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Archives of Osteoporosis Jul 2022The efficacy of generic teriparatide in improving BMD at lumbar spine in patients with osteoporosis was similar to that of alendronate. It provided a new choice for... (Randomized Controlled Trial)
Randomized Controlled Trial
UNLABELLED
The efficacy of generic teriparatide in improving BMD at lumbar spine in patients with osteoporosis was similar to that of alendronate. It provided a new choice for osteoporosis treatment in Chinese population.
INTRODUCTION
To determine whether the efficacy of generic teriparatide is noninferior to alendronate for Chinese postmenopausal women with osteoporosis.
METHODS
Eligible patients were randomly assigned (2:1) in a 48-week, open-label design to receive 20 µg sc daily teriparatide or 70 mg oral weekly alendronate. Primary outcome was percentage change in BMD at the lumbar spine from baseline to 48 weeks and was assessed for non-inferiority. The same outcome was further assessed for superiority as a secondary endpoint.
RESULTS
Three hundred ninety-one and 196 participants were randomly assigned to the teriparatide or alendronate group, of whom 379 and 194 receiving at least one dose of teriparatide and alendronate treatment were eligible for the efficacy analysis. Teriparatide was non-inferior to alendronate for BMD change at lumbar spine (treatment difference: 0.7%, 95% CI: - 0.3 to 1.7%), which excluded the predefined non-inferiority margin of - 1.5%. However, teriparatide was not statistically superior to alendronate in improving BMD at lumbar spine (P = 0.169). At 48 weeks, changes in BMD at total hip were - 1.0% and 2.2% in teriparatide and alendronate group, respectively (P < 0.001). The incidence of new fracture showed no statistical difference between groups (P = 0.128). Serum P1NP and β-CTX levels significantly increased in the teriparatide group and markedly decreased in alendronate group (all P < 0.001 vs baseline). The adverse events (AEs) and serious AEs were more common in the teriparatide group than in the alendronate group, which were mainly teriparatide-related hypercalcemia, elevated alkaline phosphatase or parathyroid hormone, dizziness, and arthralgia.
CONCLUSIONS
Teriparatide was not inferior to alendronate in increasing BMD at lumbar spine in Chinese postmenopausal women, and they achieved these effects through different mechanisms.
Topics: Alendronate; Bone Density; Bone Density Conservation Agents; China; Female; Humans; Osteoporosis; Osteoporosis, Postmenopausal; Postmenopause; Prospective Studies; Teriparatide
PubMed: 35900607
DOI: 10.1007/s11657-022-01131-8 -
Advanced Healthcare Materials Jun 2023Osteoporosis is a degenerative bone disease resulting from bone homeostasis imbalance regulated by osteoblasts and osteoclasts. Treating osteoporotic bone defects tends...
Osteoporosis is a degenerative bone disease resulting from bone homeostasis imbalance regulated by osteoblasts and osteoclasts. Treating osteoporotic bone defects tends to be more difficult due to suppressed osteogenic differentiation, hyperactive osteoclastogenesis, and impaired angiogenesis. Hence, a drug carrier system composed of gelatin-coated hollow mesoporous silica nanoparticles (HMSNs/GM) loaded with pro-osteogenic parathyroid (PTH) and anti-osteoclastogenic alendronate (ALN) is constructed and compounded into calcium magnesium phosphate cement (MCPC). The spatial-temporal release of ions and drugs, controllable degradation rate, and abundant pore structure of MCPC composites enhance osteoporotic bone regeneration in ovariectomized rats by accelerating vascularization, promoting osteogenic differentiation and mineralization, and inhibiting osteoclastogenesis and bone resorption. The MCPC/HMSNs@ALN-PTH/GM demonstrates a synergistic threefold effect on osteogenesis, osteoclastogenesis, and angiogenesis. It improves the osteoporotic pathophysiological microenvironment and promotes osteoporotic vascularized bone defect regeneration, holding huge potential for other functional biomaterials design and clinical management.
Topics: Rats; Animals; Osteogenesis; Bone Regeneration; Osteoporosis; Osteoclasts; Biocompatible Materials; Alendronate
PubMed: 36780559
DOI: 10.1002/adhm.202203099 -
JAMA Jun 2024
Topics: Humans; Fractures, Bone; United States; United States Food and Drug Administration; Alendronate; Bone Density Conservation Agents; Hip Fractures; Bone Remodeling; Fractures, Spontaneous; Drug Approval; Drug Labeling
PubMed: 38748439
DOI: 10.1001/jama.2024.6077 -
The American Journal of Sports Medicine Jun 2023Mechanical loading and alendronate (ALN) can be used as noninvasive physical therapy methods for osteoarthritis (OA). However, the timing and efficacy for treatments are...
BACKGROUND
Mechanical loading and alendronate (ALN) can be used as noninvasive physical therapy methods for osteoarthritis (OA). However, the timing and efficacy for treatments are unknown.
PURPOSE
To determine whether the timing of mechanical loading and ALN influences the pathobiological changes of OA.
STUDY DESIGN
Controlled laboratory study.
METHODS
Mice with OA induced by anterior cruciate ligament transection were subjected to early (1-3 weeks) or late (5-7 weeks) axial compressive dynamic load or intraperitoneal injection of ALN. Changes in gait were analyzed using gait analysis system, pathobiological changes in subchondral bone, cartilage, osteophyte, and synovitis were assessed using micro-computed tomography, tartrate-resistant acid phosphatase staining, pathologic section staining, and immunohistochemistry at 1, 2, 4, and 8 weeks.
RESULTS
At 1, 2, and 4 weeks, the OA limb had lower mean footprint pressure intensity, lower bone volume per tissue volume (BV/TV) in the subchondral bone, and more osteoclasts. At 4 weeks, the early loading, ALN, and load + ALN treatments induced less cartilage destruction, with a corresponding reduction in Osteoarthritis Research Society International score and increased hyaline cartilage thickness. The treatments also resulted in fewer osteoclasts and higher BV/TV and bone mineral density of subchondral bone and suppressed inflammation and interleukin 1β- and tumor necrosis factor α-positive cells in synovium. At 8 weeks, early loading or load + ALN improved the mean footprint pressure intensity and knee flexion. At 8 weeks, early load + ALN had a synergistic effect on protecting hyaline cartilage and proteoglycans. Footprint pressure intensity and cartilage destruction were worse in late loading limbs, and no differences in BV/TV, bone mineral density, osteophyte formation, and synovium inflammation were found between the late load, ALN, and load + ALN groups and the anterior cruciate ligament transection group.
CONCLUSION
Dynamic axial mechanical loading or ALN in the early stages of knee trauma protected against OA by suppressing subchondral bone remodeling. However, late loading promoted cartilage degeneration in advanced OA, indicating that reduced loading should be performed in the late stages of OA to avoid the acceleration of OA.
CLINICAL RELEVANCE
Early low-level functional exercise or antiosteoporotic drugs could clearly slow or prevent the progression of early OA. For patients with mild to severe OA, loading reduction via brace protection or maintenance of joint stability via early ligament reconstruction surgery may ameliorate OA exacerbation.
Topics: Mice; Animals; Osteophyte; X-Ray Microtomography; Cartilage, Articular; Osteoarthritis; Alendronate; Bone Remodeling; Inflammation; Disease Models, Animal
PubMed: 37103335
DOI: 10.1177/03635465231164644 -
Journal of Internal Medicine Jun 2015Current prevention strategies for low-trauma fractures amongst older persons depend on the notions that fractures are mainly caused by osteoporosis (pathophysiology),... (Review)
Review
UNLABELLED
Current prevention strategies for low-trauma fractures amongst older persons depend on the notions that fractures are mainly caused by osteoporosis (pathophysiology), that patients at high risk can be identified (screening) and that the risk is amenable to bone-targeted pharmacotherapy (treatment). However, all these three notions can be disputed.
PATHOPHYSIOLOGY
Most fracture patients have fallen, but actually do not have osteoporosis. A high likelihood of falling, in turn, is attributable to an ageing-related decline in physical functioning and general frailty.
SCREENING
Currently available fracture risk prediction strategies including bone densitometry and multifactorial prediction tools are unable to identify a large proportion of patients who will sustain a fracture, whereas many of those with a high fracture risk score will not sustain a fracture.
TREATMENT
The evidence for the viability of bone-targeted pharmacotherapy in preventing hip fracture and other clinical fragility fractures is mainly limited to women aged 65-80 years with osteoporosis, whereas the proof of hip fracture-preventing efficacy in women over 80 years of age and in men at all ages is meagre or absent. Further, the antihip fracture efficacy shown in clinical trials is absent in real-life studies. Many drugs for the treatment of osteoporosis have also been associated with increased risks of serious adverse events. There are also considerable uncertainties related to the efficacy of drug therapy in preventing clinical vertebral fractures, whereas the efficacy for preventing other fractures (relative risk reductions of 20-25%) remains moderate, particularly in terms of the low absolute risk reduction in fractures with this treatment.
Topics: Aging; Alendronate; Bone Density; Bone Density Conservation Agents; Evidence-Based Medicine; Female; Fractures, Bone; Hip Fractures; Humans; Male; Metaphor; Osteoporosis; Risk Assessment; Risk Factors; Spinal Fractures; Treatment Outcome
PubMed: 25809279
DOI: 10.1111/joim.12366 -
Osteoporosis International : a Journal... Jul 2024This study evaluated the cost-effectiveness of sequential treatment with romosozumab-to-alendronate compared to alendronate monotherapy and teriparatide-to-alendronate,...
UNLABELLED
This study evaluated the cost-effectiveness of sequential treatment with romosozumab-to-alendronate compared to alendronate monotherapy and teriparatide-to-alendronate, in postmenopausal osteoporotic women from a Belgian healthcare perspective. Romosozumab-to-alendronate was found to be cost-effective compared to alendronate monotherapy and dominant compared to teriparatide-to-alendronate for osteoporotic women at high risk of fracture in Belgium.
PURPOSE
This study aimed to evaluate the cost-effectiveness of sequential treatment with romosozumab followed by alendronate compared to alendronate monotherapy and teriparatide followed by alendronate, in postmenopausal osteoporotic women at high risk of fracture, from a Belgian healthcare perspective. Romosozumab is reimbursed in Belgium since December 2021.
METHODS
A Markov microsimulation model was used to evaluate the cost-effectiveness of romosozumab-to-alendronate compared to alendronate monotherapy and to teriparatide-to-alendronate over a lifetime horizon. Patients transition between five different health states every 6 months based on fracture risks or death. The model was populated with Belgium-specific epidemiological and cost data, where available. The fracture risk reduction of romosozumab treatment was collated from the ARCH study, and from a published network meta-analysis. Costs were included from a healthcare perspective (NIHDI). Cost-effectiveness was reported in terms of costs per quality-adjusted life year (QALY), reported in Euro (€) 2022. Deterministic (DSA) and probabilistic sensitivity analyses (PSA) were performed.
RESULTS
Romosozumab-to-alendronate was associated with 0.12 additional QALYs at an additional cost of €2314 compared to alendronate monotherapy, resulting in an ICER of €19,978. Compared to teriparatide-to-alendronate, romosozumab-to-alendronate was found to be dominant, with higher QALYs and lower costs. The base-case results were robust to uncertainty in the input parameters when conducting the sensitivity analysis.
CONCLUSION
Sequential treatment with romosozumab followed by alendronate was found to be cost-effective compared to alendronate monotherapy and dominant compared to teriparatide followed by alendronate for postmenopausal women with osteoporosis at high risk of fracture in Belgium.
Topics: Humans; Female; Cost-Benefit Analysis; Osteoporotic Fractures; Bone Density Conservation Agents; Belgium; Osteoporosis, Postmenopausal; Quality-Adjusted Life Years; Markov Chains; Alendronate; Teriparatide; Aged; Drug Costs; Antibodies, Monoclonal; Drug Therapy, Combination; Middle Aged; Drug Administration Schedule; Drug Substitution
PubMed: 38565690
DOI: 10.1007/s00198-024-07043-2 -
Medicine Jun 2016Glucocorticoid-induced osteoporosis (GIOP) is a serious problem for patients with rheumatic diseases requiring long-term glucocorticoid treatment. Alendronate, a... (Meta-Analysis)
Meta-Analysis Review
Glucocorticoid-induced osteoporosis (GIOP) is a serious problem for patients with rheumatic diseases requiring long-term glucocorticoid treatment. Alendronate, a bisphosphonate, has been recommended in the prevention of GIOP. However, the efficacy and safety of alendronate in preventing GIOP remains controversial. We performed a meta-analysis to investigate the efficacy and safety of alendronate in preventing GIOP in patients with rheumatic diseases.We retrieved randomized controlled trials from PubMed, EMBASE, and the Cochrane Library. Two reviewers extracted the data and evaluated the risk of bias and quality of the evidence. We calculated the risk ratio (RR) with a 95% confidence interval (CI) for dichotomous outcomes, and the mean difference (MD) with a 95% CI for continuous outcomes using Review Manager, version 5.3.A total of 339 studies were found, and 9 studies (1134 patients) were included. Alendronate was not able to reduce the incidence of vertebral fractures (RR = 0.63, 95% CI: 0.10-4.04, P = 0.62) and nonvertebral fractures (RR = 0.40, 95% CI: 0.15-1.12, P = 0.08). Alendronate significantly increased the percent change in bone mineral density (BMD) at the lumbar spine (MD = 3.66, 95% CI: 2.58-4.74, P < 0.05), total hip (MD = 2.08, 95% CI: 0.41-3.74, P < 0.05), and trochanter (MD = 1.68, 95% CI: 0.75-2.61, P < 0.05). Significant differences were not observed in the percent change in BMD at the femoral neck (MD = -0.33, 95% CI: -2.79 to 2.13, P = 0.79) and total body (MD = 0.64, 95% CI: -0.06 to 1.34, P = 0.07). No significant differences in the adverse events were observed in patients treated with alendronate versus the controls (RR = 1.00, 95% CI: 0.94-1.07, P = 0.89). The odds of gastrointestinal adverse events were significantly reduced (RR = 0.77, 95% CI: 0.62-0.97, P < 0.05).Our analysis suggests that alendronate can increase the percent change in BMD at the lumbar spine, total hip, and trochanter, and is not associated with an increased incidence of gastrointestinal adverse events; however, the vertebral and nonvertebral fractures cannot be reduced. However, the results should be interpreted with caution due to the poor statistical power.
Topics: Alendronate; Bone Density; Bone Density Conservation Agents; Glucocorticoids; Humans; Osteoporosis; Rheumatic Diseases
PubMed: 27336902
DOI: 10.1097/MD.0000000000003990 -
Current Opinion in Pharmacology Jun 2018Bisphosphonates target and bind avidly to the mineral (hydroxyapatite) found in bone. This targeting ability has been exploited to design and prepare bisphosphonate... (Review)
Review
Bisphosphonates target and bind avidly to the mineral (hydroxyapatite) found in bone. This targeting ability has been exploited to design and prepare bisphosphonate conjugate prodrugs to deliver a wide variety of drug molecules selectively to bones. It is important that conjugates be stable in the blood stream and that conjugate that is not taken up by bone is eliminated rapidly. The prodrugs should release active drug at a rate appropriate so as to provide efficacy. Radiolabelling is the best method to quantify and evaluate pharmacokinetics, tissue distribution, bone uptake and release of the active drug(s). Recent reports have described bisphosphonate conjugates derived from the antiresorptive drug, alendronic acid and anabolic prostanoid drugs that effectively deliver prostaglandins and prostaglandin EP4 receptor agonists to bone and show enhanced anabolic efficacy and tolerability compared to the drugs alone. These conjugate drugs can be dosed infrequently (weekly or bimonthly) whereas the free drugs must be dosed daily.
Topics: Alendronate; Animals; Bone Diseases; Bone and Bones; Delayed-Action Preparations; Diphosphonates; Drug Carriers; Drug Compounding; Durapatite; Humans; Prodrugs; Prostaglandins; Receptors, Prostaglandin E, EP4 Subtype
PubMed: 29626715
DOI: 10.1016/j.coph.2018.03.010 -
Journal of Postgraduate Medicine 2016We present a case of polyarticular synovitis following alendronate treatment for osteoporosis. The patient had no evidence of rheumatoid arthritis, pyrophosphate...
We present a case of polyarticular synovitis following alendronate treatment for osteoporosis. The patient had no evidence of rheumatoid arthritis, pyrophosphate arthropathy, or seronegative/seropositive arthritis. Our main aim in this study is to highlight the potential adverse effects of alendronate and to warn orthopedic surgeons about the possibility of such a side effect that might lead orthopedic surgeons to administer wrong and unnecessary treatments like arthrocentesis. The withdrawal of alendronate is found to be the treatment of choice. Alendronate should be considered as a possible cause of synovitis or polyarthritis in patients treated with this agent in the absence of any other pathology. An association between alendronate and synovitis has rarely been described in the literature. We present a patient who developed polyarticular synovitis after treatment with alendronate and responded to its withdrawal.
Topics: Alendronate; Arthritis; Bone Density Conservation Agents; Drug Administration Schedule; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Middle Aged; Osteoporosis, Postmenopausal; Pain; Synovitis
PubMed: 26767974
DOI: 10.4103/0022-3859.174160 -
Aging Jan 2022To explore the anti-osteoporosis and anti-diabetes effects and potential underlying mechanisms of treatment with metformin and alendronate in diabetes mellitus mice.
BACKGROUND
To explore the anti-osteoporosis and anti-diabetes effects and potential underlying mechanisms of treatment with metformin and alendronate in diabetes mellitus mice.
METHODS
Eight-week-old C57 BL/KS db/db and db/+ female mice were evaluated according to the following treatment group for 12 weeks: control group, diabetes mellitus group, diabetes mellitus with metformin group, diabetes mellitus with Alendronate group, diabetes mellitus with metformin plus alendronate group. Glucose level, glucose tolerance test, bone mineral density, bone microarchitecture, bone histomorphometry, serum biomarkers, and qPCR analysis.
RESULTS
Combined metformin and alendronate can improve progression in glucose metabolism and bone metabolism, including blood glucose levels, blood glucose levels after 4 and 16 hours fasting, glucose tolerance test results, insulin sensitivity and reduces bone loss than the diabetes group. The use of alendronate alone can increase significantly serum glucagon-like peptide-1 levels than the diabetes group. The use of metformin alone can improve bone microstructure such as Tb.Sp and Tb.N of spine in diabetic mice.
CONCLUSION
The combined use of alendronate and metformin has an anti-diabetes and anti-osteoporotic effect compared with diabetic mice, but they appear to act no obvious synergistically between alendronate and metformin.
Topics: Alendronate; Animals; Blood Glucose; Bone Demineralization, Pathologic; Bone Density; Bone Density Conservation Agents; Diabetes Mellitus; Drug Therapy, Combination; Female; Glucose; Hypoglycemic Agents; Metformin; Mice; Mice, Inbred NOD
PubMed: 35027504
DOI: 10.18632/aging.203729