP administration in GCTB. Baseline data including BP regimen, dose and timing was summarised. The primary outcomes assessed were recurrence rate, metastases, survival rate, functional outcome, clinical outcome, radiological outcome, and adverse effect. We identified 8 articles from 2008-2020. Most studies administer 4mg of Zoledronic acid post-operatively, with five studies mentioning pre-operative administration and six studies describing post-operative administration. There was a total of 181 GCTB cases analysed in this study. The BP group presented lower recurrence rate than control group (three studies; Odds Ratio [OR] 0.15; 95% Confidence Interval [CI], 0.05 - 0.43; p<0.05; heterogeneity, I2=0%). As for survival rate, BP group is comparable to control group (two studies; OR 1.67; 95% CI, 0.06 - 48.46; p=0.77; heterogeneity, I2=65%). Bisphosphonate therapy offers satisfactory recurrence rate, functional outcome, clinical outcome, radiological outcome, survival rate and metastases rate in patients with GCTB, with minimal adverse effects. Pre- and post-operative administration of bisphosphonates in combination might be the most beneficial in minimalising the recurrence rate.

Clinical efficacy of bisphosphonates and monoclonal antibodies on bone mineral density following skeletal fractures

BackgroundBisphosphonates and monoclonal antibodies are drugs primarily developed to inhibit osteoclast-mediated bone resorption and are used to treat an array of skeletal pathologies. Their use is aimed at increasing bone health and therefore reducing fracture risks. The aim of this study was to evaluate the effectiveness of bone protection therapy on improving bone mineral density (BMD) in patients following a fracture. MethodsInclusion criteria consisted of patients who sustained a skeletal fracture and were subsequently commenced on bone protection therapy. Dual-energy X-ray Absorptiometry (DEXA) scans were performed at baseline and following a consented period of drug therapy. Bone health data included T-Scores, Z-Scores, FRAX Major, FRAX Hip and BMD. The clinical effectiveness of four bisphosphonates (alendronate, risedronate, pamidronate and zoledronate) and one monoclonal antibody (denosumab) were evaluated. ResultsA total of 100 patients were included in the study. Overall, bone protection therapy significantly improved Z-score Hip, Z-score Spine, T-score Spine and BMD Spine (p < 0.05). There was a marked difference between drug therapies. Denosumab and zoledronate were associated with the greatest treatment effect size. Alendronate only improved Z-score Spine and Z-score Hip (p < 0.05). Pamidronate and risedronate did not demonstrate any statistically significant improvement across any DEXA parameter. ConclusionOverall, bisphosphonates/monoclonal antibodies confer beneficial effects on bone health as measured by DEXA scans in patients following skeletal fractures. However, the magnitude of improvement varies among the commonly used drugs. Alendronate, zoledronate and denosumab were associated with greatest therapeutic benefit. Bone protection therapy did not improve fracture risk of patients (FRAX scores).

Bioinformatics analysis identification of AKT3 and RAC1 as key genes in postmenopausal osteoporosis.

Postmenopausal osteoporosis (PMO) is an aging-associated disease that manifests as degradation of bone tissue microstructure leading to decreased bone mass and increased bone fragility. Differentiation of peripheral blood mononuclear cells into osteoclasts is an important process in the development of PMO and identification of key genes that drive differentiation is essential to reveal the mechanism of PMO. The present study combined bioinformatics analysis of a Gene Expression Omnibus dataset of PMO and drug (bisphosphonate) target prediction using the STITCH database to identify hub genes in patients with PMO. Next, the expression of candidate hub genes was assessed in osteoclasts differentiated from THP-1 cells and small interfering RNA assays were performed to assess the function of selected hub genes. The present study identified 10 hub genes including WNT1, AKT3, disheveled segment polarity protein 1, cyclin D1, H2B clustered histone 17, JUN, EGFR, RAC1, actinin α1 (ACTN1) and ACTN2. Among these, AKT3 and RAC1 were highly upregulated during osteoclast differentiation, and knockdown of AKT3 and RAC1 using small interfering RNA enhanced the inhibitory effect of bisphosphonates on osteoclast differentiation and apoptosis of monocytes as assessed by tartrate-resistant acid phosphatase staining and flow cytometry examining Annexin V-FITC/PI staining, respectively. In conclusion, AKT3 and RAC1 were key for development of PMO and inhibiting AKT3 and RAC1 may improve the therapeutic efficacy of bisphosphonates.

Bisphosphonate therapy in otosclerosis: A scoping review.

ObjectiveOtosclerosis, a leading cause of deafness in adults, results from defective bone remodeling of the otic capsule. Bisphosphonates have been used to decrease bone remolding in many diseases, including otosclerosis. This study analyzes whether current literature supports bisphosphonate therapy as an effective treatment for otosclerosis.DesignScoping review.MethodsA search was performed in three electronic databases; PubMed, Scopus, and Cochrane Control Trials. Articles were screened independently by two masked reviewers based on prespecified inclusion and exclusion criteria. After unmasking, the two reviewers resolved discrepancies through discussion.ResultsFrom the search, 35 unique articles were identified for analysis. The dates of these publications range from 1982 to 2018. Further title and full‐text review identified six articles for inclusion in this review. Three of the studies included are randomized controlled trials (RCT)s, and three are retrospective case reviews. These studies analyzed bisphosphonate therapy regimens, but dose and study length varied, making direct comparisons difficult. Only one RCT study was able to show a statistically significant change between patients treated with bisphosphonates compared to a control group.ConclusionsThe efficacy of bisphosphonates for halting bone remodeling in otosclerosis remains unclear. Reviewing the literature, we found significant variations in experimental design and few studies of high‐level evidence. Future RCTs investigating therapies for otosclerosis are needed before a firm conclusion about bisphosphonates efficacy as a pharmacological treatment of otosclerosis.Level of Evidence: 3a.

Efficacy and safety of bisphosphonates on childhood osteoporosis secondary to chronic illness or its treatment: a meta-analysis.

Background:Bisphosphonates are a type of medication that prevents the loss of bone density. Secondary childhood osteoporosis reduces bone strength and results in an increased risk of fragility fracture. This meta-analysis aims to explore the efficacy and safety of bisphosphonates on secondary childhood osteoporosis.Methods:We performed a systematic search of PubMed, Cochrane library, and Web of Science databases up to 31 July 2022 to screen for random clinical trials (RCTs) on bisphosphonate treatment for childhood secondary osteoporosis. Data from selected studies, mainly changes in lumbar spine (LS) bone mineral density (BMD), changes in LS BMD Z-scores, fracture events, and adverse events (AEs), were extracted and analyzed.Results:Nine RCTs (n = 429 in total) were included in our meta-analysis. The meta-analysis indicated that bisphosphonates improved the changes in LS BMD [mean difference (MD) = 0.04, 95% confidence intervals (CIs) = 0.01–0.07, p < 0.01] and LS BMD Z-scores [MD = 0.52, 95% CI = 0.23–0.81, p < 0.01]. Use of bisphosphonates did not increase the risk of AEs [odds ratio (OR) = 1.61, 95% CI = 0.87–2.99, p = 0.13]. Subgroup analysis showed that routes of administration, but not causes of secondary osteoporosis, might influence the efficacy of bisphosphonates. IV bisphosphonates close to significantly improved the incidence of fracture (OR = 0.34, 95% CI: 0.11–1.08, p = 0.07).Conclusions:The use of bisphosphonates improves LS BMD without increasing AE rates, which supports the clinical use of bisphosphonates in secondary childhood osteoporosis. Further large RCTs are still warranted, especially for their long-term effects on fracture rates.

Effect of bisphosphonate on hip fracture in patients with osteoporosis or osteopenia according to age: a meta-analysis and systematic review

This meta-analysis and systematic review investigated the efficacy of bisphosphonates on the incidence of hip fracture (IHF) in patients of different ages with osteoporosis or osteopenia. We searched Web of...

Do bisphosphonates alter the clinico-radiological profile of children with Perthes disease? A systematic review and meta-analysis.

This meta-analysis is aimed to analyze the efficacy of bisphosphonates in the management of Perthes disease. A total of 8 animal and 7 human studies have been shortlisted for this analysis. In human studies, common variables for pain, Harris Hip Score (HHS), propensity for femoral head collapse, and total hip arthroplasty (THA), were assessed. In contrast, in animal studies, the data was recorded for epiphyseal quotient, trabecular volume, trabecular separation, trabecular thickness, and trabecular number. Meta-analysis of human studies on ONFH (Osteo-Necrosis of Femoral Head) revealed a statistically significant outcome in HHS [p<0.001; (95% CI: 4.79 - 8.87)], collapse of the femoral head [p=0.079; (95% CI: -0.16 - 0.01)], and THA [p=0.002; (95% CI: -0.19 - -0.04)] whereas the pain score showed an insignificant outcome [p=0.067; (95% CI: -0.62 - 0.04)]. The meta-analysis of selected variables in animal studies revealed a noteworthy outcome in bone volume (p<0.001, 95% Cl), trabecular number (p<0.001, 95% Cl), trabecular thickness (p<0.013, 95% Cl) and trabecular separation (p<0.026, 95% Cl) but not in epiphyseal quotient. Further, analysis of stratified datasets in animal studies revealed a contradictory outcome with significant observations described later in the paper. The use of bisphosphonates holds a promising treatment option in Perthes disease. Although, good quality RCTs are needed to validate it further.

Bisphosphonate therapy after liver transplant improves bone mineral density and reduces fracture rates: an updated systematic review and meta-analysis.

To investigate the efficacy of bisphosphonates and compare oral and IV formulations on bone mineral density (BMD) and fracture incidence in post-orthotopic liver transplant (OLT) patients. Electronic databases were searched, and six RCTs and three cohort studies were included out of 711 articles. Main outcomes included post-OLT BMD changes, fracture incidence, and treatment adverse reactions. Pairwise meta-analysis was conducted for binary and continuous outcomes, while pooled fracture incidence utilized single-arm meta-analysis. Post-OLT fracture incidence was reported in nine studies (n=591). Total fracture incidence was 6.6% (CI: 3.4-12.4%) in bisphosphonate group and 19.1% (CI: 14.3-25.1%) in calcium and vitamin D group. Total fractures were significantly lower in patients on bisphosphonate, compared to calcium and vitamin D (n=591; OR=0.037; CI: 0.18-0.77; P=0.008). Overall fractures were significantly lower in the oral group (n=263; OR=0.26; CI: 0.08-0.85; P=0.02) but not in the IV group (n=328; OR=0.45; CI: 0.16-1.26; P=0.129). Both oral and IV bisphosphonates are effective in reducing fracture incidence post-OLT compared to calcium and vitamin D. Oral formulations may also have an advantage over IV in reducing bone loss and fracture incidence post-OLT.

Oral bisphosphonates for osteoporosis in adult males with intellectual disabilities.

Oral bisphosphonates are first-line agents for treating osteoporosis in men, but there are no studies regarding efficacy of oral bisphosphonates for treatment of osteoporosis in ambulatory male adults with intellectual disability. Nine adult males with intellectual disability and increased fracture risk had been treated with weekly or monthly oral bisphosphonates, vitamin D and calcium for 1-3years. Post-treatment bone mineral density (BMD), serum 25(OH)D, parathyroid hormone and C-telopeptide of type I collagen were then determined for the first time. Weekly or monthly oral bisphosphonates were well tolerated and led to significant increases in BMD in all 9 individuals. Serum 25(OH)D level enhanced the "pecent increase of BMD" that occurred in response to bisphosphonate treatment (p<.05). Weekly or monthly oral bisphosphonates are well tolerated by ambulatory adult males with ID and are effective in increasing BMD. Higher serum levels of vitamin D appear to improve the efficacy of bisphosphonates and therefore reduce fracture risk in adult males with intellectual disability.

Efficacy of bisphosphonates in detection of early enamel caries using NIR fluorescence imaging and inhibition of caries progression.

NIR fluorescence imaging using bisphosphonate-Indocyanine green has been indicated for early interproximal caries detection. This study assessed diagnostic accuracy of caries detection by NIR fluorescence imaging with OsteoSense 750® (OS750) in vitro and ex vivo, and to analyze the therapeutic efficacy of a bisphosphonate (Etidronate) in inhibiting enamel caries progression in vitro.Methods: Four experiments were conducted using extracted human teeth; 1) to calculate the infiltration rate of OS750 into interproximal white spot lesions using fluorescence microscope, 2) to assess diagnostic accuracy of interproximal natural white spot lesions using desktop NIR fluorescence imaging device in vitro setting, 3) to assess diagnostic accuracy of artificially created deeper enamel carious lesion (0.5 mm~1.0 mm) using NIR fluorescence image through the head-mount display in ex vivo setting, 4) to compare the progression on the enamel caries lesions treated by Etidronate, NaF and distilled-water. Diagnostic accuracy was analyzed using sensitivity, specificity and receiver operating curves (ROC). The caries progression was calculated with micro-CT and was statistically analyzed using a two-way ANOVA and the Tukey HDS post-hoc test.Results: 1) The infiltration rate of OS750 was 101.83% ± 8.66 (Min: 90.10%, Max: 133.94%). 2) The average of sensitivity and specificity in vitro setting experiments were 86.7% ± 4.4% and 70% ± 11%, respectively. The average of area under the ROC curves (AUC) was 0.883 ± 0.059 indicating excellent performance. 3) The mean sensitivity and specificity in ex vivo setting was 82.97% ± 15% and 76.78% ± 13.27% respectively. 4) The carious lesion volume treated by Etidronate was significantly smaller at post treatment-1 (p<0.05) and treatment-2 (p<0.01) than the control. There was no significant difference in lesion volume in the Etidronate and NaF group at the time point of post treatment-1.Conclusion: This study suggests that bisphosphonates contribute to both early diagnosis of enamel caries and inhibition of caries progression.