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Journal of Clinical Pharmacology Apr 2023This systematic review and meta-analysis aimed to reveal the efficacy and safety of zoledronic acid compared with alendronate in patients with primary osteoporosis. The... (Meta-Analysis)
Meta-Analysis
This systematic review and meta-analysis aimed to reveal the efficacy and safety of zoledronic acid compared with alendronate in patients with primary osteoporosis. The PubMed, Embase, and the Cochrane Library databases were searched from the establishment of each database to April 2022 for comparative studies on the topic, including randomized controlled trials (RCTs) and cohort studies, and 2 authors individually extracted information and data concerning study design, baseline characteristics, bone mineral density (BMD), bone turnover markers, and adverse events (AEs). We identified 8 eligible trials, including 1863 participants. Pooled estimates demonstrated that, compared with alendronate, zoledronic acid showed no significant difference in increasing the BMD of the lumbar spine after 1 year (SMD = -0.03, 95%CI -0.15 to 0.09, I = 0.41%) or after 2 years (SMD = 0.16, 95%CI -0.12 to 0.43, I = 63%), and the BMD of the total hip after 1 year (SMD = -0.08, 95%CI -0.31 to 0.14, I = 64%) or after 2 years (SMD = 0.05, 95%CI -0.21 to 0.32, I = 61%). No significant difference in improving bone turnover markers, including serum C-terminal cross-linking telopeptide of type-1 collagen, urine N-terminal cross-linking telopeptide of type-1 collagen, and serum procollagen type-1 N-terminal propeptide, were found, whereas significantly higher total AE rates (RR = 2.27, 95%CI 1.60 to 3.21, I = 75%) were recorded within 3 days of infusion, but some lower AE rates, particularly of gastrointestinal AEs (RR = 0.6, 95%CI 0.44 to 0.83, I = 37%), were noted after 3 days of infusion. Compared with alendronate, zoledronic acid has achieved comparable therapeutic results in the treatment of primary osteoporosis in increasing BMD and reducing bone turnover marker levels. Zoledronic acid showed a better safety profile than alendronate with long-term use, especially with regards to gastrointestinal-related AEs.
Topics: Humans; Female; Alendronate; Zoledronic Acid; Diphosphonates; Bone Density Conservation Agents; Bone Density; Osteoporosis; Osteoporosis, Postmenopausal
PubMed: 36433675
DOI: 10.1002/jcph.2181 -
Frontiers in Endocrinology 2023Primary hyperparathyroidism (PHPT) is characterized by increased bone remodeling and hypercalcemia. Parathyroidectomy (PTX), the current standard of care, is recommended... (Meta-Analysis)
Meta-Analysis
Efficacy of antiresorptive agents bisphosphonates and denosumab in mitigating hypercalcemia and bone loss in primary hyperparathyroidism: A systematic review and meta-analysis.
PURPOSE
Primary hyperparathyroidism (PHPT) is characterized by increased bone remodeling and hypercalcemia. Parathyroidectomy (PTX), the current standard of care, is recommended in all symptomatic and some groups of asymptomatic patients. Anti-resorptive therapies (bisphosphonates and denosumab) have been used in patients where PTX is refused or contraindicated. In this meta-analysis, we investigated the effectiveness of anti-resorptives in preventing/treating PHPT-induced bone loss and mitigating hypercalcemia.
METHOD
PubMed, Scopus, and Cochrane Library databases were searched for articles with keywords containing PHPT, bisphosphonates, and denosumab in various combinations. We extracted and tabulated areal BMD (aBMD), serum mineral, and bone turnover parameters from the qualified studies and used comprehensive meta-analysis software for analysis.
RESULTS
Of the 1,914 articles screened, 13 were eligible for meta-analysis. In the pooled analysis, 12 months of anti-resoptives (bisphosphonates and denosumab) therapy significantly increased aBMD at the lumbar spine (Standard difference in means (SDM)=0.447, 95% CI=0.230 to 0.664, p=0.0001), femoral neck (SDM=0.270, 95% CI=0.049 to 0.491, p=0.017) and increased serum PTH (SDM=0.489, 95% CI=0.139 to 0.839, p=0.006), and decreased serum calcium (SDM=-0.545, 95% CI=-0.937 to -0.154, p=0.006) compared with baseline. 12 months of bisphosphonate use significantly increased aBMD only at the lumbar spine (SDM=0.330, 95% CI=0.088 to 0.571, p=0.007) with a significant increased in serum PTH levels (SDM=0.546, 95% CI= 0.162 to 0.930, p=0.005), and a decreased in serum calcium (SDM=-0.608, 95% CI=-1.048 to -0.169, p=0.007) and bone-turnover markers (BTMs) compared with baseline. Denosumab use for 12 months significantly increased aBMD at both the lumbar spine (SDM=0.828, 95% CI=0.378 to 1.278, p=0.0001) and femur neck (SDM=0.575, 95% CI=0.135 to 1.015, p=0.010) compared with baseline. Mean lumbar spine aBMD (SDM=0.350, 95% CI=0.041 to 0.659, p=0.027) and serum PTH (SDM=0.602, 95% CI= 0.145 to 1.059, p=0.010) were significantly increased after 12 months of alendronate use compared with placebo. When compared with baseline, alendronate significantly decreased BTMs after 12 months and increased aBMD without altering the PTH and calcium levels after 24 months.
CONCLUSION
Anti-resorptives are effective in mitigating bone loss and hypercalcemia in PHPT while maintaining or increasing aBMD. PTX reversed all changes in PHPT and normalized PTH levels.
Topics: Humans; Bone Density Conservation Agents; Diphosphonates; Alendronate; Denosumab; Hypercalcemia; Calcium; Hyperparathyroidism, Primary; Bone Density; Parathyroid Hormone; Bone Diseases, Metabolic; Lumbar Vertebrae
PubMed: 36817591
DOI: 10.3389/fendo.2023.1098841 -
Calcified Tissue International Nov 2023Buffered and effervescent alendronate (ALN-EFF) increases gastric pH and is reported to decrease the risk of gastrointestinal side effects compared to conventional... (Randomized Controlled Trial)
Randomized Controlled Trial
Buffered and effervescent alendronate (ALN-EFF) increases gastric pH and is reported to decrease the risk of gastrointestinal side effects compared to conventional formulations of alendronate (ALN). The clinical effectiveness of ALN-EFF, however, has not been investigated. This study aims to investigate if ALN-EFF is non-inferior to ALN in suppressing bone turnover markers (BTM). We conducted a 16-week prospective, randomized, open-label study comprising 64 postmenopausal women with BMD T-score < -1 naïve to osteoporosis treatment. Participants were randomized 1:1 to ALN or ALN-EFF. We collected blood samples at 0, 4, 8, and 16 weeks. Non-inferiority margin was determined as 12% (80% of efficacy retained), and an SD of 15% on change in CTx. CTx decreased by 58.2% ± 24.1% in the ALN group and by 46.9% ± 23.3% (CI - 38.42:- 55.35) in the ALN-EFF group (p = 0.08). The non-inferiority limit was 46.6%. With ALN-EFF the CI crosses the non-inferiority limit thus the test for non-inferiority was indeterminate. PINP decreased by 45.7 ± 22.6% in the ALN group and by 35.1 ± 20.7% in the ALN-EFF group (p = 0.07). Changes over time in the BTMs were not significantly different between the groups, p > 0.10 for both CTx and PINP. There was no difference in frequency of AEs or compliance between the two groups, but rate of discontinuation was lower with ALN-EFF. In conclusion, suppression of BTMs was not significantly different between the groups but formal non-inferiority could not be established.
Topics: Female; Humans; Alendronate; Osteoporosis, Postmenopausal; Prospective Studies; Bone Density; Bone Remodeling; Bone Density Conservation Agents
PubMed: 37803182
DOI: 10.1007/s00223-023-01140-w -
The International Journal of Oral &... 2022To evaluate the effects of ultraviolet (UV) treatment and alendronate immersion on the osseointegration of dental implants and mucosal attachment of dental implant...
PURPOSE
To evaluate the effects of ultraviolet (UV) treatment and alendronate immersion on the osseointegration of dental implants and mucosal attachment of dental implant abutments using a mongrel dog model.
MATERIALS AND METHODS
A total of 48 sandblasted, large-grit, acid-etched (SLA) titanium dental implants and 48 machined surface healing abutments in four male mongrel dogs were prepared. Implants and healing abutments were divided into four groups (n = 12 per group). The control (CON) group did not undergo additional surface treatments. The UV group was treated with UV for 15 minutes, and the alendronate-immersed (AN) group was soaked in 10-3 M alendronate for 24 hours. The UV treatment and alendronate soaking (UVAN) group was treated with alendronate, followed by UV irradiation. All implants were placed in the mandible of mongrel dogs, and the animals were sacrificed at 4 and 8 weeks postoperatively. Bone-to-implant contact (BIC), bone density, and connective tissue attachment were measured.
RESULTS
In cortical bone, the UV group exhibited significantly higher BIC compared to the CON and AN groups (P < .05). In contrast, the AN and UVAN groups did not have significantly higher BIC. In the trabecular bone, there was no statistical difference between the groups. No significant increase in bone density and connective tissue attachment was shown in any group.
CONCLUSION
UV treatment of SLA surface implants significantly increased osseointegration in cortical bone. The alendronate immersion did not increase osseointegration, and there was no synergic effect with UV treatment. Further, UV treatment and alendronate immersion of machined healing abutments did not significantly increase connective tissue attachment.
Topics: Male; Animals; Dogs; Osseointegration; Dental Implants; Alendronate; Immersion; Mucous Membrane
PubMed: 36450020
DOI: 10.11607/jomi.9626 -
Frontiers in Endocrinology 2021A link has been proposed between glucose homeostasis and bone metabolism. Bisphosphonates are first-line treatment of osteoporosis, and we aimed to investigate whether...
OBJECTIVE
A link has been proposed between glucose homeostasis and bone metabolism. Bisphosphonates are first-line treatment of osteoporosis, and we aimed to investigate whether the risk of developing type 2 diabetes was associated with prior use of alendronate.
RESEARCH DESIGN AND METHODS
We conducted a population-based nested case-control study through access to all discharge diagnoses (ICD-10 system) from the National Danish Patient Registry along with all redeemed drug prescriptions (ATC classification system) from the Health Service Prescription Registry. All cases with a diagnosis of type 2 diabetes between 2008 and 2018 were matched on sex and age with 3 randomly selected controls by incidence-density sampling. Exposure was defined as ever use of alendronate and further grouped as effective and compliant use. ORs were calculated by conditional logistic regression analysis with adjustment for several confounders and test for trend for dose-response relationship.
RESULTS
We included 163,588 patients with type 2 diabetes and 490,764 matched control subjects with a mean age of 67 years and 55% male subjects. The odds of developing type 2 diabetes were lower among ever users of alendronate (multiple adjusted OR: 0.64 [95% CI 0.62-0.66]). A test for trend suggested a dose-response relationship between longer effective use of alendronate and lower risk of type 2 diabetes.
CONCLUSION
These results suggest a possible protective effect of alendronate in a dose-dependent manner against development of type 2 diabetes.
Topics: Aged; Aged, 80 and over; Alendronate; Bone Density Conservation Agents; Case-Control Studies; Denmark; Diabetes Mellitus, Type 2; Diphosphonates; Female; Humans; Incidence; Male; Middle Aged; Osteoporosis; Registries
PubMed: 34867816
DOI: 10.3389/fendo.2021.771426 -
Bone Jan 2022Age-related trabecular microstructural deterioration and conversion from plate-like trabeculae to rod-like trabeculae occur because of unbalanced rapid remodeling. As... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Age-related trabecular microstructural deterioration and conversion from plate-like trabeculae to rod-like trabeculae occur because of unbalanced rapid remodeling. As denosumab achieves greater remodeling suppression and lower cortical porosity than alendronate, we hypothesized that denosumab might also preserve trabecular plate microstructure, bone stiffness and strength more effectively than alendronate.
METHODS
In this post hoc analysis of a phase 2 study, postmenopausal women randomized to placebo (P, n = 74), denosumab (D, n = 72), or alendronate (A, n = 68). HR-pQCT scans of the distal radius and tibia were performed at baseline and Month-12 (M12). Trabecular compartment was subjected to Individual Trabecula Segmentation while finite element analysis was performed to estimate stiffness and strength. Percent change from baseline at M12 of each parameter was compared between patient groups.
RESULTS
At the distal tibia, in the placebo group, plate surface area (pTb.S, -1.3%) decreased while rod bone volume fraction (rBV/TV, +4.5%) and number (rTb.N, +2.1%) increased. These changes were prevented by denosumab but persisted despite alendronate therapy (pTb.S: -1.7%; rBV/TV: +6.9%; rTb.N: +3.0%). Both treatments improved whole bone stiffness (D: +3.1%; A: +1.8%) and failure load (D: +3.0%; A: +2.2%); improvements using denosumab was significant compared to placebo (stiffness: p = 0.004; failure load: p = 0.003). At the distal radius, denosumab increased total trabecular bone volume fraction (BV/TV, +3.4%) and whole bone failure load (+4.0%), significantly different from placebo (BV/TV: p = 0.044; failure load: p = 0.046). Significantly different effects of either drug on plate and rod microstructure were not detected.
CONCLUSIONS
Denosumab preserved trabecular plate microstructure. Alendronate did not. However, estimated strength did not differ between denosumab and alendronate treated groups.
Topics: Alendronate; Bone Density; Denosumab; Female; Humans; Radius; Tibia
PubMed: 34530172
DOI: 10.1016/j.bone.2021.116187 -
Aging Clinical and Experimental Research Mar 2023Percutaneous vertebroplasty was the most common strategy for osteoporotic vertebral compression fracture. However, refracture after vertebroplasty also occurred and bone...
Sequential treatment of teriparatide and alendronate versus alendronate alone for elevation of bone mineral density and prevention of refracture after percutaneous vertebroplasty in osteoporosis: a prospective study.
BACKGROUND
Percutaneous vertebroplasty was the most common strategy for osteoporotic vertebral compression fracture. However, refracture after vertebroplasty also occurred and bone mineral density (BMD) was one of the main factors associated with refracture after percutaneous vertebroplasty.
AIMS
To investigate the efficacy of a short-sequential treatment of teriparatide followed by alendronate on prevention of refracture after percutaneous vertebroplasty in osteoporotic patients, and compare it with the therapy of alendronate alone.
METHODS
From January 2018 to January 2020, we recruited 165 female osteoporosis patients after percutaneous vertebroplasty who were assigned into sequential treatment of teriparatide followed by alendronate group (TPTD + ALN group) and alendronate alone group (ALN group). The vertebral fracture occurred during this process was also recorded in both the groups. A total of 105 participants completed the 1-year follow-up. Furthermore, BMD and serum procollagen type I N-terminal propeptide (PINP) and C-terminal cross-linking telopeptide of type I collagen (CTX) were compared between the two groups during 1-year follow-up.
RESULTS
The 105 patients were finally included, with 59 in ALN group and 46 in TPTD + ALN group. During 1-year follow-up, the vertebral refracture rate in TPTD + ALN group was much lower than that in ALN group (2.2% vs. 13.6%, p < 0.05). At 12 months, the BMDs at lumbar in TPTD + ALN group were significantly elevated when compared to the ALN group (0.65 ± 0.10 vs. 0.57 ± 0.07, p < 0.001).
DISCUSSION AND CONCLUSION
A short-sequential administration of teriparatide followed by alendronate was more effective in elevating the BMD and decreasing the refracture rate at 12-month follow-up, compared to the counterpart with alendronate alone.
Topics: Humans; Female; Teriparatide; Alendronate; Bone Density; Prospective Studies; Bone Density Conservation Agents; Osteoporosis, Postmenopausal; Fractures, Compression; Spinal Fractures; Osteoporosis; Vertebroplasty
PubMed: 36708462
DOI: 10.1007/s40520-023-02342-w -
Current Topics in Medicinal Chemistry 2021Osteoporosis is a worldwide healthcare challenge. Conventional medications for osteoporosis prevention are not clinically effective or associated with gastrointestinal...
BACKGROUND AND OBJECTIVE
Osteoporosis is a worldwide healthcare challenge. Conventional medications for osteoporosis prevention are not clinically effective or associated with gastrointestinal tract adverse effects. The present study aimed to comparatively investigate the effects of technetium-99 conjugated with methylene diphosphonate (Tc-MDP) and calcium carbonate and alendronate on the prevention and treatment of osteoporosis in glucocorticoid-induced osteoporosis rabbit model through evaluating bone alkaline phosphatase (B-ALP), TRAP-5b levels and histopathological parameters.
METHODS
Forty healthy female New Zealand rabbits were randomly divided into five groups (each n=8), including control group (Control Group), osteoporosis model group (GIO Group), osteoporosis model + Tc-MDP group (Tc-MDP Group), osteoporosis model + alendronate group (Alendronate Group), and osteoporosis model + calcium carbonate group (calcium carbonate Group). Animals in each group were treated with corresponding interventions for 14 weeks. The blood samples were collected at the first and 14th week, and B-ALP and TRAP-5b levels were detected by enzyme- linked immunosorbent assay (ELISA). The rabbits were anesthetized at the 14th week, and pathological cytological observation was performed on both femurs.
RESULTS
The age and weights of rabbits in different groups had no statistically significant differences (P>0.05). B-ALP levels in serum of all groups except for the Control Group decreased after treatment, but the differences were not statistically significant (P>0.05). TRAP-5b levels in serum of all groups increased after treatment. Specifically, differences in the GIO Group and calcium carbonate group were statistically significant (P<0.05), while differences in Tc-MDP Group and alendronate Group were not statistically significant (P<0.05). Pathological sections revealed that the control group presented normal bone tissue morphology. The bone tissue morphology of the Tc- MDP group and alendronate group was similar to control group and GIO group. Moreover, the calcium carbonate group and GIO group exhibited similar bone tissue morphology.
CONCLUSION
Tc-MDP has a preventive effect on the glucocorticoid-induced osteoporotic rabbit model. This osteoporosis preventive effect might be attributed to the capacities of Tc-MDP in promoting the osteoblasts generation and inhibiting the generation and reducing the activity of osteoclasts.
Topics: Alendronate; Animals; Bone Density Conservation Agents; Calcium Carbonate; Diphosphonates; Disease Models, Animal; Female; Glucocorticoids; Osteoporosis; Rabbits; Technetium
PubMed: 34348621
DOI: 10.2174/1568026621666210804114744 -
Bone Sep 2020The first clinical use of bisphosphonates was in Paget's disease of bone (PDB) when disodium etidronate was found to be effective at suppressing metabolic activity of...
The first clinical use of bisphosphonates was in Paget's disease of bone (PDB) when disodium etidronate was found to be effective at suppressing metabolic activity of the disease. Subsequently, PDB became a testing ground for many bisphosphonates using changes in alkaline phosphatase (ALP) as the primary outcome measure in clinical trials. Bisphosphonates are now considered to be the treatment of choice for PDB since they are highly effective at suppressing the elevations in bone turnover that are characteristic of the disease. Short term studies have shown that treatment with alendronate and risedronate can promote formation of lamellar bone in affected sites and improve x-ray appearances in some patients. Bisphosphonates have also been shown to improve bone pain in PDB and within the bisphosphonates, zoledronic acid (ZA) is most likely to give a favourable pain response. Many patients with PDB do not have pain however, even when there is increased metabolic activity and more research is needed to find out why this is the case. The effects of bisphosphonates on complications of PDB such as deformity, pathological fractures and deafness have not been adequately studied since most clinical trials have been short term and have not collected information on these important outcomes. The PRISM and PRISM-EZ studies investigated the long-term effects of bisphosphonates in patients with established PDB using a treat-to-target approach and showed that intensive bisphosphonate therapy aimed at normalising ALP was no more effective than symptom directed treatment with bisphosphonates at preventing complications of PDB. The Zoledronate in the Prevention of Paget's Disease (ZiPP) trial, which is currently in progress, seeks to determine whether early intervention with this potent bisphosphonate might be effective in preventing disease progression. Should the ZiPP study yield positive results, genetic testing coupled to prophylactic bisphosphonate therapy might represent a new indication for these highly effective inhibitors of bone resorption in future years.
Topics: Alendronate; Diphosphonates; Humans; Osteitis Deformans; Risedronic Acid; Zoledronic Acid
PubMed: 32512166
DOI: 10.1016/j.bone.2020.115465 -
Frontiers in Immunology 2023Antiretroviral therapy (ART) is not curative due to the existence of cellular reservoirs of latent HIV-1 that persist during therapy. Current research efforts to cure...
Antiretroviral therapy (ART) is not curative due to the existence of cellular reservoirs of latent HIV-1 that persist during therapy. Current research efforts to cure HIV-1 infection include "shock and kill" strategies to disrupt latency using small molecules or latency-reversing agents (LRAs) to induce expression of HIV-1 enabling cytotoxic immune cells to eliminate infected cells. The modest success of current LRAs urges the field to identify novel drugs with increased clinical efficacy. Aminobisphosphonates (N-BPs) that include pamidronate, zoledronate, or alendronate, are the first-line treatment of bone-related diseases including osteoporosis and bone malignancies. Here, we show the use of N-BPs as a novel class of LRA: we found in assays using primary cells from ART-suppressed people living with HIV-1 that N-BPs induce HIV-1 from latency to levels that are comparable to the T cell activator phytohemagglutinin (PHA). RNA sequencing and mechanistic data suggested that reactivation may occur through activation of the activator protein 1 signaling pathway. Stored samples from a prior clinical trial aimed at analyzing the effect of alendronate on bone mineral density, provided further evidence of alendronate-mediated latency reversal and activation of immune effector cells. Decay of the reservoir measured by IPDA was however not detected. Our results demonstrate the novel use of N-BPs to reverse HIV-1 latency while inducing immune effector functions. This preliminary evidence merits further investigation in a controlled clinical setting possibly in combination with therapeutic vaccination.
Topics: Humans; HIV Infections; HIV-1; Virus Activation; Virus Latency; Alendronate; HIV Seropositivity
PubMed: 37744358
DOI: 10.3389/fimmu.2023.1219250