Our library of drug research abstracts drawn from the medical literature is updated on a regular schedule, and you can be assured that new alendronate research articles will be listed here shortly after becoming available to us.
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Medical research on alendronate
Isosorbide mononitrate versus alendronate for postmenopausal osteoporosis.
Int J Gynaecol Obstet. 2008 Sep 20;
Nabhan AF, Rabie NH
OBJECTIVE: To compare the effectiveness, safety, and affordability of isosorbide mononitrate with alendronate for postmenopausal osteoporosis. METHODS: A randomized controlled trial of 60 postmenopausal women with osteoporosis. Participants were randomly assigned to receive either 20 mg daily of isosorbide mononitrate or 70 mg weekly of alendronate for 12 months. Bone mineral density (BMD) was measured using dual X-ray absorptiometry (DXA) at baseline and after 12 months. RESULTS: Both groups showed significant improvement in BMD. Isosorbide mononitrate yielded a comparable effect to alendronate for BMD and T-score at the end of the follow-up period. For BMD and T score the mean differences between the 2 groups were -0.005 (95% CI, -0.02 to 0.03) and 0.31 (95% CI, -0.03 to 0.64), respectively. A 10.8% and 12.1% change in BMD after 12 months was seen for isosorbide mononitrate and alendronate, respectively. CONCLUSION: Isosorbide mononitrate is comparable to alendronate. Nitric oxide donors may be an effective and affordable therapy to improve bone mineral density.
Delivery of serotonin to the brain by monocytes following phagocytosis of liposomes.
J Control Release. 2008 Sep 4;
Afergan E, Epstein H, Dahan R, Koroukhov N, Rohekar K, Danenberg HD, Golomb G
Many drugs are not able to enter the brain due to the presence of the blood-brain barrier (BBB) and therefore cannot be used in the treatment of diseases of the brain. Since it is now known that the brain is under immunological surveillance, we hypothesized that phagocytic cells of the innate immune system, mainly neutrophils and monocytes, can be exploited as transporters of drugs to the brain. To target circulating mononuclear phagocytic cells, negatively-charged nano-sized liposomes were formulated encapsulating serotonin, a BBB impermeable neurological drug. Brain uptake, biodistribution, and the mechanism of brain transport were examined in vitro and in rats and rabbits by utilizing double-radiolabeled (3)H (in the membrane) and (14)C-serotonin (in the core), and liposomes with fluorescent markers (membrane and core). The brain uptake of liposomal serotonin was significantly higher (0.138%+/-0.034 and 0.097%+/-0.011, vs. 0.068%+/-0.02 and 0.057%+/-0.01, 4 h and 24 h after IV administration in rats, serotonin liposomes and in solution, respectively). The same brain uptake of both empty and serotonin liposomes, the co-localization in the brain of both markers, and the unchanged ratio of (3)H:(14)C suggest that intact liposomes entered the brain. Since treatment of animals by liposomal alendronate resulted with inhibition of monocytes but not of neutrophils, and with no brain delivery, it is suggested that monocytes are the main transporters of liposomes to the brain.
J Clin Oncol. 2008 Sep 20; 26(27): 4426-34
Greenspan SL, Nelson JB, Trump DL, Wagner JM, Miller ME, Perera S, Resnick NM
PURPOSE: Androgen-deprivation therapy (ADT) for prostate cancer is associated with bone loss and osteoporotic fractures. Our objective was to examine changes in bone density and turnover with sustained, discontinued, or delayed oral bisphosphonate therapy in men receiving ADT. PATIENTS AND METHODS: A total of 112 men with nonmetastatic prostate cancer receiving ADT were randomly assigned to alendronate 70 mg once weekly or placebo in a double-blind, partial-crossover trial with a second random assignment at year 2 for those who initially received active therapy. Outcomes included bone mineral density and bone turnover markers. RESULTS: Men initially randomly assigned to alendronate and randomly reassigned at year 2 to continue had additional bone density gains at the spine (mean, 2.3% +/- 0.7) and hip (mean, 1.3% +/- 0.5%; both P < .01); those randomly assigned to placebo in year 2 maintained density at the spine and hip but lost (mean, -1.9% +/- 0.6%; P < .01) at the forearm. Patients randomly assigned to begin alendronate in year 2 experienced improvements in bone mass at the spine and hip, but experienced less of an increase compared with those who initiated alendronate at baseline. Men receiving alendronate for 2 years experienced a mean 6.7% (+/- 1.2%) increase at the spine and a 3.2% (+/- 1.5%) at the hip (both P < .05). Bone turnover remained suppressed. CONCLUSION: Among men with nonmetastatic prostate cancer receiving ADT, once-weekly alendronate improves bone density and decreases turnover. A second year of alendronate provides additional skeletal benefit, whereas discontinuation results in bone loss and increased bone turnover. Delay in bisphosphonate therapy appears detrimental to bone health.
Osteoporos Int. 2008 Sep 18;
Imai K, Ohnishi I, Matsumoto T, Yamamoto S, Nakamura K
A QCT-based nonlinear FEM was used to assess vertebral strength and mechanical parameters in postmenopausal women. It had higher discriminatory power for vertebral fracture than aBMD and vBMD. Alendronate effects were detected at 3 months, and marked bone density increases were noted in juxta-cortical areas compared to inner trabecular areas. INTRODUCTION: QCT-based finite element method (QCT/FEM) can predict vertebral compressive strength ex vivo. This study aimed to assess vertebral fracture risk and alendronate effects on osteoporosis in vivo using QCT/FEM. METHODS: Vertebral strength in 104 postmenopausal women was analyzed, and the discriminatory power for vertebral fracture was assessed cross-sectionally. Alendronate effects were also prospectively assessed in 33 patients with postmenopausal osteoporosis who were treated with alendronate for 1 year. RESULTS: On the age and body weight adjusted logistic regression, vertebral strength had stronger discriminatory power for vertebral fracture (OR per SD change: 6.71) than areal BMD and volumetric BMD. The optimal point for the vertebral fracture threshold was 1.95 kN with 75.9% sensitivity and 78.7% specificity. At 3 months, vertebral strength significantly increased by 10.2% from baseline. The minimum principal strain distribution showed that the area of high fracture risk decreased. At 1 year, the density of the inner cancellous bone increased by 8.3%, while the density of the juxta-cortical area increased by 13.6%. CONCLUSIONS: QCT/FEM had higher discriminatory power for vertebral fracture than BMD and detected alendronate effects at 3 months. Alendronate altered density distributions, thereby decreasing the area with a high fracture risk, resulting in increased vertebral strength.
J Med Invest. 2008 Aug; 55(3-4): 297-302
Takata S, Takao S, Yoshida S, Hayashi F, Yasui N
We studied the therapeutic effects of one-year alendronate treatment in three cases (two males and one female) of osteoporosis with parietal thinning of skull. Plain radiography and three dimensional computed tomography revealed asymmetric external thinning of the posteromedial part of the bilateral parietal bones. Technetium-99m methylenediphosphate bone scintigraphy did not show any changes in these three cases. Pretreatment levels of urinary type I collagen cross-linked N-telopeptides (NTX) in all three cases were high compared to the normal range. Pretreatment levels of serum bone-specific alkaline phosphatase (BAP) in the two male patients were high in contrast to the normal values in the female patient. Pretreatment mean bone mineral density (BMD) values of the 2nd to 4th lumbar vertebrae (L2-4BMD), head BMD, femoral neck BMD, and whole body BMD of all three patients were low compared with the respective normal ranges. One-year alendronate treatment decreased both urinary NTX and serum BAP in all three cases to normal values. Treatment also increased the whole body BMD in all three cases, the L2-4BMD of the female patient, the femoral neck BMD of the female patient and one male patient, and the head BMD of the female patient when compared to pretreatment levels.
Spine J. 2008 Sep 12;
Tanriover MD, Oz SG, Sozen T, Kilicarslan A, Guven GS
BACKGROUND CONTEXT: Pregnancy- and lactation-associated osteoporosis is an uncommon condition that may be a consequence of preexisting low bone density, loss of bone mineral content during pregnancy, and increased bone turnover. PURPOSE: To present a case of severe osteoporosis associated with pregnancy and lactation and its treatment protocol. STUDY DESIGN/SETTING: A tertiary care hospital. PATIENT SAMPLE: A young female after twin pregnancy presenting with severe osteoporosis. METHODS: The diagnosis was done on the basis of bone mineral density (BMD) measurement. The patient was treated with first alendronate and then strontium ranelate. She was considered as a candidate for kyphoplasty. RESULTS: A dramatic increase in the BMD and palliation of back pain were observed. CONCLUSIONS: Strontium ranelate may be a new alternative in the treatment of pregnancy- and lactation-associated osteoporosis.
Alendronate for fracture prevention in postmenopause.
Am Fam Physician. 2008 Sep 1; 78(5): 579-81
Holder KK, Kerley SS
BACKGROUND: Osteoporosis is an abnormal reduction in bone mass and bone deterioration leading to increased fracture risk. Alendronate (Fosamax) belongs to the bisphosphonate class of drugs, which act to inhibit bone resorption by interfering with the activity of osteoclasts. OBJECTIVES: To assess the effectiveness of alendronate in the primary and secondary prevention of osteoporotic fractures in postmenopausal women. SEARCH STRATEGY: The authors searched Central, Medline, and EMBASE for relevant randomized controlled trials published from 1966 to 2007. DATA COLLECTION AND ANALYSIS: The authors undertook study selection and data abstraction in duplicate. The authors performed meta-analysis of fracture outcomes using relative risks, and a relative change greater than 15 percent was considered clinically important. The authors assessed study quality through reporting of allocation concealment, blinding, and withdrawals. MAIN RESULTS: Eleven trials representing 12,068 women were included in the review. Relative and absolute risk reductions for the 10-mg dose were as follows. For vertebral fractures, a 45 percent relative risk reduction was found (relative risk [RR] = 0.55; 95% confidence interval [CI], 0.45 to 0.67). This was significant for primary prevention, with a 45 percent relative risk reduction (RR = 0.55; 95% CI, 0.38 to 0.80) and 2 percent absolute risk reduction; and for secondary prevention, with 45 percent relative risk reduction (RR = 0.55; 95% CI, 0.43 to 0.69) and 6 percent absolute risk reduction. For nonvertebral fractures, a 16 percent relative risk reduction was found (RR = 0.84; 95% CI, 0.74 to 0.94). This was significant for secondary prevention, with a 23 percent relative risk reduction (RR = 0.77; 95% CI, 0.64 to 0.92) and a 2 percent absolute risk reduction, but not for primary prevention (RR = 0.89; 95% CI, 0.76 to 1.04). There was a 40 percent relative risk reduction in hip fractures (RR = 0.60; 95% CI, 0.40 to 0.92), but only secondary prevention was significant, with a 53 percent relative risk reduction (RR = 0.47; 95% CI, 0.26 to 0.85) and a 1 percent absolute risk reduction. The only significance found for wrist fractures was in secondary prevention, with a 50 percent relative risk reduction (RR = 0.50; 95% CI, 0.34 to 0.73) and a 2 percent absolute risk reduction. For adverse events, the authors found no statistically significant difference in any included study. However, observational data raise concerns about potential risk for upper gastrointestinal injury and, less commonly, osteonecrosis of the jaw. AUTHORS' CONCLUSIONS: At 10 mg of alendronate per day, clinically important and statistically significant reductions in vertebral, nonvertebral, hip, and wrist fractures were observed for secondary prevention. The authors found no statistically significant results for primary prevention, with the exception of vertebral fractures, for which the reduction was clinically important.
Osteoarthritis Cartilage. 2008 Sep 9;
Hofstaetter JG, Wang J, Yan J, Glimcher MJ
OBJECTIVE: Characterize the effects of alendronate (ALN) on the repair process of the osteonecrotic femoral head as well as the development of secondary osteoarthritis in the ipsilateral hip in an established experimental model of osteonecrosis. METHODS: Osteonecrosis of the femoral head was induced surgically in 60 adult, male New Zealand white rabbits. Animals were randomized in two placebo- (saline) and two treatment-groups (ALN 150mug/kg/day S.C., 3x per wk) and were euthanized at 6 and 12 months post-operatively. Contralateral hip was used as control. Micro-Quantitative-CT (muQCT) analysis as well as histological assessment was performed in the femoral head and the acetabulum. Mankin Score was used to assess cartilage degeneration in the acetabulum. RESULTS: Repair in the osteonecrotic femoral head in the placebo group led to a significantly increased bone volume fraction (BVF) and volumetric bone mineral density (vBMD) in the trabecular region and to an increase in porosity in the cortical and subchondral region when compared to the normal femoral head on the contralateral side. ALN treatment significantly further increased BVF and vBMD in the trabecular region, and significantly reduced porosity and increased vBMD in the necrotic subchondral and cortical bone when compared to placebo. ALN led to a significant increase in vBMD in the subchondral region of the osteoarthritic acetabulum as well as to a significant reduction in articular cartilage degeneration. CONCLUSION: Inhibition of bone resorption by ALN treatment during repair of the osteonecrotic femoral head significantly increased bone mass in the trabecular region of the femoral head, inhibited subchondral resorption and reduced cartilage degeneration in the acetabulum.
J Pharm Sci. 2008 Sep 9;
Asnani M, Vyas K, Bhattacharya A, Devarakonda S, Chakraborty S, Mukherjee AK
Sodium alendronate, a member of bisphosphonate class of compounds commonly used for treatment of generalized bone disorders, exists in various hydrated forms. Dehydration of sodium alendronate trihydrate has been studied using variable temperature X-ray powder diffraction technique. The crystal structure of anhydrous sodium alendronate, prepared by heating the trihydrate sodium alendronate at 150 degrees C, has been determined from X-ray powder data using direct space global optimization technique for structure solution, followed by the Rietveld refinement. The structure of the anhydrous form of sodium alendronate is compared with that of the trihydrate form, which was determined previously from single crystal X-ray diffraction data. Both anhydrous and trihydrate sodium alendronate crystallize in monoclinic system with space group P2(1)/n. The crystal structure of the anhydrous sodium alendronate is built by edge-sharing of NaO(6) octahedra into a two-dimensional molecular sheet in the (011) plane, whereas in the trihydrate compound, one-dimensional chain along the (010) direction is generated by corner sharing of NaO(6) octahedra. (c) 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci.
Am J Manag Care. 2008 Sep; 14(9): 605-15
Tosteson AN, Burge RT, Marshall DA, Lindsay R
OBJECTIVE: To evaluate the cost-effectiveness of osteoporosis treatments for women at high fracture risk and estimate the population-level impact of providing bisphosphonate therapy to all eligible high-risk US women. STUDY DESIGN: Fractures, healthcare costs, and quality-adjusted life-years (QALYs) were estimated over 10 years using a Markov model. METHODS: No therapy, risedronate, alendronate, ibandronate, and teriperatide (PTH) were compared among 4 risk groups. Sensitivity analyses examined the robustness of model results for 65-year-old women with low bone density and previous vertebral fracture. RESULTS: Women treated with a bisphosphonate experienced fewer fractures and more QALYs compared with no therapy or PTH. Total costs were lowest for the untreated cohort, followed by risedronate, alendronate, ibandronate, and PTH in all risk groups except women aged 75 years with previous fracture. The incremental cost-effectiveness of risedronate compared with no therapy ranged from cost saving for the base case to $66,722 per QALY for women aged 65 years with no previous fracture. Ibandronate and PTH were dominated in all risk groups. (A dominated treatment has a higher cost and poorer outcome.) Treating all eligible women with a bisphosphonate would cost an estimated additional $5563 million (21% total increase) and would result in 390,049 fewer fractures (35% decrease). In the highest risk group, the additional cost of therapy was offset by other healthcare cost savings. CONCLUSIONS: Osteoporosis treatment of high-risk women is cost-effective, with bisphosphonates providing the most benefit at lowest cost. For highest risk women, costs are offset by savings from fracture prevention.