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The New England Journal of Medicine Jan 2017
Review
Topics: Alendronate; Bone Density Conservation Agents; Clinical Trials as Topic; Clinical Trials, Phase III as Topic; Drug Discovery; Drug Industry; Humans; Rotavirus Vaccines
PubMed: 28052221
DOI: 10.1056/NEJMra1510069 -
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 -
Medicine Oct 2018Alendronate has been used to prevent or treat glucocorticoid-induced osteoporosis (GIO), data regarding its efficacy are inconsistent. We conducted the current... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Alendronate has been used to prevent or treat glucocorticoid-induced osteoporosis (GIO), data regarding its efficacy are inconsistent. We conducted the current systematic review and meta-analysis to evaluate both efficacy and safety of alendronate in the treatment of GIO.
METHODS
PubMed, Embase, the Cochrane Controlled Trials Registry, and the China Academic Journal Network Publishing Databases were searched up through March 1, 2018. Randomized controlled trials (RCTs) involving patients which received alendronate treatment were included. Outcome measures were bone mineral density (BMD) changes, bone fractures, and adverse reactions. Data from the individual studies were pooled using random or fixed effect models based on heterogeneity. Effect size was reported as standardized mean differences (SMD) for continuous outcomes and pooled odds ratios (OR) for dichotomous outcomes, with 95% confidence interval (CI).
RESULTS
Overall, 10 studies involving 1002 patients were included in the present investigation. Alendronate treatment significantly increased BMD of the lumbar spine and femoral neck during 6 to 24 months. These beneficial effects were apparent at 12 months after treatment for the lumbar spine but not the femoral neck BMD. Alendronate treatment did not significantly change fracture risk nor induce significant differences in adverse gastrointestinal effects.
CONCLUSION
Alendronate significantly increases BMD of the lumbar spine and femoral neck in patients with GIO, but does not appear to reduce the risk of fractures. As relatively insufficient data regarding the GIO fracture incidence has been reported, more RCTs need to be carried out to determine the efficacy of alendronate in the prevention of GIO fracture.
Topics: Alendronate; Bone Density; Bone Density Conservation Agents; Female; Glucocorticoids; Humans; Male; Osteoporosis; Osteoporotic Fractures; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 30334952
DOI: 10.1097/MD.0000000000012691 -
Medical Science Monitor : International... Nov 2014Osteonecrosis or avascular osteonecrosis (AVN) of the femoral head is a devastating multifactorial disease that affects 20 000 persons each year in the United States.... (Meta-Analysis)
Meta-Analysis Review
Osteonecrosis or avascular osteonecrosis (AVN) of the femoral head is a devastating multifactorial disease that affects 20 000 persons each year in the United States. The purpose of this systematic review was to determine the efficacy and safety of alendronate for adult AVN during short- and long-term follow-up. Electronic databases were searched for randomized or nonrandomized clinical trials, cohort, case-control studies, and series of cases in which alendronate was used for treatment of adult AVN of the femoral head. Relevant articles with adequate data on reduction of pain, improvement of articular function, slowing of bone collapse progression, or need for total hip arthroplasty (THA) were included after applying inclusion and exclusion criteria. Eight articles involving 788 hips with evidence level 1b to 3b were included in this systematic review. Most studies suggested a positive short-term efficacy of alendronate treatment in reducing pain, improving articular function, slowing of bone collapse progression, and delaying the need for THA for adult AVN patients. The favorable long-term results were also presented in those treated patients after 10-year follow-up. In addition, there were no severe adverse effects associated with alendronate treatment observed during short- and long-term follow-up, and most of the included studies suggested use of alendronate in early AVN with small necrotic lesion to achieve better outcomes. The findings support consideration of alendronate use for adult AVN, particularly with early stage and small necrotic size. The lack of large-scale, randomized, and double-blind studies justifies new studies to demonstrate the detailed indication and the optimized strategy of alendronate treatment. Level of evidence: Level 3a.
Topics: Adolescent; Adult; Aged; Alendronate; Demography; Female; Femur Head Necrosis; Humans; Male; Middle Aged; Time Factors; Treatment Outcome; Young Adult
PubMed: 25424061
DOI: 10.12659/MSM.891123 -
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 -
Medicine May 2017Osteoporosis remains a clinical challenge. Teriparatide is an anabolic drug and alendronate is an antiresorptive agent; both are used in the treatment of osteoporosis.... (Comparative Study)
Comparative Study Meta-Analysis Review
OBJECTIVES
Osteoporosis remains a clinical challenge. Teriparatide is an anabolic drug and alendronate is an antiresorptive agent; both are used in the treatment of osteoporosis. Comprehensive reviews investigating the comparative safety and efficacy of teriparatide versus alendronate are scarce. Therefore, we conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the safety and efficacy of teriparatide versus alendronate for the treatment of postmenopausal osteoporosis.
METHODS
We conducted a comprehensive literature review of the PubMed, EMBASE, Cochrane Controlled Trials Registry, and the China Academic Journal Network Publishing databases for relevant RCTs of teriparatide versus alendronate in postmenopausal osteoporosis patients. Outcome measures were percentage change in lumbar spine and femoral neck bone mineral density (BMD) and incidence of vertebral and nonvertebral fractures. Effect size was reported as weighted mean differences (WMDs) for continuous outcomes and odds ratios (OR) for dichotomous outcomes, with associated 95% confidence intervals (CIs).
RESULTS
Six trials involving 618 patients were included. The meta-analysis demonstrated a significant increase in lumbar spine BMD (WMD: 3.46, 95% CI: 2.15-4.77, P < .00001), but not femoral neck BMD (WMD = 1.50, 95% CI: 0.04-2.95, P = .04), in postmenopausal osteoporosis patients treated with teriparatide compared with alendronate for 6 to 18 months. These beneficial effects were apparent in the lumbar spine at 12 months of treatment (WMD: 4.49, 95% CI: 2.57-6.40, P < .01). Teriparatide was not superior to alendronate in reducing fracture risk (OR: -0.03, 95% CI: -0.12 to 0.07; P = .52).
CONCLUSION
Teriparatide may be superior to alendronate for increasing lumbar spine BMD in postmenopausal osteoporosis. The efficacy and safety of long-term teriparatide and alendronate treatment in postmenopausal osteoporosis should be further investigated in clinical trials.
Topics: Alendronate; Bone Density Conservation Agents; Humans; Osteoporosis, Postmenopausal; Randomized Controlled Trials as Topic; Teriparatide
PubMed: 28538396
DOI: 10.1097/MD.0000000000006970 -
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 -
Bone May 2021To compare the efficacy of denosumab and alendronate on raising spine bone mineral density (BMD) in long-term glucocorticoid (GC) users. (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVES
To compare the efficacy of denosumab and alendronate on raising spine bone mineral density (BMD) in long-term glucocorticoid (GC) users.
METHODS
Adult patients receiving long-term prednisolone (≥2.5 mg/day for ≥1 year) were recruited and randomized to either subcutaneous denosumab (60 mg/6 months) or oral alendronate (70 mg/week). BMD (lumbar spine, femoral neck, hip) and bone markers (serum P1NP and CTX) were measured at month 0, 6 and 12. The difference in spine BMD (primary outcome) at month 12 was compared between the two groups.
RESULTS
139 subjects were recruited (age 50.0 ± 12.7 years; 96% women): 69 assigned denosumab and 70 assigned alendronate. At entry, 73(53%) patients were osteoporotic and 82(59%) patients were naive to the bisphosphonates. Baseline clinical characteristics and BMD values were similar in the two groups. At month 12, a significant gain in mean BMD at the lumbar spine (+3.5 ± 2.5%; p<0.001), hip (+0.9 ± 2.8%; p=0.01) and femoral neck (+1.04 ± 4.1%; p=0.047); was observed in denosumab-treated patients, whereas the corresponding change was +2.5 ± 2.9% (p<0.001), +1.6 ± 2.7% (p<0.001) and + 1.5 ± 3.9% (p=0.002) in the alendronate group. The spine, but not the hip or femoral neck, BMD at month 12 was significantly higher in the denosumab than alendronate group after adjustment for baseline BMD values, age, sex, osteoporosis risk factors and the cumulative prednisolone doses received in one year. The drop in P1NP and CTX was significantly higher in the denosumab than alendronate group. Frequency of adverse events (AEs), including infections, was similar in the two treatment arms. Seven patients withdrew from the study but not related to AEs.
CONCLUSIONS
In patients receiving long-term GCs, denosumab is superior to alendronate in raising the spine BMD after 12 months. Both drugs are well-tolerated.
Topics: Adult; Alendronate; Bone Density; Bone Density Conservation Agents; Denosumab; Female; Glucocorticoids; Humans; Male; Middle Aged
PubMed: 33631355
DOI: 10.1016/j.bone.2021.115902 -
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