-
BMJ Open Dec 2015Concerns have been raised about a possible link between bisphosphonate use, and in particular alendronate, and upper gastrointestinal (UGI) cancer. A number of... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
Concerns have been raised about a possible link between bisphosphonate use, and in particular alendronate, and upper gastrointestinal (UGI) cancer. A number of epidemiological studies have been published with conflicting results. We conducted a systematic review and meta-analysis of observational studies, to determine the risk of esophageal and gastric cancer in users of bisphosphonates compared with non-users.
DESIGN
We searched PubMed, MEDLINE, EMBASE, Web of Knowledge and Cochrane Database of Systematic Reviews for studies investigating bisphosphonates and esophageal or gastric cancer. We calculated pooled ORs and 95% CIs for the risk of esophageal or gastric cancer in bisphosphonate users compared with non-users. We performed a sensitivity analysis of alendronate as this was the most common single drug studied and is also the most widely used in clinical practice.
RESULTS
11 studies (from 10 papers) examining bisphosphonate exposure and UGI cancer (gastric and esophageal), met our inclusion criteria. All studies were retrospective, 6/11 (55%) case-control and 5/11(45%) cohort, and carried out using data from 5 longitudinal clinical databases. Combining 5 studies (1 from each database), we found no increased risk, OR 1.11 (95% CI 0.97 to 1.27) of esophageal cancer in bisphosphonate users compared with non-users and no increased risk of gastric cancer in bisphosphonate users, OR 0.96 (95% CI 0.82 to 1.12).
CONCLUSION
This is the fourth and most detailed meta-analysis on this topic. We have not identified any compelling evidence for a significantly raised risk of esophageal cancer or gastric cancer in male and female patients prescribed bisphosphonates.
Topics: Alendronate; Bone Density Conservation Agents; Diphosphonates; Esophageal Neoplasms; Humans; Stomach Neoplasms
PubMed: 26644118
DOI: 10.1136/bmjopen-2014-007133 -
Aging Clinical and Experimental Research Nov 2022Oral bisphosphonates are a key intervention in the treatment of osteoporosis and in reducing the risk of fragility fractures. Their use is supported by over 3 decades of... (Review)
Review
Oral bisphosphonates are a key intervention in the treatment of osteoporosis and in reducing the risk of fragility fractures. Their use is supported by over 3 decades of evidence; however, patient adherence to oral bisphosphonates remains poor in part due to complex dosing instructions and adverse events, including upper gastrointestinal symptoms. This problem has led to the development of novel oral bisphosphonate formulations. Buffered, effervescent alendronate is dissolved in water and so seeks to reduce upper gastro-intestinal adverse events, and gastro-resistant risedronate aims to reduce the complexity of dosing procedure (e.g. fasting prior to consumption) whilst still maintaining the efficacy of fracture risk reduction. Clinical trials and real-world data have been employed to demonstrate some benefits in terms of reduced upper gastro-intestinal adverse events, adherence, persistence and health economic outcomes. This report describes the result of an ESCEO (European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis) expert working group, which explores where oral bisphosphonates sit in current clinical practice guidelines, review their risk-benefit profile and the consequences of poor adherence before exploring novel oral bisphosphonate formulations and their potential clinical and health economic impact. Further research is required but there are signs that these novel, oral bisphosphonate formulations may lead to improved tolerance of oral bisphosphonates and thus, improved adherence and fracture outcomes.
Topics: Humans; Osteoporosis; Diphosphonates; Fractures, Bone; Risedronic Acid; Alendronate
PubMed: 36331798
DOI: 10.1007/s40520-022-02272-z -
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 -
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 -
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 -
International Journal of Surgery... Dec 2015The etiology of osteonecrosis of the femoral head (ONFH) is multifactorial. Treatment of ONFH is disease stage dependent. For early stages, femoral head preservation... (Review)
Review
The etiology of osteonecrosis of the femoral head (ONFH) is multifactorial. Treatment of ONFH is disease stage dependent. For early stages, femoral head preservation procedures are preferred including core decompression, muscle pedicle grafting and de-rotational osteotomy. Core decompression with bone grafting is considered the gold standard. However, the results are inconsistence and unpredictable. An effective non-invasive method of treatment is imperative. Recently, extracorporeal shockwave therapy (ESWT) has shown beneficial effects in ONFH. ESWT improves pain and function of the hip and regression of the ONFH lesion. ESWT is more effective than core decompression with or without bone grafting, cocktail therapy that combined HBO, ESWT and oral alendronate is shown effective for patients with early osteonecrosis. The purpose of the article is to review, update and summarize the clinical treatment of ONFH using shockwave therapy.
Topics: Alendronate; Bone Density Conservation Agents; Combined Modality Therapy; Femur Head Necrosis; High-Energy Shock Waves; Humans; Hyperbaric Oxygenation; Lupus Erythematosus, Systemic
PubMed: 26188081
DOI: 10.1016/j.ijsu.2015.06.080 -
Polish Journal of Pharmacology 2004Alendronate sodium, an aminobisphosphonate with potent antiresorptive activity, is used in the treatment of postmenopausal osteoporosis. Retinol, as a component of...
Alendronate sodium, an aminobisphosphonate with potent antiresorptive activity, is used in the treatment of postmenopausal osteoporosis. Retinol, as a component of multivitamin preparations, is frequently used especially by elderly people. There are no reports on the interaction of alendronate sodium and retinol. The aim of the present study was to investigate the effect of administration of alendronate sodium and retinol on mechanical properties of the femoral bone in bilaterally ovariectomized rats. The experiments were carried out on 3-month-old Wistar rats, divided into 7 groups: I - sham-operated control rats, II - ovariectomized control rats, III - ovariectomy + alendronate sodium 3 mg/kg po, IV - ovariectomy + retinol 700 IU/kg po, V - ovariectomy + retinol 3500 IU/kg po, VI - ovariectomy + alendronate sodium 3 mg/kg po + retinol 700 IU/kg po, VII - ovariectomy + alendronate sodium 3 mg/kg po + retinol 3500 IU/kg po. The drugs were administered to the rats daily by oral gavage for 28 days. Body mass gain, bone mass, bone mineral content and calcium content in the femur and L-4 vertebra and mechanical properties of the whole femur (extrinsic stiffness, ultimate load, breaking load, deformation caused by the ultimate load) and the neck of the femur (load at fracture), were examined. Bilateral ovariectomy induced osteopenic changes in the rat skeletal system. Alendronate sodium (3 mg/kg po) counteracted the development of osteopenia induced by ovariectomy. Retinol at both used doses unfavorably affected the examined bone parameters of ovariectomized rats. Retinol administered with alendronate sodium lessened the preventive action of alendronate on the development of osteopenic changes in the skeletal system of ovariectomized rats.
Topics: Alendronate; Animals; Bone Density; Bone Density Conservation Agents; Female; Femur; Rats; Vitamin A; Vitamins
PubMed: 15662095
DOI: No ID Found -
American Family Physician Oct 2004Osteoporosis is characterized by low bone mineral density and a deterioration in the microarchitecture of bone that increases its susceptibility to fracture. The World... (Review)
Review
Osteoporosis is characterized by low bone mineral density and a deterioration in the microarchitecture of bone that increases its susceptibility to fracture. The World Health Organization defines osteoporosis as a bone mineral density that is 2.5 standard deviations or more below the reference mean for healthy, young white women. The prevalence of osteoporosis in black women is one half that in white and Hispanic women. In white women 50 years and older, the risk of osteoporotic fracture is nearly 40 percent over their remaining lifetime. Of the drugs that have been approved for the prevention or treatment of osteoporosis, the bisphosphonates (risedronate and alendronate) are most effective in reducing the risk of vertebral and nonvertebral fractures. Risedronate has been shown to reduce fracture risk within one year in postmenopausal women with osteoporosis and in patients with glucocorticoid-induced osteoporosis. Hormone therapy reduces fracture risk, but the benefits may not outweigh the reported risks. Teriparatide, a recombinant human parathyroid hormone, reduces the risk of new fractures and is indicated for use in patients with severe osteoporosis. Raloxifene has been shown to lower the incidence of vertebral fractures in women with osteoporosis. Salmon calcitonin is reserved for use in patients who cannot tolerate bisphosphonates or hormone therapy.
Topics: Aged; Alendronate; Bone Density; Etidronic Acid; Female; Fractures, Bone; Humans; Male; Middle Aged; Osteoporosis, Postmenopausal; Raloxifene Hydrochloride; Randomized Controlled Trials as Topic; Risedronic Acid; Selective Estrogen Receptor Modulators
PubMed: 15508540
DOI: No ID Found -
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